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Prostate cancer (PCa) incidence is reportedly lower in men with HIV compared to men without HIV for unknown reasons. We describe PCa incidence by HIV status in Medicaid beneficiaries, allowing for comparison of men with and without HIV who are similar with respect to socioeconomic characteristics and access to healthcare. Men (N = 15,167,636) aged 18–64 with ≥7 months of continuous enrollment during 2001–2015 in 14 US states were retained for analysis. Diagnoses of HIV and PCa were identified using non-drug claims. We estimated cause-specific (csHR) comparing incidence of PCa by HIV status, adjusted for age, race-ethnicity, state of residence, year of enrollment, and comorbid conditions, and stratified by age and race-ethnicity. Hazard of PCa was lower in men with HIV than men without HIV (csHR = 0.89; 95% CI: 0.80, 0.99), but varied by race-ethnicity, with similar observations among non-Hispanic Black (csHR = 0.79; 95% CI: 0.69, 0.91) and Hispanic (csHR = 0.85; 95% CI: 0.67, 1.09), but not non-Hispanic white men (csHR = 1.17; 95% CI: 0.91, 1.50). Findings were similar in models restricted to men aged 50–64 and 40–49, but not in men aged 18–39. Reported deficits in PCa incidence by HIV status may be restricted to specific groups defined by age and race ethnicity. [ABSTRACT FROM AUTHOR]

Long-acting injectable (LAI) antiretroviral therapy (ART) is available to people with HIV (PWH), but it is unknown which PWH prefer this option. Using the Andersen Behavioral Model this study identifies characteristics of PWH with greater preference for LAI ART. Cross-sectional data from the Florida Cohort, which enrolled adult PWH from community-based clinics included information on predisposing (demographics), enabling (transportation, income), and need (ART adherence <90%) factors. ART preference was assessed via a single question (prefer pills, quarterly LAI, or no preference). Confounder-adjusted multinomial logistic regressions compared those who preferred pills to the other preference options, with covariates identified using directed acyclic graphs. Overall, 314 participants responded (40% non-Hispanic Black, 62% assigned male, 63% aged 50+). Most (63%) preferred the hypothetical LAI, 23% preferred pills, and 14% had no preference. PWH with access to a car (aRRR 1.97 95%CI 1.05–3.71), higher income (aRRR 2.55 95%CI 1.04–6.25), and suboptimal ART adherence (aRRR 7.41 95% CI 1.52–36.23) were more likely to prefer the LAI, while those who reported having no social network were less likely to prefer the LAI (aRRR 0.32 95% CI 0.11–0.88). Overall LAI interest was high, with greater preference associated with enabling and need factors. [ABSTRACT FROM AUTHOR]

Disparities in HIV care by socioeconomic status, place of residence, and race/ethnicity prevent progress toward epidemic control. No study has comprehensively characterized the HIV care cascade among people with HIV enrolled in Medicaid – an insurance source for low-income individuals in the US. We analyzed data from 246,127 people with HIV enrolled in Medicaid 2001–2015, aged 18–64, living in 14 US states. We estimated the monthly prevalence of four steps of the care cascade: retained in care/adherent to ART; retained/not adherent; not retained/adherent; not retained/not adherent. Beneficiaries were retained in care if they had an outpatient care encounter every six months. Adherence was based on medication possession ratio. We estimated prevalence using a non-parametric multi-state approach, accounting for death as a competing event and for Medicaid disenrollment using inverse probability of censoring weights. Across 2001–2015, the proportion of beneficiaries with HIV who were retained/ART adherent increased, overall and in all subgroups. By 2015, approximately half of beneficiaries were retained in care, and 42% of beneficiaries were ART adherent. We saw meaningful differences by race/ethnicity and region. Our work highlights an important disparity in the HIV care cascade by insurance status during this time period. [ABSTRACT FROM AUTHOR]

The journey towards ending AIDS epidemic in Bangladesh by 2030 is ambitious yet achievable. Although Bangladesh has always had a low rate of HIV among its general population, it remains one of seven countries in Asia and the Pacific where new HIV cases are rising. This study evaluates the effectiveness of HIV programmatic strategies and investment scenarios using the AIDS Epidemic Model (AEM) from 2023 to 2030, focusing on optimizing resource allocation and interventions. The findings indicate that without improved program effectiveness, new HIV infections will increase to 1,382 by 2030, failing to meet the targets of the Global AIDS Strategy 2021–2026. If Bangladesh improves its HIV program effectiveness according to the Global AIDS Strategy 2021–2026, the NSP and Global AIDS Strategy targets could significantly lower new infections and AIDS-related deaths and increase treatment coverage to meet Ending AIDS targets. The NSP targets could reduce new HIV infections to under 275 annually and achieve treatment goals by 2030. The study reveals that NSP targets are the most cost-effective, offering the highest benefit-cost ratio, highlighting the urgent need to enhance HIV prevention program effectiveness, particularly among key populations, to achieve both public health and economic benefits. [ABSTRACT FROM AUTHOR]

Weight gain effects of Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in people with HIV (PWH) have been sparsely studied. Participants were enrolled in the Copenhagen Comorbidity in HIV Infection (COCOMO) study. PWH receiving a backbone of emtricitabine, or lamivudine combined with abacavir, tenofovir disoproxil, or tenofovir alafenamide were analysed. Weight gain according to ART backbone and to the third drug was analysed using a multiple linear regression model. Non-ART risk factors were also determined using multiple linear regression. A total of 591 participants were included in the analysis. The majority were middle-aged, virally suppressed males with a mean BMI just above the normal range. Both tenofovir disoproxil/emtricitabine or lamivudine and abacavir /emtricitabine or lamivudine, but not tenofovir alafenamide /emtricitabine or lamivudine were associated with weight gain over two years (0.6 kg, p = 0.025; 1.0 kg, p = 0.005). The third drugs associated with weight increase were non-nucleoside reverse transcriptase inhibitors (NNRTI) (p = 0.035), dolutegravir (p = 0.008) and atazanavir (p = 0.040). Non-ART risk factors for gaining weight were low or normal BMI, age <40 years, underweight, inactivity or highly active at baseline. Tenofovir disoproxil and abacavir-based ART regimens were associated with a small weight gain. Third drug NNRTI, dolutegravir and atazanavir were associated with an increase in weight. [ABSTRACT FROM AUTHOR]

Many older adults living with HIV face unique challenges, including comorbidities, loneliness, and isolation. This community-academic partnered study elicited viewpoints from older adults living with HIV about the characteristics of a digital environment ("Virtual Village") to combat against loneliness and isolation. We utilized Choice-Based Conjoint Analyses to determine preferred attributes of a Virtual Village. We also conducted focus groups and interviews with older adults living with HIV and used an iterative, data-driven approach to systematically identify emergent themes. Participants (N = 82) were aged 50–82 years and racially/ethnically diverse. The majority were men (78%), gay (66%), and lived with HIV for ≥15 years (83%). Cost was the factor that most drove participants' preference for joining a Virtual Village. Thematic concerns included lack of technological confidence, internet access, potential for harassment in digital environments, privacy, and preference for in-person interactions. Praises centered on convenience and making connections across geographic distances. Participants emphasized the need for purposive strategies to form a cohesive and supportive community for older adults living with HIV. A moderated environment was recommneded to create a safe, structured, and comfortable digital environment for older adults living with HIV. A Virtual Village should be viewed as a bridge to in-person interactions. [ABSTRACT FROM AUTHOR]

Migrants often encounter heightened health risks during crises. We analysed the disparities in the burden of HIV between Japanese nationals and international migrants in Japan by comparing new HIV infections, AIDS cases, and HIV-related deaths between 2018–2019 (pre-COVID-19) and 2020–2021 (during the COVID-19 pandemic). Between 2018 and 2021, 4,705 new HIV infections were reported in Japan (2,813 Japanese nationals and 522 international migrants). Additionally, 1,370 AIDS cases (1,188 Japanese nationals, 182 international migrants) were recorded, representing 29.1% of the total. Comparative analysis of HIV incidence and mortality rates between Japanese nationals and international migrants indicates elevated disparities: During the COVID-19 pandemic, the HIV incidence rate among Japanese nationals decreased from 1.8 to 1.5 cases/100,000 people, while the rate among international migrants remained high at 12.8 cases/100,000 people. The AIDS incidence also increased for international migrants from 2.8 to 3.8 per 100,000 people, while Japanese nationals maintained a low at 0.5 per 100,000 people. International migrants living with HIV experienced a significantly younger age at death due to HIV-related illness (coefficient = −11.7, p <.01). The COVID-19 pandemic may have exacerbated the disparities with more international migrants living with HIV being diagnosed late and with less precise reporting. Investment in more equitable HIV care is warranted. [ABSTRACT FROM AUTHOR]

