Posted September 2015
In the medical literature, as in this guideline, the terms acute HIV infection and primary HIV infection both describe the period immediately after infection when the patient is viremic and has detectable p24 antigen and/or HIV RNA without diagnostic HIV antibodies. For consistency, the term acute HIV infection is used in these guidelines.
The term recent infection is generally used to describe the 6-month period after infection occurs. Early infection refers to both acute and recent infection, after which infection is defined as chronic.
In the United States, acutely infected individuals account for less than 1% of all those with HIV infection. However, the estimated range of incident HIV transmission in the setting of acute infection is 8.6% to 50%.1-5 The risk of sexual transmission of HIV during acute or recent infection is significantly higher than during chronic infection.6-9 Although estimates are sensitive to modeling assumptions,10 this difference likely correlates with high levels of viremia and is consistent with other routes of transmission. Many challenges are inherent in modeling transmission risk; the refinement of these models will have important implications for HIV treatment as a prevention strategy.11
Accumulating evidence supports a decision to begin HIV treatment at the time of diagnosis.12 Initiation of antiretroviral therapy (ART) during acute infection may have a number of 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.13-24 The public health benefit of early initiation of ART is well documented, with a significant reduction of HIV transmission among virally suppressed individuals.
Recognizing and diagnosing acute infection is crucial to linking patients to care early and presents an important opportunity for prevention. Factors that may contribute to the increased risk for transmission during acute infection include:
- Hyperinfectivity associated with both markedly increased viral load levels (often much greater than 10 million viral copies/mm3) and increased infectiousness of the virus25-26
- Missed HIV diagnosis27 because the nonspecific flu- or mono-like symptoms during acute illness are frequently unrecognized; a diagnosis would prompt providers to recommend treatment and risk-reduction counseling that could reduce both viral load levels and high-risk behavior28-30
For many reasons, detection of acute HIV infection can be a very important 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 testing28,29 and are linked to primary HIV care.31 In addition, for those who elect to initiate ART, their risk of transmission is significantly diminished.32
II. PRESENTATION AND DIAGNOSIS OF ACUTE HIV INFECTION
Clinicians should include acute HIV infection in the differential diagnosis for anyone (regardless of reported risk) with a flu- or mono-like illness (AIII), especially when the patient:
- Presents with a rash (AII)
- Requests HIV testing (AIII)
- Reports recent sexual or parenteral exposure to a person with or at risk for HIV infection (AII)
- Presents with a newly diagnosed sexually transmitted infection (AII)
- Presents with aseptic meningitis (AII)
- Is pregnant or breastfeeding (AIII)
- Is currently on pre- or post-exposure prophylaxis (PrEP or PEP) (AIII)
According to New York State Law, physicians must also offer an HIV test to all patients between the ages of 13 and 64 years (or older/younger with risk) if a previous test is not documented, even in the absence of symptoms consistent with acute HIV. Although written consent to HIV testing is no longer required in New York State, patients must be given the opportunity to decline, and verbal consent must be documented in the medical record.
When acute HIV infection is suspected:
- A plasma HIV RNA assay should always be used in conjunction with an antigen/antibody combination screening test (AII)
- A fourth-generation antigen/antibody combination assay is recommended as the initial HIV screening test according to the CDC HIV testing algorithm.a If the screening test is reactive, an HIV-1/HIV-2 antibody-differentiation immunoassay should be performed to confirm HIV infection; Western blot is no longer recommended as the confirmatory test (AII)
- Detection of HIV RNA with ≥5,000 copies/mL should be considered a presumptive diagnosis of acute infection even if the screening and antibody-differentiation tests are nonreactive or indeterminate (AII)
- HIV RNA testing should be repeated to exclude a false-positive result when low-level quantitative results (<5000 copies/mL) from an HIV RNA assay are reported in the absence of serologic evidence of HIV infectionb (AII)
- If a diagnosis of HIV infection is made on the basis of HIV RNA testing alone, a new specimen should be collected 3 weeks later and HIV diagnostic testing should be repeated according to the CDC HIV testing algorithm (AII)
a When rapid antibody screening is performed, including screening with a rapid fourth-generation test, a laboratory-based fourth-generation immunoassay is recommended in follow-up diagnostic HIV testing (see the CDC HIV testing algorithm).
b The absence of serologic evidence of HIV infection is defined as a nonreactive screening result (antibody or antibody/antigen combination) or a reactive screening result with a nonreactive or indeterminate antibody-differentiation confirmatory result.
