Purpose of This Guideline
Lead author: Sanjiv S. Shah, MD, MPH, AAHIVS
Publication date: October 8, 2021
Writing Group: Joseph P. McGowan, MD; Steven M. Fine, MD, PhD; Rona M. Vail, MD; Samuel T. Merrick, MD; Asa E. Radix, MD, MPH, PhD; Christopher J. Hoffmann, MD, MPH; Charles J. Gonzalez, MD
Committee: Medical Care Criteria Committee
The New York State Department of Health (NYSDOH) AIDS Institute (AI) developed this guideline for primary care providers and other clinicians who may diagnose and treat patients with HIV-2 infection. The guideline is designed to achieve the following goals:
- Inform clinicians about when to suspect and how to diagnose and manage the care of adults with HIV-2.
- Identify the similarities and differences in treatment for individuals with HIV-1 and HIV-2.
- Recommend preferred antiretroviral (ARV) regimens for treatment and identify ARVs to avoid.
- Encourage clinicians to use the services of the NYSDOH Wadsworth Center, the NYS public health laboratory, for testing used in monitoring HIV-2.
- Integrate current evidence-based clinical recommendations into the healthcare-related implementation strategies of the Ending the Epidemic (ETE) initiative, which seeks to end the AIDS epidemic in NYS by the end of 2020.
HIV-2 Overview
Lead author: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; October 2021
The HIV-2 virus was first isolated in West Africa in the mid-1980s among individuals living with AIDS [Clavel, et al. 1986]. HIV-2 infection is endemic in West Africa, with the highest prevalence in Cape Verde, the Ivory Coast, Gambia, Guinea-Bissau, Mali, Mauritania, Nigeria, and Sierra Leone [Gottlieb, et al. 2018]. Although rare, HIV-2 infection has also been reported in several countries in Europe, South America, and Asia, and in the United States [Gottlieb 2018]. As of June 2010, 166 cases of HIV-2 had been reported in the United States and 46% of those were from New York City [CDC 2011]. The majority of individuals with HIV-2 are from West Africa or have had sexual contact or shared injection drug equipment with someone from this region [Torian, et al. 2010].
HIV-2 infection is associated with slower disease progression than HIV-1 infection because of lower plasma viral load levels of HIV-2 [van der Loeff, et al. 2010; MacNeil, et al. 2007; Gottlieb, et al. 2002; Popper, et al. 1999; Simon, et al. 1993]. With lower levels of virus, HIV-2 is transmitted less efficiently than HIV-1 through sexual behavior and from mother to child [Burgard, et al. 2010; O’Donovan, et al. 2000; Adjorlolo-Johnson, et al. 1994]. Similar to HIV-1, HIV-2 disease progression correlates with increasing plasma HIV-2 viral load [Gottlieb, et al. 2002]. Although HIV-2 is less virulent than HIV-1, individuals with HIV-2 manifest clinical signs, symptoms, and opportunistic infections (OIs) similar to those seen with HIV-1. In addition, the majority of individuals with HIV-2, if untreated, will eventually progress to AIDS and death [Esbjornsson, et al. 2018].
There are many similarities in the management of patients with HIV-1 and those with HIV-2, including prophylaxis for and treatment of OIs and timing of antiretroviral therapy (ART) initiation. As noted in the section on treatment, below, ART should be recommended for all patients diagnosed with HIV-2 [Ba, et al. 2018]. As with HIV-1, the patient should make the final decision of whether and when to initiate ART.
A key difference in the clinical management of HIV-2 compared with HIV-1 is that resistance testing is not commercially available in the United States and guidance in interpreting mutations is not readily available for HIV-2. Another important difference in management is that the non-nucleoside reverse transcriptase inhibitor (NNRTI) class of ARV medications is not effective against HIV-2. Furthermore, unlike in HIV-1, there are no randomized clinical trials of ARV treatment for HIV-2 that indicate the optimal time to initiate treatment or the preferred initial regimen. Therefore, treatment recommendations for HIV-2 are in large part derived from clinical studies conducted in HIV-1. Because HIV-1 and HIV-2 share the same pathogenic process, extrapolating to HIV-2 from HIV-1 is a clinically valid approach.
