Purpose of This Guideline

Date of current publication: June 20, 2023 Lead author: Sanjiv S. Shah, MD, MPH, AAHIVS Writing group: Steven M. Fine, MD, PhD; Rona M. Vail, MD; Joseph P. McGowan, 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 Date of original publication: July 8, 2019

The New York State Department of Health AIDS Institute (NYSDOH AI) developed this guideline for primary care providers and other clinicians who may diagnose and treat adults 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 patients 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 New York State 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 New York State.

Note on “experienced” and “expert” HIV care providers: Throughout this guideline, when reference is made to “experienced HIV care provider” or “expert HIV care provider,” those terms are referring to the following 2017 NYSDOH AI definitions:

• Experienced HIV care provider: Practitioners who have been accorded HIV Experienced Provider status by the American Academy of HIV Medicine or have met the HIV Medicine Association’s definition of an experienced provider are eligible for designation as an HIV Experienced Provider in New York State. Nurse practitioners and licensed midwives who provide clinical care to individuals with HIV in collaboration with a physician may be considered HIV Experienced Providers as long as all other practice agreements are met (8 NYCRR 79-5:1; 10 NYCRR 85.36; 8 NYCRR 139-6900). Physician assistants who provide clinical care to individuals with HIV under the supervision of an HIV Specialist physician may also be considered HIV Experienced Providers (10 NYCRR 94.2)
• Expert HIV care provider: A provider with extensive experience in the management of complex patients with HIV.

HIV-2 Overview

The HIV-2 virus was first isolated in West Africa in the mid-1980s among individuals 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 [UpToDate 2023]. A surveillance report covering the period 1987 to 2009 identified 166 cases of HIV-2 in the United States; 46% of those were from New York City [CDC 2011]. The majority of individuals with HIV-2 were from West Africa or had sexual contact or shared injection drug equipment with someone from this region [Torian, et al. 2010]. A subsequent HIV testing surveillance analysis covering the period 2010 to 2017 reported that among 327,700 HIV cases diagnosed in the United States, 102 were confirmed HIV-2 infections and 11 were dual HIV-1/HIV-2 infections [Peruski, et al. 2020]. The report also confirmed that the cases of HIV-2 were diagnosed predominantly in people from West Africa who were living in the northeast United States and had acquired HIV-2 through heterosexual transmission. The number of HIV-2 cases was proportionate between males and females [Peruski, et al. 2020]. An analysis of New York State surveillance data covering the period 2010 to 2020 found that among 34,949 diagnosed HIV cases, 43 had HIV-2 infection, 3 had dual HIV-1/HIV-2 infection, and 25 had probable HIV-2 infection. Among the 71 HIV-2 cases, 54% were male, 79% were non-Hispanic Black, and 31% were ≥55 years old at diagnosis [NYSDOH 2022].

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. Elevated markers of B-cell perturbations and colonic damage were observed in treatment-naive individuals with HIV-2 and no detectable virus; these findings were not observed in antiretroviral therapy (ART)-treated individuals with HIV-1 and viral suppression [Johansson, et al. 2023]. In addition, the majority of individuals with HIV-2, if untreated, will eventually progress to AIDS and death [Esbjornsson, et al. 2019].

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 guideline section Treatment of HIV-2, ART should be recommended for all individuals 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 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 on 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.

Diagnosis of HIV-2

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 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 Centers for Disease Control and Prevention (CDC)/Association of Public Health Laboratories algorithm begins with an FDA-approved HIV-1/2 Ag/Ab combination immunoassay [CDC 2018], which detects HIV-1 p24 Ag and HIV-1 and HIV-2 antibodies but not HIV-2 Ag. If the combination immunoassay is reactive, a supplemental HIV-1/HIV-2 Ab differentiation immunoassay is performed. Clinicians should consider HIV-2 infection in the 4 scenarios described below.

• HIV-1/HIV-2 differentiation immunoassay is reactive for HIV-2 Ab: The individual is considered HIV-2 Ab positive, and a clinical evaluation for HIV-2 infection should be performed (see guideline section Treatment of HIV-2).
• HIV-1/HIV-2 differentiation immunoassay is reactive for HIV-1 and HIV-2 Ab: 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 Wadsworth Center Bloodborne Viruses Laboratory (see Box 1, below).
• HIV-1/HIV-2 differentiation immunoassay is nonreactive or indeterminate for HIV-1 and/or HIV-2 Ab: 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 an individual with HIV-2 infection, the absence of HIV-2 RNA does not exclude HIV-2 infection. Therefore, in an individual at high risk of 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.

