Background In Peru, one-third of transgender women (TW) are estimated to be living with HIV. While TW are recognized as a priority population, their sexual partners are an at-risk hidden population ...with unmet needs for HIV services. We conducted a study examining the practices and preferences for HIV services among partners of transgender women (PTW), as compared to TW, to better understand the needs of PTW and inform HIV service delivery for them in Peru. Methods Between July-October 2022 we conducted a cross-sectional mixed methods study among PTW and TW in Lima, Peru. Using an explanatory sequential design, we administered online surveys to PTW (n = 165) and TW (n = 69), then interviewed a subset of participants (n = 20: 16 PTW, 4 TW). We quantitatively and qualitatively described PTW practices/perspectives on HIV testing and treatment and compared them to TW practices/preferences; we also compared practices/preferences among PTW based on their relationship with TW. Results Overall, PTW and TW shared similar experiences and preferences for HIV testing/treatment, but fewer PTW reported accessing non-traditional HIV testing options and PTW expressed less strong preferences for HIV services. PTW practices/preferences varied by type of relationship with TWs. Surveys and interviews highlighted a need to prioritize efficiency for HIV testing, eliminate gender/sexuality-based discrimination in healthcare settings, increase privacy when delivering HIV services, and increase awareness of pre-exposure prophylaxis. Conclusion PTW identified many aspects related to the location, convenience, and privacy of HIV services as important. Next steps could include a discrete choice experiment to further clarify priorities for HIV services for PTW in Peru.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In Peru, there is an ongoing high-incidence HIV epidemic among men who have sex with men (MSM) and transgender women (TW). Sexual concurrency, or having sex with a partner in between two acts of sex ...with another partner, may be a key factor in onward HIV transmission. In this study, we quantify concurrency, evaluate factors associated with concurrency, and assess condom use with concurrent partners among MSM and TW in Peru.
We conducted a secondary analysis of data from the 2011 Peruvian Biobehavioral Survey. Pearson's Chi-squared test was used to identify individual-level characteristics associated with concurrency. We estimated the association between participant characteristics, concurrent partnerships, partnership type (stable vs. non-stable), and CLAI within the context of concurrent partnerships using multivariate and repeated-measure Poisson regression.
3-month cumulative prevalence of concurrency was higher among TW compared to MSM (30.7% vs 25.2%, p = 0.014). Among those with concurrent stable and non-stable partners, 45% used condoms with both partners (95% CI: 40%-50%) and 30% preferentially had CLAI with the stable partner only (95%CI: 26%-35%). Factors associated with CLAI within the context of concurrent partnerships varied between MSM and TW.
Although concurrency is common among TW and MSM in Peru, patterns of concurrency and differential condom use may vary between TW and MSM. Future research may explore differential condom use with stable and non-stable partners to better understand behavioral factors that may alter vulnerability to HIV in TW compared to MSM.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Innovative approaches are needed to increase lay health workers in HIV programs. The Youth Health Africa (YHA) program is a novel approach that places young adults seeking work experience in one-year ...internships in health facilities to support HIV-related programming (e.g., HIV testing) or administration (e.g., filing).
We implemented a pragmatic, randomized trial among 20 facilities in Ngaka Modiri Molema district in North West province from October 2020-August 2021 to assess impact of YHA interns on HIV testing, treatment initiation, and retention in care. The primary outcome was proportion of patients tested for HIV. Secondary outcomes assessed HIV positivity, initiation in care, retention in care, and HIV testing among males and adolescents/young adults. We conducted an intention-to-treat analysis accounting for variations in baseline outcomes between control and intervention facilities using difference-in-difference and controlled time series approaches. We repeated this using as-treated groupings for sensitivity analyses.
Fifty interns were placed in 20 facilities; thirty-four interns remained at 18 facilities through August 2021. Compared to control facilities, intervention facilities had a greater improvement in HIV testing (ΔΔ+5.7%, 95% Confidence Interval (CI): -3.7%-15.1%) and treatment initiation (ΔΔ+10.3%, 95% CI: -27.8-48.5%), but these differences were not statistically significant. There was an immediate increase in HIV testing in intervention facilities after program interns were placed, which was not observed in control facilities; this difference was significant (ΔΔ+8.4%, 95% CI: 0.5-16.4%, p = 0.036). There were no other differences in outcomes observed between intervention and control facilities.
