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Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis.

ABSTRACT: Antiretroviral therapy plays a major role in reducing the impact of Human Immunodeficiency Virus/Acquired Immune Disease Syndrome, especially in resource-limited settings. However, without proper infrastructure, it has resulted in emergence of drug resistance mutations in infected populations. To determine drug resistance mutations among patients attending a comprehensive care facility in Nairobi, 65 blood samples were successfully sequenced.Whole blood samples were also tested for CD4+T-cell count and plasma HIV-1 RNA Viral load. Drug-resistance testing targeting the HIV-1 RT gene was determined. Patients were on first line ART that consisted of two NRTIs, and one NNRTI.Females were younger (mean 42) than males (mean 45) and lower median CD4+ counts (139 cells/?l) than males (152 cells/?l). The prevalence of drug resistance mutations (any major mutation) in this population was 23.1% (15/65). Major NRTI mutations were detected in 11 patient samples, which included M184V (n = 6), M41L (n=3), D67N (n=2), K219Q (n=3) and T215F (n=2). Major NNRTI mutations were detected in 14 patient samples. They included K103N (n = 10), G190A (n = 1), Y181C (n = 1) and Y188L (n = 1).Presence of major mutations in this study calls for proper laboratory infrastructure to monitor treatment as well as regular appraisals of available regimens.

SUBMITTER: Kinyua JG

PROVIDER: S-EPMC6061825 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis.

Kinyua Joyceline Gaceri JG Lihana Raphael Wekesa RW Kiptoo Michael M Muasya Timothy T Odera Irene I Muiruri Patrick P Songok Elijah Maritim EM

The Pan African medical journal 20180402

<h4>Introduction</h4>Antiretroviral therapy plays a major role in reducing the impact of Human Immunodeficiency Virus/Acquired Immune Disease Syndrome, especially in resource-limited settings. However, without proper infrastructure, it has resulted in emergence of drug resistance mutations in infected populations. To determine drug resistance mutations among patients attending a comprehensive care facility in Nairobi, 65 blood samples were successfully sequenced.<h4>Methods</h4>Whole blood sampl ...[more]

PMID: 30061964

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Project description:BackgroundAn increasing number of people on antiretroviral therapy (ART) in sub-Saharan Africa has led to declines in HIV related morbidity and mortality. However, virologic failure (VF) and acquired drug resistance (ADR) may negatively affect these gains. This study describes the prevalence and correlates of HIV-1 VF and ADR among first-line ART experienced adults at a rural HIV clinic in Coastal Kenya.MethodsHIV-infected adults on first-line ART for ?6 months were cross-sectionally recruited between November 2008 and March 2011. The primary outcome was VF, defined as a one-off plasma viral load of ?400 copies/ml. The secondary outcome was ADR, defined as the presence of resistance associated mutations. Logistic regression and Fishers exact test were used to describe correlates of VF and ADR respectively.ResultsOf the 232 eligible participants on ART over a median duration of 13.9 months, 57 (24.6% [95% CI: 19.2 - 30.6]) had VF. Fifty-five viraemic samples were successfully amplified and sequenced. Of these, 29 (52.7% [95% CI: 38.8 - 66.3]) had at least one ADR, with 25 samples having dual-class resistance mutations. The most prevalent ADR mutations were the M184V (n?=?24), K103N/S (n?=?14) and Y181C/Y/I/V (n?=?8). Twenty-six of the 55 successfully amplified viraemic samples (47.3%) did not have any detectable resistance mutation. Younger age (15-34 vs. ?35 years: adjusted odd ratios [95% CI], p-value: 0.3 [0.1-0.6], p?=?0.002) and unsatisfactory adherence (<95% vs. ?95%: 3.0 [1.5-6.5], p?=?0.003) were strong correlates of VF. Younger age, unsatisfactory adherence and high viral load were also strong correlates of ADR.ConclusionsHigh levels of VF and ADR were observed in younger patients and those with unsatisfactory adherence. Youth-friendly ART initiatives and strengthened adherence support should be prioritized in this Coastal Kenyan setting. To prevent unnecessary/premature switches, targeted HIV drug resistance testing for patients with confirmed VF should be considered.