Treatment of HIV-2

Resistance testing: Although baseline genotypic drug resistance testing is recommended for all individuals with HIV-1 before ART initiation, HIV-2 resistance tests are not commercially available in the United States.

ART regimen options: All U.S. Food and Drug Administration-approved NRTIs effectively inhibit HIV-2 reverse transcriptase [Menendez-Arias and Alvarez 2014]. Three HIV protease inhibitors (PIs) effectively inhibit HIV-2, but given the availability of darunavir (DRV), the 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].

Based on limited clinical trial data using the INSTIs elvitegravir and raltegravir (RAL), retrospective observational studies with other INSTIs, and in vitro data, it is expected that INSTIs as a class are active against HIV-2, and a dolutegravir (DTG)- or bictegravir (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 (elvitegravir/cobicistat/tenofovir disoproxil fumarate/emtricitabine [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]. A retrospective observational study from Spain among participants with HIV-2 reported that after approximately 13 months of follow-up on INSTI-based regimens (including DTG), 89% of treatment-naive and 65% of treatment-experienced participants achieved an undetectable viral load [Requena, et al. 2019]. A similar study from India showed that on a DTG-based regimen, 86% of treatment-naive participants with HIV-2 achieved an undetectable viral load [Pujari, et al. 2020] However, without genotypic resistance testing, the 2-drug regimen of lamivudine/DTG should not be used by patients with HIV-2 because using this regimen requires advance confirmation that they do not have virus with the M184V mutation.

In treatment-experienced patients with HIV-2, the antiretrovirals (ARVs) listed in Tables 1 and 2, above, 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 cases of virologic failure. Algorithms are available to interpret HIV-2 genetic sequences obtained from research laboratories for the presence of resistance-associated mutations and coreceptor use; however, clinical decisions should not be made solely on these predictions. See:

• Stanford University HIV Resistance Database: HIVdb Program for HIV-2 (beta)
• Collaborative HIV and Anti-HIV Drug Resistance Network: HIV2EU Algorithm
• Max Planck Institute for Informatics: Geno2pheno [coreceptor-hiv2] 1.0

BIC is highly potent against HIV-2 in vitro [Le Hingrat, et al. 2019; Smith, et al. 2019; Tsiang, et al. 2016]. Preliminary findings from a small observational study indicate the regimen is well tolerated and effective in achieving or maintaining HIV-2 suppression [Joly, et al. 2023]. If no drug resistance testing is available, DTG and BIC should be used with caution in treatment-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 attachment inhibitor fostemsavir has no activity against HIV-2 [FDA 2020].

Ibalizumab (IBA), 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 [Le Hingrat, et al. 2022]. However, the in vivo efficacy of an IBA-containing regimen in individuals with ARV-resistant HIV-2 infection has not been established.

Lenacapavir (LEN), a multistage inhibitor of HIV-1 capsid function, is active against HIV-2 isolates but 11- to 16-fold less potent against HIV-2 compared to HIV-1 [Smith, et al. 2023]. In patients with HIV-2 and limited antiretroviral options, treatment with a LEN-based regimen would require careful monitoring to assess virologic and immunologic responsiveness.

In patients with 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.

Monitoring ART in Individuals With HIV-2

There is no U.S. Food and Drug Administration-approved, HIV-2 quantitative viral load assay commercially available. However, an HIV-2 quantitative viral load test is available by contacting the Wadsworth Center Bloodborne Viruses Laboratory (see Box 1). In New York State, HIV-2 viral load testing should be used to determine the effectiveness of an antiretroviral therapy (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 a patient with HIV-2 has a sustained or progressive decline in CD4 count or experiences clinical disease progression on therapy. Data from a multicohort study indicate that patients with HIV-2 who were initiated on a first-line combination ART regimen had less robust CD4 count increases than those with HIV-1, even after adjustment for plasma viral load levels [Wittkop, et al. 2017]. In HIV-2, a muted CD4 count increase from baseline after treatment initiation may not necessarily imply that the regimen is ineffective.

HIV-2 disease progression has been reported in individuals with undetectable HIV-2 viral loads [Raugi, et al. 2021], and resistance mutations have been reported in the presence of suppressive ART (viral load <25 copies/mL) [Gottlieb, et al. 2009]. Therefore, even with persistent undetected or unquantifiable viral load, CD4 count monitoring is recommended for patients with HIV-2 at least every 6 months.

