Diagnosis and Management of Acute HIV Infection

Diagnosis and Management of Acute HIV Infection

Purpose and Development of This Guideline

Reviewed and updated: Ethan A. Cowan, MD, MS; July 2021
Writing group: Joseph P. McGowan, MD, FACP, FIDSA; Steven M. Fine, MD, PhD; Rona Vail, MD; Samuel T. Merrick, MD; Asa Radix, MD, MPH, PhD; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD
Committee: Medical Care Criteria Committee
Date of original publication: September 2018

Goals

This guideline on diagnosis and management of acute HIV infection was developed by the Medical Care Criteria Committee of New York State Department of Health AIDS Institute (NYSDOH AI) to guide clinicians in NYS who provide ambulatory, inpatient, and emergency medical care for adults ≥18 years old who present with signs or symptoms of acute HIV infection or report an exposure within the past 4 weeks.

This guideline provides evidence-based clinical recommendations for the diagnosis and treatment of acute HIV infection in adults, with the goals of ensuring that NYS clinicians are able to:

  • Recognize the risks for and signs and symptoms of acute HIV, include HIV infection in the differential diagnosis, and consider HIV testing in any person who presents with signs and symptoms suggestive of influenza (“flu”), mononucleosis (“mono”), or other viral syndromes, including suspected COVID-19.
  • Perform appropriate diagnostic and confirmatory testing when HIV infection is suspected and manage the treatment of acute HIV.
  • Meet the NYS requirements for reporting and partner notification.
  • Recommend or offer immediate initiation of antiretroviral therapy (ART) to improve the patient’s health and reduce the risk of HIV transmission; refer and confirm that patients can access optimal HIV care.
  • Initiate or refer the patient for prevention services.
TERMINOLOGY
  • Acute HIV infection: Describes the period immediately after infection with HIV when an individual is viremic and has detectable p24 antigen or has HIV RNA without diagnostic HIV antibodies. In the medical literature, “primary HIV infection” may describe this same period.
  • Recent infection: Generally used to describe the 6-month period after infection occurs.
  • Early infection: May refer to acute or recent infection, after which infection is defined as chronic.

Early diagnosis for early treatment: Accumulating evidence supports a decision to begin HIV treatment at the time of diagnosis [Lundgren, et al. 2015]. Initiation of ART during acute infection may have several beneficial clinical outcomes, including improved preservation of immunologic function, significantly reduced time to viral suppression, and reduction of the viral reservoir, which could be important for cure strategies [Pires, et al. 2004; Streeck, et al. 2006; Koegl, et al. 2009; Hocqueloux, et al. 2010; Ananworanich, et al. 2012; Buzon, et al. 2012; Lafeuillade, et al. 2012; Margolick, et al. 2012; Phanuphak, et al. 2012; Le, et al. 2013; Saez-Cirion, et al. 2013; Pilcher C, et al. 2015]. The risk of sexual transmission of HIV during acute or recent infection is significantly higher than during chronic infection [Pilcher CD, et al. 2004; Hollingsworth, et al. 2008; Pinkerton 2008; Hollingsworth, et al. 2015]; this difference likely correlates with high levels of viremia and is consistent with other routes of transmission [Bellan, et al. 2015]. The public health benefit of early ART initiation is well documented, with a significant reduction of HIV transmission among virally suppressed individuals. Further, in September 2017, the NYSDOH endorsed the consensus from the Prevention Access Campaign that Undetectable = Untransmittable (“U = U”), which indicates that individuals with a durable (≥6 months) undetectable viral load will not sexually transmit HIV [NYSDOH 2017; Prevention Access Campaign 2018].

Recognizing and diagnosing acute HIV infection is crucial to linking patients to care early and presents an important opportunity to reduce HIV transmission. Factors that may contribute to the increased risk for transmission during acute infection include:

  • Hyperinfectivity associated with both markedly high viral load levels (often much greater than 10 million viral copies/mm3) and increased infectiousness of the virus [Quinn, et al. 2000; Ma, et al. 2009].
  • Missed HIV diagnosis [Chin, et al. 2013; Nakao, et al. 2014]. Because the nonspecific flu- or mono-like symptoms are frequently unrecognized as symptoms of acute HIV infection or attributed to a nonspecific viral syndrome, the diagnosis is often missed. Missed diagnosis of acute HIV infection results in a lost opportunity to recommend treatment and risk-reduction counseling that could reduce both viral load levels and high-risk behavior [Colfax, et al. 2002; Steward, et al. 2009; Fonner, et al. 2012; Kroon, et al. 2017; Rutstein, et al. 2017].

For many reasons, detecting acute HIV infection is an essential link in the chain of prevention. Evidence demonstrates that patients with a recent diagnosis of HIV are more likely to reduce risk behaviors if they are given counseling at the time of testing [Steward, et al. 2009; Fonner, et al. 2012] and are linked to primary HIV care [Metsch, et al. 2008]. In addition, for those who elect to initiate ART, their risk of transmission is significantly diminished [Cohen, et al. 2011; Cohen, et al. 2016].

KEY POINTS
  • HIV is highly transmissible during acute infection; rapid initiation of antiretroviral therapy (ART) reduces transmission, with significant public health benefits, and early viral suppression preserves immune function, with significant clinical benefits for the individual with HIV.
  • Acute HIV often has nonspecific signs and symptoms and often goes unsuspected and undetected. This committee urges a high index of suspicion for acute infection and HIV testing for any individual who reports recent high-risk behavior or presents with signs or symptoms of influenza, mononucleosis, or other viral syndromes.
  • When HIV infection is diagnosed, immediate linkage to care is essential; ART dramatically reduces HIV-related morbidity and mortality, and viral suppression prevents HIV transmission.
  • The urgency of ART initiation is even greater if the newly diagnosed patient is pregnant, has acute HIV infection, is ≥50 years old, or has advanced disease. For these patients, every effort should be made to initiate ART immediately, ideally on the same day as diagnosis.
  • All clinical care settings should be prepared, either on-site or with a confirmed referral, to support patients in initiating ART as rapidly as possible after diagnosis.
  • When a diagnosis of acute HIV infection is made, clinicians should discuss the importance of notifying all recent contacts and refer patients to partner notification services, as mandated by New York State Law. The NYSDOH can provide assistance if necessary.
new york state law
  • New York State Law mandates that physicians must offer an HIV test to all patients aged 13 years and older (or younger with risk) if a previous test is not documented, even in the absence of symptoms consistent with acute HIV.
  • Effective November 28, 2016, amendments to the New York State Public Health Law removed the requirement for written or oral informed consent prior to ordering an HIV-related test, including elimination of written consent for HIV testing in New York State correctional facilities and removing references to consent forms. The objective of the update is to eliminate barriers to HIV testing and make HIV testing comparable to the manner in which other important laboratory tests are conducted. HIV testing remains voluntary, and patients have the right to refuse an HIV test, but obtaining written or oral consent for testing is no longer required in any setting. At a minimum, patients must be advised orally that an HIV test is going to be performed.
  • NYS Public Health Law Article 21 (Chapter 163 of the Laws of 1998) requires the reporting of individuals with HIV as well as AIDS to the NYSDOH. The law also requires that reports contain the names of sex or needle-sharing partners known to the medical provider or whom the infected individual wishes to have notified. The Medical Provider Report Form (PRF) (DOH-4189) must be completed within 14 days of diagnosis for individuals with the following diagnoses or with known sex or needle-sharing partners:
    • Initial/new HIV diagnosis: First report of HIV antibody positive test results.
    • Previously diagnosed HIV infection (non-AIDS): Applies to a medical provider who is seeing the patient for the first time.
    • Initial/new diagnosis of AIDS: Including <200 CD4 cells/µL or opportunistic infection (AIDS-defining illness).
    • Previously diagnosed AIDS: Applies to a medical provider who is seeing the patient for the first time.
    • Known sex or needle-sharing partners of individuals with diagnosed HIV infection.

Guideline Development

This guideline was developed by the NYSDOH AI Clinical Guidelines Program, which is a collaborative effort between the NYSDOH AI Office of the Medical Director and the Johns Hopkins University School of Medicine, Division of Infectious Diseases.

Established in 1986, the goal of the Clinical Guidelines Program is to develop and disseminate evidence-based, state-of-the-art clinical practice guidelines to improve the quality of care provided to people who have HIV, HCV, or sexually transmitted infections; people with substance use issues; and members of the LGBTQ community. NYSDOH AI guidelines are developed by committees of clinical experts through a consensus-driven process.

The NYSDOH AI charged the Medical Care Criteria Committee (adult HIV and related guidelines) with developing evidence-based clinical recommendations for the diagnosis and management of acute HIV infection. The resulting recommendations are based on an extensive review of the medical literature and reflect a consensus among this panel of experts. Each recommendation is rated for strength and quality of the evidence (see below). If recommendations are based on expert opinion, the rationale for the opinion is included.

AIDS Institute Clinical Guidelines Program: Recommendations Ratings
(updated June 2019 [a])
Strength of Recommendation Ratings
A Strong recommendation
B Moderate recommendation
C Optional
Quality of Supporting Evidence Ratings
1 Evidence is derived from published results of at least one randomized trial with clinical outcomes or validated laboratory endpoints.
* Evidence is strong because it is based on a self-evident conclusion(s); conclusive, published, in vitro data; or well-established practice that cannot be tested because ethics would preclude a clinical trial.
2 Evidence is derived from published results of at least one well-designed, nonrandomized clinical trial or observational cohort study with long-term clinical outcomes.
2† Evidence has been extrapolated from published results of well-designed studies (including non-randomized clinical trials) conducted in populations other than those specifically addressed by a recommendation. The source(s) of the extrapolated evidence and the rationale for the extrapolation are provided in the guideline text. One example would be results of studies conducted predominantly in a subpopulation (e.g., one gender) that the committee determines to be generalizable to the population under consideration in the guideline.
3 Recommendation is based on the expert opinion of the committee members, with rationale provided in the guideline text.
  1. With the June 2019 update, the ratings for quality of supporting evidence were expanded to add the * rating and the 2† rating.
References

Ananworanich J, Schuetz A, Vandergeeten C, et al. Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection. PLoS One 2012;7(3):e33948. [PMID: 22479485

Bellan SE, Dushoff J, Galvani AP, et al. Reassessment of HIV-1 acute phase infectivity: accounting for heterogeneity and study design with simulated cohorts. PLoS Med 2015;12(3):e1001801. [PMID: 25781323

Buzon M, Siess K, Sone A. Treatment of early HIV infection reduces viral reservoir to levels found in elite controllers. Abstract 151. CROI; 2012 Mar 5-8; Seattle, WA.