This was largely a null trial, but there were signals that program interns may have positive impact on HIV testing and treatment initiation. As implemented in this study, addition of YHA program interns had little impact on facility-based HIV service delivery. A higher number of interns placed per facility may be necessary to affect HIV services.
Registration: This trial was registered with the ISRCTN (Registration number: ISRCTN67031403) in October 2022.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation (“immediate”, at diagnosis, versus “deferred”, at 24 weeks ...post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women, we conducted a retrospective study comparing inflammatory biomarkers in participants’ specimens collected before infection and after ≥2 years of effective ART. We measured biomarkers in four longitudinally collected plasma, including two specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression. Biomarkers were quantified by enzyme-linked immuno-assay or Meso Scale Discovery. When evaluating systematic variation in these markers over time, we found that multiple biomarkers consistently varied across participants’ two pre-infection or two post-ART-suppression specimens. Additionally, we compared changes in biomarkers after vs before HIV acquisition. Across 47 participants, the levels of C-reactive protein (CRP), monocyte chemo-attractant protein-1, tumor necrosis factor-α and interferon gamma-induced protein-10 significantly increased while leptin and lipopolysaccharide binding protein (LBP) significantly decreased following HIV infection. Randomization to deferred-ART initiation was associated with greater increases in CRP and no decrease in LBP. Acquisition of HIV appeared to induce systemic inflammation, with elevation of biomarkers previously associated with infections and cardiovascular disease. Initiation of ART during the early weeks of infection tempered the increase in pro-inflammatory biomarkers compared to delaying ART for ~24 weeks after HIV diagnosis. These findings provide insight into potential mediators by which immediate-ART initiation improves health outcomes, perhaps because immediate-ART limits the size of the HIV reservoir or limits immune dysregulation that in turn trigger systemic inflammation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To better understand how innate immune responses to vaccination can lead to lasting protective immunity, we used a systems approach to define immune signatures in humans over 1 wk following ...MRKAd5/HIV vaccination that predicted subsequent HIV-specific T-cell responses. Within 24 h, striking increases in peripheral blood mononuclear cell gene expression associated with inflammation, IFN response, and myeloid cell trafficking occurred, and lymphocyte-specific transcripts decreased. These alterations were corroborated by marked serum inflammatory cytokine elevations and egress of circulating lymphocytes. Responses of vaccinees with preexisting adenovirus serotype 5 (Ad5) neutralizing antibodies were strongly attenuated, suggesting that enhanced HIV acquisition in Ad5-seropositive subgroups in the Step Study may relate to the lack of appropriate innate activation rather than to increased systemic immune activation. Importantly, patterns of chemoattractant cytokine responses at 24 h and alterations in 209 peripheral blood mononuclear cell transcripts at 72 h were predictive of subsequent induction and magnitude of HIV-specific CD8 ⁺ T-cell responses. This systems approach provides a framework to compare innate responses induced by vectors, as shown here by contrasting the more rapid, robust response to MRKAd5/HIV with that to yellow fever vaccine. When applied iteratively, the findings may permit selection of HIV vaccine candidates eliciting innate immune response profiles more likely to drive HIV protective immunity.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Summary Background Observational data and non-human primate challenge studies suggest that cell-mediated immune responses might provide control of HIV replication. The Step Study directly assessed ...the efficacy of a cell-mediated immunity vaccine to protect against HIV-1 infection or change in early plasma HIV-1 levels. Methods We undertook a double-blind, phase II, test-of-concept study at 34 sites in North America, the Caribbean, South America, and Australia. We randomly assigned 3000 HIV-1-seronegative participants by computer-generated assignments to receive three injections of MRKAd5 HIV-1 gag/pol/nef vaccine (n=1494) or placebo (n=1506). Randomisation was prestratified by sex, adenovirus type 5 (Ad5) antibody titre at baseline, and study site. Primary objective was a reduction in HIV-1 acquisition rates (tested every 6 months) or a decrease in HIV-1 viral-load setpoint (early plasma HIV-1 RNA measured 3 months after HIV-1 diagnosis). Analyses were per protocol and modified intention to treat. The study was stopped early because it unexpectedly met the prespecified futility boundaries at the first interim analysis. This study is registered with ClinicalTrials.gov , number NCT00095576. Findings In a prespecified interim analysis in participants with baseline Ad5 antibody titre 200 or less, 24 (3%) of 741 vaccine recipients became HIV-1 infected versus 21 (3%) of 762 placebo recipients (hazard ratio HR 1·2 95% CI 0·6–2·2). All but one infection occurred in men. The corresponding geometric mean plasma HIV-1 RNA was comparable in infected male vaccine and