skip navigation

Skip Nav

Clinical Guidelines Portal

Clinical Guidelines Portal

Table of Contents

Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents

Considerations for Antiretroviral Use in Special Patient Populations

HIV-2 Infection

(Last updated: January 10, 2011; last reviewed: January 10, 2011)

HIV-2 infection is endemic in West Africa. Although HIV-2 has had only limited spread outside this area, it should be considered in persons of West African origin or those who have had sexual contact or shared needles with persons of West African origin. The prevalence of HIV-2 infection is also disproportionately high in countries with strong socioeconomic ties to West Africa (e.g., France; Spain; Portugal; and former Portuguese colonies such as Brazil, Angola, Mozambique, and parts of India near Goa).

The clinical course of HIV-2 infection is generally characterized by a longer asymptomatic stage, lower plasma HIV-2 viral loads, and lower mortality rates compared with HIV-1 infection [1-2]. However, HIV-2 infection can progress to AIDS, and thus antiretroviral therapy (ART) may become necessary during the course of infection. Concomitant HIV-1 and HIV-2 infection may occur and should be considered in patients from an area with high prevalence of HIV-2. In the appropriate epidemiologic setting, HIV-2 infection should be suspected in patients with clinical conditions suggestive of HIV infection but with atypical serologic results (e.g., a positive screening assay with an indeterminate HIV-1 Western blot) [3]. The possibility of HIV-2 infection should also be considered in the appropriate epidemiologic setting in patients with serologically confirmed HIV infection but low or undetectable viral loads or in those with declining CD4 counts despite apparent virologic suppression on ART.

The Multispot HIV-1/HIV-2 Rapid Test (Bio-Rad Laboratories) is Food and Drug Administration (FDA) approved for differentiating HIV-1 from HIV-2 infection. Commercially available HIV-1 viral load assays do not reliably detect or quantify HIV-2, and no HIV-2 commercial viral load assays are currently available [4-5]. Most studies reporting HIV-2 viral loads use “in-house” assays that are not widely available, making it difficult to monitor virologic response in the clinical setting. In addition, no validated HIV-2 genotypic or phenotypic antiretroviral (ARV) resistance assays are available.

To date, there have been no randomized trials addressing the question of when to start ART or the choice of initial or second-line therapy for HIV-2 infection [6]; thus, the optimal treatment strategy has not been defined. HIV-2 appears intrinsically resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs) [7] and to enfuvirtide [8]. In vitro data suggest HIV-2 is sensitive to the currently available nucleoside reverse transcriptase inhibitors (NRTIs), although with a lower barrier to resistance than HIV-1 [9-10]. Variable sensitivity among protease inhibitors (PIs) has been reported; lopinavir (LPV), saquinavir (SQV), and darunavir (DRV) are more active against HIV-2 than other approved PIs [11-14]. The integrase inhibitor, raltegravir (RAL) [15], and the CCR5 antagonist, maraviroc (MVC), appear active against some HIV-2 isolates, although no approved assays to determine HIV-2 coreceptor tropism exist and HIV-2 is known to utilize multiple minor coreceptors in addition to CCR5 and CXCR4 [16]. Several small studies suggest poor responses among HIV-2 infected individuals treated with some ARV regimens, including dual-NRTI regimens, regimens containing two NRTIs + NNRTI, and some unboosted PI-based regimens including nelfinavir (NFV) or indinavir (IDV) plus zidovudine (ZDV) and lamivudine (3TC) [6, 17-19]. Clinical data on the utility of triple-NRTI regimens are conflicting [20-21]. In general, boosted PI-containing regimens have resulted in more favorable virologic and immunologic responses [21]. One small study suggested satisfactory responses to lopinavir/ritonavir (LPV/r)-containing regimens in 17 of 29 (59%) of ARV-naive subjects [22].

Resistance-associated mutations develop commonly in HIV-2 patients on therapy [17, 21, 23]. Genotypic algorithms used to predict drug resistance in HIV-1 may not be applicable to HIV-2, because pathways and mutational patterns leading to resistance may differ [10, 21, 24]. CD4 cell recovery on therapy may be poor [25], suggesting that more reliable methods for monitoring disease progression and treatment efficacy in HIV-2 infection are needed.

Some groups have recommended specific preferred and alternative regimens for initial therapy of HIV-2 infection [24], though as yet there are no controlled trial data to reliably predict their success. Until more definitive data are available in an ART-naive patient with HIV-2 mono-infection or with HIV-1/HIV-2 dual infection who requires treatment, clinicians should initiate a regimen containing two NRTIs and a boosted PI. Monitoring of virologic response in such patients is problematic because of the lack of a commercially available HIV-2 viral load assay; however, clinical and CD4 count improvement can be used to assess treatment response.