HIV-2 treatment failure is defined as a persistent increase in viral load. In the absence of HIV-2 viral load testing, treatment failure can be assessed using changes in CD4 count (e.g., a 30% decrease in CD4 count or a 3-point decrease in CD4%, confirmed by repeat testing [StatPearls 2023]) or clinical disease progression. In cases of treatment failure, it is critically important to address adherence to therapy and to eliminate drug interactions that could adversely affect antiretroviral efficacy, especially given the limited number of ART regimen options. In the absence of HIV-2 genotypic resistance testing, it is reasonable to recommend that a patient with HIV-2 taking a failing integrase strand transfer inhibitor (INSTI)-based regimen switch to an active boosted protease inhibitor (PI)-based regimen. Similarly, it is reasonable to recommend that a patient with HIV-2 on a failing boosted PI-based regimen switch to an INSTI-based regimen. This approach is preferable to switching to other drugs within the INSTI or PI drug class. As noted above, other antiretrovirals, such as maraviroc, ibalizumab, and lenacapavir, have in-vitro activity against HIV-2 and may be included in subsequent treatment regimens. If patients with HIV-2 have either immunologic or virologic treatment failure, clinicians are strongly urged to refer them to or consult with an experienced HIV-2 clinical management specialist.

In addition to monitoring ART, patients with HIV-2 require the same laboratory and diagnostic testing, use and appropriate discontinuation of prophylaxis for opportunistic infections, and use of immunizations as patients with HIV-1.

Management of HIV-2 in Pregnancy

A combination of abacavir/lamivudine (3TC) (if HLA-B*5701 is negative) or tenofovir alafenamide/emtricitabine (FTC) or tenofovir disoproxil fumarate (TDF/FTC) or TDF/3TC plus dolutegravir or twice-daily raltegravir or twice daily ritonavir-boosted darunavir is recommended during pregnancy (see Table 3, below). 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 to HIV-1 (see the DHHS guideline Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States > Special Populations: HIV-2 Infection and Pregnancy). 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 Bloodborne Viruses Laboratory Services (see Box 1). 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.

Pre- and Post-Exposure Prophylaxis for HIV-2

As with HIV-1, TDF/FTC, tenofovir alafenamide/FTC, and cabotegravir are active against HIV-2 [Smith, et al. 2018; Menendez-Arias and Alvarez 2014] and could be used as a pre-exposure prophylaxis (PrEP) regimen to prevent HIV-2 infection.

For more information on evaluating patients for PEP and PrEP, see the NYSDOH AI guidelines PEP to Prevent HIV Infection and PrEP to Prevent HIV and Promote Sexual Health.

