Durability of antiretroviral therapy and predictors of virologic failure among perinatally HIV-infected children in Tanzania: a four-year follow-up.
BACKGROUND
In Tanzania, HIV-1 RNA testing is rarely available and not standard of care. Determining virologic failure is challenging and resistance mutations accumulate, thereby compromising second-line therapy. We evaluated durability of antiretroviral therapy (ART) and predictors of virologic failure among a pediatric cohort at four-year follow-up.


METHODS
This was a prospective cross-sectional study with retrospective chart review evaluating a perinatally HIV-infected Tanzanian cohort enrolled in 2008-09 with repeat HIV-1 RNA in 2012-13. Demographic, clinical, and laboratory data were extracted from charts, resistance mutations from 2008-9 were analyzed, and prospective HIV RNA was obtained.


RESULTS
161 (78%) participants of the original cohort consented to repeat HIV RNA. The average age was 12.2 years (55% adolescents ≥12 years). Average time on ART was 6.4 years with 41% receiving second-line (protease inhibitor based) therapy. Among those originally suppressed on a first-line (non-nucleoside reverse transcriptase based regimen) 76% remained suppressed. Of those originally failing first-line, 88% were switched to second-line and 72% have suppressed virus. Increased level of viremia and duration of ART trended with an increased number of thymidine analogue mutations (TAMs). Increased TAMs increased the odds of virologic failure (p = 0.18), as did adolescent age (p < 0.01).


CONCLUSIONS
After viral load testing in 2008-09 many participants switched to second-line therapy. The majority achieved virologic suppression despite multiple resistance mutations. Though virologic testing would likely hasten the switch to second-line among those failing, methods to improve adherence is critical to maximize durability of ART and improve virologic outcomes among youth in resource-limited settings.
Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. dorothy.dow@duke.edu.
Dorothy E
DE
Dow
Aisa M
AM
Shayo
Coleen K
CK
Cunningham
Elizabeth A
EA
Reddy
D000293:Adolescent; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D003430:Cross-Sectional Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000635:transmission; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D012189:Retrospective Studies; D013636:Tanzania; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D012367:RNA, Viral