The inference of HIV-1 transmission direction between a man who has sex with men and his heterosexual wife based on the sequences of HIV-1 quasi-species.
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ABSTRACT:
SUBMITTER: Zhou Z
PROVIDER: S-EPMC8676586 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAntiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations.MethodsWe conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services.ResultsWe enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study.ConclusionsOral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).
| S-EPMC3770474 | biostudies-literature
Project description:Somatic mtDNA mutations and deletions in particular are known to clonally expand within cells, eventually reaching detrimental intracellular concentrations. The possibility that clonal expansion is a slow process taking a lifetime had prompted an idea that founder mutations of mutant clones that cause mitochondrial dysfunction in the aged tissue might have originated early in life. If, conversely, expansion was fast, founder mutations should predominantly originate later in life. This distinction is important: indeed, from which mutations should we protect ourselves - those of early development/childhood or those happening at old age? Recently, high-resolution data describing the distribution of mtDNA deletions have been obtained using a novel, highly efficient method (Taylor et al., ). These data have been interpreted as supporting predominantly early origin of founder mutations. Re-analysis of the data implies that the data actually better fit mostly late origin of founders, although more research is clearly needed to resolve the controversy.
| S-EPMC4326951 | biostudies-literature
Project description:An 84-year-old man presented to the emergency department following recurrent falls over several weeks and onset of new left-sided weakness. CT of the brain revealed a large air cavity (pneumatocoele) in the right frontal lobe thought to be secondary to an ethmoidal osteoma communicating through the cribriform plate allowing air to be forced into the skull under pressure. Subsequent MRI confirmed these findings and also revealed a small focal area of acute infarction in the adjacent corpus callosum. The patient had a prolonged hospital stay, declined neurosurgical intervention and was discharged home on secondary stroke prevention.
| S-EPMC5847910 | biostudies-literature
Project description:High-risk human papillomavirus (HR-HPV) viral load is associated with HR-HPV transmission and HR-HPV persistence in women. It is unknown whether HR-HPV viral load is associated with persistence in HIV-negative or HIV-positive men.HR-HPV viral load and persistence were evaluated among 703 HIV-negative and 233 HIV-positive heterosexual men who participated in a male circumcision trial in Rakai, Uganda. Penile swabs were tested at baseline and 6, 12 and 24?months for HR-HPV using the Roche HPV Linear Array, which provides a semiquantitative measure of HPV shedding by hybridisation band intensity (graded: 1-4). Prevalence risk ratios (PRR) were used to estimate the association between HR-HPV viral load and persistent detection of HR-HPV.HR-HPV genotypes with high viral load (grade:3-4) at baseline were more likely to persist than HR-HPV genotypes with low viral load (grade: 1-2) among HIV-negative men (month 6: adjPRR=1.83, 95% CI 1.32 to 2.52; month 12: adjPRR=2.01, 95% CI 1.42 to 3.11), and HIV-positive men (month 6: adjPRR=1.33, 95% CI 1.06 to 1.67; month 12: adjPRR=1.73, 95% CI 1.18 to 2.54). Long-term persistence of HR-HPV was more frequent among HIV-positive men compared with HIV-negative men (month 24: adjPRR=2.27, 95% CI 1.47 to 3.51). Persistence of newly detected HR-HPV at the 6-month and 12-month visits with high viral load were also more likely to persist to 24?months than HR-HPV with low viral load among HIV-negative men (adjPRR=1.67, 95% CI 0.88 to 3.16).HR-HPV genotypes with high viral load are more likely to persist among HIV-negative and HIV-positive men, though persistence was more common among HIV-positive men overall. The results may explain the association between high HR-HPV viral load and HR-HPV transmission.
| S-EPMC4030299 | biostudies-literature
Project description:BackgroundWe evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission.MethodsFor 33 pairs of HIV-infected patients (hereafter, "index patients") and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, "SC samples"); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, "early index samples") were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees.ResultsDoT was predicted correctly for both single-pair and subtype-specific trees in 22 pairs (67%) by using SC samples and in 23 pairs (74%) by using early index samples. DoT was predicted incorrectly for 4 pairs (15%) by using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) by using SC samples and for 24 pairs (73%) by using early index samples. DoT was predicted incorrectly for 7 pairs (21%) by using SC samples and for 4 pairs (13%) by using early index samples.ConclusionsPhylogenetic methods based solely on the tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.
