Hindawi Publishing Corporation AIDS Research and Treatment Volume 2011, Article ID 463704, 11 pages doi:10.1155/2011/463704 Review Article Antiretroviral Therapy for HIV-2 Infection: Recommendations for Management in Low-Resource Settings Kevin Peterson,1 Sabelle Jallow,2 Sarah L. Rowland-Jones,2 and Thushan I. de Silva1, 3 1 Medical Research Council (UK) Laboratories, Atlantic Road, P.O. Box 273, Fajara, Gambia 2 Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliﬀe Hospital, Oxford, UK 3 MRC/UCL Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, UK Correspondence should be addressed to Kevin Peterson, viraload@gmail.com Received 27 May 2010; Accepted 12 December 2010 Academic Editor: Ann Duerr Copyright © 2011 Kevin Peterson et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. HIV-2 contributes approximately a third to the prevalence of HIV in West Africa and is present in signiﬁcant amounts in several low-income countries outside of West Africa with historical ties to Portugal. It complicates HIV diagnosis, requiring more expensive and technically demanding testing algorithms. Natural polymorphisms and patterns in the development of resistance to antiretrovirals are reviewed, along with their implications for antiretroviral therapy. Nonnucleoside reverse transcriptase inhibitors, crucial in standard ﬁrst-line regimens for HIV-1 in many low-income settings, have no eﬀect on HIV-2. Nucleoside analogues alone are not suﬃciently potent enough to achieve durable virologic control. Some protease inhibitors, in particular those without ritonavir boosting, are not suﬃciently eﬀective against HIV-2. Following review of the available evidence and taking the structure and challenges of antiretroviral care in West Africa into consideration, the authors make recommendations and highlight the needs of special populations. 1. Introduction HIV-2 represents a distinct lineage of HIV, stemming from SIVsm instead of the SIVcpz responsible for HIV-1. Like HIV-1 it appears to have made the transition to humans more than once, giving rise to eight distinct groups, of which groups A and B account for nearly all of the cases identiﬁed thus far [1]. HIV-2 diﬀers from HIV-1 most strikingly in its lower rate of progression and infectivity, with the majority of those infected likely to be long-term nonprogressors [2–4]. Those with progressive disease experience the same likelihood of morbidity and mortality as are seen with HIV-1 [5, 6]. People with advanced HIV-2 infection require treat- ment with antiretroviral therapy (ART), but most individual antiretroviral drugs and regimens have been designed and optimized for HIV-1 and cannot be assumed to provide optimal viral suppression for HIV-2 infection. In some instances, antiretroviral susceptibility diﬀers signiﬁcantly between HIV-1 and HIV-2, such that HIV-2 is intrinsically resistant to two of the major classes of antiretroviral drugs: the fusion inhibitors and the nonnucleoside reverse tran- scriptase inhibitor- (NNRTI-) based regimens that are the standard therapy for HIV-1 in West Africa [7, 8]. The challenge of treating HIV-2 infection falls mainly upon West Africa [6], with current prevalence estimates ranging up to 1% where reported, compared with HIV-1 prevalence rates of up to 3.4%, therefore comprising a substantial portion of all HIV infections in the subregion [9]. The exception to this is Guinea-Bissau, where the prevalence amongst adults was estimated to be 8%–10% two decades ago [10]. This has now changed to a current prevalence of around 4%, compared to an HIV-1 prevalence of 2.9% in rural areas and 4.2% in urban areas [11–13]. European countries with colonial links to West Africa such as Portugal, France, and the United Kingdom, as well as other countries with prior Portuguese ties, such as Angola, Brazil, India, and Mozambique, also have sizeable cohorts of HIV-2 infected individuals [14–18]. Although the absolute numbers of patients infected with HIV-2 in European cohorts are small, the earlier availability of ART in these countries has provided