References
Adjorlolo-Johnson G, De Cock KM, Ekpini E, et al. Prospective comparison of mother-to-child transmission of HIV-1 and HIV-2 in Abidjan, Ivory Coast. JAMA 1994;272(6):462-466. [PMID: 8040982]
Ba S, Raugi DN, Smith RA, et al. A trial of a single tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate for the initial treatment of HIV-2 infection in a resource-limited setting: 48 week results from Senegal, West Africa. Clin Infect Dis 2018. [PMID: 29672676]
Burgard M, Jasseron C, Matheron S, et al. Mother-to-child transmission of HIV-2 infection from 1986 to 2007 in the ANRS French Perinatal Cohort EPF-CO1. Clin Infect Dis 2010;51(7):833-843. [PMID: 20804413]
CDC. HIV-2 infection surveillance–United States, 1987-2009. MMWR Morb Mortal Wkly Rep 2011;60(29):985-988. [PMID: 21796096]
Clavel F, Guyader M, Guetard D, et al. Molecular cloning and polymorphism of the human immune deficiency virus type 2. Nature 1986;324(6098):691-695. [PMID: 3025743]
Esbjornsson J, Mansson F, Kvist A, et al. Long-term follow-up of HIV-2-related AIDS and mortality in Guinea-Bissau: a prospective open cohort study. Lancet HIV 2018. [PMID: 30392769]
Gottlieb G. Treatment of HIV-2 infection. 2018 May 25. https://www.uptodate.com/contents/treatment-of-hiv-2-infection [accessed 2019 Jun 6]
Gottlieb G, Raugi DN, Smith RA. 90-90-90 for HIV-2? Ending the HIV-2 epidemic by enhancing care and clinical management of patients infected with HIV-2. Lancet HIV 2018;5(7):e390-e399. [PMID: 30052509]
Gottlieb G, Sow PS, Hawes SE, et al. Equal plasma viral loads predict a similar rate of CD4+ T cell decline in human immunodeficiency virus (HIV) type 1- and HIV-2-infected individuals from Senegal, West Africa. J Infect Dis 2002;185(7):905-914. [PMID: 11920314]
MacNeil A, Sarr AD, Sankale JL, et al. Direct evidence of lower viral replication rates in vivo in human immunodeficiency virus type 2 (HIV-2) infection than in HIV-1 infection. J Virol 2007;81(10):5325-5330. [PMID: 17329334]
O’Donovan D, Ariyoshi K, Milligan P, et al. Maternal plasma viral RNA levels determine marked differences in mother-to-child transmission rates of HIV-1 and HIV-2 in The Gambia. MRC/Gambia Government/University College London Medical School working group on mother-child transmission of HIV. AIDS 2000;14(4):441-448. [PMID: 10770548]
Popper SJ, Sarr AD, Travers KU, et al. Lower human immunodeficiency virus (HIV) type 2 viral load reflects the difference in pathogenicity of HIV-1 and HIV-2. J Infect Dis 1999;180(4):1116-1121. [PMID: 10479138]
Simon F, Matheron S, Tamalet C, et al. Cellular and plasma viral load in patients infected with HIV-2. AIDS 1993;7(11):1411-1417. [PMID: 7904166]
Torian LV, Eavey JJ, Punsalang AP, et al. HIV type 2 in New York City, 2000-2008. Clin Infect Dis 2010;51(11):1334-1342. [PMID: 21039219]
van der Loeff MF, Larke N, Kaye S, et al. Undetectable plasma viral load predicts normal survival in HIV-2-infected people in a West African village. Retrovirology 2010;7:46. [PMID: 20482865]
Diagnosis of HIV-2
Lead author: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; October 2021
RECOMMENDATIONS |
Diagnosis
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Before the HIV-1/2 Ag/Ab combination and HIV-1/HIV-2 Ab differentiation immunoassays for HIV testing became widely available, clinicians suspected chronic HIV-2 infection in certain clinical scenarios, such as a declining CD4 cell count in an HIV-1–seropositive, untreated individual with an undetectable HIV-1 plasma viral load, or an opportunistic infection in an individual from West Africa who is not HIV-1 seropositive.
