Sub-optimal outcomes with switching to zidovudine vs. recycling tenofovir in second-line treatment in Haiti
BACKGROUND: World Health Organization (WHO) guidelines recommend an optimized nucleoside reverse transcriptase inhibitor (NTRI) backbone for second-line ART, including switching from tenofovir (TDF) to zidovudine (AZT), with presumed low-level AZT resistance. However, many providers in resource-poor countries recycle TDF in second-line treatment due to concerns for toxicity and twice-daily dosing of AZT and due to demonstrated efficacy of NRTIs (in spite of genotypic resistance found in several recent studies).
METHODS: Using electronic medical records from GHESKIO (Port-au-Prince, Haiti), we identified adult patients who failed first-line Efavirenz (EFV)/TDF/3TC and were switched to a second-line regimen that included ritonavir-boosted protease inhibitor (bPI), in combination with either TDF/3TC or AZT/3TC. Retention, adherence, and viral suppression outcomes were evaluated at 12 month after initiation of second-line regimen. Adherence was approximated using pharmacy refill data. Multivariable logistic regression was used to determine predictors of virologic suppression.
RESULTS: From 2012 to 2018, 1,017 patients met study criteria and were analyzed. Of these, 509/1017 (50.0%) were women. Median patient age was 40.7 years. 733/1017 (72.1%) patients continued on TDF/3TC on second-line, while 284/1017 (27.9%) were switched to AZT/3TC. Retention was similar in both groups with 612/733 (83.5%) in the TDF/3TC and 236/284 (83.1%) in the AZT/3TC group remaining in care. Of the patients with viral load at 12 months, 253/480 (52.7%) had VL<200 copies/mL in TDF/3TC vs 72/200 (36.0%) in the AZT/3TC group (p<0.001). Viral suppression in patients with â?¥90% adherence was also better in the TDF/3TC group with 166/230 (72.2%) compared to 43/75 (57.3%) in the AZT/3TC group (p<0.016). Predictors of viral suppression included recycled TDF/3TC (odds ratio [OR]: 2.08; 95% CI: 1.46, 2.97), secondary or higher education level (OR: 1.53; 95% CI: 1.10, 2.14) and being married/living together (OR 1.51; 95% CI: 1.00, 2.27).
CONCLUSIONS: The WHO-recommended optimized NTRI backbone for second-line ART, which includes switching from TDF to AZT, was associated with lower rates of viral suppression than recycled TDF in Haiti. This may potentially be due to twice-daily dosing and poor tolerability of AZT. ART adherence was found to be poor regardless of NRTI backbone, therefore additional interventions are needed to improve adherence in this population.
S. Pierre * (1), C. Nguyen (2), B. Iryna (2), F. Homeus (1), V. Guillaume (1), C.P.J. Pierre (1), G. Sainvil (1), A. Julien (1), G. Julmiste (1), Y. Macius (1), G.P.-L. Florestal (1), V. Rouzier (1), P. Severe (1), P. Cremieux (2), M.M. Deschamps (1), B. Liautaud (1), S. Koenig (3), J.W. Pape (1)
(1) GHESKIO Centers, Research, Port-au-Prince, Haiti, (2) Analysis Group, Boston, United States, (3) Brigham Women Hospital, Boston, United States