Plasma nevirapine concentrations predict virological and adherence failure in Kenyan HIV-1 infected patients with extensive antiretroviral treatment exposure.

Treatment failure is a key challenge in the management of HIV-1 infection. We conducted a mixed-model survey of plasma nevirapine (NVP) concentrations (cNVP) and viral load in order to examine associations with treatment and adherence outcomes among Kenyan patients on prolonged antiretroviral therapy (ART). Blood plasma was collected at 1, 4 and 24 hours post-ART dosing from 58 subjects receiving NVP-containing ART and used to determine cNVP and viral load (VL). Median duration of treatment was 42 (range, 12-156) months, and 25 (43.1%) of the patients had virologic failure (VF). cNVP was significantly lower for VF than non- VF at 1hr (mean, 2,111ng/ml vs. 3,432ng/ml, p = 0.003) and at 4hr (mean 1,625ng/ml vs. 3,999ng/ml, p = 0.001) but not at 24hr post-ART dosing. Up to 53.4%, 24.1% and 22.4% of the subjects had good, fair and poor adherence respectively. cNVP levels peaked and were > = 3µg.ml at 4 hours in a majority of patients with good adherence and those without VF. Using a threshold of 3µg/ml for optimal therapeutic nevirapine level, 74% (43/58), 65.5% (38/58) and 86% (50/58) of all patients had sub-therapeutic cNVP at 1, 4 and 24 hours respectively. cNVP at 4 hours was associated with adherence (p = 0.05) and virologic VF (p = 0.002) in a chi-square test. These mean cNVP levels differed significantly in non-parametric tests between adherence categories at 1hr (p = 0.005) and 4hrs (p = 0.01) and between ART regimen categories at 1hr (p = 0.004) and 4hrs (p<0.0001). Moreover, cNVP levels correlated inversely with VL (p< = 0.006) and positively with adherence behavior. In multivariate tests, increased early peak NVP (cNVP4) was independently predictive of lower VL (p = 0.002), while delayed high NVP peak (cNVP24) was consistent with increased VL (p = 0.033). These data strongly assert the need to integrate plasma concentrations of NVP and that of other ART drugs into routine ART management of HIV-1 patients.

Co-Infection Burden of Hepatitis C Virus and Human Immunodeficiency Virus among Injecting Heroin Users at the Kenyan Coast.

BACKGROUND: Injection drug use is steadily rising in Kenya. We assessed the prevalence of both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections among injecting heroin users (IHUs) at the Kenyan Coast. METHODS: A total of 186 IHUs (mean age, 33 years) from the Omari rehabilitation center program in Malindi were consented and screened for HIV-1 and HCV by serology and PCR and their CD4 T-cells enumerated by FACS. RESULTS: Prevalence of HIV-1 was 87.5%, that of HCV was 16.4%, co-infection was 17.9% and 18/152 (11.8%) were uninfected. Only 5.26% of the HIV-1 negative injectors were HCV positive. Co-infection was higher among injectors aged 30 to 40 years (20.7%) and among males (22.1%) than comparable groups. About 35% of the injectors were receiving antiretroviral treatment (ART). Co-infection was highest among injectors receiving D4T (75%) compared to those receiving AZT (21.6%) or TDF (10.5%) or those not on ART (10.5%). Mean CD4 T-cells were 404 (95% CI, 365 - 443) cells/mm3 overall, significantly lower for co-infected (mean, 146; 95% CI 114 - 179 cells/mm3) than HIV mono infected (mean, 437, 95% CI 386 - 487 cells/mm3, p<0.001) or uninfected (mean, 618, 95% CI 549 - 687 cells/mm3, p<0.001) injectors and lower for HIV mono-infected than uninfected injectors (p=0.002). By treatment arm, CD4 T-cells were lower for injectors receiving D4T (mean, 78; 95% CI, 0.4 - 156 cells/mm3) than TDF (mean 607, 95% CI, 196 - 1018 cells/mm3, p=0.005) or AZT (mean 474, 95% CI -377 - 571 cells/mm3, p=0.004). CONCLUSION: Mono and dual infections with HIV-1 and HCV is high among IHUs in Malindi, but ART coverage is low. The co-infected IHUs have elevated risk of immunodeficiency due to significantly depressed CD4 T-cell numbers. Coinfection screening, treatment-as-prevention for both HIV and HCV and harm reduction should be scaled up to alleviate infection burden.

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.