Currently, all HIV testing performed according to the CDC/APHL algorithm begins with a FDA-approved HIV-1/2 Ag/Ab combination immunoassay [CDC 2018], which detects HIV-1 p24 antigen and HIV-1 and HIV-2 antibodies but not HIV-2 antigen. If the combination immunoassay is reactive, a supplemental HIV-1/HIV-2 Ab differentiation immunoassay is performed. There are 4 scenarios, described below, in which clinicians should consider HIV-2 infection.
- HIV-1/HIV-2 differentiation immunoassay is reactive for HIV-2 antibody: The individual is considered HIV-2 antibody positive, and a clinical evaluation for HIV-2 infection should be performed (see Monitoring ART in Individuals With HIV-2 in this guideline).
- HIV-1/HIV-2 differentiation immunoassay is reactive for HIV-1 and HIV-2 antibody: The individual is considered HIV positive, undifferentiated, and HIV-1 RNA and HIV-2 RNA or DNA testing should be performed to confirm or exclude HIV-1/HIV-2 coinfection. A minority of individuals with HIV-2 are coinfected with HIV-1. Qualitative and quantitative HIV-2 viral load testing is available by contacting the Bloodborne Viruses Laboratory at the Wadsworth Center (see Box 1: Wadsworth Center Bloodborne Viruses Laboratory Services, below).
- HIV-1/HIV-2 differentiation immunoassay is nonreactive or indeterminate for HIV-1 and/or HIV-2 antibody: Plasma HIV-1 RNA testing should be performed to confirm or exclude acute HIV-1 infection [CDC 2018].
- If the Ab differentiation immunoassay is nonreactive or HIV-1 indeterminate and HIV-1 RNA is not detected, the individual is considered negative for HIV-1 and HIV-2.
- If the Ab differentiation immunoassay is either HIV-2 indeterminate or HIV indeterminate and HIV-1 RNA is not detected, then HIV-2 RNA testing may be used to confirm HIV-2 infection. However, because HIV-2 RNA levels can be low or undetectable in a person with HIV-2 infection, the absence of HIV-2 RNA does not exclude HIV-2 infection. Therefore, in a person at high risk for HIV-2 infection who has undetectable HIV-2 RNA, clinicians should consider testing for HIV-2 DNA or repeating the HIV testing algorithm in 2 to 4 weeks, starting with the HIV-1/2 Ag/Ab combination immunoassay. If results remain unclear, clinicians may consider obtaining other HIV-2–specific tests through public health or commercial laboratories or the CDC.
- Nonreactive HIV-1/2 Ag/Ab combination immunoassay and suspected recent exposure to HIV-2 (e.g., exposure from a sex partner from an HIV-2 endemic area): HIV-2 RNA testing may be required or the HIV testing algorithm may be repeated, beginning with the HIV-1/2 Ag/Ab combination immunoassay, 4 weeks (and not later than 12 weeks) after the first test.
