Sexually Transmitted Bedfellows: Exquisite Association Between HIV and Herpes Simplex Virus Type 2 in 21 Communities in Southern Africa in the HIV Prevention Trials Network 071 (PopART) Study.

Background: Human immunodeficiency virus (HIV) and herpes simplex virus type 2 (HSV2) are strongly associated, although mechanisms are not fully understood. An HIV prevention trial allowed reexamination of this association at individual and community levels. Methods: The HIV Prevention Trials Network 071 (PopART) study evaluates a combination prevention intervention in 21 urban communities in Zambia and South Africa. To measure impact on HIV infection incidence, a cohort of approximately 2000 adults (age range, 18-44 years) was selected randomly from each community. Baseline data on sociodemographic characteristics, behavior, and HIV/HSV2 serologic findings were used to examine the association between HIV and HSV2. At the community level, HIV prevalence was plotted against HSV2 prevalence. Results: A total of 38691 adults participated. HSV2 prevalence among women and men was 50% and 22%, respectively, in Zambia and 60% and 27%, respectively, in South Africa. Estimated HSV2 infection incidence among those aged 18-24 years was 8.06 cases/100 person-years (95% confidence interval [CI], 6.76-9.35) and 1.76 cases/100 person-years (95% CI, 1.30-2.22) among women and men, respectively. A 6-fold higher odds of HIV infection was seen in HSV2-infected individuals in both sexes, after adjustment for confounders (odds ratio, 6.66 [95% CI, 6.07-7.31] among women and 6.57 [95% CI, 5.56-7.77] among men). At the community-level, there was a strong linear relationship between HIV and HSV2 prevalence (ρ = 0.92; P < .001). Conclusions: There was an exquisite association between these 2 infections, at the individual and community levels, likely due in part to a powerful cofactor effect of HSV2 on HIV transmission. HSV2 control could contribute to HIV prevention

Associations between HIV stigma and health-related quality-of-life among people living with HIV: cross-sectional analysis of data from HPTN 071 (PopART)

People living with HIV (PLHIV) report lower health-related quality-of-life (HRQoL) than HIV-negative people. HIV stigma may contribute to this. We explored the association between HIV stigma and HRQoL among PLHIV. We used cross-sectional data from 3991 randomly selected PLHIV who were surveyed in 2017–2018 for HPTN 071 (PopART), a cluster randomised trial in Zambia and South Africa. Participants were 18–44 years, had laboratory-confirmed HIV infection, and knew their status. HRQoL was measured using the EuroQol-5-dimensions-5-levels (EQ-5D-5L) questionnaire. Stigma outcomes included: internalised stigma, stigma experienced in the community, and stigma experienced in healthcare settings. Associations were examined using logistic regression. Participants who had experienced community stigma (n = 693/3991) had higher odds of reporting problems in at least one HRQoL domain, compared to those who had not (adjusted odds ratio, aOR: 1.51, 95% confidence interval, 95% Cl: 1.16–1.98, p = 0.002). Having experienced internalised stigma was also associated with reporting problems in at least one HRQoL domain (n = 552/3991, aOR: 1.98, 95% CI: 1.54–2.54, p < 0.001). However, having experienced stigma in a healthcare setting was less common (n = 158/3991) and not associated with HRQoL (aOR: 1.04, 95% CI: 0.68–1.58, p = 0.850). A stronger focus on interventions for internalised stigma and stigma experienced in the community is required

Determination of HIV status and identification of incident HIV infections in a large, community-randomized trial: HPTN 071 (PopART).

INTRODUCTION: The HPTN 071 (PopART) trial evaluated the impact of an HIV combination prevention package that included "universal testing and treatment" on HIV incidence in 21 communities in Zambia and South Africa during 2013-2018. The primary study endpoint was based on the results of laboratory-based HIV testing for> 48,000 participants who were followed for up to three years. This report evaluated the performance of HIV assays and algorithms used to determine HIV status and identify incident HIV infections in HPTN 071, and assessed the impact of errors on HIV incidence estimates. METHODS: HIV status was determined using a streamlined, algorithmic approach. A single HIV screening test was performed at centralized laboratories in Zambia and South Africa (all participants, all visits). Additional testing was performed at the HPTN Laboratory Center using antigen/antibody screening tests, a discriminatory test and an HIV RNA test. This testing was performed to investigate cases with discordant test results and confirm incident HIV infections. RESULTS: HIV testing identified 978 seroconverter cases. This included 28 cases where the participant had acute HIV infection at the first HIV-positive visit. Investigations of cases with discordant test results identified cases where there was a participant or sample error (mixups). Seroreverter cases (errors where status changed from HIV infected to HIV uninfected, 0.4% of all cases) were excluded from the primary endpoint analysis. Statistical analysis demonstrated that exclusion of those cases improved the accuracy of HIV incidence estimates. CONCLUSIONS: This report demonstrates that the streamlined, algorithmic approach effectively identified HIV infections in this large cluster-randomized trial. Longitudinal HIV testing (all participants, all visits) and quality control testing provided useful data on the frequency of errors and provided more accurate data for HIV incidence estimates

