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HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value ≤0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings. ClinicalTrials.gov: NCT01900977.

Two phase 2 trials assessed the efficacy and safety of intravenous infusions of a broadly neutralizing antibody, VRCO1, to prevent HIV-1 infection. VRC01 did not cause adverse events and did not prevent overall HIV-1 acquisition significantly more effectively than placebo. In secondary analyses, VRC01 prevented transmission of VRC01-sensitive HIV-1 isolates.

HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value [less than or equal to]0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings.

Background. Preexposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone reduces the risk of human immunodeficiency virus (HIV) acquisition. Understanding the risk of antiretroviral resistance selected by PrEP during breakthrough infections is important because of the risk of treatment failure during subsequent antiretroviral use. Methods. Within the largest randomized trial of FTC/TDF versus TDF as PrEP, plasma samples were tested for HIV with resistance mutations associated with FTC (K65R and M184IV) and TDF (K65R and K70E), using 454 sequencing. Results. Of 121 HIV seroconverters, 25 received FTC/TDF, 38 received TDF, and 58 received placebo. Plasma drug levels in 26 individuals indicated PrEP use during or after HIV acquisition, of which 5 had virus with resistance mutations associated with their PrEP regimen. Among those with PrEP drug detected during infection, resistance was more frequent in the FTC/TDF arm (4 of 7 [57%]), compared with the TDF arm (1 of 19 [5.3%]; P = .01), owing to the FTC-associated mutation M184IV. Of these cases, 3 had unrecognized acute infection at PrEP randomization, and 2 were HIV negative at enrollment. Conclusions. These results suggest that resistance selected by PrEP is rare but can occur both with PrEP initiation during acute seronegative HIV infection and in PrEP breakthrough infections and that FTC is associated with a greater frequency of resistance mutations than TDF.

Abstract Background Herpes simplex virus type 2 (HSV2) is an important cofactor for HIV acquisition and transmission. Associations between the infections are reexamined in longitudinal data from an HIV prevention trial. Methods The HPTN 071 (PopART) trial evaluated a combination prevention intervention in 21 urban communities in Zambia and South Africa. HIV incidence was measured in a cohort of approximately 2000 adults (age, 18–44 years) selected randomly from each community and followed up for 36 months. Incidence of HSV2 infection was estimated, and the effects of risk factors were examined. The association between HIV incidence and HSV2 infection was examined at individual and community levels. Results An overall 10 539 participants were HSV2 negative at baseline and retested after 36 months. Estimated HSV2 incidence was 5.4 per 100 person-years (95% CI, 5.0–5.7) for women and 2.9 per 100 person-years (95% CI, 2.6–3.2) for men. When compared with those remaining HSV2 negative, HIV incidence was higher in those who were HSV2 positive at baseline (women: adjusted rate ratio [aRR], 3.24 [95% CI, 2.50–4.20]; men: aRR, 2.57 [95% CI, 1.60–4.11]) and even higher in those who seroconverted to HSV2 during follow-up (women: aRR, 5.94 [95% CI, 4.42–7.98]; men: aRR, 8.37 [95% CI, 5.18–13.52]). At the community level, strong associations were seen between HIV incidence and HSV2 prevalence (R2 = 0.48, P < .001) and incidence (R2 = 0.36, P = .004). Conclusions There were strong associations between HIV incidence and HSV2 prevalence and incidence at individual and community levels. HSV2 control could contribute to HIV prevention.

Purpose This study aims to evaluate the feasibility and efficacy of an 8-week supervised exercise program in de-conditioned cancer survivors within 2–6 months of chemotherapy completion. Methods Participants were randomly assigned to an 8-week, twice-weekly, supervised aerobic exercise training regime ( n  = 23) or a usual care group ( n  = 20). Feasibility was assessed by recruitment rate, program adherence and participant feedback. The primary outcome was aerobic fitness assessed by the Modified Bruce fitness test at baseline (0 weeks), post-intervention (8 weeks) and at 3-month follow-up. Secondary outcomes included physical activity, waist circumference, fatigue and quality of life. Results The recruitment rate was 81 % and adherence to the supervised exercise was 78.3 %. Meaningful differences in aerobic fitness between the exercise and usual care groups at both the 8-week [mean 3.0 mL kg −1 min −1 (95 % CI −1.1–7.0)] and 3-month follow-up [2.1 mL kg −1 min −1 (−2.3–6.6)] were found, although these differences did not achieve statistical significance ( p values >0.14). Self-reported physical activity increased in the exercise group (EG) compared to the usual care group at both 8-week ( p  = 0.01) and 3-month follow-up ( p  = 0.03) and significant differences in favour of the EG were found for physical well-being at both the 8-week ( p  = 0.03) and 3-month follow-up ( p  = 0.04). Improvements in fatigue ( p  = 0.01), total quality of life plus fatigue ( p  = 0.04), and a composite physical functioning score ( p  = 0.01) at the 3-month follow-up were also found. Conclusion The PEACH trial suggests that 8 weeks of supervised aerobic exercise training was feasible and may improve aerobic fitness, fatigue and quality of life in de-conditioned cancer survivors during the early survivorship phase. Implications for Cancer Survivors Exercise interventions commenced in the early survivorship phase appear safe, feasible and may lead to improvements in QOL and fatigue.