Chin T, Hicks C, Samsa G, et al. Diagnosing HIV infection in primary care settings: missed opportunities. AIDS Patient Care STDS 2013;27(7):392-397. [PMID: 23802143]

Cohen MS, Chen YQ, McCauley M, et al. Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med 2016;375(9):830-839. [PMID: 27424812

Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011;365(6):493-505. [PMID: 21767103

Colfax GN, Buchbinder SP, Cornelisse PG, et al. Sexual risk behaviors and implications for secondary HIV transmission during and after HIV seroconversion. AIDS 2002;16(11):1529-1535. [PMID: 12131191

Fonner VA, Denison J, Kennedy CE, et al. Voluntary counseling and testing (VCT) for changing HIV-related risk behavior in developing countries. Cochrane Database Syst Rev 2012;(9):Cd001224. [PMID: 22972050

Hocqueloux L, Prazuck T, Avettand-Fenoel V, et al. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS 2010;24(10):1598-1601. [PMID: 20549847

Hollingsworth TD, Anderson RM, Fraser C. HIV-1 transmission, by stage of infection. J Infect Dis 2008;198(5):687-693. [PMID: 18662132

Hollingsworth TD, Pilcher CD, Hecht FM, et al. High transmissibility during early HIV infection among men who have sex with men-San Francisco, California. J Infect Dis 2015;211(11):1757-1760. [PMID: 25542958

Koegl C, Wolf E, Hanhoff N, et al. Treatment during primary HIV infection does not lower viral set point but improves CD4 lymphocytes in an observational cohort. Eur J Med Res 2009;14(7):277-283. [PMID: 19661009

Kroon E, Phanuphak N, Shattock AJ, et al. Acute HIV infection detection and immediate treatment estimated to reduce transmission by 89% among men who have sex with men in Bangkok. J Int AIDS Soc 2017;20(1):21708. [PMID: 28691441

Lafeuillade A, Hittinger G, Lambry V. Long-term control of HIV reservoir after a 2-year ART course at acute infection. Abstract 358. CROI; 2012 Mar 5-8; Seattle, WA.

Le T, Wright EJ, Smith DM, et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med 2013;368(3):218-230. [PMID: 23323898]

Lundgren JD, Babiker AG, Gordin F, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 2015;373(9):795-807. [PMID: 26192873

Ma ZM, Stone M, Piatak M, Jr., et al. High specific infectivity of plasma virus from the pre-ramp-up and ramp-up stages of acute simian immunodeficiency virus infection. J Virol 2009;83(7):3288-3297. [PMID: 19129448

Margolick J, Apuzzo L, Tossonian H. Effect of randomized HAART on viral suppression off therapy in patients with acute/early HIV infection. Abstract 356. CROI; 2012 Mar 5-8; Seattle, WA.

Metsch LR, Pereyra M, Messinger S, et al. HIV transmission risk behaviors among HIV-infected persons who are successfully linked to care. Clin Infect Dis 2008;47(4):577-584. [PMID: 18624629

Nakao JH, Wiener DE, Newman DH, et al. Falling through the cracks? Missed opportunities for earlier HIV diagnosis in a New York City Hospital. Int J STD AIDS 2014;25(12):887-893. [PMID: 24535693

NYSDOH. Dear colleague letter. 2017 Sep. https://www.health.ny.gov/diseases/aids/ending_the_epidemic/docs/september_physician_letter.pdf [accessed 2018 Aug 21]

Phanuphak N, Teeratakulpisarn N, Mungyu P. Time to undetectable HIV RNA in ano-genital compartment of acute HIV Thai male subjects treated with 5- and 3-drug HAART. Abstract 555. CROI; 2012 Mar 5-8; Seattle, WA.

Pilcher C, Hatano H, Dasgupta A, et al. Providing same-day, observed ART to newly diagnosed HIV+ outpatients is associated with improved virologic suppression. 8th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2015 Jul 19-22; Vancouver, Canada.

Pilcher CD, Tien HC, Eron JJ, Jr., et al. Brief but efficient: acute HIV infection and the sexual transmission of HIV. J Infect Dis 2004;189(10):1785-1792. [PMID: 15122514

Pinkerton SD. Probability of HIV transmission during acute infection in Rakai, Uganda. AIDS Behav 2008;12(5):677-684. [PMID: 18064559

Pires A, Hardy G, Gazzard B, et al. Initiation of antiretroviral therapy during recent HIV-1 infection results in lower residual viral reservoirs. J Acquir Immune Defic Syndr 2004;36(3):783-790. [PMID: 15213561]

Prevention Access Campaign. Prevention Access Campaign consensus statement: Risk of sexual transmission of HIV from a person living with HIV who has an undetectable viral load. 2018 Jan 28. https://www.preventionaccess.org/consensus [accessed 2018 Aug 21]

Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000;342(13):921-929. [PMID: 10738050

Rutstein SE, Ananworanich J, Fidler S, et al. Clinical and public health implications of acute and early HIV detection and treatment: a scoping review. J Int AIDS Soc 2017;20(1):21579. [PMID: 28691435

Saez-Cirion A, Bacchus C, Hocqueloux L, et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog 2013;9(3):e1003211. [PMID: 23516360

Steward WT, Remien RH, Higgins JA, et al. Behavior change following diagnosis with acute/early HIV infection-a move to serosorting with other HIV-infected individuals. The NIMH Multisite Acute HIV Infection Study: III. AIDS Behav 2009;13(6):1054-1060. [PMID: 19504178

Streeck H, Jessen H, Alter G, et al. Immunological and virological impact of highly active antiretroviral therapy initiated during acute HIV-1 infection. J Infect Dis 2006;194(6):734-739. [PMID: 16941338

Presentation and Diagnosis

Reviewed and updated: Ethan A. Cowan, MD, MS, with the Medical Care Criteria Committee; July 2021

RECOMMENDATIONS
Presentation
  • Clinicians should include acute HIV infection in the differential diagnosis for anyone (regardless of reported risk) who presents with signs or symptoms of influenza (“flu”), mononucleosis (“mono”), or other viral syndromes (A3), especially when the patient:
    • Presents with a rash. (A2)
    • Requests HIV testing. (A3)
    • Reports recent sexual or parenteral exposure to a person with or at risk of HIV infection. (A2)
    • Presents with a newly diagnosed sexually transmitted infection. (A2)
    • Presents with aseptic meningitis. (A2)
    • Is pregnant or breastfeeding. (A3)
    • Is currently taking antiretroviral medications for pre- or post-exposure prophylaxis (PrEP or PEP). (A3)
  • Diagnostic HIV RNA testing should be considered for patients who present with compatible symptoms (see Box 1: Acute Retroviral Syndrome), particularly in the presence of a sexually transmitted infection [Patel, et al. 2006] or a recent sexual or parenteral exposure with a partner known to have HIV or with unknown HIV serostatus. (A2)
When Acute HIV Infection Is Suspected
  • Clinicians should always perform a plasma HIV RNA assay in conjunction with an antigen/antibody combination screening test. (A2)
  • Clinicians should use a 4th-generation antigen/antibody combination assay (preferred) as the initial HIV screening test according to the CDC’s Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens.
    • If the screening test is reactive, clinicians should perform an HIV-1/HIV-2 antibody-differentiation immunoassay to confirm HIV infection. (A1)
    • Note: When rapid antibody screening is performed, even with a rapid 4th-generation test, a laboratory-based 4th-generation immunoassay is recommended for follow-up diagnostic HIV testing.
Diagnosis
  • Clinicians can presume the diagnosis of acute HIV when high levels (>10,000 copies/mL) of HIV RNA are detected in plasma with sensitive nucleic acid amplification testing (NAAT), and the result of the HIV screening or type-differentiation test is negative or indeterminate. (A2)
  • When a low-level quantitative HIV RNA viral load result (<10,000 copies/mL) is obtained in the absence of serologic evidence of HIV infection, the clinician should repeat HIV RNA testing and perform a 4th-generation antigen/antibody combination assay to exclude a false-positive result. (A2)
    • Note: A serologic test result that does not meet the criteria for HIV infection is a nonreactive screening result (antibody or antibody/antigen combination) or a reactive screening result with a nonreactive or indeterminate antibody-differentiation confirmatory result.
  • Clinicians should seek expert consultation when an ambiguous HIV result is obtained for an individual taking PrEP because the diagnosis of acute HIV can be particularly challenging in patients taking PrEP. (A3) See NYSDOH AI guideline PrEP to Prevent HIV and Promote Sexual Health > Suspected Acute HIV.
ART Initiation
Partner Notification
  • Clinicians should offer assistance with partner notification and refer patients to other sources for partner notification assistance (NYSDOH Partner Services or NYC CNAP). (A2)

The time from HIV infection to detection of the virus depends on the test that is used. Figure 1: Window of Detection for HIV, Based on Test Used illustrates the window of detection of HIV infection according to antibody, antibody/antigen combination, and HIV RNA tests.

Figure 1: Window of Detection for HIV, Based on Test Used [a]

Note: Nucleic acid amplification testing (NAAT) is performed to detect HIV RNA. Enzyme immunoassay testing (EIA) is performed to detect HIV antibodies (second- and third-generation EIA) or HIV antibody/antigen (fourth-generation EIA).

  1. Reprinted from CDC > HIV Diagnostic Tests > Newer, Improved HIV Tests Allow for Earlier HIV Detection

Presentation

Patients acutely infected with HIV will often experience at least some symptoms of acute retroviral syndrome (ARS). Fever and influenza- or mononucleosis-like symptoms are common in acute HIV infection but are nonspecific. Rash, mucocutaneous ulcers, oropharyngeal candidiasis, and meningismus are more specific and should raise the index of suspicion (see below for a more extensive list of signs and symptoms). The mean time from exposure to onset of symptoms is generally 2 to 4 weeks, with a range of 5 to 29 days; however, some cases have presented with symptoms up to 3 months after exposure [Apoola, et al. 2002]. Theoretically, this time course may be prolonged in patients who become infected while on PEP or PrEP.

