ABSTRACT
INTRODUCTION: Men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa (SSA) are profoundly affected by HIV with high HIV prevalence and incidence. This population also faces strong social stigma and legal barriers, potentially impeding participation in research. To date, few multi-country longitudinal HIV research studies with MSM/TGW have been conducted in SSA. Primary objective of the HIV Prevention Trials Network (HPTN) 075 study was to assess feasibility of recruiting and retaining a multinational prospective cohort of MSM/TGW in SSA for HIV prevention research. METHODS: HPTN 075, conducted from 2015 to 2017, was designed to enroll 400 MSM/TGW at four sites in SSA (100 per site: Kisumu, Kenya; Blantyre, Malawi; Cape Town, South Africa; and Soweto, South Africa). The number of HIV-positive persons was capped at 20 per site; HIV-positive persons already in care were excluded from participation. The one-year study included five biobehavioural assessments. Community-based input and risk mitigation protocols were included in study design and conduct. RESULTS: Of 624 persons screened, 401 were enrolled. One in five participants was classified as transgender. Main reasons for ineligibility included: (a) being HIV positive after the cap was reached (29.6%); (b) not reporting anal intercourse with a man in the preceding three months (20.6%); and (c) being HIV positive and already in care (17.5%). Five (1.2%) participants died during the study (unrelated to study participation). 92.9% of the eligible participants (368/396) completed the final study visit and 86.1% participated in all visits. The main, overlapping reasons for early termination included being (a) unable to adhere to the visit schedule, predominantly because of relocation (46.4%), and (b) unable to contact the participant (32.1%). Participants reported strong motivation to participate and few participation barriers. Four participants reported social harms (loss of confidentiality and sexual harassment by study staff) that were successfully addressed. CONCLUSIONS: HPTN 075 successfully enrolled a multinational sample of MSM/TGW in SSA in a prospective HIV prevention research study with a high retention rate and few documented social harms. This supports the feasibility of conducting large-scale research trials in this population to address its urgent, unmet HIV prevention needs.
Subject(s)
HIV Infections/prevention & control , Homosexuality, Male , Patient Acceptance of Health Care , Patient Selection , Sexual and Gender Minorities , Transgender Persons , Adolescent , Adult , Africa South of the Sahara , Cohort Studies , Feasibility Studies , Female , Humans , Malawi , Male , Prospective Studies , Social Stigma , Young AdultABSTRACT
OBJECTIVE: Decreasing the risk of HIV transmission from HIV-positive individuals is an important public health priority. We evaluated the effectiveness of a computer-based sexual risk reduction counseling intervention (CARE+) among HIV-positive persons enrolled in care. METHODS: HIV-positive eligible participants (N=1075) were enrolled from 11 care sites in the Bronx, NY and Washington, DC and randomized 1:1 to either a tablet-based self-administered CARE+ intervention or standard of care (SOC). The primary outcome was the proportion of participants reporting any unprotected vaginal/anal sex at last sex, among all partners, HIV-negative or HIV-unknown-status partners and for primary and non-primary partners. RESULTS: At baseline, 7% of participants in both arms reported unprotected sex with an HIV-negative or HIV-unknown-status partner, while 13% in the CARE+ arm and 17% in the SOC arm reported unprotected sex with any partner. Most participants (88%) were on antiretroviral therapy (ART) at baseline. There was no significant difference in changes over time in unprotected vaginal/anal sex between the CARE+ and SOC arms for any partners (p=0.67) or either HIV-negative or HIV-unknown-status partners (p=0.40). At the Month 12 visit, most participants (85%) either strongly agreed or agreed that computer counseling would be a good addition to in-person counseling by a provider. CONCLUSION: The CARE+ intervention was not effective at reducing sexual risk behaviors among HIV-positive patients in care, most of whom were on ART. Further research may be warranted around the utility of computer-based counseling for HIV prevention.