Background: Incidence of rectal gonorrhea (GC) has been hypothesized as a correlate of HIV exposure risk in HIV prevention trial cohorts, because both infections occur after condomless anal sex. High rectal GC rates might be a useful measure for selecting sites for HIV prevention or vaccine trials, and high rectal GC incidence in trial participants of new biomedical prevention drugs may provide supportive evidence for ongoing HIV risk. Methods: Rectal gonorrhea and HIV are routinely tested in sexual health clinics (SHCs) throughout England and pseudonymised, patient-level data are reported to Public Health England. Through evaluation of repeated visits to SHCs by individual clients, we assessed HIV incidence and new rectal GC diagnoses in HIV-negative MSM from 2010 to 2018, predating widespread roll-out of PrEP. We used meta-analysis regression to assess the population-level association between (log) HIV and rectal GC incidence over the 9 years, both overall and adjusted for geographic region. Results: Between 2010 to 2018, 625,273 MSM attended SHCs in England, 322,857 person years were included in the assessment of HIV incidence, 205,946 in assessment of rectal GC. HIV incidence assessed each calendar year among MSM attending SHCs fell from 1.45/100 PY in 2010 to 0.46/100 PY in 2018. Rectal GC rates increased from 20/100 PY to 34/100 PY over the same period. Figures 1a and b show a negative correlation between rectal GC and HIV both overall (slope = 0.139, p = <0.001), and when adjusted for different regions (slope = 0.100, p < 0.001). Conclusions: Among MSM attending SHCs in England, rectal GC incidence substantially increased while HIV incidence substantially decreased from 2010 to 2018. HIV incidence likely decreased through expanded HIV testing, prompt ART initiation and increased viral suppression in HIV-positive (U=U), interventions that did not decrease rectal GC. Interpretation of rectal gonorrhea as a correlate of HIV exposure risk is complex and context-dependent, given effective HIV prevention interventions in both HIV-positive and uninfected MSM.

In an open-label, randomized study involving men who have sex with men, doxycycline use after high-risk sexual exposure reduced the incidence of sexually transmitted infections (chlamydia, gonorrhea, and syphilis).

High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners. Participants in our prospective cohort analysis were from a randomised placebo-controlled trial that enrolled heterosexual African adults who were seropositive for both HIV-1 and herpes simplex virus type 2, and their HIV-1 seronegative partners. At enrolment, HIV-1 infected participants had CD4 counts of 250 cells per μL or greater and did not meet national guidelines for ART initiation; during 24 months of follow-up, CD4 counts were measured every 6 months and ART was initiated in accordance with national guidelines. Uninfected partners were tested for HIV-1 every 3 months. The primary outcome was genetically-linked HIV-1 transmission within the study partnership. We assessed rates of HIV-1 transmission by ART status of infected participants. 3381 couples were eligible for analysis. 349 (10%) participants with HIV-1 initiated ART during the study, at a median CD4 cell count of 198 (IQR 161–265) cells per μL. Only one of 103 genetically-linked HIV-1 transmissions was from an infected participant who had started ART, corresponding to transmission rates of 0·37 (95% CI 0·09–2·04) per 100 person-years in those who had initiated treatment and 2·24 (1·84–2·72) per 100 person-years in those who had not—a 92% reduction (adjusted incidence rate ratio 0·08, 95% CI 0·00–0·57, p=0·004). In participants not on ART, the highest HIV-1 transmission rate (8·79 per 100 person-years) was from those with CD4 cell counts lower than 200 cells per μL. In couples in whom the untreated HIV-1 infected partner had a CD4 cell count greater than 200 cells per μL, 66 (70%) of 94 transmissions occurred when plasma HIV-1 concentrations exceeded 50 000 copies per mL. Low CD4 cell counts and high plasma HIV-1 concentrations might guide use of ART to achieve an HIV-1 prevention benefit. Provision of ART to HIV-1 infected patients could be an effective strategy to achieve population-level reductions in HIV-1 transmission. Bill & Melinda Gates Foundation; US National Institutes of Health.