placebo recipients (4·61 vs 4·41 log10 copies per mL, one tailed p value for potential benefit 0·66). The vaccine elicited interferon-γ ELISPOT responses in 75% (267) of the 25% random sample of all vaccine recipients (including both low and high Ad5 antibody titres) on whose specimens this testing was done (n=354). In exploratory analyses of all study volunteers, irrespective of baseline Ad5 antibody titre, the HR of HIV-1 infection between vaccine and placebo recipients was higher in Ad5 seropositive men (HR 2·3 95% CI 1·2–4·3) and uncircumcised men (3·8 1·5–9·3), but was not increased in Ad5 seronegative (1·0 0·5–1·9) or circumcised (1·0 0·6–1·7) men. Interpretation This cell-mediated immunity vaccine did not prevent HIV-1 infection or reduce early viral level. Mechanisms for insufficient efficacy of the vaccine and the increased HIV-1 infection rates in subgroups of vaccine recipients are being explored. Funding Merck Research Laboratories; the Division of AIDS, National Institute of Allergy and Infectious Diseases, in the US National Institutes of Health (NIH); and the NIH-sponsored HIV Vaccine Trials Network (HVTN).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PURPOSE OF REVIEWTwo phase IIb test-of-concept studies evaluated the replication-defective adenovirus type 5 (Ad5) vaccine MRK gag/pol/nef HIV vaccine to prevent infection or decrease early plasma ...viral load in disparate populations. The STEP study enrolled men and women in the Americas, Caribbean and Australia; the Phambili trial enrolled men and women in South Africa, where the modes of sexual transmission and HIV-1 risk, subtypes of HIV-1, and background Ad5 seroprevalence differed.
RECENT FINDINGSVaccination in both studies were stopped, after the first interim efficacy analysis of the STEP study crossed predetermined nonefficacy boundaries. Neither trial demonstrated a decrease in HIV acquisition nor decreased early plasma viral load in vaccinees compared with placebo recipients. Post-hoc analyses of men enrolled in the STEP study showed a larger number of HIV infections in the subgroup of vaccinated men who were Ad5-seropositive and uncircumcised compared with a comparable placebo group. This was not demonstrated in the Phambili study, in which most men were heterosexual, whereas most in STEP were homosexual/bisexual. Further analysis of the STEP study has yet to explain the effect of Ad5 seroprevalence on increased HIV-1 susceptibility in men receiving the vaccine. However, promising vaccine effects on early viral control were seen, and the possibility of effects on early viral load set-point in women in Phambili was seen.
SUMMARYThese trials have provided a number of lessons about the importance of clinical trials in the HIV vaccine discovery process, and insight into the type and level of immune response that will be required for control of viral replication.
In sub-Saharan Africa (SSA), adolescent girls and young women (AGYW) ages 15 to 24 years represent <10% of the population yet account for 1 in 5 new HIV infections. Although oral pre-exposure ...prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) can be highly effective, low persistence in PrEP programs and poor adherence have limited its ability to reduce HIV incidence among women. A total of 336 AGYW participating in the PEPFAR-funded DREAMS PrEP program in western Kenya were enrolled into a study of PrEP use conducted between 6/2019 to 1/2020. AGYW, who used daily oral TDF/FTC, completed interviews and provided dried blood spots (DBS) for measurement of tenofovir-diphosphate (TFV-DP) concentrations at enrollment and 3 months later, and 176/302 (58.3%, 95% confidence interval 95% CI 52.3 to 63.8) met our definition of PrEP persistence: having expressed intention to use PrEP and attended both the second interview and an interim refill visit. Among AGYW with DBS taken at the second interview, only 9/197 (4.6%, 95% CI 1.6 to 7.5) had protective TFV-DP levels (greater than or equal to700 fmol/punch) and 163/197 (82.7%, 95% CI 77.5 to 88) had levels consistent with no recent PrEP use (<10 fmol/punch). Perception of being at moderate-to-high risk for HIV if not taking PrEP was associated with persistence (adjusted odds ratio, 10.17 95% CI 5.14 to 20.13, p < 0.001) in a model accounting for county of residence and variables that had p-value 90% indicated they were using PrEP to prevent HIV, although almost all had non-protective TFV-DP levels. Limitations included short study duration and inclusion of only DREAMS participants. Many AGYW persisted in the PrEP program without taking PrEP frequently enough to receive benefit. Notably, AGYW who persisted had a higher self-perceived risk of HIV infection. These AGYW may be optimal candidates for long-acting PrEP.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Lay health workers (LHWs) can support the HIV response by bridging gaps in human resources for health. Innovative strategies are needed to expand LHW programs in many low- and middle-income ...countries. Youth Health Africa (YHA) is a novel LHW approach implemented in South Africa that places young adults needing work experience in one-year non-clinical internships at health facilities to support HIV programs (e.g., as HIV testers, data clerks). While research suggests YHA can increase HIV service delivery, we need to understand healthcare worker perceptions to know if this is an acceptable and appropriate approach to strengthen human resources for health and healthcare delivery.
