The effect of primary drug resistance on CD4 cell decline and the viral load set-point in HIV positive individuals before the start of antiretroviral therapy

OBJECTIVE: To evaluate the effect of primary resistance and selected polymorphic amino-acid substitutions in HIV reverse transcriptase (RT) and protease (PR) on the CD4 count and viral load (VL) set point before the start of ART. DESIGN: Prospective cohort study. METHODS: 6,180 individuals with a resistance test prior to starting ART accessing care in HIV clinics across Europe who had at least 1 VL and 1 CD4 test available were included in the analysis. The impact of amino-acid substitutions variants on VL and CD4 trends was investigated using linear mixed models. Clusters of mutations were studied using principal component analysis. RESULTS: Overall, the detection of any primary resistance was not associated with either the speed of CD4 decline or the viral load set point. However, transmitted nucleoside RT inhibitor and PR inhibitor resistance appeared to be weakly associated with lower VL set points, as were the polymorphic G16E or Q92K PR mutations. There was some evidence suggesting that these effects varied according to HIV subtype, with the effects of transmitted NRTI and PR resistance being particularly marked among individuals with a subtype B virus. A cluster of five polymorphic PR substitutions at position 20, 13, 36, 69 and 89 was associated with less steep CD4 declines and lower VL set points. CONCLUSIONS: Although we found little evidence for an association between primary resistance and CD4 speed of decline and VL set point, the potential role of polymorphic PR (alone or in clusters) and their interplay with HIV subtype needs to be further evaluated.