From the time of the first description of immunodeficiency caused by what we now know to be HIV-1 infection, infection rates have reached pandemic levels worldwide . Since 1981, more than 60 million people have been infected, with sub-Saharan Africa bearing the greatest burden of the infection. In contrast, the related HIV-2 strain is confined primarily to West Africa. In endemic countries, HIV-2 seroprevalence is declining which is drastically different from the increasing rate of global HIV-1 infections.
Despite an approximately 30-60% similarity between HIV-1 and HIV-2, the disease course characteristic of the two infections shows substantial variation. Studies from the MRC field station in Caio, Guinea-Bissau, where approximately 8% of adults are infected with HIV-2, show that survival is not affected by HIV-2 status for the great majority of infected adults. The plasma viral load is significantly lower in HIV-2 compared to HIV-1-infected people despite a similar pro-viral load at the same stage of infection. The lower viremia is likely responsible for the low sexual and perinatal HIV-2 transmission. However, a minority of people with HIV-2 infection behave as progressors, with high levels of plasma virus and declining CD4+ T cell levels, leading to a clinical picture indistinguishable from AIDS caused by HIV-1.
The dichotomy in clinical outcomes in HIV-2-infected people is a striking feature that has emerged from the longitudinal studies from the Caio community cohort that is in sharp contrast to HIV-1 infection, where long-term non-progressors (LTNPs) are rare in the absence of anti-retroviral therapy (ART). Thus HIV-2 infection presents an intriguing picture of a largely non-pathogenic human retrovirus and most infected people behave as LTNPs.
Several hypotheses have been raised to reconcile the discrepancy between the plasma and pro-viral load in most HIV-2-infected patients, including an enhanced immune control of viral replication, defective HIV-2 replicative capacity, or a combination of these mechanisms. Elucidating the reasons for the relatively attenuated course of HIV-2 infection and identifying the key differences between progressors and non-progressors with HIV-2 infection could shed light on the mechanisms of HIV-1 pathogenesis and provide a better understanding of protective immunity to HIV infection. This is the main goal of the HIV component of the Viral Diseases Programme, with studies examining the contribution of the immune response, host genetics, and the viral characteristics that may determine the superior outcome of HIV-2 infection.
The Genito-Urinary Medicine (GUM) clinic on the main MRC campus in Fajara provides clinical care for HIV-1, HIV-2, and HIV-dually positive patients, with over 200 patients benefiting from antiretroviral therapy. Therapy is also being initiated in the Caio community cohort in Guinea Bissau. This provides the opportunity for clinical research studies looking at the most optimal ways to treat HIV infection in West African, where HIV-2 and HIV-dual infections complicate therapy decisions. A further interest of the Unit is the high proportion of HIV-infected people who are co-infected with tuberculosis. Ongoing studies are exploring the role of prophylactic TB treatment in patients with late-stage HIV disease and the immunology of the two infections.