We conducted a convergent mixed methods study to assess healthcare worker acceptance and perceived appropriateness of YHA as implemented in Gauteng and North West provinces, South Africa and identify issues promoting or hindering high acceptability and perceived appropriateness. To do this, we adapted the Johns Hopkins Measure of Acceptability and Appropriateness to survey healthcare workers who supervised interns, which we analyzed descriptively. In parallel, we interviewed frontline healthcare workers who worked alongside YHA interns and conducted an inductive, thematic analysis. We merged quantitative and qualitative results using the Theoretical Framework of Acceptability to understand what promotes or hinders high acceptance and appropriateness of YHA.
Sixty intern supervisors responded to the survey (91% response rate), reporting an average score of 3.5 for acceptability and 3.6 for appropriateness, on a four-point scale. Almost all 33 frontline healthcare workers interviewed reported the program to be highly acceptable and appropriate. Perceptions that YHA was mutually beneficial, easy to integrate into facilities, and helped facilities be more successful promoted a strong sense of acceptability/appropriateness amongst healthcare workers, but this was tempered by the burden of training interns and limited program communication. Overall, healthcare workers were drawn to the altruistic nature of YHA.
Healthcare workers in South Africa believed YHA was an acceptable and appropriate LHW program to support HIV service delivery because its benefits outweighed its costs. This may be an effective, innovative approach to strengthen human resources for HIV services and the broader health sector.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Since 2018, Youth Health Africa (YHA) has placed unemployed young adults at health facilities across South Africa in 1‐year non‐clinical internships to support HIV services. While YHA is ...primarily designed to improve employment prospects for youth, it also strives to strengthen the health system. Hundreds of YHA interns have been placed in programme (e.g. HIV testing and counselling) or administrative (e.g. data and filing) roles, but their impact on HIV service delivery has not been evaluated.
Methods
Using routinely collected data from October 2017 to March 2020, we conducted an interrupted time‐series analysis to explore the impact of YHA on HIV testing, treatment initiation and retention in care. We analysed data from facilities in Gauteng and North West where interns were placed between November 2018 and October 2019. We used linear regression, accounting for facility‐level clustering and time correlation, to compare trends before and after interns were placed for seven HIV service indicators covering HIV testing, treatment initiation and retention in care. Outcomes were measured monthly at each facility. Time was measured as months since the first interns were placed at each facility. We conducted three secondary analyses per indicator, stratified by intern role, number of interns and region.
Results
Based on 207 facilities hosting 604 interns, YHA interns at facilities were associated with significant improvements in monthly trends for numbers of people tested for HIV, newly initiated on treatment and retained in care (i.e. loss to follow‐up, tested for viral load VL and virally suppressed). We found no difference in trends for the number of people newly diagnosed with HIV or the number initiating treatment within 14 days of diagnosis. Changes in HIV testing, overall treatment initiation and VL testing/suppression were most pronounced where there were programme interns and a higher number of interns; change in loss to follow‐up was greatest where there were administrative interns.
Conclusions
Placing interns in facilities to support non‐clinical tasks may improve HIV service delivery by contributing to improved HIV testing, treatment initiation and retention in care. Using youth interns as lay health workers may be an impactful strategy to strengthen the HIV response while supporting youth employment.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
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