  1. Matheron S, Pueyo S, Damond F, et al. Factors associated with clinical progression in HIV-2 infected-patients: the French ANRS cohort. AIDS. 2003;17(18):2593-2601.
  2. Marlink R, Kanki P, Thior I, et al. Reduced rate of disease development after HIV-2 infection as compared to HIV-1. Science. 1994;265(5178):1587-1590.
  3. O'Brien TR, George JR, Epstein JS, et al. Testing for antibodies to human immunodeficiency virus type 2 in the United States. MMWR Recomm Rep. 1992;41(RR-12):1-9.
  4. Chan PA, Wakeman SE, Flanigan T, et al. HIV-2 diagnosis and quantification in high-risk patients. AIDS Res Ther. 2008;5:18.
  5. Damond F, Benard A, Ruelle J, et al. Quality control assessment of human immunodeficiency virus type 2 (HIV-2) viral load quantification assays: results from an international collaboration on HIV-2 infection in 2006. J Clin Microbiol. 2008;46(6):2088-2091.
  6. Gottlieb GS, Eholie SP, Nkengasong JN, et al. A call for randomized controlled trials of antiretroviral therapy for HIV-2 infection in West Africa. AIDS. 2008;22(16):2069-2072; discussion 2073-2064.
  7. Tuaillon E, Gueudin M, Lemee V, et al. Phenotypic susceptibility to nonnucleoside inhibitors of virion-associated reverse transcriptase from different HIV types and groups. J Acquir Immune Defic Syndr. 2004;37(5):1543-1549.
  8. Poveda E, Rodes B, Toro C, et al. Are fusion inhibitors active against all HIV variants? AIDS Res Hum Retroviruses. 2004;20(3):347-348.
  9. Boyer PL, Sarafianos SG, Clark PK, et al. Why do HIV-1 and HIV-2 use different pathways to develop AZT resistance? PLoS Pathog. 2006;2(2):e10.
  10. Smith RA, Anderson DJ, Pyrak CL, et al. Antiretroviral drug resistance in HIV-2: three amino acid changes are sufficient for classwide nucleoside analogue resistance. J Infect Dis. 2009;199(9):1323-1326.
  11. Parkin NT, Schapiro JM. Antiretroviral drug resistance in non-subtype B HIV-1, HIV-2 and SIV. Antivir Ther. 2004;9(1):3-12.
  12. Desbois D, Roquebert B, Peytavin G, et al. In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors. Antimicrob Agents Chemother. 2008;52(4):1545-1548.
  13. Brower ET, Bacha UM, Kawasaki Y, et al. Inhibition of HIV-2 protease by HIV-1 protease inhibitors in clinical use. Chem Biol Drug Des. 2008;71(4):298-305.
  14. Rodes B, Sheldon J, Toro C, et al. Susceptibility to protease inhibitors in HIV-2 primary isolates from patients failing antiretroviral therapy. J Antimicrob Chemother. 2006;57(4):709-713.
  15. Roquebert B, Damond F, Collin G, et al. HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro. J Antimicrob Chemother. 2008;62(5):914-920.
  16. Owen SM, Ellenberger D, Rayfield M, et al. Genetically divergent strains of human immunodeficiency virus type 2 use multiple coreceptors for viral entry. J Virol. 1998;72(7):5425-5432.
  17. Gottlieb GS, 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.
  18. Jallow S, Kaye S, Alabi A, et al. Virological and immunological response to Combivir and emergence of drug resistance mutations in a cohort of HIV-2 patients in The Gambia. AIDS. 2006;20(10):1455-1458.
  19. Adje-Toure CA, Cheingsong R, Garcia-Lerma JG, et al. Antiretroviral therapy in HIV-2-infected patients: changes in plasma viral load, CD4+ cell counts, and drug resistance profiles of patients treated in Abidjan, Cote d'Ivoire. AIDS. 2003;17 Suppl 3:S49-54.
  20. Matheron S, Damond F, Benard A, et al. CD4 cell recovery in treated HIV-2-infected adults is lower than expected: results from the French ANRS CO5 HIV-2 cohort. AIDS. 2006;20(3):459-462.
  21. Ruelle J, Roman F, Vandenbroucke AT, et al. Transmitted drug resistance, selection of resistance mutations and moderate antiretroviral efficacy in HIV-2: analysis of the HIV-2 Belgium and Luxembourg database. BMC Infect Dis. 2008;8:21.
  22. Benard A, Damond F, Campa P, et al. Good response to lopinavir/ritonavir-containing antiretroviral regimens in antiretroviral-naive HIV-2-infected patients. AIDS. 2009;23(9):1171-1173.
  23. Damond F, Matheron S, Peytavin G, et al. Selection of K65R mutation in HIV-2-infected patients receiving tenofovir-containing regimen. Antivir Ther. 2004;9(4):635-636.
  24. Gilleece Y, Chadwick DR, Breuer J, et al. British HIV Association guidelines for antiretroviral treatment of HIV-2-positive individuals 2010. HIV Med. 2010;11(10):611-619.
  25. Drylewicz J, Matheron S, Lazaro E, et al. Comparison of viro-immunological marker changes between HIV-1 and HIV-2-infected patients in France. AIDS. 2008;22(4):457-468.

Back to Top