Box 1: Wadsworth Center Bloodborne Viruses Laboratory Services |
Note: HIV-2 phenotypic and genotypic resistance testing is not offered at Wadsworth or commercially available in the United States. |
Reference
CDC. 2018 Quick reference guide: Recommended laboratory HIV testing algorithm for serum or plasma specimens. 2018 Jan. https://stacks.cdc.gov/view/cdc/50872 [accessed 2019 Jun 6]
Treatment of HIV-2
Lead author: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; October 2021
RECOMMENDATIONS |
Treatment
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Table 1: Preferred ART Regimens for Initial Treatment of Nonpregnant Adults With HIV-2 [a] (listed alphabetically; for specific details, see drug package inserts; for full recommendations on initiating ART in patients with HIV, see the NYSDOH AI guideline Selecting an Initial ART Regimen) Download PDF |
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Regimen | Comments | Rating |
Available as a Single-Tablet Formulation | ||
Abacavir/lamivudine/dolutegravir [b,c] (ABC/3TC/DTG; Triumeq) |
|
A1 |
Lamivudine/dolutegravir [b,c] (3TC/DTG; Dovato) |
|
A1 |
Tenofovir alafenamide/ emtricitabine/bictegravir [c] (TAF 25 mg/FTC/BIC; Biktarvy) |
|
A1 |
Available as a Multi-Tablet Regimen With Once-Daily Dosing | ||
Tenofovir alafenamide/emtricitabine or tenofovir disoproxil fumarate/emtricitabine and dolutegravir [b,c] (TAF 25 mg/FTC or TDF 300 mg/FTC and DTG; Descovy or Truvada and Tivicay) |
|
A1 |
Tenofovir alafenamide/emtricitabine or tenofovir disoproxil fumarate/emtricitabine and raltegravir HD [c] (TAF 25 mg/FTC or TDF 300 mg/FTC and RAL HD; Descovy or Truvada and Isentress HD) |
|
A2 |
Abbreviations: ART, antiretroviral therapy; CrCl, creatinine clearance; DHHS, U.S. Department of Health and Human Services; NRTI, nucleoside/nucleotide reverse transcriptase inhibitors. Notes:
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Table 2: Alternative ART Regimens for Initial Treatment of Nonpregnant Adults With HIV-2 [a] (listed alphabetically; for specific details, see drug package inserts; for full recommendations on initiating ART in patients with HIV, see the NYSDOH AI guideline Selecting an Initial ART Regimen) Download PDF |
||
Regimen | Comments | Rating |
Available as a Single-Tablet Formulation | ||
Tenofovir alafenamide/ emtricitabine/ darunavir/ cobicistat [b] (TAF 10 mg/FTC/DRV/COBI; Symtuza) |
|
B2 |
Tenofovir alafenamide/ emtricitabine/ elvitegravir/ cobicistat [b] (TAF 10 mg/FTC/EVG/COBI; Genvoya) |
|
B1 |
Available as a Multi-Tablet Regimen With Twice-Daily Dosing | ||
Tenofovir alafenamide/ emtricitabine or tenofovir disoproxil fumarate/emtricitabine and raltegravir [b] (TAF 25 mg/FTC or TDF 300 mg/FTC and RAL; Descovy or Truvada and Isentress) |
|
B3 |
Abbreviations: ART, antiretroviral therapy; CrCl, creatinine clearance; CYP, cytochrome P450; DHHS, U.S. Department of Health and Human Services. Notes:
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All FDA-approved NRTIs effectively inhibit HIV-2 reverse transcriptase [Menendez-Arias and Alvarez 2014]. Three HIV protease inhibitors effectively inhibit HIV-2, but given the availability of darunavir, use of lopinavir and saquinavir should be limited. Atazanavir, fosamprenavir, tipranavir, and nelfinavir have no or greatly reduced in vitro inhibitory activity against HIV-2. As a class, NNRTIs are not active against HIV-2 [Menendez-Arias and Alvarez 2014].
KEY POINTS |
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Based on limited clinical trial data using the INSTIs elvitegravir and raltegravir, and in vitro data, it is expected that a DTG- or BIC-based regimen with 2 NRTIs can be used to treat treatment-naive patients with HIV-2. In one study of a single-tablet regimen (EVG/COBI/TDF/FTC), 93.3% of subjects had viral suppression at 48 weeks [Ba, et al. 2018]. A study of a multi-tablet regimen (TDF/FTC and RAL) demonstrated that 96% of participants with HIV-2 completing the 48-week follow-up had an HIV-2 viral load <40 copies/mL [Matheron, et al. 2018]. It is important to involve patients in the decision-making process regarding initiation of ART, and clinicians should work to remove barriers to treatment initiation, such as lack of access to combination therapy.