ABSTRACT
AIM: The purpose of the study was to assess whether ex vivo measures of low-density lipoprotein (LDL) oxidation improved prediction of carotid artery disease (CAAD) case-control status compared to standard lipid and smoking measures. METHODS: One hundred and forty cases with a high degree of carotid artery stenosis aged 40-83 years and an equal number of controls without stenosis or other vascular disease were matched by censored age within 2 years. Matched logistic regression evaluated the significance of copper-induced oxidative measures with and without covariates. The relationship of LDL oxidation measures with statin use and current smoking was also evaluated. RESULTS: Logistic regression demonstrated a significant effect of the three correlated measures of oxidative susceptibility (lag time, oxidation rate and maximal rate of oxidation) separately on disease prediction (all p<0.05). These oxidative measures remained significant predictors of case-control status when other cardiovascular disease predictors (age; LDL-C, HDL-C and ApoAI levels; current smoking, ever smoking and pack-years smoked) were jointly considered. This relationship was not attributable to the effects of statin use on LDL oxidation. CONCLUSIONS: Ex vivo measures of oxidation improved the prediction of carotid artery disease status, suggesting that this is an important determinant of atherosclerotic risk in this older population.
Subject(s)
Carotid Artery Diseases/epidemiology , Carotid Artery Diseases/metabolism , Cholesterol, LDL/metabolism , Adult , Aged , Aged, 80 and over , Carotid Artery Diseases/diagnosis , Carotid Stenosis/diagnosis , Carotid Stenosis/epidemiology , Carotid Stenosis/metabolism , Case-Control Studies , Humans , Logistic Models , Male , Middle Aged , Oxidation-Reduction , Predictive Value of Tests , Risk Factors , Smoking/epidemiologyABSTRACT
OBJECTIVE: Paraoxonase (PON1), an esterase physically associated with high density lipoprotein, has been shown to inhibit atherogenic low density lipoprotein and high density lipoprotein oxidation. PON1 activity appears to be primarily under genetic control with some environmental modification and is a predictor of vascular disease. Vitamins C and E, dietary antioxidants, scavenge free-oxygen radical products that may depress PON1 activity. Therefore, we evaluated the relationship between dietary vitamin C and E intake and PON1 activity. METHODS AND RESULTS: The vitamin C and E intakes of male white subjects (n=189) were estimated by using a standardized food frequency survey. With covariates, vitamin C or E intakes were found to be significant positive predictors of PON1 activity for the hydrolysis of paraoxon and diazoxon with the use of linear regression. Smoking and use of statins were independent predictors of PON1 activity. CONCLUSIONS: PON1 activity, which is primarily genotype dependent, varies with antioxidant vitamins, cigarette smoking, and statin drug use. Because PON1 activity is a better predictor of vascular disease than is the currently described genetic variation in PON1, further studies of the environmental influences on PON1 activity and additional PON1 genetic variants are warranted.
Subject(s)
Ascorbic Acid/administration & dosage , Diet , Esterases/metabolism , Vitamin E/administration & dosage , Aged , Aged, 80 and over , Arteriosclerosis/metabolism , Arteriosclerosis/prevention & control , Aryldialkylphosphatase , Cholesterol, HDL/metabolism , Cholesterol, LDL/metabolism , Esterases/genetics , Genotype , Humans , Hypolipidemic Agents/therapeutic use , Lipid Peroxidation , Male , Middle Aged , Smoking/adverse effectsABSTRACT
The genetic factors associated with carotid artery disease (CAAD) are not fully known. Because of its role in lipid metabolism, we hypothesized that common genetic variation in the very low density lipoprotein receptor (VLDLR) gene is associated with severe CAAD (>80% stenosis), body mass index (BMI), and lipid traits in humans. VLDLR was resequenced for variation discovery in 92 subjects, and single nucleotide polymorphisms (tagSNPs) were chosen for genotyping in a larger cohort (n = 1,027). Of the 17 tagSNPs genotyped, one tagSNP (SNP 1226; rs1454626) located in the 5' flanking region of VLDLR was associated with CAAD, BMI, and LDL-associated apolipoprotein B (apoB). We also identified receptor-ligand genetic interactions between VLDLR 1226 and APOE genotype for predicting CAAD case status. These findings may further our understanding of VLDLR function, its ligand APOE, and ultimately the pathogenesis of CAAD in the general population.