If a diagnosis of acute infection is made on the basis of HIV RNA testing, initiation of ART should be recommended while awaiting serologic confirmation. (AII)
When pregnant women are diagnosed with acute infection by HIV RNA testing, clinicians should not wait for results of a confirmatory test to initiate ART; initiation of ART is strongly recommended for pregnant women (see Acute HIV Infection in Pregnancy). (AII)
Clinicians must report confirmed cases of HIV according to New York State Law (see www.health.ny.gov/
- 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.
- Diagnostic HIV RNA testing should be considered for patients who present with compatible symptoms (see Appendix A), particularly in the context of a sexually transmitted infection33 or a recent sexual or parenteral exposure with a known HIV-infected partner or a partner of unknown HIV serostatus.
The time from HIV infection to detection of the virus depends on the test that is used. Figure 1 illustrates the window of detection of HIV infection according to antibody, antibody/antigen combination, and HIV RNA tests.
Patients acutely infected with HIV will often experience at least some symptoms of acute retroviral syndrome. Fever and flu- or mono-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 Appendix A 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.34 Theoretically, this time course may be prolonged in patients who become infected while on PEP or PrEP.
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 person’s blood or body fluids and who is presenting with a febrile, flu-, or mono-like illness. Identification of acute HIV infection during pregnancy is particularly important to ensure appropriate steps are taken to prevent mother-to-child transmission.35
When clinicians suspect acute infection, a test for plasma HIV RNA should be performed. High levels of HIV RNA detected in plasma through use of sensitive nucleic acid amplification testing (NAAT), in combination with a negative or indeterminate HIV screening or type-differentiation test, support the presumptive diagnosis of acute HIV infection.
When low-level viremia is reported by HIV RNA testing (<5000 copies/mL) in the absence of serologic evidence of HIV infection, HIV RNA testing should be repeated to exclude a false-positive result.36 Repeat HIV RNA testing with a result of low-level viremia may represent true HIV infection, warranting appropriate counseling regarding transmission risk. ART should be recommended in the setting of low-level viremia that has been confirmed by repeat HIV RNA testing.
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. Plasma HIV RNA levels during acute infection do not appear significantly different in patients who have symptoms versus those who are asymptomatic.37 Viremia occurs approximately 2 weeks prior to 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).38,39
- Patients undergoing HIV testing who are not suspected to have acute infection should receive screening according to the standard protocol (see the CDC HIV testing algorithm). Patients with clinical signs or symptoms of acute retroviral syndrome or who are at high risk for acute infection should receive HIV screening and HIV RNA testing simultaneously.
- A positive HIV RNA assay is a preliminary diagnosis of HIV; ART should be recommended while waiting for confirmatory testing.
- Individual laboratories have internal protocols for reporting HIV tests with preliminary results: indeterminate, inconclusive, nondiagnostic, and pending validation are among the terms used when preliminary results cannot be classified definitively. The clinician should contact the appropriate laboratory authority to determine the significance of the nondefinitive results and the supplemental testing that would be indicated. This is of particular importance in tests from patients with suspected acute HIV infection. Clinicians should become familiar with the internal test-reporting policies of their institutions.
Figure 2 illustrates diagnostic testing for acute HIV infection.
III. MANAGEMENT OF ACUTE HIV INFECTION, INCLUDING WHILE ON PEP OR PrEP
ART should be recommended for all patients with a diagnosis of acute HIV infection. (AII)
Clinicians should counsel patients about the increased risk of transmitting HIV during acute HIV infection. (AII)
As part of the initial management of patients diagnosed with acute HIV infection, clinicians should:
- Consult with a provider experienced in the treatment of acute HIV infection (AIII)
- Obtain baseline HIV genotypic resistance testing, regardless of whether ART is being initiated (AII)
When acute HIV infection is diagnosed in a person receiving PEP, ART should be continued pending consultation with an experienced HIV care provider. (AIII)
When acute HIV infection is diagnosed in a person receiving PrEP, a fully active ART regimen should be recommended in consultation with an experienced HIV care provider. (AIII)
If the clinician and patient have made a decision to initiate ART during acute HIV infection:
- Treatment should be implemented with the goal of suppressing plasma HIV RNA to below detectable levels (AI)
- Treatment should not be withheld while awaiting the results of recommended resistance testing; adjustments may be made to the regimen once resistance results are available (AIII)
Clinicians who do not have access to experienced HIV care providers should call the Clinical Education Initiative (CEI) Line at 1-866-637-2342.
