The chronic inflammation induced by human immunodeficiency virus (HIV) contributes to increased risk of coronary heart disease (CHD) in HIV-infected individuals. HIV-infected patients generally benefit from being treated with antiretroviral drugs, but some antiretroviral agents have side effects, such as dyslipidemia and hyperglycemia. There is general consensus that antiretroviral drugs induce a long-term risk of CHD, although the levels of that risk are somewhat controversial. The intention of this cross-sectional study was to describe the lipid profile and the long-term risk of CHD among HIV-positive outpatients at an HIV treatment clinic in Harare, Zimbabwe. Two hundred and fifteen patients were investigated (females n=165, mean age 39.8 years; males n=50; mean age 42.0 years). Thirty of the individuals were antiretroviral-naïve and 185 had been on antiretroviral therapy (ART) for a mean 3.9±3.4 years. All participants had average lipid and glucose values within normal ranges, but there was a small difference between the ART and ART-for total cholesterol (TC) and high-density lipoprotein (HDL). Those on a combination of D4T or ZDV/NVP/3TC and PI-based ART were on average oldest and had the highest TC levels. Framingham risk showed 1.4% prevalence of high CHD risk within the next ten years. After univariate analysis age, sex, TC/HDL ratio, HDL, economic earnings and systolic BP were associated with medium to high risk of CHD. After multivariate regression analysis and adjusting for age or sex only age, sex and economic earnings were associated with medium to high risk of CHD. There is small risk of developing CHD, during the next decade in HIV infected patients at an HIV treatment clinic in Harare.
Introduction There have been very few randomized clinical trials of interventions for alcohol use disorders (AUD) in people living with HIV (PLWH) in African countries. This is despite the fact that alcohol use is one of the modifiable risk factors for poor virological control in PLWH on antiretroviral therapy. Methods Sixteen clinic clusters in Zimbabwe were selected through stratified randomization and randomized 1: 1 to Intervention and Control arms. Inclusion criteria for individual participants were being adult, living with HIV and a probable alcohol use disorder as defined by a score of 6 (women) or 7 (men) on the Alcohol Use Disorders Identification Test (AUDIT). In the Intervention clusters, participants received 8 to 10 sessions of Motivational Interviewing blended with brief Cognitive Behavioural Therapy (MI‐CBT). In the control clusters, participants received four Enhanced Usual Care (EUC) sessions based on the alcohol treatment module from the World Health Organisation mhGAP intervention guide. General Nurses from the clinics were trained to deliver both treatments. The primary outcome was a change in AUDIT score at six‐month post‐randomization. Viral load, functioning and quality of life were secondary outcomes. A random‐effects analysis‐of‐covariance model was used to account for the cluster design. Results Two hundred and thirty‐four participants (n = 108 intervention and n = 126 control) were enrolled across 16 clinics. Participants were recruited from November 2016 to November 2017 and followed through to May 2018. Their mean age was 43.3 years (SD = 9.1) and 78.6% (n = 184) were male. At six months, the mean AUDIT score fell by −6.15 (95% CI −6.32; −6.00) in the MI‐CBT arm, compared to a fall of − 3.09 95 % CI − 3.21; −2.93) in the EUC arm (mean difference −3.09 (95% CI −4.53 to −1.23) ( p = 0.05). Viral load reduced and quality of life and functioning improved in both arms but the difference between arms was non‐significant. Conclusions Interventions for hazardous drinking and AUD comprising brief, multiple alcohol treatment sessions delivered by nurses in public HIV facilities in low‐income African countries can reduce problematic drinking among PLWH. Such interventions should be integrated into the primary care management of AUD and HIV and delivered by non‐specialist providers. Research is needed on cost‐effectiveness and implementation of such interventions, and on validation of cut‐points for alcohol use scales in low resource settings, in partnership with those with lived experience of HIV and AUD.
The extremely high prevalence of HIV/AIDS in sub-Saharan Africa and limitations of current antiretroviral medicines demand new tools to optimize therapy such as pharmacogenomics for person-toperson variations. African populations exhibit greater genetic diversity than other world populations, thus making it difficult to extrapolate findings from one population to another. Nevirapine, an antiretroviral medicine, displays large plasma concentration variability which adversely impacts therapeutic virological response. This study, therefore, aimed to identify sources of variability in nevirapine pharmacokinetics and pharmacodynamics, focusing on genetic variation in CYP2B6 and CYP1A2. Using a cross-sectional study design, 118 HIV-infected adult Zimbabwean patients on nevirapine-containing highly active antiretroviral therapy (HAART) were characterized for three key functional single nucleotide polymorphisms (SNPs), CYP2B6 c.516G>T (rs3745274), CYP2B6 c.983T>C (rs28399499), and CYP1A2 g.-163C>A (rs762551). We investigated whether genotypes at these loci were associated with nevirapine plasma concentration, a therapeutic biomarker, and CD4 cell count, a biomarker of disease progression. CYP2B6 and CYP1A2 were chosen as the candidate genes based on reports in literature, as well as their prominence in the metabolism of efavirenz, a drug in the same class with nevirapine. Nevirapine plasma concentration was determined using LC-MS/MS. The mean nevirapine concentration for CYP2B6 c.516T/T genotype differed significantly from that of 516G/G ( p < 0.001) and 516G/T ( p < 0.01) genotypes, respectively. There were also significant differences in mean nevirapine concentration between CYP2B6 c.983T > C genotypes ( p = 0.04). Importantly, the CYP1A2 g.-163C>A SNP was significantly associated with the pharmacodynamics endpoint, the CD4 cell count ( p = 0.012). Variant allele frequencies for the three SNPs observed in this Zimbabwean group were similar to other African population groups but different to observations among Caucasian and Asian populations. We conclude that CYP2B6 c.516G>T and CYP2B6 c.983T>C could be important sources of nevirapine pharmacokinetic variability that could be considered for dosage optimization, while CYP1A2 g.-163C>A seems to be associated with HIV disease progression. These inter-and intra-population pharmacokinetic and pharmacodynamics differences suggest that a single prescribed dosage may not be appropriate for the treatment of disease. Further research into a personalized nevirapine regimen is required.
HIV infection, together with ART, is associated with changes in biochemical, metabolic parameters and lipid profiles. The aim of this study was to compare changes in lipid profiles among HIV positive outpatients over nine months. 171 patients were investigated, 79% were ART experienced, and 82% of ART experienced patients were on NVP/EFV first line at baseline, but some patients changed ART groups over follow-up and classification was based on intent to treat. More than 60% ART naïve and ART experienced patients had some form of dyslipidemia either at baseline or at follow-up, but mean lipid values for the two groups were within normal limits. At baseline and follow-up, mean levels of TC and HDL were slightly higher in the ART experienced group. Interestingly, there was higher increase in HDL over time in the ART negative group compared to the ART positive group. There was a decrease in TC/HDL ratio in both groups over time, suggesting a reduction in calculated risk of CHD over time. HIV positive patients frequently show various forms of dyslipidemia, but there are no changes in average atherogenic lipid levels and results suggest reduced risk of CHD, mainly due to increases in HDL, after nine months of observation time.
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