Implementation and Operational Research: Correlates of Adherence and Treatment Failure Among Kenyan Patients on Long-term Highly Active Antiretroviral Therapy

Abstract

Background: Universal access to highly active antiretroviral therapy (HAART) is still elusive in most developing nations. We asked whether peer support influenced adherence and treatment outcome and if a single viral load (VL) could define treatment failure in a resource-limited setting.

Methods: A multicenter longitudinal and cross-sectional survey of VL, CD4 T cells, and adherence in 546 patients receiving HAART for up to 228 months. VL and CD4 counts were determined using m2000 Abbott RealTime HIV-1 assay and FACS counters, respectively. Adherence was assessed based on pill count and on self-report.

Results: Of the patients, 55.8%, 22.2%, and 22% had good, fair, and poor adherence, respectively. Adherence, peer support, and regimen, but not HIV disclosure, age, or gender, independently correlated with VL and durability of treatment in a multivariate analysis (P < 0.001). Treatment failure was 35.9% using sequential VL but ranged between 27% and 35% using alternate single VL cross-sectional definitions. More patients failed stavudine (41.2%) than zidovudine (37.4%) or tenofovir (28.8%, P = 0.043) treatment arms. Peer support correlated positively with adherence (χ(2), P < 0.001), with nonadherence being highest in the stavudine arm. VL before the time of regimen switch was comparable between patients switching and not switching treatment. Moreover, 36% of those switching still failed the second-line regimen.

Conclusion: Weak adherence support and inaccessible VL testing threaten to compromise the success of HAART scale-up in Kenya. To hasten antiretroviral therapy monitoring and decision making, we suggest strengthening patient-focused adherence programs, optimizing and aligning regimen to WHO standards, and a single point-of-care VL testing when multiple tests are unavailable.

Figure 1. The pattern of viral load and treatment outcome between various categories of patients.

Viral load (VL) is compared for various treatment response groups according to duration on HAART (A) for those treated for less than 12 months (open/left bars), 12-60 months (grey/middle bars) or for longer than 60 months (solid/right bars). Difference is not significant (NS) between these groups. Patients are grouped by adherence as having good, fair and poor adherence and also according to levels of CPS. Estimated marginal mean VL is shown for each adherence and CPS categories of all patients (B), and mean VL is shown for each adherence category of only patients failing treatment (C). A cumulative failure hazard is depicted using Cox proportional hazards model, showing risk and time-to failure for all patients separated by CPS groups (D). Failure risk was significantly increased in patients not participating in CPS (p<0.001). Patients are grouped according to a 9-factor compliance matrix featuring the 3 adherence and 3 CPS categories and their VL compared between groups (E). † VL is significantly higher than * (p-value= <0.028). ‡VL is significantly lower than + (p=<0.05). Finally, a Cox proportional hazard is developed for patients switching regimen, showing time-dependent risk of treatment failure separated by CPS groups (F). C=CPS (community Peer Support Network), Ad, Adherence. ‘++’ Represents active CPS or good adherence; ‘+’, partial CPS or fair adherence; ‘-’ no CPS or poor adherence. Patients in the assorted first-line HAART arm (n=32) are excluded.