| S-EPMC6761953 | biostudies-literature
Project description:Objectives. To identify the impact of a strengths-focused HIV prevention program among high-risk heterosexual Black men. Methods. Barbershops in Brooklyn, New York, neighborhoods with high rates of heterosexually transmitted HIV were randomized to the intervention or an attention control program. Men were recruited from barbershops between 2012 and 2016 and participated in a single small group, peer-led session focused on HIV risk reduction skills and motivation, community health empowerment, and identification of personal strengths and communication skills. The outcome was defined as 1 or more acts of condomless anal or vaginal sex in the preceding 90 days at a 6-month interview. Results. Fifty-three barbershops (24 intervention, 29 control) and 860 men (436 intervention, 424 control) were recruited; follow-up was completed by 657 participants (352 intervention, 305 control). Intervention exposure was associated with a greater likelihood of no condomless sex (64.4%) than control group participation (54.1%; adjusted odds ratio = 1.61; 95% confidence interval = 1.05, 2.47). Conclusions. Program exposure resulted in reduced sexual risk behaviors, and the program was acceptable for administration in partnership with barbershops. Public Health Implications. Dissemination of similar programs could improve public health in communities with high rates of HIV attributable to heterosexual transmission.
| S-EPMC6611102 | biostudies-literature
Project description:BackgroundMortality in HIV-infected individuals might differ by sex and mode of HIV acquisition. We aimed to study mortality in HIV-infected women, heterosexual men, and men who have sex with men (MSM) in a cohort from Rio de Janeiro, Brazil.MethodsIn this observational cohort study, we included HIV-infected women, heterosexual men, and MSM (aged ≥18 years) from the Instituto Nacional de Infectologia Evandro Chagas database who were enrolled between Jan 1, 2000, and Oct 30, 2011, and who had at least 60 days of follow-up. Causes of deaths, defined with the Coding of Death in HIV protocol, were documented. Cox proportional hazards models accounting for competing risks were used to explore risk factors for AIDS-related and non-AIDS-related deaths.FindingsWe had 10 142 person-years of follow-up from 2224 individuals: 817 (37%) women, 554 (25%) heterosexual men, and 853 (38%) MSM. Of 103 deaths occurred, 64 were AIDS related, 31 were non-AIDS related, and eight were of unknown causes. In unadjusted analyses, compared with women, the hazard of AIDS-related deaths was higher for heterosexual men (hazard ratio [HR] 3·52, 95% CI 1·30-9·08; p=0·009) and for MSM (2·30, 0·89-5·94; p=0·084). After adjustment for age, CD4 cell counts, last HIV viral load, antiretroviral therapy use, and AIDS-defining infection, AIDS-defining malignant disease, and hospital admission during follow-up, the excess risk of AIDS-related death decreased for heterosexual men (adjusted HR 1·99, 0·75-5·25; p=0·163) but was unchanged for MSM (2·24, 0·82-6·11; p=0·114). Non-AIDS-related mortality did not differ by group.InterpretationCompared with women, increased risk of AIDS-related death in heterosexual men was partly mitigated by risk factors for AIDS mortality, whereas the excess risk in MSM was unchanged. Further study of reasons for disparity in AIDS-related mortality by mode of transmission is needed.FundingUS National Institutes of Health, Brazilian National Council of Technological and Scientific Development (CNPq), and Research Funding Agency of the State of Rio de Janeiro (FAPERJ).
| S-EPMC5084911 | biostudies-literature
Project description:BackgroundChina's National Free Antiretroviral Treatment Program (NFATP) has substantially reduced morbidity and HIV/AIDS incidence since 2003. However, HIV resistance to antiretroviral drugs (ARVs) has been a major challenge for the current treatment of HIV/AIDS in China.MethodsIn the current study, we established a nested dynamic model to predict the multi-drug resistance dynamics of HIV among the heterosexual population and evaluated the impact of intervention measures on the transmission of drug resistance. We obtained an effective reproductive number [Formula: see text] from each sub-model held at different stages of the dynamic model. Meanwhile, we applied Bayesian phylogenetic methods to infer the weighted average effective reproductive number [Formula: see text] from four HIV subtypes that sampled from 912 HIV-positive patients in China. It is an original and innovative method by fitting [Formula: see text] to [Formula: see text] by Markov Chain Monte Carlo (MCMC) to generate unknown parameters in [Formula: see text].ResultsBy analyzing the HIV gene sequences, we inferred that the most recent common ancestor of CRF01AE, CRF07BC, CRF08BC, and CRFBC dated from 1994, 1990, 1993 and 1990, respectively. The weighted average effective reproductive number [Formula: see text] dropped from 1.95 in 1994 to 1.73 in 2018. Considering different interventions, we used a macro dynamic model to predict the trend of HIV resistance. The results show that the number of new infections and total drug resistance under the baseline parameter (S1) are 253,422 and 213,250 in 2025, respectively. Comparing with the numbers under the target treatment rate (S2), they were 219,717 and 236,890, respectively. However, under the ideal treatment target (S3, the treatment rate reaches 90% and the treatment success rate reaches 90%), the number of new infections shows a declining trend and will decrease to 46,559 by 2025. Compared with S1 and S2, the total number of resistance also decreased to 160,899 in 2025.ConclusionWith the promotion of NFATP in China, HIV resistance to ARVs is inevitable. The strategy of increasing the treatment rate would not only ineffectively curb the epidemic, but also deteriorate drug resistance issue. Whereas, a combination of intervention strategies (the treatment rate reaches 90% and the treatment success rate reaches 90%) can greatly reduce both infection and drug resistance rate than applying one strategy alone.