Retention in HIV care is a critical precursor to ending the epidemic yet remains suboptimal in the United States. Gaining an understanding of the challenges faced by adolescents and young adults (AYA) living with HIV is essential to improving retention in HIV care. This study explored the barriers and facilitators to retention in care among Black and Hispanic AYA living with HIV. Audio-recorded semi-structured interviews were conducted with 20 AYA living with HIV ages 16–29 years in New York City. Our methods entailed an inductive content analysis to explore key concepts, reconcile codes, and identify a theme, categories, and subcategories. Bronfenbrenner's socioecological model evolved as an organizing framework around barriers and facilitators to retention in care at the individual, interpersonal, healthcare system, and structural level. Data analysis yielded one overarching theme—the influence of psychosocial factors on retention in HIV care. Psychological struggles, powerlessness, clinic-level characteristics, and socioeconomic struggles were barriers reported by participants. Self-responsibility, social support, patient-friendly healthcare services, and socioeconomic resources emerged as facilitators. Retention in HIV care among AYA living with HIV is a multifaceted and complex phenomenon that involves multiple systems. Strengthening patients, healthcare system, and community partnerships can help address some of the HIV-related health disparities. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) has been adopted as a form of HIV treatment and prevention. This study assesses rapid ART initiation using clinical outcomes such as viral load (VL) and CD4+ T lymphocytes count. Over the course of one year, the progress of newly diagnosed people living with HIV who started ART early in a hospital in Panama City was followed. The evaluation of early initiation of ART in achieving viral suppression (VL <200 copies/ml) was analyzed using descriptive statistics. Additionally, the cost difference between early (first 7 days) and late initiation of ART was evaluated from the perspective of the service provider. In total, 209 people were followed up during the study; 85% were male, 70% started ART on same day from hospital arrival, 80% had suppressed viral load at 6 months, and the median count of CD4 increased from 285 (IQR: 166–429) to 509 (IQR: 373–696) over 12 months. Starting ART early led to a 42% increase for the provider in terms of staffing costs; however, the clients had the opportunity to decrease absenteeism in daily activities. The results reveal that early initiation of ART generates clinical and economic benefits for the person in treatment. [ABSTRACT FROM AUTHOR]

Justice-impacted persons may inconsistently access HIV testing. This cross-sectional secondary analysis investigates lifetime HIV testing prevalence among adults with prior histories of incarceration in Southern California, United States, participating in health-focused programming (n = 3 studies). Self-reported demographic and lifetime HIV testing data were collected between 2017–2023; descriptive analyses were conducted. Across the three samples, at least 74% of participants were male; Latino and African American individuals accounted for nearly two-thirds of participants. Lifetime HIV testing ranged from 72.8% to 84.2%. Males were significantly more likely than females to report never being tested in two samples and accounted for >95% of those never tested. No statistically significant differences in testing were observed by race/ethnicity. Single young adults (ages 18–26) were less likely than their partnered peers to report testing. HIV testing is critical for ensuring that individuals access prevention and treatment. HIV testing among justice-impacted adults in this study was higher than in the general population, potentially due to opt-out testing in correctional settings. Nevertheless, these findings underscore the importance of implementing targeted interventions to reduce structural (e.g., health insurance, access to self-testing kits) and social barriers (e.g., HIV stigma) to increase HIV testing among justice-impacted males and single young adults. [ABSTRACT FROM AUTHOR]

The federal Ending the HIV Epidemic (EHE) initiative was created to reduce new US HIV infections, largely through pre-exposure prophylaxis and HIV treatments that reduce HIV transmissibility to zero. Behavioral health disorders (mental health and substance use) remain significant barriers to achieving EHE goals. Addressing behavioral health (BH) disorders within HIV primary care settings has been promoted as a critical EHE strategy. Implementation of efficacious HIV-BH care integration and its impact on HIV-related health outcomes is not well documented. In a federally-funded, exploratory phase implementation science study, we used the Collective Impact Framework to engage partners in seven EHE jurisdictions about the feasibility, acceptability, and sustainability of implementing HIV-BH integration interventions within local HIV settings. Partners concluded that full integration will remain the exception unless health systems invest in collaborative practice, professional training, appropriate health technology, and inter-system communication. Partners supported smaller incremental improvements including transdiagnostic approaches to reinforce each team member's sense of value in the shared endeavor. This early phase implementation science study identified research and implementation gaps that are critical to fill to end the HIV epidemic. Both the Collective Impact Framework and implementation science show promise for guiding future implementation of evidence-based HIV-BH intervention integration. [ABSTRACT FROM AUTHOR]

Women living with HIV in Sub-Saharan Africa struggle for health equity while also facing the constraints of economic hardship and patriarchy. In this article, we describe the experiences of women who participated in economic empowerment groups for women living with HIV in Wakiso district, Uganda. Fifty women engaged in economic empowerment groups and ten social worker and community health worker key informants enrolled in the study. Taking a phenomenological approach, we used field notes, qualitative interviews, and focus groups with participants and key informants to describe the experiences of the women who joined the groups. We present the findings including enhanced management of HIV and increased property and business ownership due to economic empowerment group participation. We discuss the findings through an economic empowerment framework and offer implications for social work interventions and research. [ABSTRACT FROM AUTHOR]

Purpose: Therapeutic drug monitoring (TDM) is a standard clinical procedure that uses the pharmacokinetic and pharmacodynamic parameters of the drug in the body to determine the optimal dose. The pharmacokinetic variability of the drug(s) is a significant contributor to poor treatment outcomes, including the development of acquired drug resistance. TDM aids in dose optimization and improves outcomes while lessening drug toxicity. TDM is used to manage patients with tuberculosis (TB) who exhibit a slow response to therapy, despite good compliance and drug-susceptible organisms. Additional indications include patients at risk of malabsorption or delayed absorption of TB drugs and patients with drug-drug interaction and drug toxicity, which confirm compliance with therapy. TDM usually requires two blood samples: the 2 h and the 6 h post-dose. This narrative review will discuss the pharmacokinetics and pharmacodynamics of TB drugs, determinants of poor response to therapy, indications of TDM, methods of performing TDM, and its interpretations. Methods: This is a narrative review. We searched PubMed, Embase, and the CINAHL from inception to April 2024. We used the following search terms: tuberculosis, therapeutic drug monitoring, anti-TB drugs, pharmacokinetics, pharmacodynamics, limited sample strategies, diabetes and TB, HIV and TB, and multidrug-resistant TB. All types of articles were selected. Results: TDM is beneficial in managing TB, especially in patients with slow responses, drug-resistance TB, recurrent TB, and comorbidities such as diabetes mellitus and human immunodeficiency virus infection. Conclusion: TDM is beneficial for improving outcomes, reducing the risk of acquired drug resistance, and avoiding side effects. [ABSTRACT FROM AUTHOR]

Introduction: HIV self-testing is a complementary screening strategy that could facilitate access to HIV care services for street adolescents. The objectives of this study were to assess the acceptability and feasibility of HIV self-testing and their associated factors, to estimate HIV prevalence among street adolescents in Togo, and to describe the sexual behavior of this population. Methods: A cross-sectional study was conducted between July 2021 and May 2022 in Lomé and Kara (Togolese cities with the highest number of street adolescents). Street adolescents aged 13–19 years were included. An oral HIV self-test (OraQuick®) was used. Acceptability was defined as the proportion of adolescents who completed the test, and feasibility was defined as the proportion of adolescents who reported a test with a valid result. An HIV serological test was performed for all participants. A weighted logistic regression model was used to identify the factors associated with the acceptability and feasibility of HIV self-testing. Results: A total of 432 street adolescents (12.3% female) with a median age of 15 years, interquartile range (IQR) [14–17], were included in this study. Of the 231 sexually active adolescents, only 30.3% (n = 70) reported having used a condom during their last sexual intercourse. HIV self-test was offered to a sub-sample of 294 street adolescents. Acceptability was 96.6% (284/294), (95%CI = [93.8–98.3]) and feasibility 98.9% (281/284), (95%CI = [97.0–100.0]). Being 16 years of age or older (aOR = 28.84; p<0.001) was associated with HIV self-test acceptability. Reporting drug abuse (aOR = 0.47; p = 0.020) was negatively associated to acceptability. Having an educational level at least equivalent to secondary school was associated to HIV self-testing feasibility (aOR = 3.92; p = 0.040). Self-test results were correctly interpreted by 98.6% of street adolescents. HIV prevalence was estimated at 0.9% (95%CI [0.4–2.4]). Conclusion: HIV self-testing is acceptable and feasible among street adolescents, a population at high risk of HIV infection in Togo. The provision of HIV self-testing kits, coupled with condom distribution, represents an opportunity to improve access to HIV care services. [ABSTRACT FROM AUTHOR]