In treatment-experienced patients with HIV-2, the ARVs listed in Tables 1 and 2 can be considered if their potency has not been compromised by prior treatment failure and the likely emergence of drug resistance/cross-resistance. There are no commercially available genotypic or phenotypic drug resistance assays for HIV-2 available in the United States that can be used to guide the selection of an alternative ART regimen in the setting of virologic failure.
Bictegravir is highly potent against HIV-2 in vitro [Smith, et al. 2019; Le Hingrat, et al. 2018; Tsiang, et al. 2016]; however, there are no published data on the use of TAF/FTC/BIC in patients with HIV-2. If no drug resistance testing is available, DTG and BIC should be used with caution in ART-experienced patients with HIV-2 who have virologic failure on a RAL- or EVG- based ART regimen. The chemokine receptor antagonist maraviroc (MVC) is active against HIV-2 strains that exclusively use CCR5 for viral entry [Borrego, et al. 2012]. However, its use in the treatment of HIV-2 is limited because there is no commercially available tropism assay for HIV-2 to predict susceptibility to MVC. The fusion inhibitor enfuvirtide has no in vitro activity against HIV-2 [FDA 2018; Menendez-Arias and Alvarez 2014]. The recently approved attachment inhibitor fostemsavir has no activity against HIV-2 [FDA 2020]. Ibalizumab, a humanized monoclonal IgG-4 antibody that prevents HIV cell entry by binding to the host CD4 receptor, has in vitro evidence of activity against HIV-2 with IC50 levels comparable to those found in HIV-1 group M strains [Hingrat 2020]. However, the in vivo efficacy of an ibalizumab-based regimen in individuals with antiretroviral-resistant HIV-2 infection has not been established.
In the setting of HIV-1/HIV-2 coinfection, HIV-1 drug resistance testing should be performed to guide the choice of an initial regimen or to modify a regimen if virologic failure develops. If HIV-1 drug-resistant virus has been identified, ARV agents that are active only against HIV-1 (such as an NNRTI) can be used to treat individuals with HIV-1/HIV-2 coinfection, as long as a combination of anti–HIV-2 active agents is also used to fully suppress both viruses.
References
Ba S, Raugi DN, Smith RA, et al. A trial of a single tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate for the initial treatment of HIV-2 infection in a resource-limited setting: 48 week results from Senegal, West Africa. Clin Infect Dis 2018. [PMID: 29672676]
Borrego P, Calado R, Marcelino JM, et al. Baseline susceptibility of primary HIV-2 to entry inhibitors. Antivir Ther 2012;17(3):565-570. [PMID: 22293827]
Cavaco-Silva J, Aleixo MJ, Van Laethem K, et al. Mutations selected in HIV-2-infected patients failing a regimen including atazanavir. J Antimicrob Chemother 2013;68(1):190-192. [PMID: 22977160]
Eron JJ, Orkin C, Gallant J, et al. A week-48 randomized phase-3 trial of darunavir/cobicistat/emtricitabine/tenofovir alafenamide in treatment-naive HIV-1 patients. Aids 2018;32(11):1431-1442. [PMID: 29683855]
FDA. U.S. Food and Drug Administration. Fuzeon (enfuvirtide) for injection. Precribing information. 2018 Dec. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021481s032lbl.pdf [accessed 2020 Sep 28]