Subject(s)
Apolipoproteins E/genetics , Carotid Artery Diseases/genetics , Polymorphism, Single Nucleotide , Receptors, LDL/genetics , 5' Flanking Region , Apolipoproteins B , Body Mass Index , DNA Mutational Analysis , Genetic Predisposition to Disease , Genotype , Humans , Molecular Epidemiology , Risk FactorsABSTRACT
OBJECTIVE: We evaluated if receiving HIV test results over the telephone was associated with a change in the number of persons who received results. STUDY DESIGN: Data were collected from individuals testing for HIV from 1995 to 2002 at selected public clinics in King County, WA. Rates of receiving HIV test results were calculated for periods before and after telephone results were offered, for persons who were offered and accepted, offered but declined, and not offered telephone results. RESULTS: For persons testing HIV positive, overall rates of receiving results before and after telephone results were offered increased from 85% to 94% (P = 0.07). After controlling for confounders, people in the group offered and accepting telephone results were 2.5 (95% CI 1.7-3.6) times more likely to get HIV results compared to persons in the group not offered telephone results. CONCLUSIONS: Notifying persons of their HIV test results over the telephone may increase the numbers of people receiving results.
Subject(s)
HIV Infections/epidemiology , Telephone/statistics & numerical data , AIDS Serodiagnosis/methods , Adolescent , Adult , Female , HIV Infections/prevention & control , HIV Infections/virology , Homosexuality, Male , Humans , Male , Middle Aged , Washington/epidemiologyABSTRACT
Paraoxonase 1 (PON1) activity is consistently predictive of vascular disease, although the genotype at four functional PON1 polymorphisms is not. To address this inconsistency, we investigated the role of all common PON1 genetic variability, as measured by tagging single-nucleotide polymorphisms (tagSNPs), in predicting PON1 activity for phenylacetate hydrolysis, LDL susceptibility to oxidation ex vivo, plasma homocysteine (Hcy) levels, and carotid artery disease (CAAD) status. The biological goal was to establish whether additional common genetic variation beyond consideration of the four known functional SNPs improves prediction of these phenotypes. PON2 and PON3 tagSNPs were secondarily evaluated. Expanded analysis of an additional 26 tagSNPs found evidence of previously undescribed common PON1 polymorphisms that affect PON1 activity independently of the four known functional SNPs. PON1 activity was not significantly correlated with LDL oxidative susceptibility, but genotypes at the PON1(-108) promoter polymorphism and several other PON1 SNPs were. Neither PON1 activity nor PON1 genotype was significantly correlated with plasma Hcy levels. This study revealed previously undetected common functional PON1 polymorphisms that explain 4% of PON1 activity and a high rate of recombination in PON1, but the sum of the common PON1 locus variation does not explain the relationship between PON1 activity and CAAD.
Subject(s)
Aryldialkylphosphatase/genetics , Carotid Stenosis/genetics , Lipoproteins, LDL/metabolism , Polymorphism, Single Nucleotide/genetics , Adult , Aged , Aged, 80 and over , Aryldialkylphosphatase/metabolism , Esterases , Genetic Techniques , Haplotypes , Homocysteine/blood , Humans , Male , Middle Aged , Oxidation-ReductionABSTRACT
Paraoxonase (PON1) is an HDL-associated enzyme. Low PON1 activity predicts vascular disease status and is a more reliable predictor of vascular disease than are functional PON1 genotypes. There is evidence that the relationship of PON1 to vascular disease is, in part, due to its antioxidant activity. However, the physical relationship of PON1 with HDL and the existence of cholesterol pathway regulatory elements at the PON1 locus suggest a further relationship of PON1 with lipoproteins, which may contribute to its role in vascular disease. We investigated the relationship of PON1 activity and genotype to lipid-related traits in 91 Caucasian men with severe carotid artery disease and 184 without vascular disease who were not on lipid-lowering medications. Prior studies of PON1 relationship to lipids have not stratified by disease status.. We found that PON1 activity was correlated with HDL traits in controls and with LDL- and VLDL-related traits in cases. We hypothesize differences in the joint regulation of PON1 and lipoproteins in cases and controls.