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Short communication: antiretroviral therapy resistance mutations present in the HIV type 1 subtype C pol and env regions from therapy-naive patients in Zambia.

ABSTRACT: The prevalence of antiretroviral therapy (ART) resistance mutations present in HIV-1 subtype C pol and env regions of the proviral DNA was analyzed and compared from therapy-naive individuals before (Cohort A) and after (Cohort B) the availability of free ART in Zambia. Mutations present in sequences published in a previous study from Zambian ART-naive individuals infected with subtype C were analyzed using current parameters for the classification of ART drug resistance and compared with Cohorts A and B. No statistically significant differences were observed when comparing mutations present in the pol and env of these cohorts. However, an increase in the number of minor, borderline, or partial resistance mutations as well as the presence of major resistance mutations were observed in Cohort B. These results suggest there is an increasing trend of drug resistance-associated mutations that could be a result of the availability of free ART in Zambia. Moreover, the high prevalence of resistance mutations observed for maraviroc and vicriviroc in both cohorts may suggest a limited efficacy of entry inhibitors on HIV-1 subtype C.

SUBMITTER: Gonzalez S

PROVIDER: S-EPMC2932558 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Short communication: antiretroviral therapy resistance mutations present in the HIV type 1 subtype C pol and env regions from therapy-naive patients in Zambia.

Gonzalez Sandra S Gondwe Clement C Tully Damien C DC Minhas Veenu V Shea Danielle D Kankasa Chipepo C M'soka Tendai T Wood Charles C

AIDS research and human retroviruses 20100701 7

The prevalence of antiretroviral therapy (ART) resistance mutations present in HIV-1 subtype C pol and env regions of the proviral DNA was analyzed and compared from therapy-naive individuals before (Cohort A) and after (Cohort B) the availability of free ART in Zambia. Mutations present in sequences published in a previous study from Zambian ART-naive individuals infected with subtype C were analyzed using current parameters for the classification of ART drug resistance and compared with Cohort ...[more]

PMID: 20623996

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Project description:ObjectivesThere are limited data on the prevalence of doravirine (DOR)-associated drug resistance mutations in people with HIV (PWH) in Botswana. This cross-sectional, retrospective study aimed to explore the prevalence of DOR-associated resistance mutations among ART-naïve and -experienced PWH in Botswana enrolled in the population-based Botswana Combination Prevention Project (BCPP).MethodsA total of 6078 HIV-1C pol sequences were analysed for DOR-associated resistance mutations using the Stanford HIV drug resistance database, and their levels were predicted according to the Stanford DRM penalty scores and resistance interpretation. Virologic failure was defined as HIV-1 RNA load (VL) >400 copies/mL.ResultsAmong 6078 PWH, 5999 (99%) had known ART status, and 4529/5999 (79%) were on ART at time of sampling. The suppression rate among ART-experienced was 4517/4729 (96%). The overall prevalence of any DOR-associated resistance mutations was 181/1473 (12.3% [95% confidence interval {CI}: 10.7-14.1]); by ART status: 42/212 (19.8% [95% CI: 14.7-25.4]) among ART-failing individuals (VL ≥400 copies/mL) and 139/1261 (11.0% [95% CI: 9.3-12.9]) among ART-naïve individuals (P < 0.01). Intermediate DOR-associated resistance mutations were observed in 106/1261 (7.8% [95% CI: 6.9-10.1]) in ART-naïve individuals and 29/212 (13.7% [95% CI: 9.4-8.5]) among ART-experienced participants (P < 0.01). High-level DOR-associated resistance mutations were observed in 33/1261 (2.6% [95% CI: 1.8-3.7]) among ART-naïve and 13/212 (6.1% [95% CI: 3.6-10.8]) among ART-failing PWH (P < 0.01). PWH failing ART with at least one EFV/NVP-associated resistance mutation had high prevalence 13/67 (19.4%) of high-level DOR-associated resistance mutations.ConclusionDOR-associated mutations were rare (11.0%) among ART-naive PWH but present in 62.7% of Botswana individuals who failed NNRTI-based ART with at least one EFV/NVP-associated resistance mutation. Testing for HIV drug resistance should underpin the use of DOR in PWH who have taken first-generation NNRTIs.

Project description:BackgroundThe mass scale-up of antiretroviral therapy (ART) in Zambia has taken place in the context of limited infrastructure and human resources resulting in many operational side-effects. In this study, we aimed to empirically measure current workload of ART clinic staff and patient wait times and service utilization.MethodsWe conducted time and motion (TAM) studies from both the healthcare worker (HCW) and patient perspectives at 10 ART clinics throughout Zambia. Trained personnel recorded times for consecutive discrete activities based on direct observation of clinical and non-clinical activities performed by counselors, clinical officers, nurses, and pharmacy technicians. For patient TAM, we recruited consenting patients and recorded times of arrival and departure and major ART services utilized. Data from 10 clinics were pooled to evaluate median time per patient spent for each activity and patient duration of stay in the clinic.ResultsThe percentage of observed clinical time for direct patient interaction (median time per patient encounter) was 43.1% for ART counselors (4?min, interquartile range [IQR] 2-7), 46.1% for nurses (3?min, IQR 2-4), 57.2% for pharmacy technicians (2?min, IQR 1-2), and 78.5% for clinical officers (3?min, IQR 2-5). Patient workloads for HCWs were heaviest between 8?AM and 12?PM with few clinical activities observed after 2?PM. The length of patient visits was inversely associated with arrival time - patients arriving prior to 8?AM spent 61% longer at the clinic than those arriving after 8?AM (277 vs. 171?min). Overall, patients spent 219?min on average for non-clinical visits, and 244?min for clinical visits, but this difference was not significant in rural clinics. In comparison, total time patients spent directly with clinic staff were 9 and 12?min on average for non-clinical and clinical visits.ConclusionCurrent Zambian ART clinic operations include substantial inefficiencies for both patients and HCWs, with workloads heavily concentrated in the first few hours of clinic opening, limiting HCW and patient interaction time. Use of a differentiated care model may help to redistribute workloads during operational hours and prevent backlogs of patients waiting for hours before clinic opening, which may substantially improve ART delivery in the Zambian context.

Dataset Information

Short communication: antiretroviral therapy resistance mutations present in the HIV type 1 subtype C pol and env regions from therapy-naive patients in Zambia.

Publications

Short communication: antiretroviral therapy resistance mutations present in the HIV type 1 subtype C pol and env regions from therapy-naive patients in Zambia.

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