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BackgroundThe HIV Prevention Trials Network (HPTN) 083 trial showed that long-acting injectable cabotegravir was more effective than tenofovir disoproxil fumarate plus emtricitabine in preventing HIV in cisgender men and transgender women who have sex with men. We aimed to characterise the cohort of transgender women included in HPTN 083.MethodsHPTN 083 is an ongoing, phase 2b/3, randomised, multicentre, double-blind, double-dummy clinical trial done at 43 sites in seven countries (Argentina, Brazil, Peru, the USA, South Africa, Thailand, and Viet Nam). HIV-negative participants were randomly assigned (1:1) to receive injectable cabotegravir or tenofovir disoproxil fumarate plus emtricitabine. The study design and primary outcomes of the blinded phase of HPTN 083 have already been reported. An enrolment minimum of 10% transgender women was set for the trial. Here we characterise the cohort of transgender women enrolled from Dec 6, 2016, to May 14, 2020, when the study was unblinded. We report sociodemographic characteristics, use of gender affirming hormone therapy, and behavioural assessments of the transgender women participants. Laboratory testing and safety evaluations are also reported. The trial is registered at ClinicalTrials.gov, NCT02720094.FindingsHPTN 083 enrolled 570 transgender women (304 tenofovir disoproxil fumarate plus emtricitabine; 266 injectable cabotegravir). Transgender women were primarily from Asia (225 [39%]) and Latin America (205 [36%]); 330 (58%) reported using gender affirming hormone therapy. Intimate partner violence was common (270 [47%] reported emotional abuse and 172 [30%] reported physical abuse) and 323 (57%) reported a history of childhood sexual abuse. 159 (28%) transgender women disagreed that they were at risk for HIV, and 142 (25%) screened positive for depressive symptoms. During study follow-up, incidence of syphilis was 16·25% (95% CI 13·28-19·69), rectal gonorrhoea was 11·66% (9·14-14·66), and chlamydia was 20·61% (17·20-24·49). Frequency of adverse events was similar between the treatment groups. Nine seroconversions occurred among transgender women during the blinded phase of the study (seven in the tenofovir disoproxil fumarate plus emtricitabine group and two in the injectable cabotegravir group); overall incidence was 1·19 per 100 person-years (95% CI 0·54-2·25): 1·80 per 100 person-years (0·73-3·72) in the tenofovir disoproxil fumarate plus emtricitabine group and 0·54 per 100 person-years (0·07-1·95) in the injectable cabotegravir group (hazard ratio 0·34 [95% CI 0·08-1·56]). Cabotegravir concentrations did not differ by gender affirming hormone therapy use.InterpretationHIV prevention strategies for transgender women cannot be addressed separately from social and structural vulnerabilities. Transgender women were well represented in HPTN 083 and should continue to be prioritised in HIV prevention studies. Our results suggest that injectable cabotegravir is a safe and effective pre-exposure prophylaxis option for transgender women.FundingNational Institute of Allergy and Infectious Diseases and ViiV Healthcare.

BackgroundPatterns of antiretroviral therapy (ART) use and immunologic correlates vary globally, and contemporary trends are not well described.MethodsThe REPRIEVE trial (Randomized Trial to Prevent Vascular Events in HIV) enrolled persons with human immunodeficiency virus (HIV) who were aged 40-75 years, receiving ART, and had low-to-moderate cardiovascular disease risk. ART use was summarized within Global Burden of Disease (GBD) super-regions, with adjusted linear and logistic regression analyses examining associations with immune parameters and key demographics.ResultsA total of 7770 participants were enrolled, with a median age of 50 years (interquartile range, 45-55 years); 31% were female, 43% were black or African American, 15% were Asian, 56% had a body mass index >25 (calculated as weight in kilograms divided by height in meters squared), and 49% were current or former smokers. The median CD4 T-cell count was 620/µL (interquartile range, 447-826/ µ L), and the median duration of prior ART use, 9.5 years (5.3-14.8) years. The most common ART regimens were nucleoside/nucleotide reverse-transcriptase inhibitor (NRTI) plus nonnucleoside reverse-transcriptase inhibitor (43%), NRTI plus integrase strand transfer inhibitor (25%), and NRTI plus protease inhibitor (19%). Entry ART varied by GBD region, with shifts during the trial enrollment period. In adjusted analyses, entry CD4 cell count and CD4/CD8 ratio were associated with GBD region, sex, entry regimen, duration of ART, and nadir CD4 cell count; CD4 and CD8 cell counts were also associated with body mass index and smoking status.ConclusionsThere were substantial variations in ART use by geographic region and over time, likely reflecting the local availability of specific medications, changes in treatment guidelines and provider/patient preferences. The analyses of CD4 cell counts and CD4/CD8 ratios may provide valuable insights regarding immune correlates and outcomes in people living with HIV.Clinical trials registrationNCT02344290.

