Data on durability of first-line regimens in resource-limited settings are limited. We reviewed data from a large ongoing multinational African Cohort study (AFRICOS) to describe reasons and assess time to switching or stopping first-line antiretroviral therapy (ART).
AFRICOS prospectively enrolls HIV-infected and uninfected adults at 12 President’s Emergency Plan for AIDS Relief (PEPFAR) supported facilities across 5 programs in Kenya (Kisumu and the South Rift Valley), Tanzania, Uganda, and Nigeria. ART regimen history is obtained at entry from available records and updated prospectively every 6 months. Reasons for switching or stopping ART are recorded by study physicians. For these analyses, we included HIV-infected participants who had documented ART start and stop dates, either prior to cohort entry or once enrolled. Time to switching or stopping a regimen was the primary endpoint used to assess durability. We generated Kaplan-Meier curves stratified by variables of interest and used the log-rank test to evaluate for significant differences.
Between January 2013 and June 2018, we enrolled 2820 HIV-infected adults (58% female) with a median age of 36 (IQR 30-44) years. Of these, 2663 (94%) were ART experienced and have initial ART start dates available, including 1154 (43%) that began ART before the study initiation in 2013. The first regimen for the majority (1396; 52%) was efavirenz/lamivudine/tenofovir disoproxl fumarate. The median duration of this regimen was 2.25 (IQR 0.94-3.88) years. The initial regimen was switched or stopped for 1207 (45%) participants for reasons including change in country guidelines (344; 29%), toxicity (281; 23%), stock-out (262; 21%) and regimen failure (107; 9%). Regimen durability did not differ by gender (Figure, panel A), but was reduced in the youngest age group evaluated (18-29 years; panel B), varied substantially by site (panel C), and was reduced with initial regimens containing D4T (panel D).
In this large African cohort, the durability of first-line ART regimens was driven largely by factors other than viral failure. Specific regimens associated with high toxicity and abbreviated durability are no longer PEPFAR standard of care, but persistent programmatic factors that contribute to drug stock-outs and other barriers to ART maintenance require further investigation and intervention, especially as PEPFAR implements the program wide first-line transition to tenofovir/lamivudine/dolutegravir (TLD).