FDA. U.S. Food and Drug Administration. Rukobia (fostemsavir) extended-release tablets, for oral use. Precribing information. 2020 Jul. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf [accessed 2020 Sep 28]
Hingrat Q, Collin, G, Charpentier, C, et al. Ibalizumab shows in vitro activity against group A and group B HIV-2 clinical isolates. AIDS 2020. Abstract PEB0122. 23rd International AIDS Conference; 2020 Jul 6-10; Virtual. https://programme.aids2020.org/Abstract/Abstract/9162
Le Hingrat Q, Collin G, Le M, et al. A new mechanism of resistance of HIV-2 to integrase inhibitors: a 5 amino-acids insertion in the integrase C-terminal domain. Clin Infect Dis 2018. [PMID: 30383215]
Matheron S, Descamps D, Gallien S, et al. First-line raltegravir/emtricitabine/tenofovir combination in human immunodeficiency virus type 2 (HIV-2) infection: A phase 2, noncomparative trial (ANRS 159 HIV-2). Clin Infect Dis 2018;67(8):1161-1167. [PMID: 29590335]
Menendez-Arias L, Alvarez M. Antiretroviral therapy and drug resistance in human immunodeficiency virus type 2 infection. Antiviral Res 2014;102:70-86. [PMID: 24345729]
Smith RA, Raugi DN, Wu VH, et al. Comparison of the antiviral activity of bictegravir against HIV-1 and HIV-2 isolates and integrase inhibitor-resistant HIV-2 mutants. Antimicrob Agents Chemother 2019;63(5). [PMID: 30803972]
Tsiang M, Jones GS, Goldsmith J, et al. Antiviral activity of bictegravir (GS-9883), a novel potent HIV-1 integrase strand transfer inhibitor with an improved resistance profile. Antimicrob Agents Chemother 2016;60(12):7086-7097. [PMID: 27645238]
Monitoring ART in Individuals With HIV-2
Lead author: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; October 2021
RECOMMENDATIONS |
Monitoring
|
There is no FDA-approved, HIV-2 quantitative viral load assay commercially available. However, an HIV-2 quantitative viral load test is available by contacting the Bloodborne Viruses Laboratory at the Wadsworth Center (see Diagnosis of HIV-2 > Box 1: Wadsworth Center Bloodborne Viruses Laboratory Services in this guideline). In New York State, HIV-2 viral load testing should be used to determine the effectiveness of an ART regimen in patients with HIV-2 [Ba, et al. 2018; Matheron, et al. 2018]. If clinicians outside of New York State do not have access to HIV-2 viral load testing, they should suspect treatment failure if an individual with HIV-2 has a sustained or progressive decline in CD4 cell count or experiences clinical disease progression on therapy. Data from a multi-cohort study indicate that patients with HIV-2 who were initiated on a first-line combination ART regimen had less robust CD4 cell count increases than individuals with HIV-1, even after adjustment for plasma viral load levels [Wittkop, et al. 2017]. In HIV-2, a muted CD4 cell count increase from baseline after treatment initiation may not necessarily imply that the regimen is ineffective. If patients with HIV-2 have either immunologic or virologic treatment failure, clinicians are strongly urged to refer them to or consult with experienced HIV-2 clinical management specialists.
In addition to monitoring ART, patients with HIV-2 require the same laboratory and diagnostic testing, use and appropriate discontinuation of prophylaxis for OIs, and use of immunizations as patients with HIV-1 (see the NYSDOH AI guideline Comprehensive Primary Care for Adults With HIV > Prevention of Opportunistic Infections and Immunizations for Adults With HIV).
