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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.

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

There is continuous need to track genetic profiles of HIV strains circulating in different geographic settings to hasten vaccine discovery and inform public health and intervention policies. We partially sequenced the reverse transcriptase region of the HIV-1 pol gene from a total of 54 Kenyan patients aged 18–56 years who continued highly active antiretroviral treatment (HAART) for between 8 and 102 months. Subtyping was done using both the JPHMM tool and phylogenetic method. HIV-1 subtype A1 was the predominant strain in circulation, representing 57.4% and 70.4% of all isolates as determined by JPHMM and phylogenetic methods, respectively. Subtypes D (14.8%, 7.4%), C (5.6%, 9.3%), and A2 (0%, 5.6%) were determined at respective prevalence by both methods. JPHMM identified 22.2% of the isolates as recombinants. This surveillance focused on the RT gene and reaffirms the predominance of subtype A and an increasing proportion of recombinant strains in the Kenyan epidemic.

There is a continuous need to genetically characterize the HIV strains in circulation in order to assess interventions and inform vaccine discovery. We partially sequenced the envelope C2V3 gene from a total of 59 Kenyan patients on highly active antiretroviral treatment (HAART) and determined HIV subtypes using both the JPHMM subtyping tool and the phylogenetic method. HIV-1 subtype A1 was the predominant strain in circulation, representing 65.5% and 74.5% of all isolates as determined by JPHMM and phylogenetic methods, respectively. Subtypes C and D were the next most prevalent pure strains at 9.1% each by both methods. JPHMM identified 9.1% of the isolates as recombinant. Four isolates had short sequences not covering the entire C2V3 region and were thus not subtyped. From this study, subtype A viruses are still the predominant HIV-1 strains in local circulation in Kenya. Constant surveillance is needed to update molecular trends under continuing HAART scale-up.

Introduction Treatment failure is a key challenge in the management of HIV-1 infection. We examined the association of nevirapine blood levels with virologic treatment outcome and adherence among Kenyan patients on antiretroviral therapy (ART). Methods A cross-sectional study involving 58 subjects receiving nevirapine as part of ART regimen. Clinical, demographic and adherence data were captured using structured questionnaires. Five millilitres of EDTA blood was collected at 1, 4 and 24 h post-dosing and used for quantification of nevirapine levels using High-Performance Liquid Chromatography (HPLC). Plasma viral load was determined on m 2000 Abbott RealTi m e HIV-1 assay platform and used to determine virologic treatment failure (VF). Results Median duration of ART was 42 months and 43.1% of the patients had VF with a mean viral load of 4.24 log 10 copies. Measured at 1 hr (log 2.93, p = 0.003) and at 4 hrs (log 3.07, p 2 p 2 = 0.218, p = 0.002) and at 4 hrs (R 2 = 0.156, p = 0.001) were significantly and inversely correlated with same day VL in a Spearman’s rho model. Up to 53.4%, 24.1% and 22.4% of the patients had good, fair and poor adherence respectively, with adherence being significantly associated with plasma nevirapine levels at 1 hr (c 2 p = 0.001) and at 4 hr (c 2 p = 0.021). No significant associations were found at 24 hrs post nevirapine dosing. Conclusion Majority of VF patients attained nevirapine levels in plasma that were significantly lower than non-VF patients. These patients were also more likely to have poor adherence than virologic responders with higher nevirapine levels. Suboptimal exposures to nevirapine may be mitigated partly by improving adherence support mechanisms. Additional investigations should focus on pharmacogenetics and other factors influencing optimal drug uptake in blood. Disclosure of interest statement ISSTDR and IUSTI recognise the considerable contribution that industry partners make to professional and research activities. We also recognise the need for transparency of disclosure of potential conflicts of interest by acknowledging these relationships in publications and presentations.