BackgroundReproductive aging may contribute to cardiometabolic comorbid conditions. We integrated data on gynecologic history with levels of an ovarian reserve marker (anti-müllerian hormone [AMH)] to interrogate reproductive aging patterns and associated factors among a subset of cisgender women with human immunodeficiency virus (WWH) enrolled in the REPRIEVE trial.MethodsA total of 1449 WWH were classified as premenopausal (n = 482) (menses within 12 months; AMH level ≥20 pg/mL; group 1), premenopausal with reduced ovarian reserve (n = 224) (menses within 12 months; AMH 12 months of amenorrhea). Excluding WWH with surgical menopause, age at final menstrual period was summarized for postmenopausal WWH (group 3) and estimated among all WWH (groups 1-3) using an accelerated failure-time model.ResultsCardiometabolic and demographic parameters associated with advanced reproductive age (controlling for chronologic age) included waist circumference (>88 vs ≤88 cm) (odds ratio [OR], 1.38; 95% confidence interval, 1.06-1.80; P = .02), hemoglobin (≥12 vs

T cell responses have been implicated in reduced risk of HIV acquisition in uninfected persons and control of viral replication in HIV-infected individuals. HIV Gag-specific T cells have been predominantly associated with post-infection control, whereas Env antigens are the target for protective antibodies; therefore, inclusion of both antigens is common in HIV vaccine design. However, inclusion of multiple antigens may provoke antigenic competition, reducing the potential effectiveness of the vaccine. HVTN 084 was a randomized, multicenter, double-blind phase 1 trial to investigate whether adding Env to a Gag/Pol vaccine decreases the magnitude or breadth of Gag/Pol-specific T cell responses. Fifty volunteers each received one intramuscular injection of 1 × 1010 particle units (PU) of rAd5 Gag/Pol and EnvA/B/C (3:1:1:1 mixture) or 5 × 109 PU of rAd5 Gag/Pol. CD4+ T cell responses to Gag/Pol measured 4 weeks after vaccination by cytokine expression were significantly higher in the group vaccinated without Env, whereas CD8+ T cell responses did not differ significantly between the two groups. Mapping of individual epitopes revealed greater breadth of the Gag/Pol-specific T cell response in the absence of Env compared to Env coimmunization. Addition of an Env component to a Gag/Pol vaccine led to reduced Gag/Pol CD4+ T cell response rate and magnitude as well as reduced epitope breadth, confirming the presence of antigenic competition. Therefore, T cell-based vaccine strategies should aim at choosing a minimalist set of antigens to reduce interference of individual vaccine components with the induction of the maximally achievable immune response.

Spectral indexes are tools widely used to analyze the composition of planetary surfaces. Many indexes have been formulated over the years to map the lunar surface, but there is no unified database for them. In this work we describe an Open‐Source Python package called MoonIndex, that recreates 38 indexes compiled from the literature, using data from the Moon Mineralogy Mapper (M3). The processing started with the filtering of the data cubes to reduce the noise, the continuum of the spectrum was then removed using a convex hull or a second‐and‐first‐order fit method. Later, the indexes were calculated, following as possible the original formulations. The results on spectral indexes calculated before the continuum removal were similar to those of the original formulations. Conversely, the results obtained for spectral indexes calculated after the continual removal were not always coherent. Some indexes, like the band depth, are especially sensitive to the removal method, as well as the derived band areas and asymmetries. We also recreated RGB composite maps, our results highlight the compositional patterns in a similar way as the ones in the literature, even if the color ramps can differ. The products of MoonIndex are open, ready for interpretation, versatile, consistent, and cross‐comparable. Plain Language Summary: Spectral indexes are parameters defined from the characteristics of reflectance spectra, and they are useful to investigate the spectral properties of a surface and to retrieve mineralogical properties of a planetary body. They can reveal the presence of specific minerals in rocks, indicate mineralogical variations from different units, highlight physical properties of a surface, or show the effect of the exposure to the space environment. For the Moon, several spectral indexes have been formulated over time using data from many spacecraft, but no unified database is available. In this work, we created an open‐source Python package called MoonIndex, which recreates 38 indexes to study the lunar surface. The indexes were collected from the literature, and our results achieved various levels of fidelity. Some of the indexes we calculated exactly reproduce those found in the literature, while in other cases, index calculations differ due to processing constraints or due to missing information in the original formulations, such as the continuum removal method used, or the band operations conducted to create the indexes. MoonIndex is a reliable and versatile tool to approach the compositional analysis of the lunar surface. Key Points: MoonIndex is an open‐source tool that successfully recreates spectral indexes for the Moon taken from the literatureThe continuum‐removal method has a major impact in the resulting indexes, so its selection should be considered when interpreting the dataThe indexes obtained with MoonIndex are consistent whit the results of previous authors, which usually used licensed software [ABSTRACT FROM AUTHOR]

