A Challenging Knowledge Gap: Estimating Modes of HIV Acquisition Among Adolescents Entering HIV Care During Adolescence.

Characterizing HIV acquisition modes among adolescents with HIV (AHIV) enrolling in care during adolescence is a challenging gap that impacts differential interventions. We explored whether primary data collection with targeted questionnaires may address this gap and improve understanding of risk factors and perceptions about adolescents' HIV acquisition, in Kenyan AHIV entering care at ≥10 years, and their mothers with HIV (MHIV). Clinical data were derived through chart review. Among 1073 AHIV in care, only 26 (2%) met eligibility criteria of being ≥10 years at care enrollment, disclosed to, and with living MHIV. Among 18/26 AHIV-MHIV dyads enrolled (median age of AHIV 14 years), none had documented HIV acquisition modes. Data suggested perinatal infection in 17/18 AHIV, with 1 reported non-perinatal acquisition risk factor, and some discordance between adolescent-mother perceptions of HIV acquisition. In this difficult-to-enroll, vulnerable population of AHIV-MHIV dyads, primary data collection can enhance understanding of AHIV acquisition modes.

Gp41 and Gag amino acids linked to HIV-1 protease inhibitor-based second-line failure in HIV-1 subtype A from Western Kenya.

INTRODUCTION: Failure of protease-inhibitor (PI)-based second-line antiretroviral therapy (ART) with medication adherence but no protease drug resistance mutations (DRMs) is not well understood. This study investigated the involvement of gp41 and gag as alternative mechanisms, not captured by conventional resistance testing and particularly relevant in resource-limited settings where third-line ART is limited. METHODS: We evaluated gp41 and gag for unique amino acids in seven subtype A infected Kenyans failing second-line therapy with no PI resistance yet detectable lopinavir (query dataset), compared to seven similar-setting patients with PI resistance or undetectable lopinavir and 69 publically available subtype A Kenyan whole-genomes sequences. RESULTS: Three gp41 (607T, 641L, 721I) and four gag (124S, 143V, 339P, 357S) amino acids were significantly more frequent in the query dataset compared to the other datasets, with significantly high co-occurrence. CONCLUSION: The genotypic analysis of a unique group of HIV-1 subtype A infected patients, identified seven amino acids that could potentially contribute to a multi-gene mechanism of PI-based ART failure in the absence of PI DR mutations.

Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya.

INTRODUCTION: Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya. METHODS: We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients' characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests. RESULTS: Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations. CONCLUSIONS: In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for widespread VL monitoring in such resource limited settings to identify early treatment failure and suggest consideration of individualized resistance testing to design effective subsequent regimens.

Antiretroviral treatment interruptions induced by the Kenyan postelection crisis are associated with virological failure.

BACKGROUND: Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. METHODS: We determined effects of unplanned TIs after the 2007-2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. RESULTS: Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. CONCLUSIONS: Unplanned conflict-related TIs are associated with increased likelihood of virological failure.

A model for extending antiretroviral care beyond the rural health centre.

BACKGROUND: A major obstacle facing many lower-income countries in establishing and maintaining HIV treatment programmes is the scarcity of trained health care providers. To address this shortage, the World Health Organization has recommend task shifting to HIV-infected peers. METHODS: We designed a model of HIV care that utilizes HIV-infected patients, community care coordinators (CCCs), to care for their clinically stable peers with the assistance of preprogrammed personal digital assistants (PDAs). Rather than presenting for the standard of care, monthly clinic visits, in this model, patients were seen every three months in clinics and monthly by their CCCs in the community during the interim two months. This study was conducted in Kosirai Division, western Kenya, where eight of the 24 sub-locations (defined geographic areas) within the division were randomly assigned to the intervention with the remainder used as controls.Prior to entering the field, CCCs underwent intensive didactic training and mentoring related to the assessment and support of HIV patients, as well as the use of PDAs. PDAs were programmed with specific questions and to issue alerts if responses fell outside of pre-established parameters. CCCs were regularly evaluated in six performance areas. An impressionistic analysis on the transcripts from the monthly group meetings that formed the basis of the continuous feedback and quality improvement programme was used to assess this model. RESULTS: All eight of the assigned CCCs successfully passed their training and mentoring, entered the field and remained active for the two years of the study. On evaluation of the CCCs, 89% of their summary scores were documented as superior during Year 1 and 94% as superior during Year 2. Six themes emerged from the impressionistic analysis in Year 1: confidentiality and "community" disclosure; roles and responsibilities; logistics; clinical care partnership; antiretroviral adherence; and PDA issues. At the end of the trial, of those patients not lost to follow up, 64% (56 of 87) in the intervention and 52% (58 of 103) in the control group were willing to continue in the programme (p = 0.26). CONCLUSION: We found that an antiretroviral treatment delivery model that shifted patient monitoring and antiretroviral dispensing tasks into the community by HIV-infected patients was both acceptable and feasible. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT00371540.