Background: Women in sub-Saharan Africa are disproportionately affected by the HIV epidemic. Young women are twice as likely to be living with HIV as men of the same age and account for 64% of new HIV infections among young people. Many studies suggest that financial needs, alongside biological susceptibility, are a leading cause of the gender disparity in HIV acquisition. New robust evidence suggests women adopt risky sexual behaviours to cope with economic shocks, the sudden decreases in household's income or consumption power, enhancing our understanding of the link between poverty and HIV. We investigated if health insurance protects against economic shocks, reducing the need for vulnerable women to engage in risky sexual behaviours and reducing HIV and sexually transmitted infection (STI) incidence. Method and findings: We conducted a randomised controlled trial to test the effectiveness of a formal shock coping strategy to prevent HIV among women at high risk of HIV (registration number: ISRCTN 22516548). Between June and August 2021, we recruited 1,508 adolescent girls and women over age 15 years who were involved in transactional sex (n = 753) or commercial sex (n = 755), using snowball sampling. Participants were randomly assigned (1:1) to receive free health insurance for themselves and their economic dependents for 12 months either at the beginning of the study (intervention; n = 579; commercial sex n = 289, transactional sex n = 290) from November 2021 or at the end of the study 12 months later (control; n = 568; commercial sex n = 290, transactional sex n = 278). We collected data on socioeconomic characteristics of participants. Primary outcomes included incidence of HIV and STIs and were measured at baseline, 6 months after randomisation, and 12 months after randomisation. We found that study participants who engaged in transactional sex and were assigned to the intervention group were less likely to become infected with HIV post-intervention (combined result of 6 months post-intervention or 12 months post-intervention, depending on the follow-up data available; odds ratio (OR) = 0.109 (95% confidence interval (CI) [0.014, 0.870]); p = 0.036). There was no evidence of a reduction in HIV incidence among women and girls involved in commercial sex. There was also no effect on STI acquisition among both strata of high-risk sexual activity. The main limitations of this study were the challenges of collecting reliable STI incidence data and the low incidence of HIV in women and girls involved in commercial sex, which might have prevented detection of study effects. Conclusion: The study provides to our knowledge the first evidence of the effectiveness of a formal shock coping strategy for HIV prevention among women who engage in transactional sex in Africa, reinforcing the importance of structural interventions to prevent HIV. Trial registration: The trial was registered with the ISRCTN Registry: ISRCTN 22516548. Registered on 31 July 2021. In a randomised control trial, Aurélia Lépine and team assess the impact of health insurance as a means of protecting women who engage in commercial sex or transactional sex from economic shocks to prevent HIV infection in Yaoundé, Cameroon. Author summary: Why was this study done?: Women in Africa, especially adolescent girls and young women, suffer a greater burden of new HIV infections than men. Evidence suggests that women may engage in risky sexual behaviours, including unprotected sex, to earn extra money when faced with high expenses or income loss, also known as economic shocks. One of the most common economic shock in Africa is medical out of pocket payments, which can be dramatically reduced with health insurance. What did the researchers do and find?: We conducted a randomised control trial assessing the impact of health insurance as a way of protecting women engaging in commercial sex or transactional sex from economic shocks to prevent HIV infection. We recruited 1,508 female participants, stratified depending on whether the participant is a female sex worker (n = 755) or engage in transactional sex (n = 753). Participants were randomly assigned (1:1) to receive free health insurance for themselves and their economic dependents for 12 months either at the beginning of the study (intervention; n = 579) from November 2021 or at the end of the study 12 months later (control; n = 568). We found that health insurance almost fully eliminated out-of-pocket medical spending and led to a small increase in health care use. Among women who received the intervention, we found large reductions in HIV infection and reductions in risky sexual behaviours for women and girls engaging in transactional sex, but there was no effect in women and girls engaging in commercial sex. What do these findings mean?: These findings showed that preventing economic shocks among women engaging in transactional sex in Africa is an effective HIV prevention strategy. The results also highlighted that women in transactional sex were more affected by HIV than female sex workers in our study, a finding that warrants attention from policy makers. The main limitation of this study was the poor sensitivity and specificity of sexually transmitted infection tests. [ABSTRACT FROM AUTHOR]

Management of undernourished children depends only on wasting yet it can coexist with underweight and/or stunting. Among children admitted to hospital with acute illness, we determined the proportion with wasting coexisting with underweight and/or stunting and their risk factors. A retrospective review of hospital records of children 6‒59 months old admitted at Garissa County referral hospital, Kenya, from January 2017 to December 2019 was conducted. Using World Health Organization 2006 growth standards, undernutrition were defined: wasting as Weight‐for‐height Z‐score < −2, stunting Height‐for‐age Z‐score < −2 and underweight Weight‐for‐age Z‐score < −2. We studied wasting coexisting with underweight and/or stunting. Among 624 children recruited, 347 (56%) were males and 511 (82%) <24 months old. Diarrhoea 210 (34%) and pallor/anaemia 310 (50%) were the most frequent admission diagnosis. HIV infection was present among 8 (1.3%) children. Wasting, underweight and stunting were present among 595 (95%), 518 (83%) and 176 (28%) children respectively. 161 (26%), 506 (81%) and 161 (26%) children had wasting coexisting with stunting, underweight and both stunting and underweight respectively. In the multivariable regression, diarrhoea was positively associated with wasting coexisting with stunting (adjusted risk ratio [aRR = 2.96] [95% CI = 2.06‒4.23]) and anaemia with wasting coexisting with underweight (aRR = 1.23) (95% CI = 1.03‒1.47). Overall, 343 (55%) children were discharged alive, 67 (11%) absconded from the wards, 164 (26%) were transferred to another hospital and 50 (8.0%) died before discharge. The risk of inpatient death was 10.3%, 7.9%, 8.4% and 6.8% among children not wasted, wasted only, wasted & underweight, and wasted and underweight and stunted respectively (Chi‐square p = 0.60). The study reports an unacceptably high levels of undernourishment, including coexisting forms of undernutrition among hospitalised children. This highlights a public health priority for current nutrition therapeutic care and need of continuity of care among those children discharged alive in the community‐based management of acute malnutrition programmes. [ABSTRACT FROM AUTHOR]

This study aimed to ascertain how the current two ART regimens used in Ghana affected HIV patients' coagulation profiles. A case-control study was conducted on 102 HIV positive patients at the Mampong Municipal Hospital. Coagulation parameters measured showed APTT was normal in majority of ART-experienced participants but prolonged in majority of ART-naïve participants. The mean platelet count was significantly higher in ART-experienced participants. No significant differences were found between the coagulation profiles of ART-experienced patients on two different drug regimens. In conclusion, current ART can enhance the coagulation profiles in HIV-infected patients, by improving platelet count and APTT. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) and major depressive disorder (MDD) drive HIV transmission in many sub-Saharan African settings. The impact of screening and treating AUD and MDD on HIV outcomes is unknown. We aimed to identify the cost-effectiveness of AUD and MDD interventions in Zimbabwe, and their potential contribution to reaching Zimbabwe's Ending the HIV Epidemic 2030 goal. Methods: Using a validated HIV compartmental transmission model in Zimbabwe, we compared four policy scenarios: prevention as usual (baseline); implement AUD screening (using AUDIT) and treatment (motivational interviewing and cognitive-behavioral therapy); implement MDD screening (using PHQ-9) and treatment (cognitive-behavioral therapy); and implement screening and treatment for both. Outcomes were HIV incidence projections, infections averted through 2030, quality-adjusted life-years gained, cost per infection averted, and cost per QALY gained. Analyses considered "spillover," when treatment for AUD also results in an improvement in MDD and the converse. Sensitivity analyses identified cost reductions necessary for AUD and MDD interventions to be as cost-effective as other HIV interventions, particularly the scale-up of long-acting PrEP. Results: AUD and MDD combined will be responsible for 21.1% of new HIV infections in Zimbabwe by 2030. Without considering spillover, compared to the baseline, MDD intervention can reduce new infections by 5.4% at $2039/infection averted and $3186/QALY. AUD intervention can reduce new infections by 5.8%, but at $2,968/infection averted and $4753/QALY, compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.1% at $2810/infection averted and $4229/QALY, compared to baseline. Considering spillover, compared to the baseline, MDD intervention can reduce new infections by 6.4% at $1714/infection averted and $2630/QALY. AUD intervention can reduce new infections by 7.4%, but at $2299/infection averted and $3560/QALY compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.9% at $2247/infection averted and $3382/QALY compared to baseline. For MDD intervention to match the cost-effectiveness of scaling long-acting PrEP, the cost of MDD intervention would need to be reduced from $16.64 to $12.88 per person. Conclusions: Implementing AUD and MDD interventions can play an important role in HIV reduction in Zimbabwe, particularly if intervention cost can be decreased while preserving effectiveness. [ABSTRACT FROM AUTHOR]

BACKGROUND Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research Only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95 % confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS We enrolled 408 transplantation candidates, of whom 198 received a kidney from deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval ICI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 9596) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 9096) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21°/0) and 3 years (21% vs. 2496). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95°/0, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.). [ABSTRACT FROM AUTHOR]

Despite the efficacy of antiretroviral therapy (ART) in reducing the global incidence of vertical HIV transmissions, more than 120,000 children are still infected with the virus each year. Since ART cannot clear the HIV reservoir that is established soon after infection, children living with HIV (CLWH) are forced to rely on therapy for their lives and suffer from long-term drug-related complications. Pediatric HIV infection, like adult infection, is associated with gut microbial dysbiosis, loss of gut epithelial integrity, bacterial translocation, CD4 + T cell depletion, systemic immune activation, and viral reservoir establishment. However, unlike in adults, HIV that is vertically acquired by infants interacts with a gut microbiome that is continuously evolving while concomitantly shaping the infant's immune ontogeny. Therefore, to determine whether there may be interventions that target the HIV reservoir through microbiome-directed approaches, understanding the complex tripartite interactions between the transmitted HIV, the maturing gut microbiome, and the developing immune system during early life is crucial. Importantly, early life is the time when the gut microbiome of an individual is highly dynamic, and this temporal development of the gut microbiome plays a crucial role in educating the maturing immune system of a child. Therefore, manipulation of the gut microbiome of CLWH to a phenotype that can reduce HIV persistence by fostering an antiviral immune system might be an opportune strategy to achieve ART-free viral suppression in CLWH. This review summarizes the current state of knowledge on the vertical transmission of HIV, the developing gut microbiome of CLWH, and the immune landscape of pediatric elite controllers, and explores the prospect of employing microbial modulation as a potential therapeutic approach to achieve ART-free viral suppression in the pediatric population. [ABSTRACT FROM AUTHOR]