Box 1: Acute Retroviral Syndrome [a]

Signs and symptoms of ARS with the expected frequency among symptomatic patients are listed below [a]. The most specific symptoms in this study were oral ulcers and weight loss; the best predictors were fever and rash. The index of suspicion should be high when these symptoms are present.

  • Fever (80%)
  • Tired or fatigued (78%)
  • Malaise (68%)
  • Arthralgias (joint pain) (54%)
  • Headache (54%)
  • Loss of appetite (54%)
  • Rash (51%)
  • Night sweats (51%)
  • Myalgias (pain in muscles) (49%)
  • Nausea (49%)
  • Diarrhea (46%)
  • Fever and rash (46%)
  • Pharyngitis (sore throat) (44%)
  • Oral ulcers (mouth sores) (37%)
  • Weight loss (>5 lb; 2.5 kg) (32%)
  • Confusion (25%)
  • Photophobia (24%)
  • Vomiting (12%)
  • Infected gums (10%)
  • Sores on anus (5%)

 

  1. Data are from Hecht FM, Busch MP, Rawal B, et al. Use of laboratory tests and clinical symptoms for identification of primary HIV infection. AIDS 2002;16(8):1119-1129. [PMID: 12004270]

Diagnosis

Acute HIV infection is often not recognized in the primary care setting because the symptom profile is similar to that of influenza, mononucleosis, and other common illnesses. Furthermore, patients often do not recognize that they may have recently been exposed to HIV. Therefore, the clinician should have a high index of suspicion for acute HIV infection in a patient who may have recently engaged in behavior involving sexual or parenteral exposure to another individual’s blood or body fluids and who is presenting with a febrile, influenza-, or mononucleosis-like illness. Identifying acute HIV infection during pregnancy is particularly important because effective intervention can prevent mother-to-child transmission [Patterson, et al. 2007].

High levels of HIV RNA detected in plasma through sensitive NAAT, combined with a negative or indeterminate HIV screening or type-differentiation test, support the presumptive diagnosis of acute HIV infection [Robb, et al. 2016; DHHS 2019].

When low-level viremia is reported by HIV RNA testing (<5,000 copies/mL) in the absence of serologic confirmation of HIV infection, HIV RNA testing should be repeated to exclude a false-positive result [Hecht, et al. 2002]. Repeat HIV RNA testing with a result that indicates the presence of low-level viremia may represent true HIV infection, warranting appropriate counseling regarding transmission risk and initiation of ART.

HIV RNA levels tend to be very high in acute infection; however, a low value may represent any point on the upward or downward slope of the viremia associated with acute infection or could simply represent chronic infection. HIV RNA can also be suppressed during acute infection in patients who are taking PrEP. Plasma HIV RNA levels during acute infection do not appear significantly different in patients who are and are not symptomatic [Patterson, et al. 2007]. Viremia occurs approximately 1 to 2 weeks before the detection of a specific immune response. Patients diagnosed with acute infection by HIV RNA testing should always receive follow-up diagnostic testing 3 weeks later to confirm infection (see the CDC HIV testing algorithm) [CDC 2013, 2014]. Figure 2: Diagnostic Testing for HIV Infection illustrates diagnostic testing for acute HIV infection.

KEY POINTS
  • The diagnosis of acute HIV infection requires a high degree of clinical awareness. The nonspecific signs and symptoms of acute HIV infection are often not recognized or attributed to another viral illness.
  • Diagnostic HIV RNA testing should be considered for all patients who present with compatible symptoms (see signs and symptoms of ARS, above), particularly in the context of a sexually transmitted infection [Patel, et al. 2006] or a recent sexual or parenteral exposure with a partner known to have HIV or a partner whose HIV serostatus is not known.
  • Individual laboratories have internal protocols for reporting HIV tests with preliminary results. The terms used when preliminary results cannot be classified include indeterminate, inconclusive, nondiagnostic, and pending validation. Clinicians can contact the appropriate laboratory authority to determine the significance of nondefinitive results and the recommended supplemental testing, particularly when acute HIV infection is suspected. Clinicians are advised to become familiar with the internal test-reporting policies of their institutions.
Click to enlarge
References

Apoola A, Ahmad S, Radcliffe K. Primary HIV infection. Int J STD AIDS 2002;13(2):71-78. [PMID: 11839160

CDC. Detection of acute HIV infection in two evaluations of a new HIV diagnostic testing algorithm – United States, 2011-2013. MMWR Morb Mortal Wkly Rep 2013;62(24):489-494. [PMID: 23784012]

CDC. Laboratory testing for the diagnosis of HIV infection: updated recommendations. 2014 Jun 27. https://stacks.cdc.gov/view/cdc/23447 [accessed 2018 Aug 21]

DHHS. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. 2019 Dec 18. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/acute-and-recent-early-hiv-infection [accessed 2021 Jun 29]

Hecht FM, Busch MP, Rawal B, et al. Use of laboratory tests and clinical symptoms for identification of primary HIV infection. AIDS 2002;16(8):1119-1129. [PMID: 12004270

Patel P, Klausner JD, Bacon OM, et al. Detection of acute HIV infections in high-risk patients in California. J Acquir Immune Defic Syndr 2006;42(1):75-79. [PMID: 16763493

Patterson KB, Leone PA, Fiscus SA, et al. Frequent detection of acute HIV infection in pregnant women. AIDS 2007;21(17):2303-2308. [PMID: 18090278

Robb ML, Eller LA, Kibuuka H, et al. Prospective study of acute HIV-1 infection in adults in East Africa and Thailand. N Engl J Med 2016;374(22):2120-2130. [PMID: 27192360

Management, Including While on PEP or PrEP

Reviewed and updated: Ethan A. Cowan, MD, MS, with the Medical Care Criteria Committee; July 2021

RECOMMENDATIONS
Management
  • Clinicians should recommend antiretroviral therapy (ART) to all patients diagnosed with acute HIV infection. (A1)
  • Clinicians should inform patients about the increased risk of transmitting HIV during acute infection and for the 6 months following infection in patients who do not initiate ART. (A2)
  • As part of the initial management of patients diagnosed with acute HIV infection, clinicians should:
    • Consult with a care provider experienced in the treatment of acute HIV infection. (A3)
    • Obtain HIV genotypic resistance testing for the protease (A2), reverse transcriptase (A2), and integrase (B2) genes at the time of diagnosis.
  • Patients taking post-exposure prophylaxis (PEP): When acute HIV infection is diagnosed in an individual receiving PEP, ART should be continued pending consultation with an experienced HIV care provider. (A3)
  • Patients taking pre-exposure prophylaxis (PrEP): Because the risk of drug-resistant mutations is higher in patients who acquire HIV while taking PrEP, clinicians should consult with an experienced HIV care provider and recommend a fully active ART regimen. (A3)
  • When a patient agrees with the clinician’s recommendation to initiate ART during acute HIV infection:
    • The clinicians should implement treatment to suppress the patient’s plasma HIV RNA to below detectable levels. (A1)
    • Clinicians should perform baseline laboratory testing listed in Box 2: Baseline Laboratory Testing Checklist for all patients initiating ART immediately; ART can be started while awaiting laboratory test results. (A3)

Patients are at greatest risk for transmitting HIV during periods of high viremia early in infection. Clinicians should counsel patients with acute HIV about the increased risk of transmission during the 6 months after infection. Partner notification [Golden, et al. 2004], counseling on safer sex, and screening for other sexually transmitted infections are all essential in the management of any new HIV diagnosis.

Consultation: When choosing an ART regimen for a patient with acute HIV infection, clinicians should consult a care provider experienced in treating acute HIV infection.

  • Data are insufficient to support ART regimens for treatment of acute HIV infection specifically; instead, the choice of regimen should be made based on recommendations for selecting an initial ART regimen.
  • The risks of transmitted resistance should be considered when prescribing ART while awaiting HIV resistance results.
  • The risks of acquired mutations should be considered in those who acquire HIV while on PrEP.

Clinicians who do not have access to experienced HIV care providers should call the CEI Line at 1-866-637-2342.

Reference

Golden MR, Hogben M, Potterat JJ, et al. HIV partner notification in the United States: a national survey of program coverage and outcomes. Sex Transm Dis 2004;31(12):709-712. [PMID: 15608584

Benefits and Risks of ART

This section is an excerpt from the NYSDOH AI guideline When to Initiate ART,
With Protocol for Rapid Initiation

Lead authors: Asa Radix, MD, MPH, and Noga Shalev, MD, with the Medical Care Criteria Committee, updated January 2020

RECOMMENDATION
Benefits and Risks of ART
  • Clinicians should recommend antiretroviral therapy to all patients with HIV infection. (A1)

Antiretroviral therapy (ART) refers to the use of pharmacologic agents that have specific inhibitory effects on HIV replication. The use of fewer than three agents is not recommended for initiating treatment. These agents belong to six distinct classes of drugs: the nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs, NtRTIs), the non-nucleoside reverse transcriptase inhibitors (NNRTIs), the protease inhibitors (PIs), the fusion inhibitors (FIs), the CCR5 co-receptor antagonists, and the integrase strand transfer inhibitors (INSTIs). See all commercially available antiretroviral drugs that are FDA-approved for the treatment of HIV/AIDS.

Benefits of ART

Effective ART has led to dramatic reductions in HIV-associated morbidity and mortality [CDC 2017]. In resource-rich settings, life expectancy of patients with HIV infection with access to early ART is approaching that of the general population [Siddiqi, et al. 2016]. A number of randomized clinical trials have demonstrated the benefits of ART in reducing HIV-related morbidity and mortality, irrespective of the degree of immune suppression at treatment initiation [Severe, et al. 2010; Lundgren, et al. 2015]. Thus, ART should be recommended to all individuals with HIV infection.

With proper selection of an initial regimen (see the NYSDOH AI guideline Selecting an Initial ART Regimen) and good patient adherence, durable virologic suppression (i.e., lifetime control of viral load) is achieved in virtually all patients with HIV infection. Virologic suppression almost invariably leads to immunological recovery, followed by reductions in the incidence of opportunistic infections and malignancies.

The measurable goals of treatment include:

  • Viral suppression as measured by HIV-1 RNA level below the limits of detection.
  • Immune reconstitution as measured by an increase in or maintenance of the CD4 cell count.
  • Reduction in HIV-associated complications, including AIDS- and non–AIDS-related conditions.

