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1.
BMC Genomics ; 25(1): 718, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39054474

RESUMEN

INTRODUCTION: Our understanding of particular gut microbiota members such as Bifidobacterium and Enterococcus in low-middle-income countries remains very limited, particularly early life strain-level beneficial traits. This study addresses this gap by exploring a collection of bacterial strains isolated from the gut of Zimbabwean infants; comparing their genomic characteristics with strains isolated from infants across North America, Europe, and other regions of Africa. MATERIALS AND METHOD: From 110 infant stool samples collected in Harare, Zimbabwe, 20 randomly selected samples were used to isolate dominant early-life gut microbiota members Bifidobacterium and Enterococcus. Isolated strains were subjected to whole genome sequencing and bioinformatics analysis including functional annotation of carbohydrates, human milk oligosaccharide (HMO) and protein degradation genes and clusters, and the presence of antibiotic resistance genes (ARGs). RESULTS: The study observed some location-based clustering within the main five identified taxonomic groups. Furthermore, there were varying and overall species-specific numbers of genes belonging to different GH families encoded within the analysed dataset. Additionally, distinct strain- and species-specific variances were identified in the potential of Bifidobacterium for metabolizing HMOs. Analysis of putative protease activity indicated a consistent presence of gamma-glutamyl hydrolases in Bifidobacterium, while Enterococcus genomes exhibited a high abundance of aspartyl peptidases. Both genera harboured resistance genes against multiple classes of antimicrobial drugs, with Enterococcus genomes containing a higher number of ARGs compared to Bifidobacterium, on average. CONCLUSION: This study identified promising probiotic strains within Zimbabwean isolates, offering the potential for early-life diet and microbial therapies. However, the presence of antibiotic resistance genes in infant-associated microbes raises concerns for infection risk and next-stage probiotic development. Further investigation in larger cohorts, particularly in regions with limited existing data on antibiotic and probiotic use, is crucial to validate these initial insights. IMPACT STATEMENT: This research represents the first investigation of its kind in the Zimbabwean context, focusing on potential probiotic strains within the early-life gut microbiota. By identifying local probiotic strains, this research can contribute to the development of probiotic interventions that are tailored to the Zimbabwean population, which can help address local health challenges and promote better health outcomes for infants. Another essential aspect of the study is the investigation of antimicrobial resistance genes present in Zimbabwean bacterial strains. Antimicrobial resistance is a significant global health concern, and understanding the prevalence and distribution of resistance genes in different regions can help inform public health policies and interventions.


Asunto(s)
Bifidobacterium , Enterococcus , Microbioma Gastrointestinal , Humanos , Zimbabwe , Lactante , Microbioma Gastrointestinal/genética , Enterococcus/genética , Enterococcus/efectos de los fármacos , Enterococcus/aislamiento & purificación , Bifidobacterium/genética , Bifidobacterium/aislamiento & purificación , Bifidobacterium/efectos de los fármacos , Genómica , Genoma Bacteriano , Heces/microbiología , Secuenciación Completa del Genoma , Estudios de Cohortes , Filogenia
2.
Oncol Rev ; 18: 1375291, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38707485

RESUMEN

Diffuse large B-cell lymphoma (DLBCL) accounts for half of non-Hodgkin lymphoma cases in people living with human immunodeficiency syndrome (PLWH). The interplay of viremia, immune dysregulation and co-infection with oncogenic viruses play a role in pathogenesis of DLBCL in PLWH (HIV-DLBCL). This scoping review aimed to describe the molecular landscape of HIV-DLBCL, investigate the impact of biomarker on clinical outcomes and describe technologies used to characterise HIV-DLBCL. Thirty-two papers published between 2001 and 2023 were included in this review. Samples of HIV-DLBCL were relatively small (16-110). Cohort effects influenced frequencies of molecular characteristics hence their impact on survival was not clear. Molecular features were distinct from HIV-unrelated DLBCL. The most frequently assessed characteristic was cell of origin (81.3% of studies). Somatic mutations were the least researched (6.3% of studies). Overall, biomarker identification in HIV-DLBCL requires broader richer data from larger or pooled samples using more powerful techniques such as next-generation sequencing.