Effect of Universal Testing and Treatment on HIV Incidence - HPTN 071 (PopART).

BACKGROUND: A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent. METHODS: In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months. RESULTS: The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P = 0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P = 0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B. CONCLUSIONS: A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977.)

Female Genital Schistosomiasis and HIV-1 Incidence in Zambian Women: A Retrospective Cohort Study.

BACKGROUND: Female genital schistosomiasis (FGS) has been associated with prevalent HIV-1. We estimated the incidence of HIV-1 infection in Zambian women with and without FGS. METHODS: Women (aged 18-31, nonpregnant, sexually active) were invited to participate in this study in January-August 2018 at the final follow-up of the HPTN 071 (PopART) Population Cohort. HIV-1-negative participants at enrollment (n = 492) were included in this analysis, with testing to confirm incident HIV-1 performed in HPTN 071 (PopART). The association of incident HIV-1 infection with FGS (Schistosoma DNA detected by polymerase chain reaction [PCR] in any genital specimen) was assessed with exact Poisson regression. RESULTS: Incident HIV-1 infections were observed in 4.1% (20/492) of participants. Women with FGS were twice as likely to seroconvert as women without FGS but with no statistical evidence for a difference (adjusted rate ratio, 2.16; 95% CI, 0.21-12.30; P = .33). Exploratory analysis suggested an association with HIV-1 acquisition among women with ≥2 positive genital PCR specimens (rate ratio, 6.02; 95% CI, 0.58-34.96; P = .13). CONCLUSIONS: Despite higher HIV seroconversion rates in women with FGS, there was no statistical evidence of association, possibly due to low power. Further longitudinal studies should investigate this association in a setting with higher schistosomiasis endemicity

Viral suppression and self-reported ART adherence after 3 years of universal testing and treatment in the HPTN 071 (PopART) community-randomised trial in Zambia and South Africa: a cross-sectional analysis.

BACKGROUND: In 2014, UNAIDS set the target that 90% of individuals on antiretroviral therapy (ART) be virally suppressed. Here, we use data from the HPTN 071 (PopART) trial to report whether the introduction of universal testing and treatment has affected viral suppression or treatment adherence among individuals who self-reported they were taking ART, and identify risk factors for these outcomes. METHODS: This was a cross-sectional study nested within the randomly selected population cohort of the PopART trial. The trial took place in 21 communities in Zambia and South Africa. Analyses included 3570 HIV-positive participants who were seen at the second follow-up visit in 2016-17 and who self-reported that they were currently taking ART. Viral suppression was defined as HIV RNA of less than 400 copies per mL from a blood sample collected during the cohort visit, and ART adherence was measured using self-reporting (reported as no missed pills in last 7 days). Prevalences of these outcomes were compared across three trial arms using a two-stage approach suitable for clustered data. Each arm consisted of seven communities, with one arm receiving a combination HIV prevention package including immediate ART initiation, one receiving a combination HIV prevention package excluding immediate ART initiation and one arm receving standard of care. Risk factors for each of the outcomes were assessed using logistic regression. FINDINGS: Among the 3570 participants who self-reported that they were currently on ART, 416 (11·7%) of 3554 were not virally suppressed (16 were missing viral suppression status) and 345 (9·7%) of 3566 reported being non-adherent to ART (four were missing adherence status). The proportion not virally suppressed was higher in communities in South Africa (195 [16·4%] of 1191) than in Zambia (221 [9·4%] of 2363). There was no evidence that the prevalence of the outcomes differed between trial arms. There was evidence that men, younger individuals, individuals who reported participating in harmful alcohol use, and those who reported internalised stigma were more likely to be non-adherent, and not virally suppressed. INTERPRETATION: The results assuaged concerns that early ART initiation in a universal testing and treatment setting could lead to reduced adherence and viral suppression. FUNDING: US National Institute of Allergy and Infectious Diseases (which is a part of the National Institutes of Health), the International Initiative for Impact Evaluation with support from the Bill &amp; Melinda Gates Foundation, US President's Emergency Plan for AIDS Relief, and Medical Research Council UK

Projected outcomes of universal testing and treatment in a generalised HIV epidemic in Zambia and South Africa (the HPTN 071 [PopART] trial): a modelling study.

