HIV-2 is responsible for a limited epidemic in West Africa. Around 20% of all infected patients will progress to AIDS, and will need antiretroviral therapy. Unfortunately, antiretrovirals were developed to suppress HIV-1 replication; not all of them are active against HIV-2, e.g. all nonnucleoside reverse transcriptase inhibitors or fusion inhibitors. Moreover, only three protease inhibitors have the same activity in HIV-1 and HIV-2: lopinavir, saquinavir and darunavir. Even if all nucleoside and nucleotide reverse transcriptase inhibitors appear to be equally efficient against HIV-2, different resistance pathways and an increased facility of resistance selection make their use much more difficult than in HIV-1. Integrase inhibitors have a potent inhibitory effect on HIV-2 replication, but questions about the best timing for their use remain unanswered, as well as those regarding the use of entry inhibitors in this setting. The lack of reliable monitoring tools adds to the difficulty of treating HIV-2-infected patients, mostly because the viral load is not as useful as it is in HIV-1, and the incomplete knowledge about resistance pathways limits the clinical usefulness of resistance testing. With all these limitations, HIV-2 treatment remains a challenge. Further research is urgently needed, since antiretroviral therapy is now becoming available in countries where the HIV-2 prevalence is significant. The need for appropriate guidelines for HIV-2 treatment has become an emergency.

1.
Clavel F, Mansinho K, Chamaret S, Guetard D, Favier V, Nina J, Santos-Ferreira MO, Champalimaud JL, Montagnier L: Human immunodeficiency virus type 2 infection associated with AIDS in West Africa. N Engl J Med 1987;316:1180–1185.
2.
UNAIDS/WHO: AIDS epidemic update. Joint United Nations Programme on HIV/AIDS (UNAIDS), Geneva, 2006.
3.
Schim van der Loeff MF, Aaby P: Towards a better understanding of the epidemiology of HIV-2. AIDS 1999;13(suppl A):S69–S84.
4.
Poulsen AG, Aaby P, Gottschau A, Kvinesdal BB, Dias F, Molbak K, Lauritzen E: HIV-2 infection in Bissau, West Africa, 1987–1989: incidence, prevalence, and routes of transmission. J Acquir Immune Defic Syndr 1993;6:941–948.
5.
de Silva TI, Cotten M, Rowland-Jones SL: HIV-2: the forgotten AIDS virus. Trends Microbiol 2008;16:588–595.
6.
Vandamme AM, Camacho RJ, Ceccherini-Silberstein F, De Luca A, Palmisano L, Paraskevis D, Paredes R, Poljack M, Schmidt JC, Soriano V, Walter H, Sönnerborg A: European recommendations for the clinical use of HIV drug resistance testing: 2011 update. AIDS Rev 2011;13:77–108.
7.
Gilleece Y, Breuer J, Hawkins D, Smit E, McCrae LX, Chadwick D, Pillat D, Anderson J, Smith N: The British HIV Association guidelines for antiretroviral treatment of HIV-2-positive individuals. HIV Med 2010;11:611–619.
8.
Almeida G, Arroz MJ, Palma AC, Cabanas J, Abecasis AB, Carvalho AP, Gonçalves MF, Diogo I, Lobo MC, Mansinho K, Camacho RJ, Gomes P: Correlation of plasma viral load with CD4+ T cell count on 411 HIV-2-infected patients (abstract PE 6.11/4). 10th European AIDS Conference/EACS, Dublin, 2005.
9.
Matheron S, Damond F, Benard A, Taieb A, Campa P, Peytavin G, Pueyo S, Brun-Vezinet F, Chene G, ANRS CO5 HIV-2 Cohort Study Group: CD4 cell recovery in treated HIV-2-infected adults is lower than expected: results from the French ANRS CO5 HIV-2 Cohort. AIDS 2006;20:459–462.
10.
Gustchina A, Weber IT: Comparative analysis of the sequences and structures of HIV-1 and HIV-2 proteases. Proteins 1991;10:325–339.
11.
Guyader M, Emerman M, Sonigo P, Clavel F, Montagnier L, Alizon M: Genome organization and transactivation of the human immunodeficiency virus type 2. Nature 1987;326:662–669.
12.
Roquebert B, Damond F, Collin G, Matheron S, Peytavin G, Benard A, Campa P, Chene G, Brun-Vezinet F, Descamps D: 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;62:914–920.
13.
Witvrouw M, Pannecouque C, Switzer WM, Folks TM, De Clercq E, Heneine W: Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and postexposure prophylaxis. Antivir Ther 2004;9:57–65.
14.
Ntemgwa M, Brenner BG, Oliveira M, Moisi D, Wainberg MA: Natural polymorphisms in the human immunodeficiency virus type 2 protease can accelerate time to development of resistance to protease inhibitors. Antimicrob Agents Chemother 2007;51:604–610.
15.
Desbois D, Roquebert B, Peytavin G, Damond F, Collin G, Benard A, Campa P, Matheron S, Chene G, Brun-Vezinet F, Descamps D, French ANRS HIV-2 Cohort (ANRS CO 04 VIH-2): In vitro phenotypic susceptibility of human immunodeficiency virus type 2 clinical isolates to protease inhibitors. Antimicrob Agents Chemother 2008;52:1545–1548.
16.
Brower ET, Bacha UM, Kawasaki Y, Freire E: Inhibition of HIV-2 protease by HIV-1 protease inhibitors in clinical use. Chem Biol Drug Des 2008;71:298–305.
17.
Smith R, Ba S, Hawes S, Toure M, Raugi D, Kim M, Mullins J, Kiviat N, Sow PS, Gottlieb G, UW-Dakar HIV-2 Study Group: Toward optimal ART for HIV-2 infection: Can genotypic and phenotypic drug resistance testing help guide therapy for HIV-2? (abstract 579). 17th Conference on Retroviruses and Opportunistic Infections (CROI), San Francisco, 2010.