ART also reduces morbidity and mortality from non–HIV-related causes. In a randomized study comparing continuous ART with CD4-guided treatment interruption, a mortality benefit was observed in subjects on continuous ART [El-Sadr, et al. 2006]. This benefit was attributed to a reduction in deaths from cardiovascular, renal, and hepatic causes. ART decreases the inflammatory milieu associated with ongoing HIV replication. It is postulated that ART-mediated reductions in pro-inflammatory cytokines lead to lower rates of clinical complications associated with the pro-inflammatory state [Hileman and Funderburg 2017].

Reducing HIV transmission: In addition to its direct health benefit to the individual with HIV infection, ART is a critical component of the overarching public health goal of eliminating HIV transmission. Antiretroviral treatment as prevention (TasP) is associated with greater reductions in HIV transmission than any preventative modality studied to date. In HPTN 052, a large randomized clinical trial of serodiscordant couples, early treatment of the infected partner was associated with a 96% reduction in HIV transmission compared with a delayed treatment approach [Cohen, et al. 2011]. In long-term follow-up of study participants, linked transmissions between partners were thought to occur only when the index partner was viremic [Cohen, et al. 2016]. In the observational PARTNERS study, no phylogenetically linked HIV transmission was observed in serodiscordant couples in which the index partner was virologically suppressed on ART [Rodger, et al. 2016]. The evidence thus suggests that the risk of sexual transmission of HIV during virological suppression is negligible. ART should be recommended to all patients with HIV infection to prevent transmission to sex partners and, by extrapolation, to needle-sharing partners. Despite its potent benefit in reducing HIV transmission, ART does not obviate the use of condoms or clean syringes. Those harm reduction measures, along with the use of PrEP for partners who do not have HIV infection, will help reduce the incidence of other STIs and viral hepatitis and should be integrated into patient counseling at ART initiation.

Reduced complications: Accumulating evidence suggests that patients who initiate ART earlier or spend less cumulative time with detectable plasma viremia are less likely to suffer certain complications, such as cardiovascular disease [El-Sadr, et al. 2006; Marin, et al. 2009; Ho, et al. 2010; Lichtenstein, et al. 2010; Ho, et al. 2012], neurocognitive dysfunction [Tozzi, et al. 2007; Ellis, et al. 2011; Garvey, et al. 2011; Winston, et al. 2012], decreased risk of severe bacterial infections [O’Connor, et al. 2017], and some non–HIV-related malignancies [Bruyand, et al. 2009; Guiguet, et al. 2009; Silverberg, et al. 2011; Sigel, et al. 2012]. Cohort data also demonstrate that although older patients are likely to achieve virologic suppression, they are less likely to achieve an immunologic response, as measured by an increase of CD4 count by 100 cells/mm3, and that patients >55 years old may be at higher clinical risk even after starting therapy [Sabin, et al. 2008]. The poor immunologic recovery seen in older patients is associated with higher morbidity and mortality, particularly cardiovascular events [van Lelyveld, et al. 2012]. In one study, men ≥50 years of age who initiated ART with CD4 counts in the 351 to 500 cells/mm3 range were able to achieve similar immunologic responses as younger men who initiated at lower CD4 counts [Li, et al. 2011].

Reduced perinatal transmission of HIV: Studies have shown that for pregnant women with HIV, the administration of ART during pregnancy or intrapartum significantly reduces the risk of mother-to-child transmission (MTCT) of HIV [Connor, et al. 1994; Guay, et al. 1999]. In addition, a large study showed a 96% reduction in transmission between serodiscordant heterosexual couples when the positive partner was receiving ART [Cohen, et al. 2011], adding to the body of evidence that lower viral load reduces transmission risk. ART is now part of the established strategy aimed at reducing HIV transmission and is an essential component of prevention interventions along with risk-reduction counseling, safer-sex practices, and avoidance of needle-sharing. Although the majority of patients both in New York and worldwide present later in the course of their HIV infection [Althoff, et al. 2010; CDC 2010, 2011], ongoing efforts to offer universal HIV testing to all patients over age 13 may begin to identify patients earlier in their disease who can benefit from immediate treatment.

Risks of ART

Despite the excellent tolerability of contemporary ART regimens, adverse reactions, side effects, long-term drug toxicities, and drug-drug interactions continue to pose some relative or limited risks. Patients must be counseled about the potential for ART-associated adverse events in the short and long term. These risks include tolerability issues, which may affect quality of life, as well as possible long-term toxicities—primarily a low relative risk of renal and cardiovascular disorders or decreased bone density of uncertain clinical significance [Friis-Moller, et al. 2010; Monteiro, et al. 2014; Hoy, et al. 2017]. Renal and bone density issues are largely eliminated with newer formulations of ARVs. Fatal drug reactions from ART are exceedingly rare.

Many ART combinations are now available in single-pill, fixed-dose combination formulations. Thus, the pill burden associated with early antiretroviral regimens has been largely eliminated. Nevertheless, lifelong adherence to medications may constitute a challenge to some, particularly when treatment with a single daily tablet is not feasible.

When compared with early antiretroviral combinations, contemporary ART regimens (see the NYSDOH AI guideline Selecting an Initial ART Regimen) are associated with higher rates of durable virologic suppression. Lack of virologic suppression in a patient on ART should prompt the clinician to evaluate patient adherence and provide intensive support for those reporting challenges in this domain. Failure to achieve and maintain virologic suppression may lead to the emergence of resistance-associated mutations (RAMs). A large cohort study has demonstrated that virologic failure with contemporary ART regimens is associated with the infrequent emergence of RAMs [Scherrer, et al. 2016]. Nevertheless, RAMs can emerge with current first-line therapies. Resistance to antiretroviral medications may compromise the potential for long-term virologic suppression, simple dosing schedules, and the tolerability of future treatment options.

ART initiation is associated with a risk of immune reconstitution inflammatory syndrome (IRIS). IRIS is a clinical syndrome characterized by new or worsening infectious and non-infectious complications observed after the initiation of ART (see the NYSDOH AI guideline Management of IRIS). The risk of IRIS increases when ART is begun at low CD4 cell counts (<100 cells/mm3) or with the presence of specific opportunistic infections. Although the risk of IRIS is not a contraindication to initiating ART, clinicians and patients should be aware that the risk of developing IRIS is increased among individuals with lower CD4 counts. Patients at increased risk should be informed of the potential for a paradoxical clinical worsening after ART initiation.

Risks of Untreated HIV

Results from the START trial [Lundgren, et al. 2015] and strong cohort data show that untreated HIV infection leads to increased morbidity and mortality from both HIV-related and non-HIV-related conditions, even at high CD4 counts. Together with the dramatic reduction of transmission risk with effective treatment, these data support the initiation of ART regardless of CD4 count in all adequately prepared patients, including patients diagnosed with acute HIV infection (for more discussion see the NYSDOH AI guideline Diagnosis and Management of Acute HIV). Patients in care who are documented long-term nonprogressors or elite controllers are a group that may warrant special consideration (see the Special Considerations section of this guideline).

In START, a randomized trial initiating ART in treatment-naïve patients with CD4 counts >500 cells/mm3 versus waiting for a decrease to ≤350 cells/mm3 before initiation showed a 53% reduction in serious illness and death in the early ART group [Lundgren, et al. 2015]. Data from NA-ACCORD, a large observational cohort study, showed that both morbidity and mortality were improved by initiation of ART in patients with CD4 counts in the high or even normal range [Kitahata, et al. 2009]. A significantly decreased risk of death was observed in patients who initiated therapy at CD4 counts >500 cells/mm3 compared to those who deferred to <500 cells/mm3, as well as in the cohort that initiated ART in the 350 to 500 cells/mm3 range compared with those deferring to <350 cells/mm3 [Kitahata, et al. 2009]. Although other cohort studies demonstrated only a minimal survival advantage [Wright, et al. 2011] or no survival advantage among those starting ART at the highest CD4 counts, they did confirm the benefits of initiating ART at levels ≤500 cells/mm3 [Cain, et al. 2011; CASCADE Collaboration 2011; Young, et al. 2012]. Another showed an approximately 33% reduction in the risk of death from end-stage liver disease, non-AIDS infections, and non-AIDS-defining cancers with every 100 cells/mm3 increase in CD4 count [Marin, et al. 2009]. A randomized study of early versus deferred therapy in patients with CD4 counts in the 350-550 cells/mm3 range showed no mortality benefit [Cohen, et al. 2011]; however, this study has significant limitations, most notably a relatively brief follow-up period.

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Rationale for Rapid ART Initiation

This section is an excerpt from the NYSDOH AI guideline When to Initiate ART,
With Protocol for Rapid Initiation

Lead authors: Asa Radix, MD, MPH, and Noga Shalev, MD, with the Medical Care Criteria Committee, updated January 2020

RECOMMENDATIONS
Rationale for Rapid ART Initiation
  • Clinicians should recommend antiretroviral therapy (ART) for all patients with a diagnosis of HIV infection. (A1)
  • Clinicians should offer rapid initiation of ART—preferably on the same day (A1) or within 72 hours—to all individuals who are candidates for rapid ART initiation (see text) and who have:
    • A confirmed HIV diagnosis (A1), or
    • A reactive HIV screening result pending results of a confirmatory HIV test (A2), or
    • Suspected acute HIV infection, i.e., HIV antibody negative and HIV RNA positive (A2).
  • Clinicians should counsel patients with seronegative partners about the reduction of HIV transmission risk after effective ART is initiated and viral suppression is achieved, and should strongly recommend ART for patients with seronegative partners. (A1)
  • Clinicians should evaluate and prepare patients for ART initiation as soon as possible; completion of the following should not delay initiation:
    • Discuss benefits and risks of ART with the patient. (A3)
    • Assess patient readiness. (A3)
    • Identify and ameliorate factors that might interfere with successful adherence to treatment, including inadequate access to medication, inadequate supportive services, psychosocial factors, active substance use, or mental health disorders. (A2)
  • Clinicians should refer patients for supportive services as necessary to address modifiable barriers to adherence. An ongoing plan for coordination of care should be established. (A3)
  • Clinicians should involve patients in the decision-making process regarding initiation of ART and which regimen is most likely to result in adherence. The patient should make the final decision of whether and when to initiate ART. (A3)
  • If the patient understands the benefits of rapid initiation but declines ART, then initiation should be revisited as soon as possible.
  • In patients with advanced HIV (or AIDS), ART should be initiated even if barriers to adherence are present. In these cases, referrals to specialized adherence programs should be made for intensified adherence support. (A2)
  • After ART has been initiated, response to therapy should be monitored by, or in consultation with, a clinician with experience in managing ART. (A2)

The New York State Department of Health (NYSDOH) HIV Clinical Guidelines Program and the U.S. Department of Health and Human Services (DHHS) recommend initiation of ART for all patients with a confirmed HIV diagnosis regardless of their CD4 cell count or viral load, for the benefit of the individual with HIV (reduced morbidity and mortality) [Zolopa, et al. 2009; Lundgren, et al. 2015] and to reduce the risk of transmission to others [Cohen, et al. 2016]. Initiating ART during early HIV infection may improve immunologic recovery (CD4 T cell counts) and reduce the size of the HIV reservoir [Jain, et al. 2013]; there is also evidence that initiating ART at the time of diagnosis reduces treatment delays and improves retention in care and viral suppression at 12 months [Ford, et al. 2018].