BACKGROUND: The long-term impact of universal home-based testing and treatment as part of universal testing and treatment (UTT) on HIV incidence is unknown. We made projections using a detailed individual-based model of the effect of the intervention delivered in the HPTN 071 (PopART) cluster-randomised trial. METHODS: In this modelling study, we fitted an individual-based model to the HIV epidemic and HIV care cascade in 21 high prevalence communities in Zambia and South Africa that were part of the PopART cluster-randomised trial (intervention period Nov 1, 2013, to Dec 31, 2017). The model represents coverage of home-based testing and counselling by age and sex, delivered as part of the trial, antiretroviral therapy (ART) uptake, and any changes in national guidelines on ART eligibility. In PopART, communities were randomly assigned to one of three arms: arm A received the full PopART intervention for all individuals who tested positive for HIV, arm B received the intervention with ART provided in accordance with national guidelines, and arm C received standard of care. We fitted the model to trial data twice using Approximate Bayesian Computation, once before data unblinding and then again after data unblinding. We compared projections of intervention impact with observed effects, and for four different scenarios of UTT up to Jan 1, 2030 in the study communities. FINDINGS: Compared with standard of care, a 51% (95% credible interval 40-60) reduction in HIV incidence is projected if the trial intervention (arms A and B combined) is continued from 2020 to 2030, over and above a declining trend in HIV incidence under standard of care. INTERPRETATION: A widespread and continued commitment to UTT via home-based testing and counselling can have a substantial effect on HIV incidence in high prevalence communities. FUNDING: National Institute of Allergy and Infectious Diseases, US President's Emergency Plan for AIDS Relief, International Initiative for Impact Evaluation, Bill & Melinda Gates Foundation, National Institute on Drug Abuse, and National Institute of Mental Health

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

Species and Spatio-temporal distribution of animal rabies

Data collected in daily registers of institutions dealing with rabies from 2009 to 2013. Data are coded according to the variables corresponding to the column heading as shown for each column when mouse passes

Data from: Overview of animal rabies in Kinshasa Province in the Democratic Republic of Congo

Introduction: Rabies is one of the major public health problems mostly affecting developing countries in Africa and Asia where 99.9% of all rabies related human deaths are recorded each year. In Democratic Republic of Congo, repeated outbreaks have been reported. Despite this, there is little reliable epidemiological data about rabies in the country for the development of effective control strategies. Materials and Methods: A retrospective study was carried out in Kinshasa Province during a period of five years (2009–2013) to describe the proportion of rabid animals and the species involved in rabies transmission and maintenance. The survey also aimed at describing the spatial-temporal distribution of rabies. To gather information, the daily registers of institutions involved in rabies diagnosis were reviewed and each rabies case was traced back to area of occurrence for collection of geographic coordinates. Results and Discussion: A total of 5,053 attacks were registered involving six animal species including dog, cat, monkey, rabbit, rat, and pig. Based on clinical observations, rabies was reported in dogs and cats while data obtained from the laboratory confirmed rabies cases included dogs, cats and a goat. The annual distribution showed a significant decrease of rabies cases from 2009 up to 2011 and a later increase up to 2013. There was no difference in rabies occurrence between seasons (p = 0.721). Rabies cases were three times higher in peri-urban zone than in urban zone OR = 3.4 (95% CI: 2.3–5.1). The positive proportion of rabies was 2.6% (95% CI: 2.1–3) based on clinical evidence and 65.9% (95% CI: 50–79.5) for laboratory confirmed cases. Conclusion and Suggestion: This study confirms the endemicity of rabies in Kinshasa where occurrence of rabies cases was related to human population density and lifestyle. In order to control rabies, there is need to set up a surveillance program and implement efficient mass vaccination campaigns of susceptible animals