Project description:PURPOSE:Engaging in positive health behaviors post-treatment is important for cancer survivors' health. However, little is known about whether survivors are practicing health promoting behaviors. We aimed to explore whether survivors are meeting the recent health behavior guidelines set forth by the National Comprehensive Cancer Network (NCCN) and to examine associations between health behaviors and distress. METHODS:Sixty-six survivors completed a cross-sectional questionnaire assessing health behaviors prior to an initial appointment at a survivorship care clinic. Information about sociodemographic, clinical, and psychosocial variables and six health behavior recommendations, including physical activity, sunscreen use, tobacco use, alcohol consumption, weight management, and annual primary care provider visits, was collected. FINDINGS:Only 7.6% of survivors met all six NCCN health behavior guidelines. One in ten (10.6%) survivors had smoked a cigarette in the previous 30 days, and half did not use sunscreen regularly (50%), had an unhealthy body mass index (53%), and did not engage in >10 MET-h/week of physical activity (50%). Approximately 1 in 6 (15.1%) survivors reported drinking beyond the recommended limit, and a similar proportion had not seen a PCP in the previous year (27.3%). Clinically significant levels of distress (>5; range 0-10) on the NCCN distress scale were reported by 64.6% of survivors. Participants with clinical levels of distress were less likely to adhere to health behavior guidelines than those who were not distressed (p = .002). CONCLUSIONS:Overall, survivors engaged at a survivorship clinic did not meet the NCCN recommended health behavior guidelines. Implications for Psychosocial Providers or Policy: Survivors' health behaviors and distress should be assessed and intervened upon during survivorship care. Survivorship clinics may provide a unique forum in which to provide ongoing behavioral health counseling and psychosocial support for these patients.

Project description:BackgroundPeripheral neuropathy (PN) is a neurological complication of untreated Human Immunodeficiency Virus (HIV) infection or exposure to certain antiretroviral drugs. In Tanzania where HIV is a major public health problem, the burden of HIV associated peripheral neuropathy has not yet been well defined in children.Thisstudy investigated the prevalence and associated factors for peripheral neuropathy among children living with HIV, attending Care and Treatment Clinic (CTC) at Muhimbili National Hospital (MNH).Materials and methodsA cross-sectional study was conducted among 383 HIV positive children aged 5 to 18 years at MNH, CTC in Dar es Salaam between October to December 2019. All participants provided written assent/consent. Structured questionnaires designed for this study was used to collect data and screening for peripheral neuropathy was done on each participant using the Pediatric modified Total Neuropathy Score (Ped m TNS) that includes subjective and objective assessment. A score of 5 or greater on the Ped m TNS was used to define peripheral neuropathy. Data analysis was done using SPSS Version 23.ResultsThe prevalence of peripheral neuropathy among HIV infected children was 14.1 % (95 % CI (10.8 - 18 %). Common neuropathic symptoms were numbness, tingling sensation, reduced ankle reflexes and reduced sensation to light touch and pain that was limited to the toes. Low CD4 cell count (OR = 12.21; 95 % CI3.75-39.66; p = 0.0001), high viral load (OR = 10.54; 95 % CI 3.19-34.77; p = 0.0001), ART regime containing NRTI plus PI (OR = 3.93; 95 % CI 1.43- 10.74; p = 0.01) and the last exposure to isoniazid more than 6 months ago (OR = 3.71; 95 % CI 1.57-8.77; p = 0.003) were independent predictors for peripheral neuropathy.ConclusionPeripheral neuropathy is common among HIV infected children attending CTC at MNH and its frequency increases with advanced disease. The choice of ART regimen and other drugs for treating comorbid conditions should carefully be evaluated.