3.
Pediatric Health Med Ther ; 14: 483-496, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38145055

RESUMEN

Background: Gut microbiota play a key role in host health, with certain Bifidobacterium strains critical for immune development. The healthy gut of breastfed infants is dominated by these pioneer microbes, especially the strains that feed on human milk oligosaccharides. Objective: This is a scoping review of gut microbiome research from Zimbabwe. It focuses on distribution and dynamic changes of bifidobacteria, and milk components that promote growth of microbes in infants, together with the distribution of associated gut microbes in adults. Design: Online databases were searched for publications from 2000 to 2023. Results and Analysis: Fourteen publications on microbiota of infants and adults were included in this scoping review. Most were cross-sectional, while three were clinical trials/cohort protocols. Publications focused on pediatrics (78.5%), pregnant women (14.3%), and men (7.2%). Zimbabwe has a high burden of HIV; hence 35.7% of study populations were delineated by HIV status. The laboratory methods used included shotgun metagenomics (62%) or 16S rRNA gene amplicon sequencing. Almost 85% of the studies focused on total microbiome profiles and rarely reported the distribution of different Bifidobacterium species and variants. None of the papers studied human breast milk composition. There were reports of reduced abundance of beneficial genera in pregnant women, children, and adolescents living with HIV. Additionally, gut microbiota was reported to be poorly predictive of child growth and vaccine response, though this was not conclusive. Conclusion: There are few studies that characterize the gut microbiome by Zimbabwe-based researchers. However, studies on strain level diversity of Bifidobacterium and other key microbes, and their role in health during and beyond infancy, lag behind in Zimbabwe and other low- and middle-income countries. Such cohorts are needed to inform future mechanistic studies and downstream translational work such as next-generation probiotics and prebiotics.

4.
PLoS One ; 16(5): e0252180, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34043718

RESUMEN

INTRODUCTION: The incidence of non-communicable diseases (NCDs) has been reported to be rising over the years leading up to 2010. In Zimbabwe, there are few studies done to examine the incidence of NCDs in people living with HIV (PLHIV) on anti-retroviral treatment (ART). OBJECTIVE: To determine the incidence of NCDs in HIV patients on ART at the Chitungwiza Central Hospital over ten years and the associated risk factors. METHODS: This was a retrospective cohort study using data from 203 patients enrolled on ART at the Chitungwiza Central Hospital between 2010 and 2019. All 500 records were considered and the selection was based on participants' consenting to the study and their strict adherence to ART without absconding. The incidence of NCDs was determined and generalized estimating equations (GEE) were used to estimate the association between NCDs and the selected risk factors. FINDINGS: Data collected at the study's baseline (2010) showed that the most prevalent NCD was hypertension, found in (18/203) 8.9% of the study participants, followed by diabetes (6.9%), then followed by cardiovascular diseases (CVD) (3.9%), and the least common NCD was cancer (1.9%). Incidences of all of these NCDs showed an increasing trend as the time of follow-up progressed. The factors found to be significantly associated with the development of NCDs were gender (p = 0.002) and follow-up time (p<0.001). Geographical location was a significant risk factor as urban patients were more likely to develop hypertension as compared to the peri-urban patients (p = 0.001). CONCLUSIONS: NCDs and HIV comorbidity is common with women more likely than males to develop NCDs as they advance in age. There is need to devise targeted intervention approach to the respective NCDs and risk factors since they affect differently in relation to the demographic details of the participants. RECOMMENDATIONS: This paper recommends a multi-stakeholder approach to the management of NCDs, with researchers, clinicians and the government and its various arms taking a leading role.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus/epidemiología , Infecciones por VIH/epidemiología , Hipertensión/epidemiología , Enfermedades no Transmisibles/epidemiología , Adulto , Comorbilidad , Países en Desarrollo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Adulto Joven , Zimbabwe/epidemiología
5.
J Int AIDS Soc ; 23(12): e25641, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33314786

RESUMEN

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.