KEY POINTS
  • Rapid ART initiation, the standard of care in New York State, is efficacious, safe, and highly acceptable, with few patients declining the offer of immediate ART.
  • Patients with active substance use, untreated mental health conditions, immigration issues, or unstable housing deserve the highest standard of HIV care, including the option of rapid initiation of ART. Potential barriers to medication adherence and care continuity can be addressed with appropriate counseling and linkage to support services.

Reduced Treatment Delays and Loss to Follow-Up

Standard practice protocols for ART initiation have produced preventable delays, and the required wait for confirmatory HIV diagnostic and baseline laboratory test results (including resistance testing) along with required medical visits can unnecessarily delay the start of treatment by as long as 4 weeks. Problems in accessing insurance or waiting for activation of public benefits may also cause delays. It is estimated that in 2016, only 75.9% of individuals diagnosed with HIV in the U.S. HIV care continuum were linked to care within 1 month [CDC 2018]. Individuals with HIV who are not linked to care are at risk of having sustained viral loads and ongoing HIV transmission.

Rapid initiation of ART may reduce delays and improve viral suppression rates in people with HIV. Rapid or same-day ART initiation, which is preferable, or initiation within 3 days of a newly positive HIV test is the strategy endorsed by the World Health Organization [WHO 2017] and is an essential component of the New York State Ending the Epidemic initiative. Mathematical modeling demonstrates that a test-and-treat strategy, with immediate initiation of ART and prevention approaches, could lead to elimination of new HIV infections [Granich, et al. 2009].

Benefits for the Patient With HIV

Several observational and clinical trials have demonstrated the individual-level benefits of rapid ART initiation [Ford, et al. 2018]. An early pilot of this approach in San Francisco, California, demonstrated that patients initiating ART within 1 or 2 days had a shorter time (median, 1.8 months) to viral suppression (HIV RNA ≤200 copies/mL) than those offered the standard of care (4.3 months) or than historical controls (7.2 months) [Pilcher, et al. 2017]. A longer-term follow-up of 225 patients at the same center found that, of patients who had access to rapid initiation, 95.8% had achieved viral suppression at least once and 92.1% had achieved it at the last recorded visit [Coffey, et al. 2019]. These individual-level benefits have been replicated in other U.S. and international studies that demonstrated improved viral suppression with shortened time to ART initiation [Rosen, et al. 2016a; Koenig, et al. 2017; Colasanti, et al. 2018]. After implementing rapid ART initiation at a hospital clinic in Atlanta, Georgia, time to viral suppression fell from 77 days, before the intervention, to 57 days [Lundgren, et al. 2015], and average time to ART initiation decreased from 21 to 7 days; both findings were statistically significant [Colasanti, et al. 2018].

Another demonstrated benefit is an improved rate of retention in care [Amanyire, et al. 2016; Rosen, et al. 2016a; Koenig, et al. 2017]. In the RapIT trial in South Africa, patients newly diagnosed with HIV were randomized to rapid ART initiation or standard of care [Rosen, et al. 2016b]. The participants in the rapid initiation arm had higher rates of ART initiation at 90 days (97% vs. 72%) and higher rates of retention in care and viral suppression (HIV RNA ≤400 copies/mL) at 10 months (relative risk, 1.26 [1.05–1.50]). The average cost per patient to achieve viral suppression was lower in the intervention arm, demonstrating that this strategy of care may also be cost-effective [Long, et al. 2017]. Studies conducted in China and South Africa support the cost-effectiveness of rapid ART initiation [Zulliger, et al. 2014; Wu, et al. 2015; Ford, et al. 2018]. Rapid ART initiation is efficacious, safe, and highly acceptable, with few patients declining the offer of immediate ART [Pilcher, et al. 2017; Coffey, et al. 2019].

Modeling evidence suggests the potential for rapid ART initiation to significantly reduce HIV transmission in the community, although this has been directly modeled only in the context of South Africa [Granich, et al. 2009]. In the United States, linkage to and retention in HIV care are significant gaps in the HIV care continuum, with an estimated 64% of individuals with HIV receiving any HIV care and 49% being retained in care during 2016 [CDC 2019]. Models have translated these gaps in care to their effect on HIV transmission in the United States, demonstrating that between 43% and 49% of new HIV transmissions are attributable to individuals who have been diagnosed with HIV but are not receiving ART and have not been retained in care [Skarbinski, et al. 2015; Li, et al. 2019]. Because it is designed to help close this care gap, rapid ART initiation greatly reduces new HIV infections, hastening the achievement of HIV incidence reduction goals in New York State.

Rapid ART Initiation Is Safe

In the San Francisco study discussed above [Pilcher, et al. 2017], 89.7% of patients used integrase strand transfer inhibitor (INSTI)-containing regimens and 12.8% used protease inhibitor-containing regimens. The predominant INSTI-based regimen was dolutegravir plus emtricitabine/tenofovir disoproxil fumarate. The clinic did not have any cases of major resistance mutations to the prescribed ART regimen, and no regimen switches were made because of resistance. Two patients had their regimens changed because of rash, and in 10 cases, the regimen was simplified to a single-tablet regimen.

Of 149 patients initiating ART through a program in New York City, only 1 required a regimen change because of subsequently detected resistance [Blank, et al. 2018].

Rapid ART initiation is safe. Most designated regimens for rapid ART initiation are the same regimens that are recommended as initial treatment in the existing NYSDOH, International Antiviral Society–USA, and DHHS guidelines. These regimens are well-tolerated and effective, and the likelihood of drug resistance is low based on the current prevalence of drug resistance [NYCDHMH 2018].

RESOURCES
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Rosen S, Maskew M, Fox MP, et al. Initiating antiretroviral therapy for HIV at a patient’s first clinic visit: The RapIT randomized controlled trial. PLoS Med 2016b;13(5):e1002015. [PMID: 27163694]

Skarbinski J, Rosenberg E, Paz-Bailey G, et al. Human immunodeficiency virus transmission at each step of the care continuum in the United States. JAMA Intern Med 2015;175(4):588-596. [PMID: 25706928]

WHO. Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy. 2017 https://apps.who.int/iris/bitstream/handle/10665/255884/9789241550062-eng.pdf;jsessionid=7B7901DF1D162BB7D16B83C444A2D417?sequence=1 [accessed 2019 Jun 18]

Wu Z, Zhao Y, Ge X, et al. Simplified HIV testing and treatment in China: analysis of mortality rates before and after a structural intervention. PLoS Med 2015;12(9):e1001874. [PMID: 26348214]

Zolopa A, Andersen J, Powderly W, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS One 2009;4(5):e5575. [PMID: 19440326]

Zulliger R, Black S, Holtgrave DR, et al. Cost-effectiveness of a package of interventions for expedited antiretroviral therapy initiation during pregnancy in Cape Town, South Africa. AIDS Behav 2014;18(4):697-705. [PMID: 24122044]

Protocol for Rapid ART Initiation

This section is an excerpt from the NYSDOH AI guideline When to Initiate ART,
With Protocol for Rapid Initiation

Lead authors: Asa Radix, MD, MPH, and Noga Shalev, MD, with the Medical Care Criteria Committee, updated January 2020

RECOMMENDATIONS
Protocol for Rapid ART Initiation
  • To determine whether a patient is a candidate for rapid antiretroviral therapy (ART) initiation, the clinician should confirm that the individual has any of the following (A1):
    • A reactive point-of-care HIV test result, or confirmed HIV diagnosis, or suspected acute HIV infection, or known HIV infection, and
    • No prior ART (i.e., treatment naive) or limited prior use of antiretroviral medications, and
    • No medical conditions or opportunistic infections that require deferral of rapid ART initiation, including suspected cryptococcal or tuberculous meningitis.
  • Clinicians should perform baseline laboratory testing listed in Box 2: Baseline Laboratory Testing Checklist for all patients who are initiating ART immediately; ART can be started while awaiting laboratory test results. (A3)
SELECTED GOOD PRACTICE REMINDERS
Protocol for Rapid ART Initiation
  • For patients with a reactive HIV antibody screening test that is pending confirmation, make sure the patient understands the benefits of rapid ART initiation and the following:
    1. Reactive screening test results are not formally diagnostic, because false-positive results are still possible;
    2. A confirmatory (diagnostic) HIV test will be performed;
    3. ART will be discontinued if the confirmatory test result is negative and continued if it is positive;
    4. The benefit of starting ART early, after a presumptive positive screening test, outweighs the negligible risk of taking ART for a few days and then stopping it if confirmed HIV negative.
  • Provide the result of the confirmatory HIV test as soon as it is available; discontinue ART if the result is negative and reinforce adherence and next steps if it is positive.
  • If a patient declines rapid ART initiation, discuss options for deferred initiation of ART, link the patient with HIV primary care, and outline next steps.

Reactive HIV Screening Test Result

Figure 1. Protocol for Rapid Antiretroviral Therapy Initiation (download PDF)

When the result of a patient’s initial HIV point-of-care screening test is reactive, established practice is to obtain a blood specimen for diagnostic HIV testing because of the possibility of false-positive screening results. This is particularly important for individuals who are not at high risk of acquiring HIV. However, supplemental testing results may not be available for several days, introducing the risk that a patient will not return. The goal of the rapid ART initiation protocol is to assess whether a person with a reactive HIV screening test result (or a confirmed HIV diagnosis) is also a candidate for same-day initiation of ART. If so, then the rapid ART initiation protocol is to provide counseling on HIV transmission and the benefits of ART, initiate ART that day or within 3 days, and link the person expeditiously to HIV primary care. Thus, the protocol recommends immediate initiation of ART while awaiting confirmatory HIV test results.