Patients are at greatest risk for transmitting HIV during periods of high viremia early in infection. Clinicians should counsel acutely infected patients about the increased risk of transmission during the 6-month period after infection. Partner notification,40 safer sex counseling, and screening for other sexually transmitted infections are all important in the management of any new HIV diagnosis.
When choosing an ART regimen for a patient with acute HIV infection, a provider experienced in the treatment of acute HIV infection should be consulted.
- Data are insufficient to support firm recommendations regarding specific regimens for treating acute HIV infection.
- The risks of transmitted resistance should be considered when prescribing ART while awaiting HIV resistance results.
Clinicians who do not have access to experienced HIV care providers should call the Clinical Education Initiative (CEI) Line at 1-866-637-2342.
If the decision to initiate treatment has been made, therapy should not be withheld while awaiting the results of resistance testing. Adjustments may be made to the regimen once resistance results are available (see Antiretroviral Therapy, Section VI. B: HIV Resistance Assays).
The rationale for early treatment (CD4 count >500 cells/mm3) in chronic infection has been definitively demonstrated with the release of preliminary results from the START study. The data show a 53% reduction in serious illness or death in the early treatment arm.12 There is also mounting evidence suggesting that ART during recent infection may have a range of beneficial effects on clinical outcomes, including an increased likelihood of CD4 cell recovery,13-15 significantly reduced time to viral suppression,16 a decrease in viral reservoir and preservation of gut-associated lymphoid tissue,17-20 and the small possibility of long-term control of HIV infection after cessation of therapy.21-24
Three randomized controlled studies compared deferred therapy versus immediate initiation of therapy in acute or recent infection.41-43 These studies demonstrated that immediate initiation of ART delayed a decrease in CD4 counts to <350 cells/mm3 compared with no therapy. One of the most notable findings across these studies was the high percentage of patients in the deferred-therapy arms who progressed to CD4 counts <350 cells/mm3 within the first year after infection. That finding suggests that if the decision is made to postpone initiation of ART, most patients will experience significant immune decline fairly rapidly.
Although these studies may have oversampled symptomatic patients, a population that has been shown to progress more rapidly,44,45 previous estimates that included more asymptomatic patients nevertheless found an average time of 1.5 years after seroconversion for CD4 counts to decline to <350 cells/mm3.46 The findings suggest that the amount of time off therapy gained by deferring initiation will be limited, relative to the need for lifelong treatment.
Notably, these studies not only used an outdated recommended CD4 count threshold (i.e., <350 cells/mm3 versus the current recommendations of early treatment at any CD4 count, including those with CD4 counts >500 cells/mm3), they also investigated various durations of ART followed by treatment interruption.41-43 With evidence that treatment interruptions carry significant risks of morbidity and mortality,47 as well as increased transmission risk during viral rebound,48,49 the findings regarding treatment interruption no longer have relevance for individualized treatment decisions in the context of acute or chronic HIV infection.
The clinician and the patient should be aware that the public health benefit of early initiation of ART is well documented despite the difficulty of designing randomized trials of sufficient size and duration that could conclusively demonstrate long-term clinical benefit from therapy for acute HIV infection. Published data increasingly support a decision to begin treatment at the time of diagnosis. There should be a discussion of the potential benefits versus the limited risks (see Table 1), with an emphasis on current recommendations for when to initiate ART, the short time between infection and CD4 count decline in randomized controlled studies, and the benefits in preventing transmission.
Resistance testing should be obtained to optimize the initial ART regimen. The increasing incidence of transmission of antiretroviral resistance51 argues for resistance testing at baseline in all HIV-infected patients, including those who are acutely infected. Antiretroviral drug resistance mutations are more likely to be detected when genotypic resistance testing is performed at the time of recent infection.51 If information about the possible source person is available, history of antiretroviral drug resistance should be obtained to assist in selection of a regimen. In cases where there are multiple possible sources, as much information should be gathered as possible. All patients should be provided a copy of their baseline resistance test in the event that they defer therapy and initiate treatment later with a different provider.
