Bacterial vaginosis (BV), a disruption of the normal vaginal flora, has been associated with a 60% increased risk of HIV-1 acquisition in women and higher concentration of HIV-1 RNA in the genital ...tract of HIV-1-infected women. However, whether BV, which is present in up to half of African HIV-1-infected women, is associated with an increase in HIV-1 transmission to male partners has not been assessed in previous studies.
We assessed the association between BV on female-to-male HIV-1 transmission risk in a prospective study of 2,236 HIV-1-seropositive women and their HIV-1 uninfected male partners from seven African countries from a randomized placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus (HSV)-2, and their HIV-1-seronegative partners. Participants were followed for up to 24 months; every three months, vaginal swabs were obtained from female partners for Gram stain and male partners were tested for HIV-1. BV and normal vaginal flora were defined as a Nugent score of 7-10 and 0-3, respectively. To reduce misclassification, HIV-1 sequence analysis of viruses from seroconverters and their partners was performed to determine linkage of HIV-1 transmissions. Overall, 50 incident HIV-1 infections occurred in men in which the HIV-1-infected female partner had an evaluable vaginal Gram stain. HIV-1 incidence in men whose HIV-1-infected female partners had BV was 2.91 versus 0.76 per 100 person-years in men whose female partners had normal vaginal flora (hazard ratio 3.62, 95% CI 1.74-7.52). After controlling for sociodemographic factors, sexual behavior, male circumcision, sexually transmitted infections, pregnancy, and plasma HIV-1 RNA levels in female partners, BV was associated with a greater than 3-fold increased risk of female-to-male HIV-1 transmission (adjusted hazard ratio 3.17, 95% CI 1.37-7.33).
This study identified an association between BV and increased risk of HIV-1 transmission to male partners. Several limitations may affect the generalizability of our results including: all participants underwent couples HIV counseling and testing and enrolled in an HIV-1 prevention trial, and index participants had a baseline CD4 count ≥ 250 cells/mm³ and were HSV-2 seropositive. Given the high prevalence of BV and the association of BV with increased risk of both female HIV-1 acquisition and transmission found in our study, if this association proves to be causal, BV could be responsible for a substantial proportion of new HIV-1 infections in Africa. Normalization of vaginal flora in HIV-1-infected women could mitigate female-to-male HIV-1 transmission.
ClinicalTrials.com NCT00194519.
Current diagnostics for HIV-associated tuberculosis are suboptimal, with missed diagnoses contributing to high hospital mortality and approximately 374 000 annual HIV-positive deaths globally. ...Urine-based assays have a good diagnostic yield; therefore, we aimed to assess whether urine-based screening in HIV-positive inpatients for tuberculosis improved outcomes.
We did a pragmatic, multicentre, double-blind, randomised controlled trial in two hospitals in Malawi and South Africa. We included HIV-positive medical inpatients aged 18 years or more who were not taking tuberculosis treatment. We randomly assigned patients (1:1), using a computer-generated list of random block size stratified by site, to either the standard-of-care or the intervention screening group, irrespective of symptoms or clinical presentation. Attending clinicians made decisions about care; and patients, clinicians, and the study team were masked to the group allocation. In both groups, sputum was tested using the Xpert MTB/RIF assay (Xpert; Cepheid, Sunnyvale, CA, USA). In the standard-of-care group, urine samples were not tested for tuberculosis. In the intervention group, urine was tested with the Alere Determine TB-LAM Ag (TB-LAM; Alere, Waltham, MA, USA), and Xpert assays. The primary outcome was all-cause 56-day mortality. Subgroup analyses for the primary outcome were prespecified based on baseline CD4 count, haemoglobin, clinical suspicion for tuberculosis; and by study site and calendar time. We used an intention-to-treat principle for our analyses. This trial is registered with the ISRCTN registry, number ISRCTN71603869.
