Sustained virological response on second‐line antiretroviral therapy following virological failure in HIV‐infected patients in rural South Africa

Abstract

Purpose of the studyOver the last decade, a massive roll‐out of antiretroviral drugs in resource‐limited settings has taken place. In general, good virological responses on first‐line antiretroviral therapy (ART) are achieved in most HIV‐infected patients residing there. Still, a growing number of patients experience virological failure over time, resulting in an increasing need for second‐line regimens [1]. This study describes the clinical, immunological and virological efficacy of protease inhibitor (PI)‐based second‐line ART in a clinic in rural South Africa.MethodsAn observational cohort study was performed on 210 patients (including 39 children) who initiated PI‐based second‐line ART at least 12 months prior to data collection. Biannual clinical, immunological and virological monitoring was performed. Primary endpoints were adequate virological response (HIV‐RNA<400 copies/ml), full virological suppression (HIV‐RNA<50 copies/ml), virological failure (HIV‐RNA>1000 after initial virological response) and on‐going viremia (HIV‐RNA never<400 copies/ml for more than six months). Data were analyzed by an on‐treatment (OT) and intention‐to‐treat (ITT) approach.ResultsMedian duration of follow‐up after switch to second‐line treatment was 21 months [IQR 14–37]. 150/210 patients (71%, ITT) were in care and on treatment at the end of follow‐up and 16/210 (8%, ITT) had died. After twelve months, an adequate virological response was seen in 106/143 patients (74%, OT), of which 86/143 (60%, OT) experienced full virological suppression and 20/143 (14%, OT) showed persisting low‐level viremia (HIV‐RNA between 50 and 400 copies/ml). Furthermore, virological responses remained stable after 24 months of second‐line ART. Virological efficacy was similar amongst adult and pediatric patients. Median increase in CD4 counts from switch until end of follow‐up was 145 cells/mm3 [IQR 1–397] in adults. As in first‐line ART, we observed a lack of correlation between virological treatment failure and WHO‐defined immunological failure in PI‐based therapy.ConclusionsPromising virological outcomes are achieved with PI‐based, second‐line antiretroviral therapy in adult and pediatric patients in rural South Africa. Results were sustainable during the two‐year follow‐up period with a high retention rate, although persisting low‐level viremia occurred in a subset of patients. The observed viro‐immunological dissociation emphasizes the need for virological monitoring.