Asunto(s)
Alcoholismo/terapia , Infecciones por VIH/psicología , Intervención Psicosocial , Adulto , Terapia Cognitivo-Conductual , Femenino , Humanos , Masculino , Persona de Mediana Edad , Entrevista Motivacional , Enfermeras y Enfermeros
6.
BMC Infect Dis ; 19(1): 219, 2019 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-30832614

RESUMEN

BACKGROUND: Schistosomiasis is a devastating parasitic disease. The mainstay of schistosomiasis control is by praziquantel treatment. The study aimed to determine benefits of annual chemotherapy of schistosomiasis on development of protective immunity in school children in a selected endemic rural area in Zimbabwe. METHODS: Urine specimens from 212 school children (7-13 years) were collected and examined to determine prevalence, intensity and reinfection of S.haematobium at baseline, 6 weeks and 2 years following annual rounds of praziquantel treatment. Blood samples from the participants were assayed for total and S. haematobium (Sh13)-specific antibodies before and 2 years after annual rounds of treatment. RESULTS: Annual treatment reduced the prevalence of S. haematobium infection (p < 0.05) from 23.1% at baseline to 0.47% after 2 years. Overall cure rate was 97.8%. Intensity of infection declined (p < 0.05) from 15.9 eggs/10 ml urine at baseline to 2 eggs/10 ml urine. After two years, overall rate of reinfection was 0.96%. At baseline, total IgG4 was higher in S. haematobium-infected children (p = 0.042) ,while all other immunoglobulins were within normal ranges. There was an increase in total IgG2 (p = 0.044) levels and a decrease in total IgG4 (p = 0.031) levels 2 years post-treatment; and no significant changes in other total immunoglobulins. Schistosoma-infected children at baseline showed an increase in anti-Sh13 IgG1 (p = 0.005) and a decrease in Sh13 IgG4 levels (p = 0.012) following treatment. CONCLUSION: Annual praziquantel treatment delivered to school children over 2 years significantly reduce prevalence, intensity of infection and reinfection of S. haematobium infection. Treatment was also observed to cause a reduction in schistosome-specific blocking IgG4 and an increase in Schistosoma-specific protecting IgG1.


Asunto(s)
Inmunidad Adaptativa , Antihelmínticos/uso terapéutico , Esquistosomiasis Urinaria/tratamiento farmacológico , Adolescente , Animales , Anticuerpos Antihelmínticos/sangre , Niño , Femenino , Hematuria/patología , Hematuria/orina , Humanos , Inmunoglobulina G/metabolismo , Isotipos de Inmunoglobulinas/sangre , Estudios Longitudinales , Masculino , Óvulo/citología , Praziquantel/uso terapéutico , Prevalencia , Schistosoma haematobium/crecimiento & desarrollo , Schistosoma haematobium/inmunología , Esquistosomiasis Urinaria/epidemiología , Esquistosomiasis Urinaria/inmunología , Resultado del Tratamiento , Zimbabwe/epidemiología
7.
J Public Health Afr ; 10(2): 1081, 2019 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-32257079

RESUMEN

Low-and-middle-income countries (LMICs) have high disease burdens, necessitating increased research. However, LMIC research output constitutes only 2% of global total. To increase output, researchers must be capacitated. The University of Zimbabwe (UZ) and the University at Buffalo (UB), developed and implemented the AIDS International Research Training Program (AITRP), in 2008, that focused on graduate scholars. The subsequent HIV Research Training Program (HRTP), begun in 2016, and piloted post-doctoral training to enhance research productivity at UZ. This report discusses the collaboration. As of 2016, prospective candidates applied by submitting letters of intent, research proposals, curriculum vitae and biographical sketches. The scholars research training included hypothesis and project development, completion of grant applications, research project budgets, research presentations to diverse audiences and the application of advanced statistics to research data. The first cohort of five postdoctoral scholars were trained at UZ and UB, between 2016 and 2019. Through the formalized postdoctoral training approach, scholars identified areas of focus. In 2017, one of the scholars obtained a National Institutes of Health (NIH) Emerging Global Leader Award and is now a highly-rated researcher based in South Africa. A second scholar made NIH D43 and K43 grant applications, while the remaining three are academicians and early researchers at UZ. Although research output in Africa and many LMICs is low, it can be built through cooperation similar to the UZ-UB HRTP. This manuscript reports on an effort aimed at building individual and institutional research capacity in Zimbabwe. This can serve as a model for building other similar training programs.

