The independent effect of highly active antiretroviral therapy on severe opportunistic disease incidence and mortality in HIV-infected adults in Cote d'Ivoire

Background: Studies in developed countries have shown highly active antiretroviral therapy (HAART) decreases incidence of severe opportunistic diseases (ODs) in HIV-infected patients beyond that which is expected from changes in CD4(+) T-cell count. Objective: To estimate the independent impact of HAART on reducing ODs and mortality in Cote d'lvoire. Methods: Within two longitudinal studies of HIV-infected adults (1996-2003), we identified time on 'cotrimoxazole alone' and 'HAART plus cotrinnoxazole' WHO stage 3-4 defining events and severe malaria were divided into those preventable and not preventable with cotrimoxazole. Incidence of ON by CD4 count stratum was estimated using incidence density analysis. CD4(+) T-cell count at time of OD was estimated using linear interpolation. Using Poisson regression, we estimated the effect of HAART on OD incidence and mortality by CD4 count stratum. Results: Totals of 446 and 135 adults were followed during 6,216 and 3,412 person-months in the cotrimoxazole alone and HAART plus cotrimoxazole periods, respectively. There was a CD4(+) T-cell-independent risk reduction for ODs and mortality during the HAART plus cotrimoxazole period compared with cotrimoxazole alone, which varied by time on HAART, CD4 count stratum and OD type. It was mainly seen after 6 months on HAART and for ODs not preventable by cotrimoxazole. The HAART effect differed significantly by CD4 count stratum (P=0.02), but was significant in all strata after 6 months on HAART. Conclusions: In these sub-Saharan African adults, HAART initiation reduced ODs and mortality beyond that which was expected through the HAART-incluced CD4(+) T-cell increase. Further studies should examine practical implications of this independent 'HAART effect' on clinical outcomes in patients on HAART.