: Introduction: ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second‐line protease inhibitor (PI)‐based antiretroviral therapy (ART) from 10 low‐ and middle‐income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third‐line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV‐1 RNA ≤200 copies/ml. We report here long‐term outcomes over 144 weeks. Methods: Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. “Extended Follow‐up” of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow‐up of ≥144 weeks), with HIV‐1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow‐up. Proportion of participants with HIV‐1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow‐up; mean CD4 count changes were estimated using loess regression. Results and Discussion: Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm[sup.3], and HIV‐1 RNA was 4.6 log[sub.10] copies/ml. Median follow‐up was 168 weeks (IQR: 156–204); 15 (6%) participants were lost to follow‐up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV‐1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74–85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm[sup.3] (95% CI 247–283). Conclusions: Third‐line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second‐line PI‐based ART prior to the availability of dolutegravir., INTRODUCTION Mathematical modelling suggests that by 2030, up to 4.6 million people living with HIV (PLWH) will require second‐line antiretroviral therapy (ART) globally [1]. Studies in Asia and Africa have [...]

BackgroundIn Peru, there is an increase in the creation of mobile health (mHealth) apps; however, this situation could present problems related to the quality of information these apps share, data security and privacy, usability, and effectiveness, as there is no specific local regulation about their creation and use. ObjectiveThe objective of this study was to review mHealth apps created, uploaded, or used in Peru, and perform an analysis of the national regulatory framework that could be applied to evaluate whether there is a need to develop and implement a specific regulation to these apps. MethodsA total of 3 reviews were performed. First, we reviewed information about Peruvian mHealth apps created up to May 2019 from scientific publications, news, government communications, and virtual stores, and evaluated their purpose, creator, and the available evidence of their usability and effectiveness. The second review was carried out by taking a sample of the 10 most commonly used mHealth apps in Peru (regardless of the country of creation), to evaluate the information they collect and classify them according to the possible risks that they could present in terms of security and privacy. In addition, we evaluated whether they refer to or endorse the information they provided. Finally, in the third review, we searched for Peruvian standards related to electronic health (eHealth) that involve information technology that can be applied to regulate these apps. ResultsA total of 66 apps meeting our inclusion criteria were identified; of these, 47% (n=31) belonged to government agencies and 47% (n=31) were designed for administrative purposes (private and government agencies). There was no evidence about the usability or effectiveness of any of these apps. Concerning the 10 most commonly used mHealth apps in Peru, about the half of them gathered user information that could be leaked, changed, or lost, thus posing a great harm to their users or to their related patients. In addition, 6/10 (60%) of these apps did not mention the source of the information they provided. Among the Peruvian norms, the Law on the Protection of Personal Data, Law on Medical Devices, and administrative directives on standards and criteria for health information systems have some regulations that could be applied to these apps; however, these do not fully cover all aspects concerning the evaluation of security and privacy of data, quality of provided information, and evidence of an app’s usability and effectiveness. ConclusionsBecause many Peruvian mHealth apps have issues related to security and privacy of data, quality of information provided, and lack of available evidence of their usability and effectiveness, there is an urgent need to develop a regulatory framework based on existing medical device and health information system norms in order to promote the evaluation and regulation of all the aforesaid aspects, including the creation of a national repository for these apps that describes all these characteristics.