If therapy is initiated during acute HIV infection, clinicians should continue to treat the patient with ART indefinitely because viremia has been documented to reappear or increase after discontinuation of therapy, and treatment interruptions have been shown to lead to greater morbidity and mortality.47
Regardless of whether or not ART for acute HIV infection is initiated, follow-up for standard HIV testing and HIV primary care should be arranged (see Primary Care Approach to the HIV-Infected Patient).
1. Brenner BG, Roger M, Routy JP, et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis 2007;195:951-959. [PubMed]
2. Yerly S, Vora S, Rizzardi P, et al. Swiss HIV Cohort Study. Acute HIV infection: Impact on the spread of HIV and transmission of drug resistance. AIDS 2001;15:2287-2292. [PubMed]
3. Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection in Rakai, Uganda. J Infect Dis 2005;191:1403-1409. [PubMed]
4. Pinkerton SD. How many sexually-acquired HIV infections in the USA are due to acute-phase HIV transmission? AIDS 2007;21:1625-1629. [PubMed]
5. Powers KA, Ghani AC, Miller WC, et al. The role of acute and early HIV infection in the spread of HIV and implications for transmission prevention strategies in Lilongwe, Malawi: A modeling study. Lancet 2011;378:256-68. [PubMed]
6. Pinkerton SD. Probability of HIV transmission during acute infection in Rakai, Uganda. AIDS Behav 2008;12:667-684. [PubMed]
7. Pilcher CD, Tien HC, Eron JJ, et al. Brief but efficient: Acute HIV infection and the sexual transmission of HIV. J Infect Dis 2004;189:1785-1792. [PubMed]
8. Hollingsworth TD, Anderson R, Fraser C. HIV-1 Transmission, by stage of infection. JID 2008;198:687-93. [PubMed]
9. 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;211:1757-1760. [PubMed]
10. 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:e1001801. [PubMed]
11. Xinyu Zhang, Lin Zhong, Ethan Romero-Severson, et al. Episodic HIV risk behavior can greatly amplify HIV prevalence and the fraction of transmissions from acute HIV infection. Stat Commun Infect Dis 2012;4(1):1041. [PubMed]
12. INSIGHT START Study Group, Lundgren JD, Babiker AG, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 2015;373:795-807. [PubMed]
13. 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;194:734-739. [PubMed]
14. 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;14:277-283. [PubMed]
15. Le T, Wright EJ, Smith DM, et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med 2013; 368:218-230. [PubMed]
16. Pilcher C, Hatano H, Dasgupta A, et al. Providing same day, observed ART to newly diagnosed HIV+ outpatients is associated with improved virologic suppression. Eighth International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2015). July 19-22, 2015, Vancouver. Abstract WEAD0105LB.
17. 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;36:783-790. [PubMed]
18. Buzon M, Siess K, Sone A, et al. Treatment of early HIV infection reduces viral reservoir to levels found in elite controllers. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012, Seattle. Abstract 151.
19. 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:e33948. [PubMed]
20. Phanuphak N, Teeratakulpisarn N, Mungyu P, et al. Time to undetectable HIV RNA in ano-genital compartment of acute HIV Thai male subjects treated with 5- and 3-drug HAART. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012, Seattle. Abstract 555.
21. 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):1598-601. [PubMed]
22. Lafeuillade A, Hittinger G, Lambry V, et al. Long-term control of HIV reservoir after a 2-year ART course at acute infection. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012, Seattle. Abstract 358.
23. Sáez-Cirión A, Bacchus C, Hocqueloux L, et al. Post-treatment HcIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog 2013;9:e1003211. [PubMed]
24. Margolick J, Apuzzo L, Tossonian H, et al. Effect of randomized HAART on viral suppression off therapy in patients with acute/early HIV infection. 19th Conference on Retroviruses and Opportunistic Infections. March 5-8, 2012, Seattle. Abstract 356.
