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
]. Those with progressive disease experience the same likelihood of morbidity and mortality as are seen with HIV-1 [5
]. People with advanced HIV-2 infection require treatment 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 transcriptase inhibitor- (NNRTI-) based regimens that are the standard therapy for HIV-1 in West Africa [7
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
]. 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
]. 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 some data to guide treatment recommendations in resource-poor settings.
Given the prevalence of HIV-2 in West Africa, it is imperative that up-to-date recommendations be available for the antiretroviral management of HIV-2 in these clinical settings, characterized by the use of standardized first-, and in some cases second-line regimens based on limited formularies, with treatment decisions driven by protocol, that are also highly sensitive to cost. At the time of writing, therapeutic drug monitoring, viral load measurement, and genotypic resistance testing are not routinely available in West Africa, nor are coreceptor tropism assays or HLA typing (to guide the safe use of CCR5 receptor blockers or abacavir, resp.). The monitoring and care of HIV in sub-Saharan Africa has, however, been a litany of barriers brought down, and the “impossible” becomes the standard, so these recommendations seek to strike a balance between optimal and current management trends.
Clinical trials of ART in HIV-2 are few compared with HIV-1, primarily because of HIV-2's lower prevalence and virulence, not to mention its concentration among some of the world's poorest people. Until there is better evidence from randomized controlled trials, judgment of what constitutes good care in HIV-2 management must therefore rely on both in vitro as well as in vivo data from small cohort studies and case series, theoretical assertions, and parallels with HIV-1 therapeutics.
As will be apparent to experienced clinicians and program officers, numerous potential factors have been left out of this work that might influence program-level decisions about ART for HIV-2 in West Africa. This is especially true where such factors affect both HIV-1 and HIV-2 infections in the same way. The current work is not intended as an exhaustive review of all aspects of a public health approach to the use of ART, nor is it intended to function as an ART primer. However, in the absence of universally accepted treatment guidelines for HIV-2, the authors seek to provide their own recommendations, based on the available literature, HIV-2 treatment meetings, discussions with colleagues from major HIV-2 treatment centers in Europe and Africa, and from personal experiences between 2003–2010 at the Genito-Urinary Medicine clinic at the MRC Laboratories in The Gambia, where ART was provided to HIV-2 infected people.