It is important to examine and comprehend how HIV interacts with the immune system in order to manage the infection, enhance patient outcomes, advance medical research, and support global health and socioeconomic stability. In this study, we formulate the dynamics of HIV infection to investigate the intricate interactions between HIV and T-cells. The Atangana-Baleanu and Caputo-Fabrizio derivative frameworks are applied to comprehensively examine the phenomenon of HIV viral transmission. The basic concepts and results of fractional calculus are presented for the analysis of the model. In our work, we focus on the dynamical behavior of HIV and immune system. We introduce numerical schemes to elucidate the solution pathways of the recommended system of HIV. We have shown the influence of various input factors on the solution pathways of the recommended fractional system and highlighted the oscillatory behavior and chaotic nature of the dynamics. Our findings demonstrate the complexity of the system under study by revealing the existence of the chaotic and oscillatory nature in the dynamics of HIV. In order to quantitatively characterize HIV dynamics, a number of simulations are carried out, providing a visual representation of the effects of different input variables. It has been observed that the chaos and the oscillatory behaviour is strongly related to the nonlinearity of the system. The present study provides a basis for further initiatives that try to enhance interventions and policies to lessen the worldwide burden of infection. [ABSTRACT FROM AUTHOR]

Recent information regarding the characteristics of people living with human immunodeficiency virus (HIV) (PLWH) is lacking. Therefore, we examined the incidence of HIV infection and epidemiologic characteristics of PLWH in South Korea using recent National Health Insurance Service database data. The HIV infection rate was 4.13 per 100,000 in 2017, 4.19 per 100,000 in 2018, 6.61 per 100,000 in 2019, 5.98 per 100,000 in 2020, 8.81 per 100,000 in 2021, and 4.14 per 100,000 in 2022. In 2016, the mean age of PLWH was 45.7 years (SD: 13.8 years), and it gradually increased to 49.0 years (standard deviation: 13.7 years) in 2022 over 7 years in South Korea. The proportion of male individuals among PLWH was 90.7% (19,970/22,026) in 2016, and it gradually increased to 92.3% (22,943/24,857) in 2022 over 7 years in South Korea. The proportion of anti-retroviral therapy (ART) users among PLWH in South Korea was 92.6% (20,388/22,026) in 2016, and it gradually increased to 97.9% (24,328/24,857) in 2022 over 7 years. In this population-based cohort analysis, we presented the HIV infection incidence and epidemiologic features of PLWH in South Korea. This study's results may influence future infection prevention strategies and policies for PLWH. [ABSTRACT FROM AUTHOR]

Background: Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory reaction that occurs in HIV/AIDS patients after antiretroviral therapy (ART) initiation. Along with immune system recovery, IRIS can overreact to existing infections or latent pathogens, causing symptoms that mimic those infections. Few studies elucidated the clinical features and prognosis of Talaromycosis marneffei (TSM)-associated IRIS in HIV/AIDS patients. The aim of our study was to evaluate the incidence, clinical characteristics, and prognosis of TSM-associated IRIS by retrospectively analyzing the clinical data of HIV/AIDS patients with TSM. Methodology/Principal findings: A total of 224 HIV/AIDS inpatients with TSM were enrolled, aged between 19 and 81 years. Among them, 86.6% were male and 13.4% were female, of which 24 (10.7%) patients developed IRIS. In IRIS group, the median time from ART initiation to IRIS occurrence was 9.0 days (IQR, 5.0–16.8 days), with 87.5% (21/24) occurring within 2 weeks. Primary clinical manifestations included recurrent fever and exacerbation of pulmonary infection. At the onset of IRIS, 54.2% (13/24) patients were treated with intravenous dexamethasone, and 12.5% (5/24) patients were treated with oral prednisone for 1–3 weeks. No significant differences in baseline characteristics or ART regimens were observed between IRIS and non-IRIS groups; however, patients in IRIS group had higher levels of CRP, CD4+ count, and CD4+/CD8+ ratio than non-IRIS group (equivalent time point: 1–2 weeks after ART initiation) at IRIS onset. The IRIS group exhibited longer hospital stays and higher readmission rates, but equivalent mortality rates compared with non-IRIS group. Conclusions/Significance: IRIS is a common complication in HIV/AIDS patients with TSM, often occurring within 2 weeks after ART initiation and exhibiting more pronounced immune reconstitution. The occurrence of IRIS significantly extended the hospitalization duration and increased the rate of readmission but had no influence on the mortality rate. Author summary: Immune reconstitution inflammatory syndrome (IRIS) is an inflammatory reaction that occurs in HIV/AIDS patients after antiretroviral therapy (ART) initiation. Along with immune system recovery, IRIS can overreact to existing infections or latent pathogens, causing symptoms that mimic those infections. The clinical characteristics of IRIS depend on the causative pathogen. Talaromycosis marneffei (TSM) is one of the common opportunistic infections in HIV/AIDS patients, and often presents a disseminated form of infection, affecting multiple organs throughout the body. However, few reports on TSM-associated IRIS lead to challenges in clinical management. In this study, we carried out a retrospective analysis of TSM-associated IRIS, elucidated the occurrence and clinical features of TSM-associated IRIS, and compared the laboratory examination data and outcomes in TSM patients with or without IRIS. This study aims to review clinical data from HIV/AIDS patients with TSM to assess the frequency, features, and outcomes of TSM-associated IRIS, to improve understanding of the condition, and to facilitate clinical treatment effectively. [ABSTRACT FROM AUTHOR]

The disease dynamics affect the human life. When one person is affected with a disease and if it is not treated well, it can weaken the immune system of the body. Human Immunodeficiency Virus (HIV) is a virus that attacks the immune system, of the body which is the defense line against diseases. If it is not treated well then HIV progresses to its advanced stages and it is known as Acquired Immunodeficiency Syndrome (AIDS). HIV is typically a disease that can transferred from one person to another in several ways such as through blood, breastfeeding, sharing needles or syringes, and many others. So, the need of the hour is to consider such important disease dynamics and that will help mankind to save them from such severe disease. For the said purpose the reaction-diffusion HIV CD4 + T cell model with drug therapy under the stochastic environment is considered. The underlying model is numerically investigated with two time-efficient schemes and the effects of various parameters used in the model are analyzed and explained in a real-life scenario. Additionally, the obtained results will help the decision-makers to avoid such diseases. The random version of the HIV model is numerically investigated under the influence of time noise in It o ^ sense. The proposed stochastic backward Euler (SBE) scheme and proposed stochastic Implicit finite difference (SIFD) scheme are developed for the computational study of the underlying model. The consistency of the schemes is proven in the mean square sense and the given system of equations is compatible with both schemes. The stability analysis proves that both schemes and schemes are unconditionally stable. The given system of equations has two equilibria, one is disease-free equilibrium (DFE) and the other is endemic equilibrium. The simulations are drawn for the different values of the parameters. The proposed SBE scheme showed the convergent behavior towards the equilibria for the given values of the parameters but also showed negative behavior that is not biological. The proposed SIFD scheme showed better results as compared with the stochastic SBE scheme. This scheme has convergent and positive behavior towards the equilibria points for the given values of the parameters. The effect of various parameters is also analyzed. Simulations are drawn to evaluate the efficacy of the schemes. [ABSTRACT FROM AUTHOR]

Body weight is influenced by an interplay of individual and environmental factors. In people with human immunodeficiency virus (HIV), weight is also influenced by disease status with loss accompanying disease progression that is reversed with effective antiretroviral therapy. Weight changes in comparative antiretroviral therapy trials differ by regimen, with greater gains observed with the integrase strand transfer inhibitors dolutegravir and bictegravir, particularly when coadministered with tenofovir alafenamide fumarate, compared with regimens that include agents such as tenofovir disoproxil fumarate that attenuate weight gain. We review weight changes in major randomized trials of preexposure prophylaxis and initial and switch HIV therapy, highlighting the challenges to assessing the role of antiretroviral therapy in weight change. This examination forms the basis for a model that questions assumptions regarding an association between integrase strand transfer inhibitors and tenofovir alafenamide fumarate and excessive weight gain and calls for more careful consideration of these data when making HIV treatment decisions. [ABSTRACT FROM AUTHOR]

The article discusses the comparative use of tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) for human immunodeficiency virus (HIV) treatment. Topics discussed include the efficacy and safety profiles of TDF and TAF, their effects on body weight and metabolic health, and considerations for treatment in specific populations, such as those with advanced HIV disease and pregnant women.