KEY POINT |
|
References
Ba S, Raugi DN, Smith RA, et al. A trial of a single tablet regimen of elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate for the initial treatment of HIV-2 infection in a resource-limited setting: 48 week results from Senegal, West Africa. Clin Infect Dis 2018. [PMID: 29672676]
Matheron S, Descamps D, Gallien S, et al. First-line raltegravir/emtricitabine/tenofovir combination in human immunodeficiency virus type 2 (HIV-2) infection: A phase 2, noncomparative trial (ANRS 159 HIV-2). Clin Infect Dis 2018;67(8):1161-1167. [PMID: 29590335]
Wittkop L, Arsandaux J, Trevino A, et al. CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: a multinational, multicohort European study. J Antimicrob Chemother 2017;72(10):2869-2878. [PMID: 29091198]
Management of HIV-2 in Pregnancy
Lead author: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; October 2021
RECOMMENDATIONS |
Management in Pregnancy
Note: For recommendations regarding administration of zidovudine for prophylaxis during labor and delivery, please see the NYSDOH AI guidance Good Practices to Prevent Perinatal HIV Transmission or the U.S. Department of Health and Human Services (DHHS) Special Populations: HIV-2 Infection and Pregnancy in the guideline Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. |
A combination of either TDF/FTC or ABC/3TC (if HLA-B*5701 is negative) plus either twice-daily RAL or twice-daily DRV/r is recommended during pregnancy. For individuals with HIV-2, viral load monitoring during pregnancy and prophylactic ART for the HIV-2–exposed infant should follow the recommendations for pregnancy and infant exposure in the setting of HIV-1 (see the NYSDOH AI guidance Good Practices to Prevent Perinatal HIV Transmission or the DHHS Special Populations: HIV-2 Infection and Pregnancy in the guideline Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States). During the early part of pregnancy, it is important that healthcare providers follow the Wadsworth Center protocol for accurate and timely submission of specimens and know the amount of time needed to return the results of HIV-2 viral load testing. For example, the Wadsworth Center Bloodborne Viruses Laboratory is not open on weekends, so if a patient’s blood is drawn on a Thursday or Friday, the separated plasma should be stored at the drawing facility in a freezer and shipped on Monday, Tuesday, or Wednesday of the following week to ensure weekday delivery to the laboratory.
Serial HIV-2 diagnostic testing in HIV-2–exposed infants to confirm or exclude HIV-2 infection is available free of charge from the Wadsworth Center (see Diagnosis of HIV-2 > Box 1: Wadsworth Center Bloodborne Viruses Laboratory Services in this guideline). For diagnostic testing of infants exposed to HIV-2, whole blood collected in an EDTA tube (purple top, prevents blood clotting) must be received in the laboratory within 3 days of collection. Collection kits for pediatric HIV diagnostic testing may be requested from the Wadsworth Center Order Desk at (518) 474-4175.
Table 3: ART Regimens for Initial Treatment of Pregnant Adults With HIV-2* | ||
Abacavir/lamivudine (ABC/3TC; Epzicom) if HLA-B*5701 is negative and HBsAg is negative OR Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC; Truvada) |
AND |
Raltegravir twice daily (RAL; Isentress) OR Ritonavir-boosted darunavir twice daily (DRV/r; Prezista and Norvir) |
*Listed alphabetically; for specific details, see NYSDOH AI guideline Selecting an Initial ART Regimen > Specific Factors to Consider and Discuss With Patients and drug package inserts. |
Pre- and Post-Exposure Prophylaxis for HIV-2
Lead author: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; October 2021
RECOMMENDATION |
PrEP and PEP for HIV-2
|
As with HIV-1, TDF/FTC is active against HIV-2 [Menendez-Arias and Alvarez 2014] and could be used as a pre-exposure prophylaxis (PrEP) regimen to prevent infection with HIV-2. For more information on evaluating patients for PrEP see NYSDOH AI guideline PrEP to Prevent HIV and Promote Sexual Health.
