The prevalent HIV-1 subtype in West Africa is less susceptible to some protease inhibitors, according to a study published in the July 15th edition of Clinical Infectious Diseases (now on-line). The investigators from Japan, Ghana and France, found that ritonavir (Norvir) had the strongest inhibitory effect and nelfinavir (Viracept) the weakest effect of any protease inhibitor included in their analysis and “propose that the combination of ritonavir and protease inhibitors other than nelfinavir is still clinically applicable” for the treatment of the HIV subtype prevalent in West Africa.
Protease inhibitors were developed and tested against subtype B of HIV-1, which is the subtype most prevalent in North America and Europe. However, HIV-1 subtypes A, G and CRF02_AG are the dominant in Africa. It has already been well-established that non-B subtypes have a sequence in their protease gene distant from type B and some studies have suggested that individuals infected with non-B subtypes have a lower susceptibility to treatment with protease inhibitors.
Access to highly active antiretroviral therapy (HAART) is increasing in resource-limited countries and before therapy with protease inhibitors is provided, it is necessary to determine the susceptibility of the locally prevalent HIV-1 subtype to protease inhibitors.
Accordingly, investigators obtained samples from 39 treatment-naive individuals with chronic HIV-1 infection from three different cities in Ghana. These individuals were judged to be representative of the HIV epidemic in West Africa. The susceptibility of each individual’s HIV to the protease inhibitors nelfinavir, lopinavir, indinavir (Crixivan), saquinavir (Fortovase), ritonavir and amprenavir (Agenerase) was assessed.
To do this, the investigators cloned and genetically compared each patient’s protease gene. Phenotypic analysis was performed in the presence of the six study protease inhibitors.
Genetic analysis revealed that HIV-1 subtype CRF02_AG was the dominant strain. This subtype is phylogenetically distinct from HIV-1 subtype B.
No major mutations conferring resistance to protease inhibitors were found.
Drug susceptibility testing was then performed. “Ghanaian HIV-1 proteases showed different levels of susceptibility to the inhibitors”, note the investigators. They found, “most of the Ghanaian proteases proved to be…considerably less susceptible to nelfinavir…and lopinavir…and moderately less susceptible to indivinavir…and saquinavir”. However, the investigators also found “relatively pronounced susceptibility to…ritonavir and amprenavir.”
The investigators stress the inhibitory effect of ritonavir on the prevalent HIV subtype in their study and suggest that ritonavir-boosted protease inhibitors would be effective.
“Our findings provide implications for the combination of protease inhibitors to be used in HAART in West Africa”, conclude the investigators.
Kinomoto M et al. HIV-1 proteases from drug-naïve west African patients are differentially less susceptible to protease inhibitors. Clin Infect Dis 41 (on-line edition), 2005.