The use of HAART regimens containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) in areas where HIV-1 sub-type C is common may be less successful than in Europe and North America, if the results of a study published in Antimicrobial Agents and Chemotherapy are borne out in larger-scale trials.
Investigators studied untreated HIV-positive Ethiopians who had migrated to Israel. They detected many ‘silent mutations’, or secondary mutations, in the sub-type C virus they were infected with, suggesting that resistance to NNRTIs would emerge rapidly. In one patient, a mutation at G190A in the reverse transcriptase was noted, which confers high levels of resistance to nevirapine. Laboratory studies found that sub-type C virus resistant to all the currently available NNRTIs emerged much more easily and rapidly than NNRTI resistant sub-type B virus. In addition, the investigators found some previously undetected resistance mutations to NNRTIs in sub-type C HIV.
Sub-type C of HIV is the most common strain of HIV in Ethiopia, as well as other areas with high rates of HIV infection including Southern Africa, India and parts of China. Given their easy dosing requirements, NNRTIs are favoured in treatment strategies in resource limited countries, including areas where sub-type C is most prevalent. Most clinical trial data, however, concern the use of NNRTIs in people infected with sub-type B, the prevalent form of HIV-1 in western Europe and north America.
Reference: Loemba H et al. Genetic divergence of human immunodeficiency virus type 1 Ethiopian clade C reverse transcriptase (RT) and rapid development of resistance against nonnucleoside inhibitors of RT. Antimicrobial Agents and Chemotherapy 46: 2087-2094, 2002.