Purpose of This Guideline
Reviewed and updated: Sanjiv S. Shah, MD, MPH, AAHIVS; August 31, 2022
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 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.
HIV-2 Overview
Reviewed and updated: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; August 31, 2022
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 [Gottlieb 2020]. 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. 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.
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;67(10):1588-1594. [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 2019;6(1):e25-e31. [PMID: 30392769]
Gottlieb G. Treatment of HIV-2 infection. 2020 Jun 8. https://www.uptodate.com/contents/treatment-of-hiv-2-infection [accessed 2022 Jun 21]
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]
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. [PMID: 10770548]
Peruski AH, Wesolowski LG, Delaney KP, 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. [PMID: 31971928]
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
Reviewed and updated: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; August 31, 2022
RECOMMENDATIONS |
Diagnosis of HIV-2
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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 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.
Box 1: Wadsworth Center Bloodborne Viruses Laboratory |
|
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
Reviewed and updated: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; August 31, 2022
RECOMMENDATIONS |
Treatment of HIV-2
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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-1, see the NYSDOH AI guideline Selecting an Initial ART Regimen) Download PDF |
||
Regimen | Comments | Rating |
Available as a Single-Tablet Formulation | ||
Abacavir/lamivudine/ (ABC/3TC/DTG; Triumeq) |
|
A1 |
Tenofovir alafenamide/ (TAF 25 mg/FTC/BIC; Biktarvy) |
|
A1 |
Available as a Multi-Tablet Regimen With Once-Daily Dosing | ||
Tenofovir alafenamide/ (TAF 25 mg/FTC or TDF 300 mg/FTC and DTG; Descovy or Truvada and Tivicay) |
|
A1 |
Tenofovir alafenamide/ (TAF 25 mg/FTC or TDF 300 mg/FTC and RAL HD; Descovy or Truvada and Isentress HD) |
|
A2 |
Abbreviations: Al, aluminum; ART, antiretroviral therapy; Ca, calcium; CrCl, creatinine clearance; Mg, magnesium. 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-1, see the NYSDOH AI guideline Selecting an Initial ART Regimen) Download PDF |
||
Regimen | Comments | Rating |
Available as a Single-Tablet Formulation | ||
Tenofovir alafenamide/ (TAF 10 mg/FTC/DRV/COBI; Symtuza) |
|
B2 |
Tenofovir alafenamide/ (TAF 10 mg/FTC/EVG/COBI; Genvoya) |
|
B1 |
Available as a Multi-Tablet Regimen With Twice-Daily Dosing | ||
Tenofovir alafenamide/ (TAF 25 mg/FTC or TDF 300 mg/FTC and RAL; Descovy or Truvada and Isentress) |
|
B3 |
Abbreviations: Al, aluminum; ART, antiretroviral therapy; Ca, calcium; CrCl, creatinine clearance; Mg; magnesium. Notes:
|
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].
KEY POINTS |
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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.
BIC is highly potent against HIV-2 in vitro [Le Hingrat, et al. 2019; Smith, et al. 2019; Tsiang, et al. 2016]; however, there are no published data on the use of tenofovir alafenamide/FTC/BIC in patients with HIV-2. 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.
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.
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;67(10):1588-1594. [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. Fuzeon (enfuvirtide) for injection. 2018 Dec. 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 Jul. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212950s000lbl.pdf [accessed 2020 Sep 28]
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. [PMID: 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. [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]
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. [PMID: 32277827]
Requena S, Lozano AB, Caballero E, et al. Clinical experience with integrase inhibitors in HIV-2-infected individuals in Spain. J Antimicrob Chemother 2019;74(5):1357-1362. [PMID: 30753573]
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):e00014-00019. [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
Reviewed and updated: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; August 31, 2022
RECOMMENDATIONS |
Monitoring ART
|
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 [Li, et al. 2022]) 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. 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 (see the NYSDOH AI guideline Immunizations for Adults With HIV).
KEY POINT |
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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;67(10):1588-1594. [PMID: 29672676]
Gottlieb G, Badiane NM, Hawes SE, 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. [PMID: 19143530]
Li R, Duffee D, Gbadamosi-Akindele MF. StatPearls: CD4 count. 2022 May 8. https://www.ncbi.nlm.nih.gov/books/NBK470231/ [accessed 2022 Jun 21]
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]
Raugi DN, 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. [PMID: 33527119]
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
Reviewed and updated: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; August 31, 2022
RECOMMENDATIONS |
Management of HIV-2 in Pregnancy
——— Note:
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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.
Table 3: ART Regimens for Initial Treatment of Pregnant Adults With HIV-2 [a] | ||
Abacavir/lamivudine (ABC/3TC; Epzicom) if HLA-B*5701 is negative and HBsAg is negative OR Tenofovir alafenamide/emtricitabine (TAF/FTC; Descovy) OR Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC; Truvada) OR Tenofovir disoproxil fumarate/lamivudine (TDF/3TC; multiple brands) |
AND |
Dolutegravir (DTG; Tivicay) [b,c] OR Raltegravir twice daily (RAL; Isentress) OR Ritonavir-boosted darunavir twice daily (DRV/r; Prezista and Norvir) |
Notes:
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Reference
Zash R, Holmes LB, 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
Pre- and Post-Exposure Prophylaxis for HIV-2
Reviewed and updated: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; August 31, 2022
RECOMMENDATION |
PEP for HIV-2
——— Note:
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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 PrEP, see the NYSDOH AI guideline PrEP to Prevent HIV and Promote Sexual Health.
References
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, Wu VH, Zavala CG, et al. In vitro antiviral activity of cabotegravir against HIV-2. Antimicrob Agents Chemother 2018;62(10):e01299-01218. [PMID: 30012774]
Zash R, Holmes LB, 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
All Recommendations
Reviewed and updated: Sanjiv S. Shah, MD, MPH, AAHIVS, with the Medical Care Criteria Committee; August 31, 2022
ALL RECOMMENDATIONS: DIAGNOSIS AND MANAGEMENT OF HIV-2 IN ADULTS |
Diagnosis of HIV-2
Treatment of HIV-2
Monitoring ART
Management of HIV-2 in Pregnancy
PEP for HIV-2
——— Notes:
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Reference
Zash R, Holmes LB, 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
Guideline Information and Updates
Guideline Information | |
Intended users |
New York State clinicians who may diagnose and treat adults with HIV-2 infection |
Last reviewed and updated |
August 31, 2022 |
Lead author |
Sanjiv S. Shah, MD, MPH, AAHIVS |
Original publication |
June 2019 |
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 | |
Developer and funding |
New York State Department of Health AIDS Institute (NYSDOH AI) |
Development |
See Guideline Development and Recommendation Ratings Scheme, below. |
Peer Reviewers |
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Updates | |
August 31, 2022 |
Sanjiv S. Shah, MD, MPH, AAHIVS, with the MCCC:
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October 2021 |
Recommended initial ART regimens were updated to reflect corresponding updates to the NYSDOH AI guideline Selecting an Initial ART Regimen. DTG before 8 weeks of pregnancy was removed from the list of ART regimens to avoid for a pregnant individual with HIV-2. |
September 2020 |
Treatment of HIV-2: Text added: “The recently approved 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 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. |