Patients who are candidates for rapid ART initiation:

  • Have a new reactive point-of-care HIV test result or a new HIV diagnosis (confirmed through the Centers for Disease Control and Prevention HIV testing algorithm) or acute HIV infection (HIV antibody negative and HIV RNA positive) or known HIV, and
  • Are treatment-naive, or
  • Have a history of limited ART use (e.g., a person who stopped first-line therapy for reasons other than regimen failure), as long as concern for acquired drug resistance is low (requires a case-by-case determination).

Patients with a new reactive HIV test result can be retested using a second point-of-care test from a manufacturer different from that of the first test to further minimize the possibility of a false-positive result. It is not necessary to retest with a second point-of-care test before providing ART, but given the possibility of a false-positive screening result, a laboratory-based confirmatory HIV test should always be performed to establish a diagnosis of HIV. If the confirmatory HIV test result is negative, ART can be discontinued.

KEY POINT
  • Patients with a new reactive HIV test result can be retested using a second point-of-care test from a different manufacturer than that of the first test, if available, to further minimize the possibility of a false-positive result.

Counseling

A reactive HIV screening result should prompt a care provider to counsel the patient about the benefits and risks of ART and about HIV transmission risk, including the consensus that Undetectable Equals Untransmittable (U=U). When patients are initiated on ART on the same day as their reactive HIV test result, the priorities for patient education and counseling include:

  • Confirming the diagnosis of HIV.
  • Managing disclosure, if indicated.
  • Adhering to the ART regimen.
  • Recognizing and responding to side effects.
  • Following through with clinic visits.
  • Assessing health literacy.
  • Managing lifelong ART: Navigating acquisition of and paying for medications required for lifelong therapy, including pharmacy selection, insurance requirements and restrictions, co-pays, and prescription refills.
  • Identifying and addressing psychosocial issues that may pose barriers to treatment.
  • Referring for substance use and behavioral health counseling if indicated.
  • Referring for housing assistance if indicated.
  • Ensuring the patient knows how to reach the care team if needed, to address the adverse effects of medications or other concerns.
KEY POINT: HEALTH LITERACY

Medical and Psychosocial Assessment

Medical assessment of a patient with a new reactive HIV test result should include history or signs or symptoms of opportunistic infection(s). ART should be delayed and appropriate medical management initiated if tuberculous (TB) meningitis or cryptococcal meningitis are suspected (see below) [WHO 2017], if cytomegalovirus retinitis is suspected, or if the patient has any evidence of advanced HIV disease on clinical exam.

To identify the potential for pre-existing drug-resistant virus, the initial assessment should also include the patient’s history of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) use and previous ART use for people who are re-engaging in care [Ford, et al. 2018]. See Box 1: Medical History Checklist, below.

Box 1: Medical History Checklist

When taking a medical history before rapid ART initiation, ask about:

  • Date and result of last HIV test
  • Serostatus of sex partners and their ART regimens if known
  • Previous use of antiretroviral medications, including as PrEP or PEP, with dates of use
  • Comorbidities, including a history of renal or liver disease, particularly hepatitis B infection
  • Prescribed and over-the-counter medications
  • Drug allergies
  • Substance use
  • Symptoms, to assess for active cryptococcal and TB meningitis
  • Psychiatric history, particularly depressive or psychotic symptoms or any history of suicidality
  • Possible pregnancy and childbearing plans in individuals of childbearing potential

Deferral of ART initiation: If the patient understands the benefits of rapid initiation but declines ART, then initiation should be revisited as soon as possible. In some circumstances, such as in the rare case of suspected cryptococcal or TB meningitis, rapid ART is not recommended (see the Patients With Acute Opportunistic Infections section of this guideline). Patients who present with signs and symptoms suggestive of pulmonary or intracranial and ophthalmologic infections should receive further assessment before initiating ART on the same day as a reactive HIV screening test result.

ART initiation should be delayed in any person presenting with signs or symptoms suggestive of meningitis, including headache, nausea or vomiting, light sensitivity, and changes in mental status. Treatment of TB meningitis was investigated in a clinical trial in Vietnam in which immediate initiation of ART was compared with ART initiated 2 months after TB treatment [Torok, et al. 2011]. There were significantly more grade 4 adverse effects in individuals who initiated ART immediately than in those who delayed. Among patients with cryptococcal meningitis, early initiation of ART has been associated with adverse outcomes, including death [Boulware, et al. 2014]; therefore, it is recommended that ART be deferred until after the induction phase of treatment for cryptococcal meningitis has been completed (see DHHS: Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV).

It is clear that co-treatment of HIV and pulmonary TB improves survival. In the SAPIT trial in South Africa, there was a 56% relative reduction in mortality when ART was initiated within 4 weeks of TB treatment initiation, compared with when it was started after TB treatment was completed (hazard ratio, 0.44; 95% confidence interval, 0.25–0.79; P=.003), although symptoms of immune reconstitution inflammatory syndrome (IRIS) were greater in patients who started ART earlier [Abdool Karim, et al. 2010]. However, it is not clear that ART initiation prior to initiation of pulmonary TB treatment is the best course of action. Care providers should weigh the benefits of rapid ART initiation against the potential drawbacks of pill burden, drug interactions, and the risk of IRIS.

Baseline Laboratory and Resistance Testing

All patients with a reactive HIV test result should undergo the baseline laboratory testing listed in Box 2, below. For discussion of baseline testing, see the NYSDOH AI guideline Selecting an Initial ART Regimen > ART-Initiation Laboratory Testing. It is not necessary to wait for these test results before initiating ART. 

Box 2: Baseline Laboratory Testing Checklist
  • HIV-1/2 antigen/antibody assay
  • HIV quantitative viral load
  • Baseline HIV genotypic resistance profile
  • Baseline CD4 cell count
  • Testing for hepatitis A, B, and C viruses
  • Comprehensive metabolic panel (creatinine clearance, hepatic profile)
  • See CDC > Sexually Transmitted Infections Treatment Guidelines, 2021 > Screening
  • Urinalysis
  • Pregnancy test for individuals of childbearing potential
References

Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med 2010;362(8):697-706. [PMID: 20181971]

Boulware DR, Meya DB, Muzoora C, et al. Timing of antiretroviral therapy after diagnosis of cryptococcal meningitis. N Engl J Med 2014;370(26):2487-2498. [PMID: 24963568]

Ford N, Migone C, Calmy A, et al. Benefits and risks of rapid initiation of antiretroviral therapy. AIDS 2018;32(1):17-23. [PMID: 29112073]

Torok ME, Yen NT, Chau TT, et al. Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)–associated tuberculous meningitis. Clin Infect Dis 2011;52(11):1374-1383. [PMID: 21596680]

WHO. Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy. 2017 https://apps.who.int/iris/bitstream/handle/10665/255884/9789241550062-eng.pdf;jsessionid=7B7901DF1D162BB7D16B83C444A2D417?sequence=1 [accessed 2019 Jun 18]

All Recommendations

Reviewed and updated: Ethan A. Cowan, MD, MS, with the Medical Care Criteria Committee; July 2021