Between Oct 26, 2015, and Sept 19, 2017, we screened 4788 HIV-positive adults, of which 2600 (54%) were randomly assigned to the study groups (n=1300 for each group). 13 patients were excluded after randomisation from analysis in each group, leaving 2574 in the final intention-to-treat analysis (n=1287 in each group). At admission, 1861 patients were taking antiretroviral therapy and median CD4 count was 227 cells per μL (IQR 79–436). Mortality at 56 days was reported for 272 (21%) of 1287 patients in the standard-of-care group and 235 (18%) of 1287 in the intervention group (adjusted risk reduction aRD −2·8%, 95% CI −5·8 to 0·3; p=0·074). In three of the 12 prespecified, but underpowered subgroups, mortality was lower in the intervention group than in the standard-of-care group for CD4 counts less than 100 cells per μL (aRD −7·1%, 95% CI −13·7 to −0·4; p=0.036), severe anaemia (−9·0%, −16·6 to −1·3; p=0·021), and patients with clinically suspected tuberculosis (−5·7%, −10·9 to −0·5; p=0·033); with no difference by site or calendar period. Adverse events were similar in both groups.
Urine-based tuberculosis screening did not reduce overall mortality in all HIV-positive inpatients, but might benefit some high-risk subgroups. Implementation could contribute towards global targets to reduce tuberculosis mortality.
Joint Global Health Trials Scheme of the Medical Research Council, the UK Department for International Development, and the Wellcome Trust.
•A significant weight gain occurs after switching from non-integrase inhibitor-based antiretroviral therapy to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide ...(E/C/F/TAF).•Weight gain is correlated with later clinic visit, baseline weight, diabetes mellitus, and age.•The switch to E/C/F/TAF is associated with dyslipidemia and an increase in HbA1c level.
To evaluate the evolution of weight and lipid profiles before and after switch to co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) among virally suppressed HIV-positive patients.
Patients switching to E/C/F/TAF between March and July 2018 were included. Weight, lipid profile (triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)), and glycated hemoglobin (HbA1c) levels at 48 weeks before and after the switch were analyzed using generalized estimating equations in order to identify the associated factors.
A total of 693 patients were included, and a weight gain was noted after the switch at weeks 12 (mean +0.63 kg), 24 (+1.25), 36 (+1.58), and 48 (+1.75) (all p < 0.0001). The weight change after the switch was significantly greater than that observed within the preceding 48-week period before the switch (+1.75 kg vs +0.54, p < 0.0001) and was correlated with switch to E/C/F/TAF (coefficient 0.29), later clinic visit (0.15), baseline weight (0.99), diabetes mellitus (coefficient −0.96), and age (−0.02) (all p < 0.01). At week 48, significant increases were observed for TG (mean +62.93 mg/dl), TC (+22.30), LDL-C (+9.70), HDL-C (+3.65) (all p < 0.01), and HbA1c (+0.08%) (p < 0.05), but not TC/HDL-C ratio (+0.12, p = 0.38).
Virally suppressed HIV-positive patients gained a moderate amount of weight and had significant increases in lipid levels after switching to E/C/F/TAF.
Successful treatment of HIV-associated multicentric Castleman disease (HIV+MCD) with rituximab-based approaches has dramatically improved survival and reduced the risk of human herpesvirus 8 ...(HHV8)-associated lymphoma. Longer term outcomes including relapse rates have not been described and are important to establish the potential role of maintenance therapy. A prospective cohort of 84 patients with biopsy-proven HIV+MCD were treated with risk-stratified rituximab-based therapy. Four patients (5%) died of refractory HIV+MCD and 80 achieved clinical remission. The median follow-up for the 80 patients was 6.9 years and their 5-year overall survival was 92% (95% confidence interval CI, 85 to 99). Eighteen have relapsed (all histologically confirmed), including 5 with concomitant HHV8-associated lymphoma and MCD at relapse. The 5-year relapse-free survival is 82% (95% CI, 72 to 92). No clinical or laboratory findings that were present at MCD diagnosis predicted subsequent relapse, and the median time to first relapse was 30 months (maximum, 10 years). There were no significant differences in clinicopathological features at initial diagnosis and at relapse. All patients were successfully retreated at relapse with rituximab-based therapy. Only 1 patient died of relapsed MCD (at fifth relapse 9.4 years after initial diagnosis). Despite the use of rituximab, the risk of developing HHV8-associated lymphoma was significantly elevated in this cohort, with an incidence of 11.4/1000 person-years. The relatively low relapse rate and high salvage rates at relapse reduce the potential benefit of maintenance therapy; this should only be advocated in the context of a clinical trial.
•HIV-associated MCD remains a relapsing remitting disease despite rituximab-based therapy.•Most patients can be salvaged at relapse by retreating with rituximab, but the risk of developing HHV8-associated lymphomas remains.