25. 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;83:3288-3297. [PubMed]
26. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. N Engl J Med 2000;342:921-929. [PubMed]
27. Chin T, Hicks C, Samsa G, et al. Diagnosing HIV infection in primary care settings: Missed opportunities. AIDS Patient Care STDS 2013;27:392-397. [PubMed]
28. 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. [PubMed]
29. 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;13:1054-1060. [PubMed]
30. 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):1529-35. [PubMed]
31. 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;47:577-584. [PubMed]
32. Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011;365:493-505. [PubMed]
33. 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):75-9. [PubMed]
34. Apoola A, Ahmad S, Radcliffe K. Primary HIV infection. Int J STD AIDS 2002;13:71-78. [PubMed]
35. Patterson KB, Leone PA, Fiscus SA. Frequent detection of acute HIV infection in pregnant women. AIDS 2007;21(17):2303-8. [PubMed]
36. Hecht FM, Busch MP, Rawal B, et al. Use of laboratory tests and clinical symptoms for identification of primary HIV infection. AIDS 2002;16:1119-1129. [PubMed]
37. Pilcher CD, Price MA, Hoffman IF, et al. Frequent detection of acute primary HIV infection in men in Malawi. AIDS 2004;18:517-524. [PubMed]
38. Centers for Disease Control and Prevention. Quick Reference Guide—Laboratory Testing for the Diagnosis of HIV Infection: Updated Recommendations. June 27, 2014. Available at: www.cdc.gov/
39. Centers for Disease Control and Prevention. 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):489-94. [PubMed]
40. Golden M, Hogben M, Potterat JJ, Handsfield HH. HIV partner notification in the United States: a national survey of program coverage and outcomes. Sex Transm Dis 2004;31(12):709-12. [PubMed]
41. Fidler S, Porter K, Ewings F, et al. Short-course antiretroviral therapy in primary HIV infection. N Engl J Med 2013;368:207-217. [PubMed]
42. Grijsen ML, Steingrover R, Wit FW, et al. No treatment versus 24 or 60 weeks of antiretroviral treatment during primary HIV infection: the randomized Primo-SHM trial. PLoS Med 2012:9;1001196. [PubMed]
43. Hogan C, DeGruttola V, Sun X, et al. The setpoint study (ACTG A5217): effect of immediate versus deferred antiretroviral therapy on virologic set point in recently HIV-1–infected individuals. J Infect Dis 2012;205:87-96. [PubMed]
44. Lavreys L, Baeten JM, Chohan V, et al. Higher set point plasma viral load and more-severe acute HIV type 1 (HIV-1) illness predict mortality among high-risk HIV-1-infected African women. Clin Infect Dis 2006; 42:1333-9. [PubMed]
45. Vanhems P, Lambert J, Cooper DA. Severity and prognosis of acute human immunodeficiency virus type 1 illness: a dose-response relationship. Clin Infect Dis 1998;26:323-9. [PubMed]
46. CASCADE Collaboration. Changes in the uptake of antiretroviral therapy and survival in people with known duration of HIV infection in Europe: results from CASCADE. HIV Med 2000;1:224-231. [PubMed]
47. El-Sadr WM, Lundgren J, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. Strategies for management of antiretroviral therapy. N Engl J Med. 2006;355:2283-2296. [PubMed]
48. Hamlyn E, Ewings FM, Porter K, et al. Plasma HIV viral rebound following protocol-indicated cessation of ART commenced in primary and chronic HIV infection. PLoS One 2012;7:e43754. [PubMed]
49. Rieder P, Joos B, von Wyl V, et al. HIV-1 transmission after cessation of early antiretroviral therapy among men having sex with men. AIDS 2010;24(8):1177-83. [PubMed]
50. Redd AD, Quinn TC, Tobian AA. Frequency and implications of HIV superinfection. Lancet Infect Dis 2013;13:622-628. [PubMed]
51. Kim D, Ziebell R, Saduvala N, et al. Trend in transmitted HIV-1 ARV drug resistance-associated mutations: 10 HIV surveillance areas, US, 2007-2010. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013, Atlanta. Abstract 149.
Cohen MS, Shaw GM, McMichael AJ, et al. Acute HIV-1 infection. N Engl J Med 2011;364:1943-1954. [PubMed]
Ginocchio CG, Branson BM, eds. HIV Laboratory Diagnosis: New Tests and a New Algorithm. J Clin Virol 2013;58 Suppl 1. Available at: http://www.journalofclinicalvirology.com/
Lichterfeld M, Rosenberg ES. Acute HIV-1 infection: a call to action. Ann Intern Med 2013;159(6):425-7. [PubMed]
O’Brien M, Markowitz M. Should we treat acute HIV infection? Curr HIV/AIDS Rep 2012;9(2):101-10. [PubMed]
APPENDIX A. ACUTE RETROVIRAL SYNDROME: ASSOCIATED SIGNS AND SYMPTOMS (EXPECTED FREQUENCY AMONG PATIENTS WHO ARE SYMPTOMATIC)