Dataset Information

Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014.

ABSTRACT: Background:Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort. Methods:We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ?2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184?V, or K65R by oligonucleotide ligation assay and Illumina sequencing. PDR prevalence was calculated by demographics and codon, stratifying by prior ARV experience. Poisson regression was used to estimate prevalence ratios. Results:PDR prevalences (95% confidence interval [CI]) in 815 ARV-naive adults, 136 ARV-experienced adults, and 36 predominantly ARV-naive children were 9.4% (7.5%-11.7%), 12.5% (7.5%-19.3%), and 2.8% (0.1%-14.5%), respectively. Median mutant frequency within an individual's HIV quasispecies was 67%. PDR prevalence in ARV-naive women 18-24 years old was 21.9% (9.3%-40.0%). Only age in females associated with PDR: A 5-year age decrease was associated with adjusted PDR prevalence ratio 1.20 (95% CI, 1.06-1.36; P = .004). Conclusions:The high PDR prevalence may warrant resistance testing and/or alternative ARVs in high HIV prevalence settings, with attention to young women, likely to have recent infection and higher rates of resistance. Clinical Trials Registration:NCT01898754.

SUBMITTER: Silverman RA

PROVIDER: S-EPMC5853791 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014.

Silverman Rachel A RA Beck Ingrid A IA Kiptinness Catherine C Levine Molly M Milne Ross R McGrath Christine J CJ Bii Steve S Richardson Barbra A BA John-Stewart Grace G Chohan Bhavna B Sakr Samah R SR Kiarie James N JN Frenkel Lisa M LM Chung Michael H MH

The Journal of infectious diseases 20171201 12

<h4>Background</h4>Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of human immunodeficiency virus (HIV) treatment failure. We determined PDR prevalence and correlates in a Kenyan cohort.<h4>Methods</h4>We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants. PDR was defined as ≥2% mutant frequency in a participant's HIV quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay and Illu ...[more]

PMID: 29040633

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Project description:Abstract Background Single-nucleotide polymorphisms (SNPs) in CYP2B6 have previously been associated with a 10-fold range in trough plasma efavirenz concentrations, but associations between these SNPs and efavirenz (EFV)-mediated viral suppression and tolerability remain unclear. Methods We evaluated three SNPs in CYP2B6 (rs3745274, rs28399499, and rs4803419, Illumina OmniExpress) among HIV-infected Ugandans observed in a cohort study every 3–4 months from 2005–2015. Genotypes from these SNPs were used to group participants into previously described pharmacokinetic strata: extensive (EXT), intermediate (INT), and slow metabolizers (Figure 1). The primary outcomes were viral suppression, defined by an undetectable viral load in the first measurement a minimum of three months after ART initiation, and incident depression in the first two years, defined by a mean score >1.75 on the Hopkins Symptom Checklist. We fitted standard and generalized estimating equations (GEE) logistic regression models for viral suppression and depression, respectively. Models were adjusted for clinical and demographic covariates that reached a significance of P < 0.25 in unadjusted models. Results Among 103 participants with genotyping, there were no differences in pre-ART viral load or depression by metabolism strata (P > 0.5). Minor allele frequencies for rs3745274, rs28399499, and rs4803419 were 33%, 7%, and 4%, respectively. Approximately 79%, 78%, and 94% of participants were suppressed at their first viral load measurement in the extensive, intermediate, and slow metabolizer strata, respectively (Figure 2; P = 0.35). In adjusted models, metabolism strata were not associated with viral suppression (AORINT 0.81, 95% CI 0.26–2.56; AORSLOW 3.92, 95% CI 0.39–39.40) or with depression (AORINT 1.95, 95% CI 0.75–5.09; AORSLOW 0.72, 95% CI 0.17–3.02; Table). Conclusion We did not identify an association between efavirenz-metabolizing polymorphisms and viral suppression or depression in a cohort of HIV-infected individuals initiating ART in southwestern Uganda. Future work should reassess these relationships with larger samples and longer-term outcomes and explore additional polymorphisms that may be associated with efavirenz metabolism in this population. Disclosures P. Hunt, Merck: Consultant, Consulting fee; Gilead: Consultant, Consulting fee; Viiv: Consultant, Consulting fee

Project description:BackgroundOutbreaks of methanol poisoning occur frequently on a global basis, affecting poor and vulnerable populations. Knowledge regarding methanol is limited, likely many cases and even outbreaks go unnoticed, with patients dying unnecessarily. We describe findings from the first three large outbreaks of methanol poisoning where Médecins Sans Frontières (MSF) responded, and evaluate the benefits of a possible future collaboration between local health authorities, a Non-Governmental Organisation and international expertise.MethodsRetrospective study of three major methanol outbreaks in Libya (2013) and Kenya (May and July 2014). Data were collected from MSF field personnel, local health personnel, hospital files, and media reports.FindingsIn Tripoli, Libya, over 1,000 patients were poisoned with a reported case fatality rate of 10% (101/1,066). In Kenya, two outbreaks resulted in approximately 341 and 126 patients, with case fatality rates of 29% (100/341) and 21% (26/126), respectively. MSF launched an emergency team with international experts, medications and equipment, however, the outbreaks were resolving by the time of arrival.InterpretationRecognition of an outbreak of methanol poisoning and diagnosis seem to be the most challenging tasks, with significant delay from time of first presentations to public health warnings being issued. In spite of the rapid response from an emergency team, the outbreaks were nearly concluded by the time of arrival. A major impact on the outcome was not seen, but large educational trainings were conducted to increase awareness and knowledge about methanol poisoning. Based on this training, MSF was able to send a local emergency team during the second outbreak, supporting that such an approach could improve outcomes. Basic training, simplified treatment protocols, point-of-care diagnostic tools, and early support when needed, are likely the most important components to impact the consequences of methanol poisoning outbreaks in these challenging contexts.