Objectives: We assessed how health care-related stigma, global medical mistrust, and personal trust in one's health care provider relate to engaging in medical care among Black men who have sex with ...men (MSM).
In 2012, we surveyed 544 Black MSM attending a community event. We completed generalized linear modeling and mediation analyses in 2013.
Twenty-nine percent of participants reported experiencing racial and sexual orientation stigma from heath care providers and 48% reported mistrust of medical establishments. We found that, among HIV-negative Black MSM, those who experienced greater stigma and global medical mistrust had longer gaps in time since their last medical exam. Furthermore, global medical mistrust mediated the relationship between stigma and engagement in care. Among HIV-positive Black MSM, experiencing stigma from health care providers was associated with longer gaps in time since last HIV care appointment.
Interventions focusing on health care settings that support the development of greater awareness of stigma and mistrust are urgently needed. Failure to address psychosocial deterrents will stymie progress in biomedical prevention and cripple the ability to implement effective prevention and treatment strategies.
Summary Background Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 ...acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners. Methods In this prospective study, we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries. Among injectable and oral hormonal contraceptive users and non-users, we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men. The primary outcome measure was HIV-1 seroconversion. We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk. Findings Among 1314 couples in which the HIV-1-seronegative partner was female (median follow-up 18·0 IQR 12·6–24·2 months), rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not (adjusted hazard ratio 1·98, 95% CI 1·06–3·68, p=0·03). Among 2476 couples in which the HIV-1-seronegative partner was male (median follow-up 18·7 IQR 12·8–24·2 months), rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception (adjusted hazard ratio 1·97, 95% CI 1·12–3·45, p=0·02). Marginal structural model analyses generated much the same results to the Cox proportional hazards regression. Interpretation Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception, especially injectable methods, and about the importance of dual protection with condoms to decrease HIV-1 risk. Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1. Funding US National Institutes of Health and the Bill & Melinda Gates Foundation.
Antiretroviral treatment (ART) is now recommended for all HIV-positive persons. UNAIDS has set global targets to diagnose 90% of HIV-positive individuals, treat 90% of diagnosed individuals with ART, ...and suppress viral replication among 90% of treated individuals, for a population-level target of 73% of all HIV-positive persons with HIV viral suppression.
To describe changes in the proportions of HIV-positive individuals with HIV viral suppression, HIV-positive individuals who had received a diagnosis, diagnosed individuals treated with ART, and treated individuals with HIV viral suppression, following implementation of a community-based testing and treatment program in rural East Africa.
Observational analysis based on interim data from 16 rural Kenyan (n = 6) and Ugandan (n = 10) intervention communities in the SEARCH Study, an ongoing cluster randomized trial. Community residents who were 15 years or older (N = 77 774) were followed up for 2 years (2013-2014 to 2015-2016). HIV serostatus and plasma HIV RNA level were measured annually at multidisease health campaigns followed by home-based testing for nonattendees. All HIV-positive individuals were offered ART using a streamlined delivery model designed to reduce structural barriers, improve patient-clinician relationships, and enhance patient knowledge and attitudes about HIV.
Primary outcome was viral suppression (plasma HIV RNA<500 copies/mL) among all HIV-positive individuals, assessed at baseline and after 1 and 2 years. Secondary outcomes included HIV diagnosis, ART among previously diagnosed individuals, and viral suppression among those who had initiated ART.
Among 77 774 residents (male, 45.3%; age 15-24 years, 35.1%), baseline HIV prevalence was 10.3% (7108 of 69 283 residents). The proportion of HIV-positive individuals with HIV viral suppression at baseline was 44.7% (95% CI, 43.5%-45.9%; 3464 of 7745 residents) and after 2 years of intervention was 80.2% (95% CI, 79.1%-81.2%; 5666 of 7068 residents), an increase of 35.5 percentage points (95% CI, 34.4-36.6). After 2 years, 95.9% of HIV-positive individuals had been previously diagnosed (95% CI, 95.3%-96.5%; 6780 of 7068 residents); 93.4% of those previously diagnosed had received ART (95% CI, 92.8%-94.0%; 6334 of 6780 residents); and 89.5% of those treated had achieved HIV viral suppression (95% CI, 88.6%-90.3%; 5666 of 6334 residents).