Reference
Menendez-Arias L, Alvarez M. Antiretroviral therapy and drug resistance in human immunodeficiency virus type 2 infection. Antiviral Res 2014;102:70-86. [PMID: 24345729]
All Recommendations
Lead author: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; October 2021
ALL RECOMMENDATIONS: DIAGNOSIS AND MANAGEMENT OF HIV-2 IN ADULTS |
Diagnosis
Treatment
Monitoring
Management in Pregnancy
Note: For recommendations regarding administration of zidovudine for prophylaxis during labor and delivery, please see the NYSDOH AI guidance Good Practices to Prevent Perinatal HIV Transmission or the U.S. Department of Health and Human Services (DHHS) Special Populations: HIV-2 Infection and Pregnancy in the guideline Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. PrEP and PEP for HIV-2
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Guideline Updates, Development, and Ratings
Guideline Information | |
Developer |
New York State Department of Health AIDS Institute (NYSDOH AI) |
Funding Source |
NYSDOH AI |
Intended Users |
NYS clinicians who provide care for adults with HIV |
Development |
See Guideline Development and Recommendation Ratings Scheme, below. |
Peer Reviewers |
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Updates | |
October 2021 |
(1) Recommended initial ART regimens were updated to reflect corresponding updates to the NYSDOH AI guideline Selecting an Initial ART Regimen. (2) Dolutegravir prior to 8 weeks of pregnancy was removed from the list of ART regimens to avoid for a pregnant individual with HIV-2. |
September 2020 |
The red text below was added to the Treatment of HIV-2 section: “Bictegravir is highly potent against HIV-2 in vitro [Tsiang, et al. 2016; Le Hingrat, et al. 2018; Smith, et al. 2019]; however, there are no published data on the use of TAF/FTC/BIC in patients with HIV-2. If no drug resistance testing is available, DTG and BIC should be used with caution in ART-experienced patients with HIV-2 who have virologic failure on a RAL- or EVG- based ART regimen. The chemokine receptor antagonist maraviroc (MVC) is active against HIV-2 strains that exclusively use CCR5 for viral entry [Borrego, et al. 2012]. However, its use in the treatment of HIV-2 is limited because there is no commercially available tropism assay for HIV-2 to predict susceptibility to MVC. The fusion inhibitor enfuvirtide has no in vitro activity against HIV-2 [Menendez-Arias and Alvarez 2014; FDA 2018]. The recently approved attachment inhibitor fostemsavir has no activity against HIV-2 [FDA 2020]. Ibalizumab, a humanized monoclonal IgG-4 antibody that prevents HIV cell entry by binding to the host CD4 receptor, has in vitro evidence of activity against HIV-2 with IC50 levels comparable to those found in HIV-1 group M strains [Hingrat 2020]. However, the in vivo efficacy of an ibalizumab-based regimen in individuals with antiretroviral-resistant HIV-2 infection has not been established.“ |
Guideline Development: New York State Department of Health AIDS Institute Clinical Guidelines Program | |
Developer | New York State Department of Health AIDS Institute (NYS DOH AI) Clinical Guidelines Program |
Funding Source | NYSDOH AI |
Program Manager |
Clinical Guidelines Program, Johns Hopkins University School of Medicine, Division of Infectious Diseases. See Program Leadership and Staff. |
Mission | To produce and disseminate evidence-based, state-of-the-art clinical practice guidelines that establish uniform standards of care for practitioners who provide prevention or treatment of HIV, viral hepatitis, other sexually transmitted infections, and substance use disorders for adults throughout New York State in the wide array of settings in which those services are delivered. |
Expert Committees |
The NYSDOH AI Medical Director invites and appoints committees of clinical and public health experts from throughout NYS to ensure that the guidelines are practical, immediately applicable, and meet the needs of care providers and stakeholders in all major regions of NYS, all relevant clinical practice settings, key NYS agencies, and community service organizations. |
Committee Structure |
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Conflicts of Interest Disclosure and Management |
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Evidence Collection and Review |
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Recommendation Development |
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Review and Approval Process |
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External Reviewers |
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Update Process |
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Recommendation Ratings Scheme | |||
Strength | Quality of Evidence | ||
Rating | Definition | Rating | Definition |
A | Strong | 1 | Based on published results of at least 1 randomized clinical trial with clinical outcomes or validated laboratory endpoints. |
B | Moderate | * | Based on either a self-evident conclusion; conclusive, published, in vitro data; or well-established practice that cannot be tested because ethics would preclude a clinical trial. |
C | Optional | 2 | Based on published results of at least 1 well-designed, nonrandomized clinical trial or observational cohort study with long-term clinical outcomes. |
2† | Extrapolated from published results of well-designed studies (including nonrandomized 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 | Based on committee expert opinion, with rationale provided in the guideline text. |