Project description:IntroductionThere are a limited number of paediatric antiretroviral drug options. Characterising the long term safety and durability of different antiretrovirals in children is important to optimise management of HIV infected children and to determine the estimated need for alternative drugs in paediatric regimens. We describe first-line antiretroviral therapy (ART) durability and reasons for discontinuations in children at two South African ART programmes, where lopinavir/ritonavir has been recommended for children <3 years old since 2004, and abacavir replaced stavudine as the preferred nucleoside reverse transcriptase inhibitor in 2010.MethodsWe included children (<16 years at ART initiation) who initiated ?3 antiretrovirals between 2004-2014 with ?1 follow-up visit on ART. We estimated the incidence of first antiretroviral discontinuation using Kaplan-Meier analysis. We determined the reasons for antiretroviral discontinuations using competing risks analysis. We used Cox regression to identify factors associated with treatment-limiting toxicity.ResultsWe included 3579 children with median follow-up duration of 41 months (IQR 14-72). At ART initiation, median age was 44 months (IQR 13-89) and median CD4 percent was 15% (IQR 9-21%). At three and five years on ART, 72% and 26% of children respectively remained on their initial regimen. By five years on ART, the most common reasons for discontinuations were toxicity (32%), treatment failure (18%), treatment simplification (5%), drug interactions (3%), and other or unspecified reasons (18%). The incidences of treatment limiting toxicity were 50.6 (95% CI 46.2-55.4), 1.6 (0.5-4.8), 2.0 (1.2-3.3), and 1.3 (0.6-2.8) per 1000 patient years for stavudine, abacavir, efavirenz and lopinavir/ritonavir respectively.ConclusionsWhile stavudine was associated with a high risk of treatment-limiting toxicity, abacavir, lopinavir/ritonavir and efavirenz were well-tolerated. This supports the World Health Organization recommendation to replace stavudine with abacavir or zidovudine in paediatric first-line ART regimens in order to improve paediatric first-line ART durability.

Project description: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.

Project description:Due to the limited availability of viral load testing for treatment outcome monitoring in resource limited settings, identifying predictive factors of antiretroviral treatment failure will help in selecting clients who will benefit most from the targeted use of viral load monitoring. Little is known about the predictors of treatment failure in the study area. This study was conducted to determine factors that predict first-line antiretroviral therapy failure among HIV-infected adult clients at Woldia Hospital, Northeast Ethiopia. For this study, antiretroviral therapy treatment failure was defined as the fulfillment of clinical and/or immunological criteria set by WHO.Case-control study was carried out from November to December 2014. Cases were adult clients who were on failing first line regimen and on active follow up while controls were those adult clients on a non-failing first-line regimen for 36 months and above and on active follow up. Data was entered in to Epi Info version 7 and was exported to SPSS version 20 for analysis. Binary logistic regression model was used to identify predictors of ART failure.A total of 59 cases and 245 controls were included in the analysis. Sixty three percent of the participants were females and the median age at ART enrollment was 33 years (IQR; 28, 40). The median baseline CD4count was not significantly different among cases and controls (105 (IQR = 60-174)vs.131 (IQR = 72.5-189.0); p = 0.301). The median peak CD4 count in the failure group (230 (IQR = 123-387)) was significantly low compared to the non-failure group (463 (IQR = 348.5-577)) [p < 0.001]. High peak CD4count (AOR = 0.993; 95% CI 0.990, 0.996) and longer duration on ART (AOR = 0.923; 95% CI 0.893, 0.954) were protective of treatment failure. In addition stavudine based regimen (AOR = 3.47; 95% CI 1.343, 10.555), low baseline BMI (AOR = 2.75; 95% CI 1.012, 7.457), unemployment (AOR = 4.93; 95% CI 1.493, 16.305) and formal educational level (AOR = 5.15; 95% CI 1.534, 17.276) were independently significant predictors of treatment failure.In this setting low peak CD4count, shorter duration on first line ART, d4T based regimen, low baseline BMI, unemployment and formal educational level were significantly associated with increased treatment failure. Retaining patients on their initial first line regimen with appropriate follow up and improving their socioeconomic status through various livelihood initiatives should be strengthened.

Dataset Information

Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis.

Publications

Antiretroviral resistance among HIV-1 patients on first-line therapy attending a comprehensive care clinic in Kenyatta National Hospital, Kenya: a retrospective analysis.

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