18.
Pieniazek D, Rayfield M, Hu DJ, Nkengasomg JN, Soriano V, Heneine W, Zeh C, Agwale SM, Wambebe C, Odama L, Wiktor SZ, Kalish ML: HIV-2 protease sequences of subtypes A and B harbor multiple mutations associated with protease inhibitor resistance in HIV-1. AIDS 2004;18:495–502.
19.
Bénard A, Damond F, Campa P, Peytavin G, Descamps D, Lascoux-Combes C, Taieb A, Simon F, Autran B, Brun-Vézinet F, Chêne G, Matheron S, ANRS CO5 HIV-2 Cohort Study Group: Good response to lopinavir/ritonavir-containing antiretroviral regimens in antiretroviral-naive HIV-2-infected patients. AIDS 2009;23:1171–1173.
20.
Smith RA, Gottlieb GS, Anderson DJ, Pyrak CL, Preston BD: Human immunodeficiency virus types 1 and 2 exhibit comparable sensitivities to Zidovudine and other nucleoside analog inhibitors in vitro. Antimicrob Agents Chemother 2008;52:329–332.
21.
Descamps D, Damond F, Matheron S, Collin G, Campa P, Delarue S, Pueyo S, Chêne G, Brun-Vezinet F, French ANRS HIV-2 Cohort Study Group: High frequency of selection of K65R and Q151M mutations in patients receiving nucleoside reverse transcriptase inhibitors containing regimen. J Med Virol 2004;74:197–201.
22.
Damond F, Collin G, Matheron S, Peytavin G, Campa P, Taieb A, Bénard A, Chêne G, Brun-Vezinet F, Descamps D, French ANRS HIV-2 Cohort (ANRS CO 5 VIH-2): In vitro phenotypic susceptibility to nucleoside reverse transcriptase inhibitors of HIV-2 isolates with the Q151M mutation in the reverse transcriptase gene. Antivir Ther 2005;10:861–865.
23.
Cavaco-Silva J, Theys K, Goncalves MF, Neves I, Vera J, Dinis A, Fonseca P, Tavares L, Faria N, Van Laethem K, Vandamme A-M, Gomes P, Mansinho K, Camacho RJ, Portuguese HIV-2 resistance study group: Bayesian network analysis of resistance pathways in HIV-2 reverse transcriptase (abstract 46). 8th European HIV Drug Resistance Workshop (oral presentation), Sorrento, 2010.
24.
Cavaco-Silva J, Miranda AC, Gonçalves MF, Valadas E, Mansinho K, Van Laethem M, Vandamme A-M, Gomes P, Camacho RJ, HIV-2 Resistance Study Group: Emergence of K65R in HIV-2-infected patients under therapy. 7th European Drug Resistance Workshop (oral presentation), Stockholm, 2009.
25.
Roquebert B, Damond F, Collin G, Matheron S, Peytavin G, Bénard A, Campa P, Chêne G, Brun-Vézinet F, Descamps D, French ANRS HIV-2 Cohort (ANRS CO 05 VIH-2): HIV-2 integrase gene polymorphism and phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitors raltegravir and elvitegravir in vitro. J Antimicrobial Chemother 2008;62:914–920.
26.
Damond F, Lariven S, Roquebert B, Males S, Peytavin G, Morau G, Toledano D, Descamps D, Brun-Vezinet F, Matheron S: Virological and immunological response to HAART regimen containing integrase inhibitors in HIV-2-infected patients. AIDS 2008;22:665–666.
27.
Bercoff DP, Trinqueneaux P, Lambert C, Oumar AA, Temes A-M, Dao S, Goubau P, Schmit J-C, Ruelle J: Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir. Retrovirology 2010;7:98.
28.
Charpentier C, Larrouy L, Collin G, Damond F, Matheron S, Chêne G, Nie T, Schinazi R, Brun-Vézinet F, Descamps D, French ANRS HIV-2 Cohort (ANRS CO 05 VIH-2): In-vitro phenotypic susceptibility of HIV-2 clinical isolates to the integrase inhibitor S/GSK1349572. AIDS 2010;24:2753–2755.
29.
Morner A, Bjorndal A, Albert J, Kewalramani VN, Littman DR, Inoue R, Thorstensson R, Fenyo EM, Bjorling E: Primary human immunodeficiency virus type 2 (HIV-2) isolates, like HIV-1 isolates, frequently use CCR5 but show promiscuity in coreceptor usage. J Virol 1999;73:2343–2349.
30.
Shi Y, Brandin E, Vincic E, Jansson M, Blaxhult M, Gyllensten K, Moberg L, Brostrom C, Fenyo EM, Albert J: Evolution of human immunodeficiency virus type 2 coreceptor usage, autologous neutralization, envelope sequence and glycosylation. J Gen Virol 2005;86:3385–3396.
31.
Armstrong-James D, Stebbing J, Scourfield A, Smit E, Ferns B, Pillay D, Nelson M: Clinical outcome in resistant HIV-2 infection treated with raltegravir and maraviroc. Antiviral Res 2010;86:224–226.
32.
Visseaux B, Hurtado-Nedelec M, Charpentier C, Collin G, Storto A, Matheron S, Larrouy L, Damond F, Brun-Vezinet F, Descamps D, ANRS CO 05 HIV-2 Cohort: Molecular determinants of HIV-2 R5-X4 tropism in the V3 loop: development of a new genotypic tool (poster 671). Conference on Retroviruses and Opportunistic Infections (CROI), Boston, 2011.
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