Background Antiretroviral therapy (ART)-related weight gain is of particular concern in people with HIV (PWH). Although weight gain was observed among PWH receiving tenofovir alafenamide (TAF), little is known about the potential reversibility after TAF discontinuation. We evaluated weight and metabolic changes 12 months after TAF discontinuation in the Swiss HIV Cohort Study. Methods We included participants who received at least 6 months of TAF-containing ART between January 2016 and March 2023. Using multivariable mixed-effect models, changes in weight and lipid levels were compared between individuals who continued TAF and those who switched to one of the following TAF-free regimens: (1) tenofovir disoproxil fumarate (TDF)-based ART, (2) dolutegravir/lamivudine (DTG/3TC), or (3) long-acting cabotegravir/rilpivirine (CAB/RPV). Results Of 6555 participants (median age 54 years, 24.3% female, 13% Black), 5485 (83.7%) continued, and 1070 (16.3%) stopped TAF. Overall, discontinuing TAF was associated with an adjusted mean weight change of −0.54 kg (95% confidence interval [CI] −.98 to −.11) after 12 months. In stratified analyses, switching from TAF to TDF led to an adjusted mean weight decrease of −1.84 kg (95% CI −2.72 to −.97), and to a decrease in mean total cholesterol (−0.44 mmol/L) and triglycerides (−0.38 mmol/L) after 12 months. Switching from TAF-based ART to DTG/3TC (−0.17 kg, 95% CI −.82 to.48) or long-acting CAB/RPV (−0.64 kg, 95% CI −2.16 to.89) did not lead to reductions in weight. Conclusions Replacing TAF with TDF in PWH led to a decrease in body weight and an improved lipid profile within 1 year. Weight changes were not observed among individuals who switched to DTG/3TC or long-acting CAB/RPV. [ABSTRACT FROM AUTHOR]

Background One month of daily rifapentine + isoniazid (1HP) is an effective, ultrashort option for tuberculosis prevention in people with human immunodeficiency virus (HIV). However, rifapentine may decrease antiretroviral drug concentrations and increase the risk of virologic failure. AIDS Clinical Trials Group A5372 evaluated the effect of 1HP on the pharmacokinetics of twice-daily dolutegravir. Methods A5372 was a multicenter, pharmacokinetic study in people with HIV (≥18 years) already on dolutegravir-containing antiretroviral therapy with HIV RNA <50 copies/mL. Participants received daily rifapentine/isoniazid (600 mg/300 mg) for 28 days as part of 1HP. Dolutegravir was increased to 50 mg twice daily during 1HP, and intensive pharmacokinetic sampling was performed on day 0 (before 1HP) and on the final day of 1HP treatment. Results Thirty-two participants (41% female; 66% Black/African; median [Q1, Q3] age, 42 [34, 49] years) were included in the pharmacokinetic analysis; 31 had HIV RNA <50 copies/mL at the end of 1HP dosing. One participant had an HIV RNA of 160 copies/mL at day 28, with HIV RNA <50 copies/mL upon repeat testing on day 42. The median (Q1, Q3) dolutegravir trough concentration was 1751 ng/mL (1195, 2542) on day 0 versus 1987 ng/mL (1331, 2278) on day 28 (day 28:day 0 geometric mean ratio, 1.05 [90% confidence interval,.93–1.2]; P =.43). No serious adverse events were reported. Conclusions Dolutegravir trough concentrations with 50 mg twice-daily dosing during 1HP treatment were greater than those with standard-dose dolutegravir once daily without 1HP. These pharmacokinetic, virologic, and safety data provide support for twice-daily dolutegravir use in combination with 1HP for tuberculosis prevention. Clinical Trials Registration NCT04272242. [ABSTRACT FROM AUTHOR]

Background Weight gain and associated metabolic complications are increasingly prevalent among people with human immunodeficiency virus (PWH). Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are incretin-based therapies for diabetes and weight management that have been shown to result in substantial weight loss; however, studies of their effects in PWH are limited. Methods A retrospective single-center cohort study was conducted among PWH who were taking GLP-1RAs at the University of California, San Diego Owen Clinic between 1 February 2021 and 1 February 2023. Baseline clinical data were collected and changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before starting GLP-1RAs compared to the most recent clinic visit were calculated (with a minimum of 3 months follow-up time required). Logistic regression was performed to identify variables associated with >5% of total body weight loss. Results A total of 225 patients received on average 13 months of GLP-1RA therapy, with 85 (37.8%) achieving the maximum GLP-1RA dose. GLP-1RA therapy resulted, on average, in a weight loss of 5.4 kg, decrease in BMI by 1.8 kg/m2, and decrease in A1C by 0.6%. In the multivariable analysis, higher baseline BMI (odds ratio [OR], 1.10 [95% confidence interval {CI}, 1.03–1.16]), treatment duration of GLP-1RA therapy >6 months (OR, 3.12 [95% CI, 1.49–6.49]), and use of tirzepatide (OR, 5.46 [95% CI, 1.44–20.76]) were significantly more likely to be associated with >5% weight loss. Conclusions Use of GLP-1RAs led to declines in weight, BMI, and A1C among PWH and offers an additional strategy to address weight gain and diabetes. [ABSTRACT FROM AUTHOR]

Background Men and women with a migration background comprise an increasing proportion of incident human immunodeficiency virus (HIV) cases across Western Europe. Methods To characterize sources of transmission in local transmission chains, we used partial HIV consensus sequences with linked demographic and clinical data from the opt-out AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort of people with HIV in the Netherlands and identified phylogenetically and epidemiologically possible HIV transmission pairs in Amsterdam. We interpreted these in the context of estimated infection dates, and quantified population-level sources of transmission to foreign-born and Dutch-born Amsterdam men who have sex with men (MSM) within Amsterdam transmission chains. Results We estimate that Dutch-born MSM were the predominant sources of infections among all Amsterdam MSM who acquired their infection locally in 2010–2021, and among almost all foreign-born Amsterdam MSM subpopulations. Stratifying by 2-year intervals indicated time trends in transmission dynamics, with a majority of infections originating from foreign-born MSM since 2016, although uncertainty ranges remained wide. Conclusions Native-born MSM have predominantly driven HIV transmissions in Amsterdam in 2010–2021. However, in the context of rapidly declining incidence in Amsterdam, the contribution from foreign-born MSM living in Amsterdam is increasing, with some evidence that most local transmissions have been from foreign-born Amsterdam MSM since 2016. [ABSTRACT FROM AUTHOR]

Background: The consequences of engaging in risky sexual behaviours (RSB) can lead to HIV infection, sexually transmitted diseases and unintended pregnancy. The relationship between neighbourhood characteristics and youth involvement in RSB such as early sexual debut and multiple sexual partnerships has been of great concern to government, researchers and policymakers. However, there are very few empirical studies using demographic and health surveys to unpack the nature of this relationship in Rwanda, Ghana and South Africa. The objective of this study was to estimate the prevalence and determinants of early sexual debut and condom use, and to explore the neighbourhood factors associated with early sexual debut and condom use in Rwanda, Ghana and South Africa.Methods: This was a cross-sectional study using the most recent Demographic and Health Survey Data (DHS 2014–2016) from Ghana, Rwanda and South Africa to investigate the relationship between neighbourhood characteristics and risky sexual behaviour among the youth.Results: The prevalence of risky sexual behaviour in the three countries ranges from 56% (South Africa), 30% (Ghana) and 12% (Rwanda). Male youth in the 20-to-24-year-old category had increased odds of engaging in multiple sexual partnerships for the three countries (AOR 4.58; 95% CI 3.40–6.16), Rwanda (AOR 2.72; 95% CI 2.04–3.68) and South Africa (AOR 4.56; 95% CI 3.33–6.24). Meanwhile, at the community level, community education significantly increased the odds of age sexual debut among female adolescents by 50% (South Africa), and 46% (Ghana), while in Rwanda, this factor had decreased odds with higher community education.Conclusion: To lower the incidence of risky sexual behaviour in the community, programmes aimed at appropriate policy options must be intensified. The implications of these findings is helpful for a developmental approach aimed at reaching Africa’s long-term development goal of eliminating STIs among young people. [ABSTRACT FROM AUTHOR]

Background: Recent changes in the infant feeding guidelines for women living with HIV from high-income countries recommend a more supportive approach focusing on shared decision-making. Limited information is available on the infant feeding knowledge of women living with HIV and how healthcare providers engage with them in this context. This multicenter, longitudinal, mixed methods study aims to get a comprehensive and nuanced understanding of infant feeding knowledge among women living with HIV of Nordic and non-Nordic origin living in Nordic countries, and their interaction with healthcare providers regarding infant feeding planning. Methods: Pregnant women living with HIV in Denmark, Finland, and Sweden were recruited in 2019–2020. The Positive Attitudes Concerning Infant Feeding (PACIFY) questionnaire was completed in the 3rd trimester (T1), three (T2), and six (T3) months postpartum. Women who completed the quantitative survey were also invited to participate in qualitative semi-structured interviews at T1 and T3. Results from the survey and interviews were brought together through merging to assess for concordance, complementarity, expansion, or discordance between the datasets and to draw meta-inferences. Results: In total, 44 women living with HIV completed the survey, of whom 31 also participated in the interviews. The merged analyses identified two overarching domains: Knowledge about breastfeeding in the U = U era and Communications with healthcare providers. The women expressed confusion about breastfeeding in the context of undetectable equals untransmittable (U = U). Women of Nordic origin were more unsure about whether breastfeeding was possible in the context of U = U than women of non-Nordic origin. Increased postpartum monitoring with monthly testing of the mother was not seen as a barrier to breastfeeding, but concerns were found regarding infant testing and infant ART exposure. Infant feeding discussions with healthcare providers were welcome but could also question whether breastfeeding was feasible, and many participants highlighted a need for more information. Conclusions: Healthcare providers caring for women living with HIV must have up-to-date knowledge of HIV transmission risks during breastfeeding and engage in shared decision-making to optimally support infant feeding choices. [ABSTRACT FROM AUTHOR]