Project description:ObjectivesWe measured gender differences in "Quality of Care" (QOC) during the first year after initiation of antiretroviral therapy and investigated factors associated with poorer QOC among women.DesignQOC was estimated using the Programmatic Compliance Score (PCS), a validated metric associated with all-cause mortality, among all patients (≥19 years) who initiated ART in British Columbia, Canada (2000-2010).MethodsPCS includes six indicators of non-compliance with treatment initiation guidelines at baseline (not having drug resistance testing before treatment; starting on a non-recommended regimen; starting therapy at CD4<200 cells/mm3) and during first-year follow-up (receiving <3 CD4 tests; receiving <3 viral load tests; not achieving viral suppression within six months). Summary scores range from 0-6; higher scores indicate poorer QOC. Multivariable ordinal logistic regression was used to measure if female gender was an independent predictor of poorer QOC and factors associated with poorer QOC among women.ResultsQOC was determined for 3,642 patients (20% women). At baseline: 42% of women (34% men) did not have resistance testing before treatment; 17% of women (9% men) started on a non-recommended regimen (all p<0.001). At follow-up: 17% of women (11% men) received <3 CD4; 17% of women (11% men) received <3 VL; 50% of women (41% men) did not achieve viral suppression (all p<0.001). Overall, QOC was better among men (mean PSC = 1.54 (SD = 1.30)) compared with women (mean = 1.89 (SD = 1.37); p<0.001). In the multivariable model, female gender (AOR = 1.16 [95% CI: 0.99-1.35]; p = 0.062) remained associated with poorer QOC after covariate adjustment. Among women, those with injection drug use history, of Aboriginal ancestry, from Vancouver Island, and who initiated ART in earlier years were more likely to have poorer QOC.ConclusionsPoorer QOC among women, especially from marginalized communities, demands that barriers undermining women's access to high-quality care be addressed to improve treatment and health for women with HIV.

Project description:BACKGROUND:Metabolic complications in human immunodeficiency virus (HIV)-infected individuals are common. Prediabetes represents a high risk for future diabetes development. This study aimed to determine the prevalence, diagnostic methods, and associated factors of prediabetes among HIV-infected individuals receiving antiretroviral therapy (ART). METHODS:A cross-sectional study was conducted among HIV-infected adults without a history of diabetes who were receiving ART. Fasting plasma glucose (FPG), 2-hour plasma glucose (2-h PG) after a 75-g oral glucose tolerance test, and hemoglobin A1c (HbA1c) were assessed. RESULTS:A total of 397 patients with a mean age of 47.0?±?9.8 years and 55.7% male, were studied. All received ART with undetectable plasma viral load. The mean duration of ART was 9.6?±?5.2 years, and the mean CD4 cell count was 554?±?235 cells/mm3. Among the patients, 28 (7.1%) had first-diagnosed diabetes, and 133 (33.5%) patients had prediabetes. Glycemia estimation by FPG, 2-h PG, and HbA1c showed a prediabetes prevalence of 17.4%, 14.7%, and 12.5%, respectively. The kappa statistics for the agreement of FPG and 2-h PG, HbA1c and 2-h PG, and HbA1c and FPG were 0.317, 0.429, and 0.396, respectively. In multivariate analysis, hypertension [odds ratio (OR) 3.38; 95% confidence interval (CI), 1.16-9.91; p?=?0.026), and triglycerides?>?150 mg/dL (OR 2.11; 95% CI, 1.01-4.44; p?=?0.047) were factors significantly associated with prediabetes. CONCLUSIONS:Prediabetes among HIV-infected individuals receiving ART is common. The agreements of glycemia estimation methods are minimal to weak. HbA1c may underestimate prediabetes prevalence. Using FPG together with HbA1c increases the detection rate to approximately three-quarters of prediabetes patients. HIV-infected individuals who had hypertension and hypertriglyceridemia should be regularly assessed for prediabetes. Trial registration ClinicalTrial.gov, NCT03545217. Registered 1 June 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03545217.

Dataset Information

Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014.

Publications

Prevalence of Pre-antiretroviral-Treatment Drug Resistance by Gender, Age, and Other Factors in HIV-Infected Individuals Initiating Therapy in Kenya, 2013-2014.

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