Antiretroviral failure despite high levels of adherence: Discordant adherence-response relationship in Botswana

Background: Although adherence to antiretroviral therapy may be higher in sub-Saharan Africa. knowledge regarding the magnitude of adherence needed to maintain virological Suppression in this setting is limited. Methods: A case-control Study among HIV-infected individuals initiating highly active antiretroviral therapy (HAART) in Gaborone, Botswana, was performed. Cases were randomly selected from subjects on HAART >= 6 months with plasma HIV-1 RNA levels (viral loads) >1000 copies/mL. Controls were randomly selected from subjects on HAART >= 6 months with all viral loads <400 copies/mL. HAART adherence was determined using pharmacy refill records. Results: In total, 302 individuals were included; 57 cases were compared with 245 controls with respect to adherence levels on nonnucleoside reverse transcriptase inhibitor-based HAART. Median adherence levels, as measured using pharmacy refill patterns, were consistently high but differed among cases and controls (91%, interquartile range 83%-97% for cases vs 97%, interquartile range 91%-100% for controls, P < 0,001, rank-sum test). Adherence <95% was independently associated with virological failure (odds ratio 4.19, 95% confidence interval 2.2 to 8.3). Conclusions: Very high rates of adherence were present in this setting, yet virological failure occurred nonetheless. Future work should explore other factors that might explain treatment failure in the setting of high levels of adherence.