Background: Since the implementation of universal antiretroviral therapy, kidney transplantation (K-Tx) has become a valuable option for treatment of end-stage kidney disease for people with HIV (PWH) with similar patient and graft survival as compared to HIV-uninfected patients. Little is known about the hazards and manifestations of infectious disease (ID) events occurring in kidney transplant recipients with HIV. Methods: Using linked information collected in the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS), we described in-depth demographical and clinical characteristics of PWH who received a K-Tx since 2008. Further, we performed recurrent time to event analyses to understand whether HIV was an independent risk factor for ID events. Results: Overall, 24 PWH with 57 ID events were included in this study (100% match of SHCS to STCS). Of these, 17 (70.8%) patients had at least one ID event: 22 (38.6%) viral (HIV not counted), 18 (31.6%) bacterial, one (1.8%) fungal and 16 (28.1%) probable infections. Most ID events affected the respiratory tract (25, 37.3%) or the urinary tract (13, 19.4%). Pathogen types and infection sites were similar in PWH and a matched control group of HIV-uninfected patients. HIV was not an independent risk factor for ID events (adjusted hazard ratio 0.94, p = 0.9). Conclusion: By linking data from two large national Swiss cohorts, we provided in-depth information on ID events in PWH receiving a K-Tx in Switzerland. HIV infection was not associated with an increased hazard for ID events after K-Tx. Summary: In a matched analysis based on longitudinal data from the Swiss HIV and Transplant Cohort Studies including all people with HIV who received a kidney transplantation, HIV was not an independent risk factor for infectious disease events post-transplant. [ABSTRACT FROM AUTHOR]

Leishmaniasis poses a significant health burden, particularly among immunocompromised patients. In Thailand, Leishmania infection caused by Leishmania martiniquensis and Leishmania orientalis lacks information about the incidence and risk factors among HIV-infected populations. This longitudinal cohort study aimed to investigate the incidence and persistence of Leishmania infection among HIV-infected individuals in an affected area, Trang Province, Southern Thailand. The study also identified risk factors associated with the incidence of Leishmania infection. The study enrolled 373 participants in the HIV clinic, Trang Hospital, who initially tested negative for Leishmania infection during 2015–2016, and 133 individuals initially tested positive for Leishmania infection. Thus, follow-up visits of 506 participants occurred during 2018–2019. Direct Agglutination Test (DAT) and nested PCR (nPCR) identified incidents and persistent cases of Leishmania infection. Cox proportional-hazards regression analyses were performed to assess risk factors for the incidence of Leishmania infection. Among the initially negative group, 12 incident cases comprised one L. orientalis infection and 11 seropositive cases using DAT, resulting in a cumulative incidence of 3.2% and an incidence density of 10.38 per 1000 person-years. Increasing age was a significant predictor of the incidence of Leishmania infection. Five persistent cases comprised one Leishmania donovani complex and four seropositive cases using DAT in the initially positive group, with a cumulative persistence rate of 3.7% and a persistence density of 12.85 per 1000 person-years. All patients were asymptomatic. This study sheds light on the incidence and persistence of Leishmania infection among HIV-infected individuals in Trang Province, Southern Thailand, underscoring the importance of continued monitoring and tailored interventions to mitigate the impact of this co-infection. Author summary: In Thailand, Leishmania martiniquensis and Leishmania orientalis are the causative agents of cutaneous (CL) and visceral leishmaniasis (VL) reported in immunocompetent and immunocompromised individuals. VL poses a significant health threat, especially to those with HIV infection. Our study conducted a cohort study among HIV-infected patients in Trang Hospital, Trang Province, Southern Thailand, to explore the incidence and persistence of Leishmania infection, a topic not extensively studied in this region. Our findings are crucial for multiple reasons. Firstly, this study reveals a significant incidence rate of 3.2% among HIV patients, and increasing age was a significant predictor of incident Leishmania infection. Secondly, the persistence of Leishmania infection in 3.7% of initially positive cases underscores the challenges in managing this co-infection. It has immediate implications for healthcare providers, policymakers, and public health officials, aiding them in implementing targeted interventions and preventive measures to reduce the impact of leishmaniasis among HIV-infected individuals. By shedding light on this understudied issue, we hope to contribute to better health outcomes for this vulnerable population. [ABSTRACT FROM AUTHOR]

Adherence to antiretroviral therapy (ART) is essential for the effective management of HIV, which includes keeping the HIV viral load undetectable. This study aimed to determine whether certain ART medications are more "forgiving" of poor adherence in achieving viral suppression. We identified subgroups of ART medication usage and determined the extent to which ART adherence is associated with viral suppression across those subgroups. Data came from claims and clinical records (2017–2019) of 3,552 HIV-positive adult members of a Medicaid managed care plan. Pharmacy fill data were examined to characterize ART medications using latent class analysis (LCA), which captures the complexity of real-world ART usage (i.e., multiple medications, ART switching). LCA yielded five ART medication patterns over three years, mostly characterized by recent medications and formulations of ART, though they varied in number of tablets and in medication class. Mixed effects logistic regression models were estimated to determine whether odds of viral suppression differed by ART adherence level. After adjusting for covariates, those with at least 90% adherence (i.e., 90 to < 95%) did not significantly differ from those with 95% adherence or greater in terms of viral suppression, which corroborates existing clinical recommendations. These findings can inform provider-patient communication for people with HIV, especially those who have difficulty maintaining adherence. This includes those experiencing unstable housing, mental health conditions, or substance use. [ABSTRACT FROM AUTHOR]

Background: Transgender individuals often face stigma, discrimination, and various forms of abuse, which negatively impact their mental and physical health. They face a significantly greater risk of HIV, with a higher prevalence than the general population. Despite these challenges, transgender people have limited access to healthcare due to violence, legal barriers, and societal stigma, further exacerbated in countries like Uganda, where transgender identities are criminalized. Therefore, this study explored the lived experiences of HIV researchers working with gender minority populations in criminalizing contexts. Methods: This was an interpretative phenomenological analysis (IPA) qualitative study. Twelve (12) research team members at all levels were involved in the study. Participants had less than five years of involvement in HIV research among gender minority populations. Data were collected using field notes, reflective journals, documentation from daily team debriefing sessions, and semi-structured interviews. The analysis used NVivo software. Results: Positive experiences, barriers, and challenges were captured. The positive experiences were 'respecting cultural diversity', 'expanding networks', 'addressing misconceptions' and 'finding allies'. The barriers included 'experiencing stigma', 'lengthy research processes', 'feeling isolated', 'fearing for personal safety', 'unexpected logistical costs', and 'criminalization of sexual and gender minorities'. The key themes that emerged from the lessons learned were: 'dealing with gatekeepers', 'diversity and sensitivity training', 'leveraging networks', 'meaningful community engagement', 'reflexivity', 'ensuring safety', 'equal partnership', 'giving feedback' and 'awareness of legal implications'. Conclusions: This study highlights the importance of cultural sensitivity, community engagement, and reflexivity in research design and implementation. The findings emphasize the need for innovative strategies to navigate legal, social, and logistical barriers that researchers and participants face. Despite these challenges, the study demonstrates that meaningful collaboration with community members and building trust can significantly enhance the research process and outcomes. Future research should continue to explore these strategies while addressing ethical and safety concerns. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions In the context of an outbreak of HIV among people who inject drugs in Glasgow, Scotland, identified in 2015, our objectives were to: (1) develop epidemiological methods to estimate HIV incidence using data linkage, and (2) examine temporal changes in HIV incidence to inform public health responses.This was a retrospective cohort study involving data linkage of laboratory HIV testing data to identify individuals with a history of drug use. Person‐years (PY) and Poisson regression were used to estimate incidence by time period (pre‐outbreak: 2000–2010 and 2011–2013; early outbreak: 2014–2016; ongoing outbreak: 2017–2019).Among 13 484 individuals tested for HIV, 144 incident HIV infections were observed from 2000 to 2019. Incidence rates increased from pre‐outbreak periods (1.00/1000 PY (95% confidence interval, CI: 0.60–1.65) in 2000–2010 and 1.70/1000 PY (95% CI: 1.14–2.54) in 2011–2013) to 3.02/1000 PY (95% CI: 2.36–3.86) early outbreak (2014–2016) and 2.35 (95% CI 1.74–3.18) during the ongoing outbreak period (2017–2019). Compared with the pre‐outbreak period (2000–2010), the incidence rates were significantly elevated during both the early outbreak (2014–16) (adjusted incidence rate ratio (aIRR) = 2.87, 95% CI: 1.62–5.09, p < 0.001) and the ongoing outbreak periods (2017–19) (aIRR = 2.12, 95% CI: 1.16–3.90, p = 0.015).Public health responses helped to curb the rising incidence of HIV infection among people with a history of drug use in Glasgow, but further efforts are needed to reduce it to levels observed prior to the outbreak. Data linkage of routine diagnostic test data to assess and monitor incidence of HIV infection provided enhanced surveillance, which is important to inform outbreak investigations and guide national strategies on elimination of HIV transmission. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV)-seropositive adults have large T cell responses to a wide range of CMV proteins; these responses have been associated with chronic inflammation and frailty in people with or without HIV infection. We analyzed the relationships between chronic HIV infection, frailty, and the breadth and polyfunctionality of CD4 and CD8 T cell responses to CMV. Peripheral blood mononuclear cells from 42 men (20 without HIV and 22 with virologically suppressed HIV) in the Multicenter AIDS Cohort Study (MACS) were stimulated with peptide pools spanning 19 CMV open reading frames (ORFs). As measured by flow cytometry and intracellular cytokine staining for IFN-γ, TNF-α, and IL-2, CD8 T cells from men with HIV responded to significant ly more CMV ORFs than those from men without HIV. This was primarily due to a broader response to ORFs that are expressed during the late phase of CMV replication. The number of ORFs to which a participant's T cells responded was positively correlated with the sum of all that individual's T cell responses; these correlations were weaker in men with than without HIV. Polyfunctional CMV-specific CD4 responses (production of more than one cytokine) were significantly lower in men with than without HIV. Frailty status did not substantially affect the breadth or magnitude of the CMV-specific T cell responses. These results suggest that immune control of CMV infection is affected more by chronic HIV infection than by frailty. The differences between men with and without HIV were similar to those reported between young and older adults without HIV. [ABSTRACT FROM AUTHOR]

