HIV type 2 (HIV-2) was identified in Senegal in 1985. It is transmitted at a lower rate than HIV-1, and has a slower disease course, with 85% of infected people remaining free of symptoms for over eight years. Although it has largely remained confined to West Africa, HIV-2 infection has recently been found in India, Europe and the United States, albeit with low prevalence.

Although currently available non-nucleoside reverse transcriptase inhibitors (NNRTIs) are ineffective in treating HIV-2, there is evidence that nucleoside analogue reverse trancriptase inhibitors (NRTIs) and most protease inhibitors can reduce HIV-2 viral loads, allow CD4 cell counts to rise and prevent or improve AIDS-related symptoms. Although further clinical studies are needed, current recommendations, mostly based on the results of test tube studies, advise the use of a protease inhibitor with two NRTIs to treat HIV-2 infection (Hightower 2003). however, although HIV-2 viral load testing has been shown to be useful in assessing the risk of disease progression, the viral load level and CD4 cell count at which treatment should be begun in HIV-2 infection is not clear (Maheron 2003).

Test tube studies and limited clinical studies in HIV-2-infected patients have indicated that HIV-2 is susceptible to the NRTIs AZT (zidovudine, Retrovir), 3TC (lamivudine, Epivir), ddI (didanosine, Videx / VidexEC), ddC (zalcitabine, Hivid) and d4T (stavudine,Zerit). The inhibitory concentrations of these drugs is similar for HIV-1 and HIV-2. Furthermore, similar mutations in the two viruses can lead to resistance to these drugs.

Of the available protease inhibitors, nelfinavir (Viracept) and saquinavir (Invirase / Fortovase) have a similar level of activity against HIV-1 and HIV-2, while ritonavir (Norvir) and indinavir (Crixivan) are between ten and 100 times less active against HIV-2. In contrast, HIV-2 is naturally resistant to amprenavir (Agenerase).

NNRTIs have very low activity against HIV-2. Test tube studies have shown that dose elevations of up to 50-fold are required in order for the currently available NNRTIs to have an anti-HIV-2 effect. Such high doses are likely to have significant toxic effects in humans, so they are not recommended for treatment.

A recent study of the use of highly active antiretroviral therapy (HAART) was undertaken in ten HIV-2-infected paients. Although the study investigators took the results from test tube studies into account when choosing drug regimens, HIV-2 viral loads were not suppressed to below the limit of detection (100 copies/ml) or a viral load decrease of more than 2 log₁₀ from baseline in any of the patients, despite increases in CD4 cell counts (Mullins 2004). Controlled clinical trials of various HAART regimens for the treatment of HIV-2 are required in order to identify effective treatment strategies.

HIV-1 and HIV-2 co-infection

A case study published in 2005 emphasised the difficulties in treating patients co-infected with both HIV-1 and HIV-2. The woman, originally from Guinea Bissau, was diagnosed with both viruses in November 2001 and initially achieved good immunological and virological outcomes after commencing a HAART regimen consisting of d4T, 3TC and ritonavir-boosted lopinavir (Kaletra). However, after switching to an efavirenz-based regimen, she experienced an increase in HIV-2 viral load to 6800 copies/ml and a fall in CD4 cell count, although this drug combination kept HIV-1 viral loads undetectable.

After a further switch to 3TC, Kaletra and atazanavir, the patien's HIV-2 viral load fell to 90 copies/ml. The investigators emphasised the importance of monitoring the effect of antiretroviral therapy on both viral loads in co-infected patients, as well as the administration of drugs active against both viruses (Rodes 2005).

References

Hightower M et al. Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review. Braz J Infect Dis 7: 7-15, 2003.

Matheron S et al. Factors associated with clinical progression in HIV-2 infected patients: the French ANRS cohort. AIDS 17: 2593-2601, 2003.

Mullins C et al. Highly active antiretroviral therapy and viral load response in HIV type 2 infection. Clin Infect Dis 38: 1771-1779, 2004.

Rodes B et al. Viral response to antiretroviral therapy in a patient co-infected with HIV type 1 and type 2. Clin Infect Dis 41 (online edition), 2005.