ALL RECOMMENDATIONS: DIAGNOSIS AND MANAGEMENT OF ACUTE HIV INFECTION
Presentation
  • Clinicians should include acute HIV infection in the differential diagnosis for anyone (regardless of reported risk) who presents with signs or symptoms of influenza (“flu”), mononucleosis (“mono”), or other viral syndromes (A3), especially when the patient:
    • Presents with a rash. (A2)
    • Requests HIV testing. (A3)
    • Reports recent sexual or parenteral exposure to a person with or at risk of HIV infection. (A2)
    • Presents with a newly diagnosed sexually transmitted infection. (A2)
    • Presents with aseptic meningitis. (A2)
    • Is pregnant or breastfeeding. (A3)
    • Is currently taking antiretroviral medications for pre- or post-exposure prophylaxis (PrEP or PEP). (A3)
  • Diagnostic HIV RNA testing should be considered for patients who present with compatible symptoms (see Box 1: Acute Retroviral Syndrome), particularly in the presence of a sexually transmitted infection [Patel, et al. 2006] or a recent sexual or parenteral exposure with a partner known to have HIV or with unknown HIV serostatus. (A2)
When Acute HIV Infection Is Suspected
  • Clinicians should always perform a plasma HIV RNA assay in conjunction with an antigen/antibody combination screening test. (A2)
  • Clinicians should use a 4th-generation antigen/antibody combination assay (preferred) as the initial HIV screening test according to the CDC’s Recommended Laboratory HIV Testing Algorithm for Serum or Plasma Specimens.
    • If the screening test is reactive, clinicians should perform an HIV-1/HIV-2 antibody-differentiation immunoassay to confirm HIV infection. (A1)
    • Note: When rapid antibody screening is performed, even with a rapid 4th-generation test, a laboratory-based 4th-generation immunoassay is recommended for follow-up diagnostic HIV testing.
Diagnosis
  • Clinicians can presume the diagnosis of acute HIV when high levels (>10,000 copies/mL) of HIV RNA are detected in plasma with sensitive nucleic acid amplification testing (NAAT), and the result of the HIV screening or type-differentiation test is negative or indeterminate. (A2)
  • When a low-level quantitative HIV RNA viral load result (<10,000 copies/mL) is obtained in the absence of serologic evidence of HIV infection, the clinician should repeat HIV RNA testing and perform a 4th-generation antigen/antibody combination assay to exclude a false-positive result. (A2)
    • Note: A serologic test result that does not meet the criteria for HIV infection is a nonreactive screening result (antibody or antibody/antigen combination) or a reactive screening result with a nonreactive or indeterminate antibody-differentiation confirmatory result.
  • Clinicians should seek expert consultation when an ambiguous HIV result is obtained for an individual taking PrEP because the diagnosis of acute HIV can be particularly challenging in patients taking PrEP. (A3) See NYSDOH AI guideline PrEP to Prevent HIV and Promote Sexual Health > Suspected Acute HIV.
ART Initiation
Partner Notification
  • Clinicians should offer assistance with partner notification and refer patients to other sources for partner notification assistance (NYSDOH Partner Services or NYC CNAP). (A2)
Management
  • Clinicians should recommend antiretroviral therapy (ART) to all patients diagnosed with acute HIV infection. (A1)
  • Clinicians should inform patients about the increased risk of transmitting HIV during acute infection and for the 6 months following infection in patients who do not initiate ART. (A2)
  • As part of the initial management of patients diagnosed with acute HIV infection, clinicians should:
    • Consult with a care provider experienced in the treatment of acute HIV infection. (A3)
    • Obtain HIV genotypic resistance testing for the protease (A2), reverse transcriptase (A2), and integrase (B2) genes at the time of diagnosis.
  • Patients taking post-exposure prophylaxis (PEP): When acute HIV infection is diagnosed in an individual receiving PEP, ART should be continued pending consultation with an experienced HIV care provider. (A3)
  • Patients taking pre-exposure prophylaxis (PrEP): Because the risk of drug-resistant mutations is higher in patients who acquire HIV while taking PrEP, clinicians should consult with an experienced HIV care provider and recommend a fully active ART regimen. (A3)
  • When a patient agrees with the clinician’s recommendation to initiate ART during acute HIV infection:
    • The clinicians should implement treatment to suppress the patient’s plasma HIV RNA to below detectable levels. (A1)
    • Clinicians should perform baseline laboratory testing listed in Box 2: Baseline Laboratory Testing Checklist for all patients initiating ART immediately; ART can be started while awaiting laboratory test results. (A3)
Benefits and Risks of ART
  • Clinicians should recommend antiretroviral therapy to all patients with HIV infection. (A1)
Rationale for Rapid ART Initiation
  • Clinicians should recommend antiretroviral therapy (ART) for all patients with a diagnosis of HIV infection. (A1)
  • Clinicians should offer rapid initiation of ART—preferably on the same day (A1) or within 72 hours—to all individuals who are candidates for rapid ART initiation (see text) and who have:
    • A confirmed HIV diagnosis (A1), or
    • A reactive HIV screening result pending results of a confirmatory HIV test (A2), or
    • Suspected acute HIV infection, i.e., HIV antibody negative and HIV RNA positive (A2).
  • Clinicians should counsel patients with seronegative partners about the reduction of HIV transmission risk after effective ART is initiated and viral suppression is achieved, and should strongly recommend ART for patients with seronegative partners. (A1)
  • Clinicians should evaluate and prepare patients for ART initiation as soon as possible; completion of the following should not delay initiation:
    • Discuss benefits and risks of ART with the patient. (A3)
    • Assess patient readiness. (A3)
    • Identify and ameliorate factors that might interfere with successful adherence to treatment, including inadequate access to medication, inadequate supportive services, psychosocial factors, active substance use, or mental health disorders. (A2)
  • Clinicians should refer patients for supportive services as necessary to address modifiable barriers to adherence. An ongoing plan for coordination of care should be established. (A3)
  • Clinicians should involve patients in the decision-making process regarding initiation of ART and which regimen is most likely to result in adherence. The patient should make the final decision of whether and when to initiate ART. (A3)
  • If the patient understands the benefits of rapid initiation but declines ART, then initiation should be revisited as soon as possible.
  • In patients with advanced HIV (or AIDS), ART should be initiated even if barriers to adherence are present. In these cases, referrals to specialized adherence programs should be made for intensified adherence support. (A2)
  • After ART has been initiated, response to therapy should be monitored by, or in consultation with, a clinician with experience in managing ART. (A2)
Protocol for Rapid ART Initiation
  • To determine whether a patient is a candidate for rapid antiretroviral therapy (ART) initiation, the clinician should confirm that the individual has any of the following (A1):
    • A reactive point-of-care HIV test result, or confirmed HIV diagnosis, or suspected acute HIV infection, or known HIV infection, and
    • No prior ART (i.e., treatment naive) or limited prior use of antiretroviral medications, and
    • No medical conditions or opportunistic infections that require deferral of rapid ART initiation, including suspected cryptococcal or tuberculous meningitis.
  • Clinicians should perform baseline laboratory testing listed in Box 2: Baseline Laboratory Testing Checklist for all patients who are initiating ART immediately; ART can be started while awaiting laboratory test results. (A3)

How This Guideline Was Developed

July 2021

This guideline was developed by the New York State (NYS) Department of Health (DOH) AIDS Institute (AI) Clinical Guidelines Program, which is a collaborative effort between the NYSDOH AI Office of the Medical Director and the Johns Hopkins University School of Medicine, Division of Infectious Diseases.

Established in 1986, the goal of the Clinical Guidelines Program is to develop and disseminate evidence-based, state-of-the-art clinical practice guidelines to improve the quality of care provided to people with HIV, hepatitis C virus, or sexually transmitted infections; people with substance use issues; and members of the LGBTQ community. NYSDOH AI guidelines are developed by committees of clinical experts through a consensus-driven process.

Medical Care Criteria Committee (MCCC) for adult HIV care guidelines: The NYSDOH AI charged the MCCC (adult HIV and related guidelines) with developing evidence-based recommendations for clinicians in NYS who provide care to individuals with HIV. The purpose of the Diagnosis and Management of Acute HIV Infection clinical practice guideline is to guide clinicians in NYS who provide ambulatory, inpatient, and emergency medical care for adults ≥18 years old who present with signs or symptoms of acute HIV infection.

Committee makeup: Members of the MCCC (see Box A1: MCCC Leaders and Members, below) were appointed by the NYSDOH AI to ensure representation of clinical practice in all major regions of the state, relevant medical disciplines and subspecialties, key NYS agencies, community stakeholders, and patient advocates. Individuals confirmed as MCCC members are required to disclose any potential conflicts of interest; disclosures are reviewed and approved by the NYSDOH AI Office of the Medical Director (see Funding and Disclosure of Potential Conflicts of Interest, below).

Committee role: Committee members actively participate in guideline development, including evidence review, drafting of recommendations and text, manuscript review, consensus approval of all recommendations, and rating of recommendations.

Committee leadership: Working with the lead author, the MCCC Writing Group reviewed and refined the manuscript, facilitated consensus approval of all recommendations, and addressed feedback from the Committee at large.

Johns Hopkins University (JHU) Editorial Role: The JHU editorial team coordinated, guided, and documented all Committee activities and edited the guideline material for clarity, flow, and style.

MCCC Writing Group (all Committee members and reviewers are listed in Box A1, below)

  • Joseph P. McGowan, MD, FACP, FIDSA, Chair
  • Steven Fine, MD, PhD, Co-Vice-Chair (effective January 2021)
  • Rona Vail, MD, Co-Vice-Chair (effective January 2021)
  • Samuel T. Merrick, MD, Chair Emeritus
  • Charles J. Gonzalez, MD, AI Medical Director
  • Asa Radix, MD, MPH, FACP, AAHIVS
  • Christopher J. Hoffmann, MD, MPH, Director, JHU-NYSDOH Guidelines Program

AIDS Institute and JHU Editorial and Program Management Team

  • Laura Duggan Russell, MPH, AI Guidelines Program Manager
  • Mary Beth Hansen, MA, JHU Guidelines Project Director
  • Johanna Gribble, MA, JHU Medical Editor
  • Jen Ham, MPH, JHU Medical Editor
  • Rachel Lastra, JHU Medical Editor
  • Jesse Ciekot, JHU Program Coordinator
Box A1: MCCC Leaders and Members (when this guideline was developed)
Unless noted otherwise, Committee members had no disclosures of financial relationships with commercial entities
Leadership
  • Chair (effective March 2018)Joseph P. McGowan, MD, FACP, FIDSA, North Shore University Hospital, Manhasset, NY
  • Co-Vice-Chair (Vice-Chair effective March 2018; Co-Vice-Chair effective January 2021)Steven M. Fine, MD, PhD, University of Rochester Medical Center, Rochester, NY
  • Co-Vice-Chair (effective January 2021): Rona M. Vail, MD, Callen-Lorde Community Health Center, New York, NY
  • Chair Emeritus (effective March 2018)Samuel T. Merrick, MD, New York-Presbyterian-Weill Cornell, New York, NY
  • Medical Director: Charles J. Gonzalez, MD, New York State Department of Health AIDS Institute, New York, NY (May 2018)
  • Clinical Advisor to the AIDS Institute (effective June 2021)Lyn Stevens, MS, NP, ACRN, New York State Department of Health AIDS Institute, Albany, NY
  • Director, JHU-NYSDOH AI Guidelines Program: Christopher J. Hoffmann, MD, MPH, Johns Hopkins University School of Medicine, Baltimore, MD
Contributing Members
  • Jessica M. Atrio, MD, MSc, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
  • Oni J. Blackstock, MD, MHS, Health Justice, New York, NY
  • James C. M. Brust, MD, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY
  • Ethan A. Cowan, MD, MS, Icahn School of Medicine at Mount Sinai, New York, NY
  • Elliot DeHaan, MD, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY
  • Mary E. Dyer, MD, Hudson River Healthcare, Monticello, NY
  • John J. Faragon, PHARMD, BCPS, AAHIVP, Albany Medical Center, Albany, New York
  • Shauna H. Gunaratne, MD, MPH, Columbia University Medical Center, New York, NY
  • Bruce E. Hirsch, MD, FACP, FIDSA, AAHIVS, North Shore University Hospital, Manhasset, NY
  • Christine A. Kerr, MD, Galileo Health
  • Jeremy D. Kidd, MD, MPH, New York-Presbyterian Hospital, Columbia University, New York, NY
  • Hector I. Ojeda-Martinez, MD, Nuvance Health/Health Quest Medical Practice, Poughkeepsie, NY
  • Asa E. Radix, MD, MPH, FACP, AAHIVS, Callen-Lorde Community Health Center, New York, NY
  • Sanjiv S. Shah, MD, MPH, AAHIVM, AAHIVS, NYC Health + Hospitals/Gotham Health, Gouverneur, New York, NY
  • Noga Shalev, MD, Columbia University Medical Center, New York, NY
  • Eugenia L. Siegler, MD, Weill Cornell Medical College, New York, NY
  • Maria Teresa (Tess) Timoney, MS, RN, CNM, Bronx Prevention Center, ICAP at Columbia, Bronx, NY
  • Benjamin W. Tsoi, MD, MPH, Bureau of HIV/AIDS Prevention and Control, New York City Department of Health and Mental Hygiene, New York, NY
  • Marguerite A. Urban, MD, University of Rochester School of Medicine and Dentistry, Rochester, NY
  • Antonio E. Urbina, MD, The Mount Sinai Hospital, Comprehensive Health Program–Downtown, New York, NY
    • Scientific Advisor: Gilead, ViiV, Merck
  • Geoffrey A. Weinberg, MD, University of Rochester School of Medicine and Dentistry, Rochester, NY

Funding and disclosure of potential conflicts of interest (COIs): NYS funds supported the development of this guideline through a grant awarded to the JHU School of Medicine, Division of Infectious Diseases, from the NYSDOH AI.