HIV establishes long-term latent infection in memory CD4+ T cells and also establishes sustained long-term productive infection in macrophages, especially in the central nervous system (CNS). To better understand how HIV sustains infection in macrophages, we performed RNAseq analysis after infection of human monocytederived macrophages (MDMs) with the brain-derived HIV-1 strain YU2 and compared this with acute infection of CD4+ T cells. HIV infection in MDM and CD4+ T cells altered many gene transcripts, but with few overlaps between these different cell types. We found interferon pathways upregulated in both MDM and CD4+ T cells, but with different gene signatures. The interferon-stimulated gene RSAD2/Viperin was among the most upregulated genes following HIV infection in MDMs, but not in CD4+ T cells. RSAD2/Viperin was induced early after infection with various HIV strains, was sustained over time, and remained elevated in established MDM infection even if new rounds of infection were blocked by antiretroviral treatment. Immunofluorescence microscopy revealed that RSAD2/Viperin was induced in HIV-infected cells, as well as in some uninfected neighboring cells. Knockdown of RSAD2/Viperin following the establishment of infection in MDMs reduced the production of HIV transcripts and viral p24 antigen. This correlated with the reduction in the number of multinucleated giant cells, and changes in the HIV DNA and chromatin structure, including an increased DNA copy number and loss of nucleosomes and histone modifications at the long terminal repeat (LTR). RNAseq transcriptomic analysis of RSAD2/Viperin knockdown during HIV infection of MDMs revealed the activation of interferon alpha/beta and gamma pathways and the inactivation of Rho GTPase pathways. Taken together, these results suggest that RSAD2/Viperin supports the sustained infection in macrophages, potentially through mechanisms involving the alteration of the LTR chromatin structure and the interferon response. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) type 2 is known to be less pathogenic than HIV-1, possibly due to more effective immune control mechanisms. The mechanism of innate sensing of HIV-2 by T cells is at present unclear. In this study, we show that several primary isolates of HIV-2 (CBL20 and CI85) and HIV-1 (A8 and D2), similar to the molecular clone HIV-1 NL4.3-GFP-I, induce a significant type I interferon response in its main target, activated CD4+ T cells. However, they are unable to do so after shRNA-mediated knock-down of cGAS. In addition, both HIV-1- and HIV-2-induced type I interferon response in CD4+ T cells was dependent on productive infection and integration, as the presence of RT or integrase inhibitor dramatically suppressed the sensing. Our findings collectively showed that the cGAS-dependent type I interferon response of CD4+ T cells to HIV infection is conserved over HIV types and critically depends on productive infection. [ABSTRACT FROM AUTHOR]

Background: Current cancer screening guidelines for transgender individuals are guided primarily by expert opinion, and are extrapolated from guidelines for cisgender populations, despite the additional unique risks that transgender populations face in cancer risk and cancer care. Aims: We examined adherence to current recommended screening guidelines as well as drivers of cancer screening in 192 transgender and gender-nonbinary (TGNB) individuals participating in Project AFFIRM, a multi-site longitudinal cohort study of TGNB individuals. Methods: We used a chi-squared analysis to look for significant associations between predictors and adherence to breast, cervical, prostate and colon cancer screening. We analyzed predictors by 3 different categories: sex/gender identity, healthcare access, and socioeconomic status. Results: Screening rates were low for breast, cervical, prostate and colon cancer in TGNB populations compared to national rates for cisgender populations. Among several significant predictors, gender-affirming surgery (hysterectomy) (p-value = <0.0001) and telling others they are transgender at a younger age (< 18) (p-value = 0.0344) were associated with increased screening adherence, while having HIV was associated with decreased screening adherence (p-value = 0.0045). Discussion: Our results suggest that interacting with the healthcare system to obtain comprehensive cancer screening can be difficult to navigate among the other healthcare needs of TGNB individuals both on an individual and systems level. Future efforts to mitigate the barriers to screening adherence should be targeted at the healthcare system level. [ABSTRACT FROM AUTHOR]

Background Progressive disseminated histoplasmosis is a significant issue in Latin America, particularly in Brazil, contributing to high mortality rates. Objectives Our objectives were to comprehensively describe histoplasmosis treatment with various amphotericin B (AmB) formulations, including mortality rates, adverse effects and risk factors for mortality. Methods This multicentre retrospective cohort study (January 2014–December 2019) evaluated medical records of patients with proven or probable histoplasmosis treated with at least two doses of AmB in seven tertiary medical centres in Brazil. We assessed risk factors associated with death during hospitalization using univariate and multivariate analyses. Results The study included 215 patients, mostly male (n  = 158, 73%) with HIV infection (n  = 187, 87%), and a median age of 40 years. Only 11 (5%) patients initiated treatment with liposomal amphotericin B (L-AmB). Amphotericin B deoxycholate (D-AmB) was administered to 159 (74%) patients without changes in the treatment. The overall mortality during hospitalization was 23% (50/215). Variables independently associated with mortality were use of D-AmB (OR 4.93) and hospitalization in ICU (OR 9.46). There was a high incidence of anaemia (n  = 19, 90%), acute kidney injury (n  = 96, 59%), hypokalaemia (n  = 73, 55%) and infusion reactions (n  = 44, 20%) during treatment. Conclusions We found that D-AmB was the main formulation, which was also associated with a higher mortality rate. Lipid formulations of AmB have become more readily available in the public health system in Brazil. Further studies to evaluate the effectiveness of L-AmB will likely show improvements in the treatment outcomes for patients with disseminated histoplasmosis. [ABSTRACT FROM AUTHOR]

Background/Objectives: The Elecsys® HCV Duo immunoassay (Roche Diagnostics International Ltd., Rotkreuz, Switzerland) detects both antibodies to hepatitis C virus (anti-HCV) and HCV core antigen (HCV-Ag) and has shown excellent diagnostic performance in blood donor samples. We aim to validate its use for diagnosing chronic HCV infection and assessing sustained virological response (SVR) post-direct-acting antivirals (DAAs) in patients with or without HIV infection. Methods: Blood samples from 100 healthy controls, as well as 64 HCV mono-infection and 136 HCV-HIV coinfections, were collected before and 12–24 weeks after DAAs. The assay performance for determining active infection at baseline and SVR was compared with HCV RNA. Results: Overall, 156 (78.0%) of HCV-infected patients had HCV genotype 1, and the SVR rate was 96.5%. The sensitivity, specificity, and area under the ROC curve (AUROC) for HCV diagnosis at baseline were 99.50% (95% confidence interval [CI], 96.82–99.97%), 100% (95%CI, 95.39–100%), and 0.998 (95%CI, 0.992–1.003), respectively. The corresponding results for HCV-Ag in determining SVR were 57.14% (95%CI, 20.24–88.19%), 97.41% (95%CI, 93.73–99.04%), and 0.773 (95%CI, 0.543–1.003), respectively. The assay also exhibited comparable sensitivity and specificity between HCV mono- and coinfection. Conclusions: Our study showed that the Elecsys® HCV Duo immunoassay effectively diagnosed HCV infection, regardless of HIV status, making it suitable for managing high-risk populations in resource-limited settings. [ABSTRACT FROM AUTHOR]

Signatures of neurodegeneration in clinical samples from a subject with multiple sclerosis (MS) acutely infected with HIV were investigated with single-cell transcriptomics using 10X Chromium technology. Sequencing was carried out on NovaSeq-TM, and the analysis was performed with Cell Ranger software (v 7.1.0) associated with a specifically established bioinformatic pipeline. A total of 1446 single-cell transcriptomes in cerebrospinal fluid (CSF) and 4647 in peripheral blood mononuclear cells (PBMCs) were obtained. In the CSF, many T-cell lymphocytes with an enriched amount of plasma cells and plasmacytoid dendritic (pDC) cells, as compared to the PBMCs, were detected. An unsupervised cluster analysis, putting together our patient transcriptomes with those of a publicly available MS scRNA-seq dataset, showed up-regulated microglial neurodegenerative gene expression in four clusters, two of which included our subject's transcriptomes. A few HIV-1 transcripts were found only in the CD4 central memory T-cells of the CSF compartment, mapping to the gag-pol, vpu, and env regions. Our data, which describe the signs of neurodegenerative gene expression in a very peculiar clinical situation, did not distinguish the cause between multiple sclerosis and HIV infection, but they can give a glimpse of the high degree of resolution that may be obtained by the single-cell transcriptomic approach. [ABSTRACT FROM AUTHOR]