Among individuals with HIV in rural Kenya and Uganda, implementation of community-based testing and treatment was associated with an increased proportion of HIV-positive adults who achieved viral suppression, along with increased HIV diagnosis and initiation of antiretroviral therapy. In these communities, the UNAIDS population-level viral suppression target was exceeded within 2 years after program implementation.
clinicaltrials.gov Identifier: NCT01864683.
Heterosexual transmission of HIV-1 is characterized by a genetic bottleneck that selects a single viral variant, the transmitted/founder (TF), during most transmission events. To assess viral ...characteristics influencing HIV-1 transmission, we sequenced 167 near full-length viral genomes and generated 40 infectious molecular clones (IMC) including TF variants and multiple non-transmitted (NT) HIV-1 subtype C variants from six linked heterosexual transmission pairs near the time of transmission. Consensus-like genomes sensitive to donor antibodies were selected for during transmission in these six transmission pairs. However, TF variants did not demonstrate increased viral fitness in terms of particle infectivity or viral replicative capacity in activated peripheral blood mononuclear cells (PBMC) and monocyte-derived dendritic cells (MDDC). In addition, resistance of the TF variant to the antiviral effects of interferon-α (IFN-α) was not significantly different from that of non-transmitted variants from the same transmission pair. Thus neither in vitro viral replicative capacity nor IFN-α resistance discriminated the transmission potential of viruses in the quasispecies of these chronically infected individuals. However, our findings support the hypothesis that within-host evolution of HIV-1 in response to adaptive immune responses reduces viral transmission potential.
Effective antiretroviral therapy (ART) has contributed greatly toward survival for people with HIV, yet many remain undiagnosed until very late. Our aims were to estimate the life expectancy of an ...HIV-infected MSM living in a developed country with extensive access to ART and healthcare, and to assess the effect of late diagnosis on life expectancy.
A stochastic computer simulation model of HIV infection and the effect of ART was used to estimate life expectancy and determine the distribution of potential lifetime outcomes of an MSM, aged 30 years, who becomes HIV positive in 2010. The effect of altering the diagnosis rate was investigated.
Assuming a high rate of HIV diagnosis (median CD4 cell count at diagnosis, 432 cells/μl), projected median age at death (life expectancy) was 75.0 years. This implies 7.0 years of life were lost on average due to HIV. Cumulative risks of death by 5 and 10 years after infection were 2.3 and 5.2%, respectively. The 95% uncertainty bound for life expectancy was (68.0,77.3) years. When a low diagnosis rate was assumed (diagnosis only when symptomatic, median CD4 cell count 140 cells/μl), life expectancy was 71.5 years, implying an average 10.5 years of life lost due to HIV.
If low rates of virologic failure observed in treated patients continue, predicted life expectancy is relatively high in people with HIV who can access a wide range of antiretrovirals. The greatest risk of excess mortality is due to delays in HIV diagnosis.
Since 2000, an increase in hepatitis C virus infection among HIV-infected (HIV+) men who have sex with men has been observed. Evidence points to blood exposure during sex as the medium of hepatitis C ...virus transmission. Hepatitis C virus prevalence among HIV + MSM overall and in relation to injection drug use is poorly characterized. In this study, a systematic review and meta-analysis examining global hepatitis C virus antibody prevalence and estimating active hepatitis C virus prevalence among HIV + MSM were conducted; 42 reports provided anti-hepatitis C virus prevalence data among HIV + MSM. Pooled prevalence produced an overall anti-hepatitis C virus prevalence among HIV + MSM of 8.1%; active HCV prevalence estimate was 5.3%-7.3%. Anti-hepatitis C virus prevalence among injection drug use and non-injection drug use HIV + MSM was 40.0% and 6.7%, respectively. Among HIV + MSM, hepatitis C virus prevalence increased significantly over time among the overall and non-injection drug use groups, and decreased significantly among injection drug use HIV + MSM. We identified a moderate prevalence of hepatitis C virus among all HIV + MSM and among non-injection drug use HIV + MSM; for both, prevalence was observed to be increasing slightly. Pooled prevalence of hepatitis C virus among HIV + MSM was higher than that observed in the 1945-1965 US birth cohort. The modest but rising hepatitis C virus prevalence among HIV + MSM suggests an opportunity to control HCV among HIV + MSM; this combined with data demonstrating a rising hepatitis C virus incidence highlights the temporal urgency to do so.
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