| S-EPMC8635345 | biostudies-literature
Project description:BackgroundIn Guangxi province of China, there is a high prevalence of HIV in the general population and in men who have sex with men (MSM). However, there is still a low proportion of MSM among people living with HIV. This apparent contradiction could be due to the high proportion of potential non-disclosed MSM (pnMSM) among reported heterosexual men. We analyzed the genetic linkage of HIV specimens to address this problem aiming to (1) identify the optimal genetic distance threshold, which gave the highest number of genetic clusters, (2) document the proportion of potential non-disclosed MSM (pnMSM) among self-reported heterosexual men, and (3) determine predictors for pnMSM.MethodsPairwise genetic distances were computed among all samples. The genetic distance threshold giving the highest number of genetic clusters was identified. Self-reported heterosexual men were identified as belonging to the pnMSM group if they could be linked to any MSM in their cluster. Multinomial logistic regression was used to determine associated factors of being pnMSM.ResultsThe optimal genetic distance threshold was 0.75% substitutions/site. Among 896 self-reported heterosexual men, the frequency (percentage and 95% confidence interval) was 62 (6.9%, 5.2-8.6%) for pnMSM, 779 (86.9%, 84.7-89.1%) for indeterminate men and 55 (6.1%, 4.5-7.7%) for potential heterosexual men, respectively. Self-reported heterosexual men who were younger, single and more educated were more likely to be pnMSM.ConclusionBased on these findings, there is a need to pay more attention to sexually active, young and educated self-reported heterosexual men and provide them with voluntary counselling and testing and specific HIV prevention services.
| S-EPMC10065240 | biostudies-literature
Project description:OBJECTIVES:Human papillomavirus (HPV) infection causes genital warts, penile cancer and cervical cancer. Africa has one of the highest rates of penile and cervical cancers, but there are little data on high-risk human papillomavirus (HR-HPV) prevalence in heterosexual men. Knowledge of HR-HPV prevalence, risk factors and genotype distribution among heterosexual men is important to establish risk-reduction prevention strategies. METHODS:1578 uncircumcised men aged 15-49 years who enrolled in male circumcision trials in Rakai, Uganda, were evaluated for HR-HPV from swabs of the coronal sulcus/glans using Roche HPV Linear Array. Adjusted prevalence risk ratios (adjPRRs) were estimated using modified Poisson multivariable regression. RESULTS:HPV prevalence (either high risk or low risk) was 90.7% (382/421) among HIV-positive men and 60.9% (596/978) among HIV-negative men (PRR 1.49, 95% CI 1.40 to 1.58). HIV-positive men had a significantly higher risk of infection with three or more HR-HPV genotypes (PRR=5.76, 95% CI 4.27 to 7.79). Among HIV-positive men, high-risk sexual behaviours were not associated with increased HR-HPV prevalence. Among HIV-negative men, HR-HPV prevalence was associated with self-reported genital warts (adjPRR 1.57, 95% CI 1.07 to 2.31). Among all men (both HIV negative and HIV positive), HR-HPV prevalence was associated with more than 10 lifetime sexual partners (adjPRR 1.30, 95% CI 1.01 to 1.66), consistent condom use (adjPRR 1.31, 95% CI 1.08 to 1.60) and HIV infection (adjPRR 1.80, 95% CI 1.60 to 2.02). HR-HPV prevalence was lower among men who reported no sexual partners during the past year (adjPRR 0.47, 95% CI 0.23 to 0.94). CONCLUSION:The burden of HR-HPV infection is high among heterosexual men in sub-Saharan Africa and most pronounced among the HIV-infected individuals.
| S-EPMC3640492 | biostudies-literature