The frequency of virus-associated cancers is growing worldwide, especially in resource-limited settings. One of the biggest challenges in cancer research among people living with HIV (PLWH) has been understanding how infection with both HIV and Kaposi sarcoma-associated herpesvirus (KSHV) promotes the pathogenesis of Kaposi sarcoma (KS), the most common cancer among PLWH worldwide and a significant public health problem in regions with high prevalence of HIV such as Sub-Saharan Africa (SSA). The AIDS and Cancer Specimen Resource (ACSR) provides samples for research, including dried blood spots (DBS) that were collected from large clinical epidemiology studies of KSHV and KS in PLWH conducted more than a decade ago in SSA. Here, we validated the quality of DNA derived from DBS samples from SSA studies and provided evidence of quantitative recovery of inflammatory cytokines using these DBS samples through comparison with paired frozen plasma. Significant differences in DNA, protein yields, and inflammatory biomarker levels were also observed between PLWH with/without KS. Establishing the fitness of DBS samples for studies of KS pathogenesis extends the number of projects that can be supported by these ACSR special collections and provides evidence that DBS collection for future KS research is a practical option in resource-limited settings. [ABSTRACT FROM AUTHOR]

BACKGROUND There are gaps in uptake of adherence to, and persistence in the use of preexposure pro-dephylaxis for human immunodeficiency virus (HIV) prevention among cisgender women. METHODS We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo. We assessed the efficacy of lenacapavir and F/TAP by comparing the incidence of HIV infection with the estimated background incidence in the screened population and evaluated relative efficacy as compared with F/TDF. RESULTS Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95°/0 confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAP group (2.02 per 100 person-years; 95°/0 CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74). Background HIV incidence in the screened population (8094 participants) was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio, 0.84; 95% CI, 0.55 to 1.28; P=0.21), and no evidence of a meaningful difference in HIV incidence was observed between FITAF and F/TDF (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). Adherence to F/TAF and F/TDF was low. No safety concerns were found. Injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.996); 4 participants in the lenacapavir group (0.296) discontinued the trial regimen owing to injection-site reactions. CONCLUSIONS No participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF. (Funded by Gilead Sciences; PURPOSE 1 ClinicalTrials.gov numben NCT04994509.). [ABSTRACT FROM AUTHOR]

Objectives: HIV/hepatitis C virus (HCV) co‐infection among people who inject drugs (PWID) remains a global health problem. The goal of our study was to evaluate, in a real‐world setting, success rates of sustained virological response (SVR) using direct‐acting antivirals (DAAs) to treat a population of PWID living with HCV/HIV. Methods: This was a prospective single‐center observational study. We collected demographic, socioeconomic, and clinical data pertaining to HIV and HCV infection in PWID with several barriers to care. We identified risk factors for SVR failure. Results: Among 130 individuals retained to HIV care, we planned HCV treatment in 119/130 (91.5%); 106/119 (89.1%) started treatment with DAAs and 100/106 (94.3%) completed treatment. People not starting treatment were more often in active opioid drug use (odds ratio [OR] 0.25; 95% confidence interval [CI] 0.07–0.97, p = 0.045) and benzodiazepine abuse (OR 0.25; 95% CI 0.07–0.95, p = 0.042). Only 86/100 (86%) were tested for SVR at 12 weeks (SVR12) and 72/86 (83.7%) achieved SVR. PWID in opioid substitution programmes tended to return for SVR12 testing more often (54.7% vs. 30%, p = 0.081). Individuals in active opioid drug use (OR 0.226; 95% CI 0.064–0.793, p = 0.02) or with poor adherence (OR 0.187; 95% CI 0.043–0.814, p = 0.025) were less likely to achieve SVR. At the end of our study period, 113/119 (95%) treatment‐eligible patients remained alive. HCV infection was cured in 68/113 (61.1%) people. Conclusions: Our findings underscore the importance of prioritizing combatting substance use to achieve HCV elimination goals. A systematic approach with effort to overcome barriers to receiving and completing treatment and encourage to enrol in opioid substitution programmes if not possible to completely abstain from use, can help increase chances of HCV cure. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this analysis was to investigate the impact of hepatitis B virus (HBV) coinfection on the risk of HIV viral rebound (VR) after achieving suppression for the first time following initiation of antiretroviral therapy (ART) in the real‐world setting. Design: Patients living with HIV (PLWH) who were enrolled in the ICONA Foundation Study cohort and achieved viral suppression ≤50 copies/mL for the first time after starting ART were prospectively evaluated and divided in three exposure groups according to serology test results: (a) HIV‐monoinfected; (b) HIV‐positive/HBcAb‐positive/HBsAg‐negative; (c) HIV‐positive/HBsAg‐positive. The occurrence of VR, defined as two consecutive HIV‐RNA values >50 copies/mL after achieving viral suppression for the first time (baseline), was investigated. Methods: Standard survival analysis by means of Kaplan–Meier curves and Cox regression analysis with the serology exposure fitted as a time‐fixed covariate measured at baseline was employed after controlling for key confounding factors. Results: Of a total of 5657 patients included, 4090 (72%) were HIV‐monoinfected, 1342 (23.7%)were HBcAb‐positive, and 225 (3.9%) were HbsAg‐positive coinfected. Overall, 654 (11.5%) PLWH experienced VR > 50 copies/mL during follow‐up. After controlling for all sources of measured confounding, coinfected PLWH showed an increased risk of experiencing VR compared with those who were HIV‐monoinfected. In particular, the strongest associations were seen for the HIV/HBsAg‐positive participants [adjusted hazard ratio (aHR) = 1.56, 95% confidence interval (CI): 1.03–2.38, p = 0.037] but an excess of risk was also seen in those who were HIV‐positive/HBcAb‐positive/HBsAg‐negative (aHR = 1.25, 95% CI: 1.00–1.55, p = 0.047). Conclusions: Coinfection with HBV seems to have an impact on the probability of maintaining HIV viral suppression achieved for the first time after ART initiation. Of note, even PLWH positive for HBcAb, a marker of inactive HBV infection, appeared to be at higher risk of VR compared with those who were HIV‐monoinfected and their HIV‐RNA should be carefully monitored. [ABSTRACT FROM AUTHOR]

Background: Low-cost, scalable strategies are necessary to reach the UNAIDS 2030 target of ending HIV as a public health threat. Use of treatment partners, informal caregivers selected by people living with HIV to support antiretroviral therapy adherence, is one such strategy that is included in many countries' HIV guidelines, including Botswana, a country with high HIV prevalence. Method: From June 2021 to June 2022, we pilot tested a clinic-based treatment partner intervention ("Mopati"), including standardized language for providers to guide patients on treatment partner selection and workshops to train treatment partners on providing non-directive support to patients using a non-confrontational, non-judgmental approach. Sixty unsuppressed patients (30 per clinic) and 45 treatment partners (17 intervention, 28 control) were recruited from an intervention–control clinic matched-pair in Gaborone, Botswana. Results: Mopati had medium-to-large effects on increasing patients' adherence, adherence self-efficacy, intrinsic adherence motivation, and perceived non-directive support from treatment partners, and decreasing treatment partner caregiver burden. Aggregate viral suppression rates significantly increased in the intervention (vs. control) clinic. Qualitative data from 14 clinic staff, 21 patients, and 16 treatment partners indicated that Mopati was viewed as effective. Providers said the guidance empowered them to be proactive in communicating about adherence; most reported using the guidance. Conclusion: This study shows preliminary support for the use of treatment partners in HIV care, and further evidence for interventions that leverage patients' existing support. This research can inform ways to improve adherence to HIV treatment as well as the treatment of HIV-related comorbid conditions in lower-resource settings. Trial Registration: ClinicalTrials.gov Identifier: NCT04796610. [ABSTRACT FROM AUTHOR]

Antiretroviral treatment of HIV infected individuals cannot eliminate the HIV reservoir and immune control of HIV is rarely seen upon treatment interruption. In long-term non-progressors (LTNP), an effective CD8 T cell response is thought to contribute to be immune control of HIV. Here we studied the transcriptional profile of virus specific CD8 T cells during the asymptomatic phase of disease, to gain molecular insights in CD8 T cell functionality in HIV progressors and different groups of LTNP: HLA-B*57 LTNP, non-HLA-B*57 LTNP and individuals carrying the MAVS minor genotype (rs7262903/rs7269320). Principal component analysis revealed distinct overall transcriptional profiles between the groups. The transcription profile of HIV-specific CD8 T cells of LTNP groups was associated with increased cytokine/IL-12 signaling and protein/RNA metabolism pathways, indicating an increased CD8 T cell functionality. Although the transcription profile of CMV-specific CD8 T cells differed from that of HIV-specific CD8 T cells, with mainly an upregulation of gene expression in progressors, similar affected pathways were identified. Moreover, CMV-specific CD8 T cells from progressors showed increased expression of genes related to effector functions and suggests recent antigen exposure. Our data shows that changes in cytokine signaling and the energy demanding RNA and protein metabolism are related to CD8 T cell dysfunction, which may indicate that mitochondrial dysfunction is an important driver of T cell dysfunctionality during chronic HIV infection. Indeed, improvement of mitochondrial function by IL-12 and mitoTempo treatment, enhanced in vitro IFNγ release by PBMC from PWH upon HIV gag and CMV pp65 peptide stimulation. Our study provides new insights into the molecular pathways associated with CD8 T cell mediated immune control of chronic HIV infection which is important for the design of novel treatment strategies to restore or improve the HIV-specific immune response. [ABSTRACT FROM AUTHOR]