8.
Open Microbiol J ; 11: 45-52, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28553415

RESUMEN

BACKGROUND: Antiretroviral therapy (ART) to suppress HIV replication has reduced morbidity and mortality yet effectiveness of current HIV drugs is threatened by HIV drug resistance (HIVDR) mutations. OBJECTIVE: To determine HIVDR mutations using proviral DNA from specimens of patients presenting to an HIV treatment clinic. METHODS: DNA from 103 patients, 86 treatment-experienced, 17 treatment-naïve, were genotyped for the HIV-1C reverse transcriptase gene (RT; codons 21-304) using Sanger sequencing and sequences analyzed using Sequencher software. Resistance mutations were interpreted using Stanford HIVDR reference database. RESULTS: Median age was 39 (IQR, 33-46) years and 80% of patients were female. Six-percent (n=6) had at least one HIVDR mutation, comprising NRTI-associated mutations, (M184V, T69D, T69N and V75I); NNRTI-associated mutations (G190A, K103N, V106M, Y181C) and thymidine analogue associated mutations (D67N, K70R, K219Q, L210W, M41L, T215Y). Of the six participants, with at least one HIVDR mutation, all were treatment experienced, five were on tenofovir, lamivudine and nevirapine and one was on tenofovir, lamivudine and atazanavir. There was no difference in median CD4 count and viral loads when patients were compared by presence of HIVDR mutations. CONCLUSION: We demonstrated the use of proviral DNA in HIVDR testing in adult patients and present that all the patients with various kinds of HIVDR mutations were treatment experienced, pointing to the role of drug regimens in driving viral mutations. Thus, the use of proviral DNA has potential to help provide surveillance on risk of HIVDR in HIV-infected individuals who are on treatment, which may assist in corrective treatment.

9.
Open Biochem J ; 11: 105-118, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29387269

RESUMEN

BACKGROUND: Recent evidence suggests that HIV infection, even with treatment, increases the risk of coronary heart disease (CHD) and that both chronic inflammation and traditional risk factors play key roles in HIV-associated CHD. SUBJECTS AND METHODS: Patients (N=152), attending Harare HIV clinic, 26% of them male and 82% of them on antiretroviral therapy (ART), were studied. Inflammatory markers comprising of cytokines such as pro-inflammatory tumor necrosis factor-α, (TNF-α), anti-inflammatory interleukin 10, (IL-10) and highly sensitive C reactive protein (hsCRP) together with lipids were assayed using enzyme linked immunosorbent assay (ELISA), immuno-turbidimetric and enzymatic assays, respectively. Correlation analysis of inflammatory markers versus lipid profiles was carried out using bivariate regression analysis. RESULTS: Anti-inflammatory cytokine IL-10 and inflammatory hsCRP levels were elevated when measured in all the HIV positive patients, while TNF-α and lipid levels were within normal ranges. Pro-inflammatory TNF-α was significantly higher in ART-naive patients than ART-experienced patients, whereas the reverse was observed for anti-inflammatory IL-10 and anti-atherogenic HDL-C. Correlation analysis indicated a significant positive linear association between IL-10 and total cholesterol (TC) levels but no other correlations were found. CONCLUSION: High cytokine ratio (TNF-α/IL-10) indicates higher CHD risk in ART-naive patients compared to the ART-exposed. The CHD risk could be further strengthened by interplay between inflammatory markers and high prevalence of low HDL-C. Lack of correlation between pro-inflammatory markers (hsCRP and TNF-α) with lipid fractions and correlation between anti-inflammatory IL-10 with artherogenic TC were unexpected findings, necessitating further studies in future.

10.
HIV AIDS (Auckl) ; 8: 165-174, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27822124

RESUMEN

Dyslipidemia, hypertension, inflammation, and coronary heart disease (CHD) are adverse events in human immunodeficiency virus (HIV)-infected patients even if they are receiving antiretroviral therapy (ART). Yet, data on CHD risk induced by HIV or ART in sub-Saharan Africa are limited. The aim of this longitudinal study was to describe changes in CHD risk profiles measured by lipids, inflammatory markers, and Framingham scores among HIV-positive patients previously reported from Harare, Zimbabwe. Patients were grouped into ART-experienced patients (n=147) and ART-naïve patients (n=23) and followed up for 9 months. Generalized least squares random-effects modeling was applied to explain changes in total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein, TC/HDL ratio, myeloperoxidase, highly sensitive C-reactive protein, and Framingham scores over the 9-month period. Independent variables included age, sex, monthly earning, body mass index, systolic blood pressure (SBP), diastolic blood pressure, duration of HIV diagnosis, duration of ART, viral load, and CD4 count. In ART-experienced patients, there was a substantial decrease in TC over time, ART-negative patients showed a significant increase in TC and HDL over time, and the increase in TC was associated with high viral load and low duration of HIV diagnosis, while increase in HDL was associated with young age, low body mass index, and low SBP. Framingham risk scores increased with time in ART-positive patients, and the change was positively correlated with age, sex, high SBP, and low HDL. There was no association between calculated CHD risk (TC/HDL ratio or Framingham score) and changes in levels of inflammatory markers (myeloperoxidase and highly sensitive C-reactive protein) in any of the patient groups. In conclusion, ART-experienced HIV-positive patients show changes in lipid values over time that makes it necessary to include lipid monitoring in order to reduce any risk of long-term CHD.