All Recommendations

References

• Adjorlolo-Johnson G., De Cock K. M., 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. [PubMed: 8040982]
• Ba S., Raugi D. N., Smith R. A., 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;67(10):1588–1594. [PMC free article: PMC6927863] [PubMed: 29672676]
• Borrego P., Calado R., Marcelino J. M., et al. Baseline susceptibility of primary HIV-2 to entry inhibitors. Antivir Ther. 2012;17(3):565–570. [PubMed: 22293827]
• 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. [PubMed: 20804413]
• Cavaco-Silva J., Aleixo M. J., 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. [PubMed: 22977160]
• CDC HIV-2 infection surveillance--United States, 1987-2009. MMWR Morb Mortal Wkly Rep. 2011;60(29):985–988. [PubMed: 21796096]
• CDC. 2018 Quick reference guide: recommended laboratory HIV testing algorithm for serum or plasma specimens. 2018. https://stacks​.cdc.gov/view/cdc/50872 [accessed 2019 Jun 6]
• 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. [PubMed: 3025743]
• Eron J. J., 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. [PMC free article: PMC6039393] [PubMed: 29683855]
• 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. 2019;6(1):e25–e31. [PubMed: 30392769]
• FDA. Fuzeon (enfuvirtide) for injection. 2018. https://www​.accessdata​.fda.gov/drugsatfda_docs​/label/2018/021481s032lbl.pdf [accessed 2020 Sep 28]
• FDA. Rukobia (fostemsavir) extended-release tablets, for oral use. 2020. https://www​.accessdata​.fda.gov/drugsatfda_docs​/label/2020/212950s000lbl.pdf [accessed 2020 Sep 28]
• Gottlieb G., Badiane N. M., Hawes S. E., et al. Emergence of multiclass drug-resistance in HIV-2 in antiretroviral-treated individuals in Senegal: implications for HIV-2 treatment in resouce-limited West Africa. Clin Infect Dis. 2009;48(4):476–483. [PMC free article: PMC3671065] [PubMed: 19143530]
• Gottlieb G., Raugi D. N., Smith R. A. 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. [PubMed: 30052509]
• Gottlieb G., Sow P. S., Hawes S. E., 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. [PubMed: 11920314]
• Johansson E., Kerkman P.F., Scharf L., et al. Hierarchical clustering shows B-cell perturbations independent of HIV-2 viraemia. CROI; 2023 Feb 19-22; Seattle, WA. https://www​.croiconference​.org/abstract/hierarchical-clustering-shows-b-cell-perturbations-independent-of-hiv-2-viraemia/
• Joly V.A., Ferré V.M., Cresta M., et al. Immuno-virological and clinical follow-up of HIV-2 patients receiving BIC/FTC/TAF. Abstract 539. CROI; 2023 Feb 19-22; Seattle, WA. https://www​.croiconference​.org/abstract/immuno-virological-and-clinical-follow-up-of-hiv-2-patients-receiving-bic-ftc-taf/
• Le Hingrat Q., Collin G., Bachelard A., et al. Ibalizumab shows in vitro activity against group A and group B HIV-2 clinical isolates. AIDS. 2022;36(8):1055–1060. [PubMed: 35262531]
• 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. 2019;69(4):657–667. [PubMed: 30383215]
• MacNeil A., Sarr A. D., Sankale J. L., 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. [PMC free article: PMC1900238] [PubMed: 17329334]
• 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. [PMC free article: PMC6160602] [PubMed: 29590335]
• Menendez-Arias L., Alvarez M. Antiretroviral therapy and drug resistance in human immunodeficiency virus type 2 infection. Antiviral Res. 2014;102:70–86. [PubMed: 24345729]
• NYSDOH. Bureau of HIV/AIDS Epidemiology: unpublished data. 2022[accessed 2022 Aug 23]
• 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. [PubMed: 10770548]
• Peruski A. H., Wesolowski L. G., Delaney K. P., et al. Trends in HIV-2 diagnoses and use of the HIV-1/HIV-2 differentiation test - United States, 2010-2017. MMWR Morb Mortal Wkly Rep. 2020;69(3):63–66. [PMC free article: PMC7367036] [PubMed: 31971928]
• Popper S. J., Sarr A. D., Travers K. U., 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. [PubMed: 10479138]
• Pujari S., Patel A., Gaikwad S., et al. Effectiveness of dolutegravir-based antiretroviral treatment for HIV-2 infection: retrospective observational study from Western India. J Antimicrob Chemother. 2020;75(7):1950–1954. [PubMed: 32277827]
• Raugi D. N., Ba S., Cisse O., et al. Long-term experience and outcomes of programmatic antiretroviral therapy for human immunodeficiency virus type 2 infection in Senegal, West Africa. Clin Infect Dis. 2021;72(3):369–378. [PMC free article: PMC7850514] [PubMed: 33527119]
• Requena S., Lozano A. B., Caballero E., et al. Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain. J Antimicrob Chemother. 2019;74(5):1357–1362. [PubMed: 30753573]
• 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. [PubMed: 7904166]
• Smith R.A., Raugi D., Nixon R., et al. Antiviral activity of lenacapavir against HIV-2 isolates. Abstract 538. CROI; 2023 Feb 19-22; Seattle, WA. https://www​.croiconference​.org/abstract/antiviral-activity-of-lenacapavir-against-hiv-2-isolates/ [PubMed: 38060982]
• Smith R. A., Raugi D. N., Wu V. H., 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):e00014–e00019. [PMC free article: PMC6496081] [PubMed: 30803972]
• Smith R. A., Wu V. H., Zavala C. G., et al. In vitro antiviral activity of cabotegravir against HIV-2. Antimicrob Agents Chemother. 2018;62(10):e01299–e01318. [PMC free article: PMC6153831] [PubMed: 30012774]
• StatPearls. CD4 count. 2023. https://www​.ncbi.nlm​.nih.gov/books/NBK470231/ [accessed 2022 Jun 21]
• Torian L. V., Eavey J. J., Punsalang A. P., et al. HIV type 2 in New York City, 2000-2008. Clin Infect Dis. 2010;51(11):1334–1342. [PubMed: 21039219]
• Tsiang M., Jones G. S., 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. [PMC free article: PMC5118987] [PubMed: 27645238]
• UpToDate. Treatment of HIV-2 infection. 2023. https://www​.uptodate​.com/contents/treatment-of-hiv-2-infection [accessed 2022 Jun 21]
• van der Loeff M. F., 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. [PMC free article: PMC2887382] [PubMed: 20482865]
• 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. [PubMed: 29091198]
• Zash R., Holmes L. B., Diseko M., et al. Update on neural tube defects with antiretroviral exposure in the Tsepamo Study, Botswana. AIDS; 2022 Jul 29-Aug 2; Montreal, Canada. https://www​.natap.org/2022/IAC/IAC_31​.htm .

Supplementary Material

Supplement: Guideline Development and Recommendation Ratings