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

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.

Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children aged less than five years: results of an open-label, randomized, single-centre study.

BACKGROUND: This open-label, randomized study evaluated efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) in treatment of uncomplicated falciparum malaria in children below five years of age, to build evidence on use of AL as first-line treatment and DP as second-line treatment in Kenya. METHODS: A total of 454 children aged six to 59 months with uncomplicated falciparum malaria were randomized (1:1) to receive AL dispersible or DP paediatric tablets and followed up for 42 days. Primary efficacy variable was corrected adequate clinical and parasitological response (ACPR) rate on day 28. Secondary variables included corrected (day 14, 28 and 42), uncorrected (day 3, 14, 28 and 42) cure rates, parasitological failure at days 3, 14 and 42. Acceptability and tolerability of both drugs were assessed by caregiver questionnaire. RESULTS: On day 28, corrected ACPR rates for AL dispersible and DP paediatric were 97.8% (95% CI: 94.9-99.3) and 99.1% (95% CI: 96.8-99.9), respectively, in intention-to-treat population, with no significant treatment differences noted between AL dispersible and DP paediatric arms. Additionally, no significant differences were observed for PCR corrected cure rates on days 14 and ACPR on day 42 for AL dispersible (100%; 96.8%) and DP paediatric (100%; 98.7%). Similarly, for PCR uncorrected cure rates, no significant differences were seen on days 3, 14, 28, and 42 for AL dispersible (99.1%; 98.7%; 81.1%; 67.8%) and DP paediatric (100%; 100%; 87.7%; 70.5%). Parasite clearance was rapid, with approximately 90% clearance achieved in 40 hours in both treatment arms. Incidence of adverse events was related to underlying disease; malaria being reported in both treatment arms. One serious adverse event was noted in AL dispersible (0.42%) arm, not related to study drug. Adherence to treatment regimen was higher for children treated with AL dispersible (93.6%) compared to DP paediatric (85.6%). Acceptability of AL dispersible regimen was assessed as being significantly better than DP paediatric. CONCLUSIONS: AL and DP were both efficacious and well tolerated, and had similar effects at day 42 on risk of recurrent malaria. No signs of Plasmodium falciparum tolerance to artemisinins were noted. TRIAL REGISTRATION: PACTR201111000316370.