11.
Open AIDS J ; 10: 190-198, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27790293

RESUMEN

BACKGROUND: Dyslipidemia does not occur in all HIV-infected or antiretroviral therapy-experienced patients suggesting role of host genetic factors but there is paucity of data on association between dyslipidemia and gene polymorphisms in Zimbabwe. OBJECTIVE: To determine association of lipoprotein levels and apolipoprotein B polymorphisms in HIV-infected adults. METHOD: Demographic data were collected from 103 consenting patients; lipoprotein levels were determined and blood samples were successfully genotyped for both apolipoprotein B 2488C>T Xba1 and apolipoprotein B 4154G>A p.Gln4154Lys EcoR1 polymorphisms by real time polymerase chain reaction. RESULTS: Mean age of genotyped patients was 40.3 ± 10.1 years, 68% were female; prevalence of dyslipidemia was 67.4%. Of 103 samples genotyped for apolipoprotein B Xba1 polymorphism, 76 (74%) were homozygous C/C, 24 (23%) were heterozygous C/T and only three (3%) were homozygous T/T. Apolipoprotein B EcoR1 polymorphism showed little variability, one participant had rare genotype A/A, 68.3% had wild type genotype G/G. CONCLUSION: Observed frequencies of apolipoprotein B XbaI and EcoRI polymorphisms matched other African studies. In spite of low numbers of rare variants, there was positive association between both total cholestrol and high density lipoprotein with ECoR1 wild type G/G genotype, suggesting that ECoRI 4154 G allele could be more protective against coronary heart disease than EcoR1 4154 A allele. There is need for further research at population level to confirm whether apolipoprotein B ECoR1 genotyping is useful for predicting risk of dyslipidemia in HIV patients in our setting.

12.
Biochem Res Int ; 2016: 3204818, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27051532

RESUMEN

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.

13.
OMICS ; 19(9): 553-62, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26348712

RESUMEN

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-to-person 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.


Asunto(s)
Citocromo P-450 CYP1A2/genética , Citocromo P-450 CYP2B6/genética , Infecciones por VIH/sangre , Infecciones por VIH/tratamiento farmacológico , Nevirapina/sangre , Nevirapina/farmacocinética , Adulto , Fármacos Anti-VIH/sangre , Fármacos Anti-VIH/farmacocinética , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Estudios Transversales , Femenino , Frecuencia de los Genes , Variación Genética/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Nevirapina/uso terapéutico
14.
HIV AIDS (Auckl) ; 7: 145-55, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25999764

RESUMEN

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.

15.
ISRN AIDS ; 2013: 383214, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24093073

RESUMEN

Antiretroviral therapy inhibits HIV replication, maintains health, and preserves life. However, both antiretroviral therapy and HIV infection have been reported to have short- and long-term effects on bone metabolism. A cross-sectional study was performed to compare serum bone profiles in HIV positive patients on highly active antiretroviral therapy and compare them to therapy-naïve patients. Serum levels of calcium, magnesium, phosphate, and albumin were measured in 40 female participants on highly active antiretroviral therapy, recruited sequentially from Parirenyatwa Opportunistic Infections Clinic, Harare, Zimbabwe. The 40 women were matched for age with 40 antiretroviral therapy-naïve women. Magnesium, phosphate, and albumin levels were significantly higher in the therapy-naïve than in therapy-experienced patients. There was no statistically significant difference in calcium levels of the two groups of women. Evidence from this study suggests that highly active antiretroviral therapy lowers levels of magnesium, phosphate, and albumin but has no effect on levels of serum calcium.

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