All active MCCC members, invited consultants and coauthors, peer reviewers, and program staff are required to disclose financial relationships with commercial entities, including gifts that may be actual conflicts of interest or may be perceived as conflicts. These individuals must disclose financial relationships annually, for themselves, their partners/spouses, and their organization/institution. On their annual disclosures, MCCC members are asked to report for the previous 12 months and the upcoming 12 months. 

All reported financial relationships with commercial entities are reviewed by the NYSDOH AI guidelines program to assess the potential for undue influence on guideline recommendations made by the Committee.

All guideline recommendations received consensus approval of the full MCCC, and the final review and approval of the recommendations were performed by the Committee Chair and the NYSDOH AI Medical Director and Deputy Medical Director, none of whom reported conflicts of interest.

Evidence collection and review: The NYSDOH AI guideline development process is based on a strategic search and analysis of the published evidence. Box A2 illustrates the evidence review and selection process.

Box A2: Evidence Collection and Review Processes
  • NYSDOH AI and MCCC defined the goal of the guideline: To inform NYS clinicians about care for patients who present with signs or symptoms of acute HIV infection.
  • MCCC appointed a lead author who conducted a systematic literature search in PubMed using MeSH terms; all searches were limited to studies that 1) were published within the previous 5 years; 2) involved only human subjects; and 3) were published in English.
  • Lead authors reviewed studies identified through searches and excluded based on the following criteria: Publication type, study design, participants, and clinical relevance to the guideline.
  • Author and editorial staff conducted additional searches using PubMed and online databases to identify:
    • Studies published prior to the 5-year search limit.
    • Studies published during the guideline development process.
    • Recent conference abstracts.
    • Older studies known to provide strong evidence in support of specific recommendations or to undergird expert opinion.
  • Lead authors developed and the Writing Group and then all MCCC members reviewed and approved evidence-based guideline recommendations:
    • Writing Group reviewed, deliberated, refined, and approved draft recommendations.
    • MCCC members reviewed, provided written comment on, deliberated, and reached consensus on recommendations.
    • Members of the Writing Group reviewed the cited evidence and assigned a 2-part rating to each recommendation to indicate the strength of the recommendation and the quality of the supporting evidence; consensus reached on ratings.
    • Additional evidence identified and cited during the rating process (see below).
  • Ongoing update process:
    • JHU editorial staff will surveil published literature on an ongoing basis to identify new evidence that may prompt changes to existing recommendations or development of new recommendations.
    • JHU editorial staff will ensure that the MCCC reviews new studies at least 4 times per year, and more often if newly published studies, new drug approval, or drug-related warning indicate the need for an immediate change to the published guideline.
    • JHU editorial staff will track, summarize, and publish ongoing changes to the guideline.
    • MCCC will review and approve substantive changes to, additions to, or deletions of recommendations.
    • MCCC will initiate a full review of the guideline 4 years after the original publication date.
    • NYSDOH AI will publish a comprehensive update 5 years after the original publication date.

Recommendation development and rating process: When this guideline was originally developed, the standard development process was followed. Clinical recommendations were developed by consensus based on a synthesis of the current evidence collected through the systematic search described above. If no data were available, the recommendations are based on expert opinion, and this status is indicated in the rating and the text. Once consensus among the Writing Group members was reached, the guideline was reviewed by the full MCCC, and consensus was reached on all recommendations. Writing Group review discussions were recorded, and recordings were reviewed carefully to ensure that all decisions and changes were captured and integrated into the manuscript. Members of the Writing Group then individually reviewed the evidence for each recommendation and assigned a 2-part rating (see below). The individual ratings were compiled into a report distributed to all raters, and conference call discussions were held to deliberate ratings for which consensus was needed. Once all raters agreed on the interpretation of evidence and ratings for all recommendations, the guideline was sent to the NYSDOH AI for review and approval.

The current guideline reflects a review and update that was completed at the 3-year anniversary of publication. New literature was reviewed by a member of the MCCC and minor updates were made, which were then reviewed and approved by the Writing Group.

AIDS Institute Clinical Guidelines Program: Recommendations Ratings
(updated June 2019 [a])
Strength of Recommendation Ratings
A Strong recommendation
B Moderate recommendation
C Optional
Quality of Supporting Evidence Ratings
1 Evidence is derived from published results of at least one randomized trial with clinical outcomes or validated laboratory endpoints.
* Evidence is strong because it is based on a self-evident conclusion(s); conclusive, published, in vitro data; or well-established practice that cannot be tested because ethics would preclude a clinical trial.
2 Evidence is derived from published results of at least one well-designed, nonrandomized clinical trial or observational cohort study with long-term clinical outcomes.
2† Evidence has been extrapolated from published results of well-designed studies (including non-randomized clinical trials) conducted in populations other than those specifically addressed by a recommendation. The source(s) of the extrapolated evidence and the rationale for the extrapolation are provided in the guideline text. One example would be results of studies conducted predominantly in a subpopulation (e.g., one gender) that the committee determines to be generalizable to the population under consideration in the guideline.
3 Recommendation is based on the expert opinion of the committee members, with rationale provided in the guideline text.
  1. With the June 2019 update, the ratings for quality of supporting evidence were expanded to add the * rating and the 2† rating.

Guideline updates: Members of the MCCC or an invited lead author who is not an MCCC member will monitor developments in an ongoing structured manner to maintain guideline currency. Once the guidelines are published on the program website, www.hivguidelines.org, and indexed in the National Library of Medicine, any updates will be made to the HTML document and all collateral materials as needed as new, peer-reviewed literature is published if evidence is made available that changes best practices.

Notification of newly published studies will be automated, and the Writing Group will review new data as available. Newly published data that provide support for existing recommendations will be cited in the text, and the studies will be added to the reference list(s).

If newly published data prompt a revision to recommendations or rationale, the lead author and the Writing Group will propose appropriate edits and determine whether the changes warrant review and approval by the entire MCCC. If MCCC review is required, JHU will distribute updates via email, and a conference call will be convened if required. Deletion of existing recommendations, addition of any new recommendations, or substantive changes to existing recommendations will prompt MCCC review and consensus.

The full guideline will be reviewed and updated on the third and the fifth anniversary of original publication and more often if an evidence-based change in recommendations is required.

Updates to This Guideline

July 2021

Recommendations on diagnosis of acute HIV infection have been updated in the Presentation and Diagnosis section:

  • Clinicians can presume the diagnosis of acute HIV when high levels (>10,000 copies/mL) of HIV RNA are detected in plasma with sensitive nucleic acid amplification testing (NAAT), and the result of the HIV screening or type-differentiation test is negative or indeterminate. (A2)
  • Clinicians should seek expert consultation when an ambiguous HIV result is obtained for an individual taking PrEP; diagnosis of acute HIV can be particularly challenging in patients taking PrEP. (A3)
  • When a low-level quantitative HIV RNA viral load result (<10,000 copies/mL) is obtained in the absence of serologic evidence of HIV infection, the clinician should repeat HIV RNA testing and perform a 4th-generation antigen/antibody combination assay to exclude a false-positive result. (A2)
    • Note: A serologic test result that does not meet the criteria for HIV infection is a nonreactive screening result (antibody or antibody/antigen combination) or a reactive screening result with a nonreactive or indeterminate antibody-differentiation confirmatory result.

Recommendations on HIV transmission and resistance have been updated in the Management, Including While on PEP or PrEP section:

  • Clinicians should inform patients about the increased risk of transmitting HIV during acute infection and for the 6 months following infection. (A2)
  • Patients taking pre-exposure prophylaxis (PrEP): Because the risk of drug-resistant mutations is higher in patients who acquire HIV while taking PrEP, clinicians should recommend a fully active ART regimen in consultation with an experienced HIV care provider. (A3)

August 2020

The following updates were made in the section Management, Including While on PEP or PrEP :

  • Rating change from A2 to A1: Clinicians should recommend antiretroviral therapy (ART) to all patients diagnosed with acute HIV infection.
  • New recommendations:
    • As part of the initial management of patients diagnosed with acute HIV infection, clinicians should obtain HIV genotypic resistance testing for the protease (A2), reverse transcriptase (A2), and integrase (B2) genes at the time of diagnosis.
    • Clinicians should perform baseline laboratory testing listed in Box 1: Baseline Laboratory Testing Checklist for all patients who are initiating ART immediately; ART can be started while awaiting laboratory test results. (A3)
  • Discussion revised:
    • Rationale for early treatment
    • Benefits and disadvantages of early treatment
    • Genotypic resistance testing
  • Addition: Box 1: Baseline Laboratory Testing Checklist

August 2018

  • Introduction:
    • Added “A New HIV Diagnosis is a Call to Action” 
    • Added a statement regarding U =U
  • Presentation and Diagnosis:
    • Updated the recommendation regarding HIV testing to reflect current NYS law, which mandates that physicians offer an HIV test to all patients aged 13 years and older, i.e., the previous upper age limit of 65 years was removed. 
    • Changed the text that follows from a key point to a recommendation: Diagnostic HIV RNA testing should be considered for patients who present with compatible symptoms (see Acute Retroviral Syndrome), particularly in the context of a sexually transmitted infection [Patel et al. 2006] or a recent sexual or parenteral exposure with a partner known to have HIV or a partner whose HIV serostatus is not known (A2).
    • Updated links to open the January 2018 update to the CDC’s HIV testing algorithm
    • Added two recommendations from the NYSDOH AI guideline PrEP to Prevent HIV and Promote Sexual Health to address prevention following a negative HIV test result.
    • Added a Key Point: A negative screening test in response to suspected acute HIV infection is an opportunity to offer or refer the individual for PrEP. See the NYSDOH AI guideline PrEP to Prevent HIV and Promote Sexual Health