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BackgroundPeople with HIV (PWH) have an increased risk of cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) has documented higher myocardial fibrosis, inflammation and steatosis in PWH, but studies have mostly relied on healthy volunteers as comparators and focused on men.MethodsWe investigated the associations of HIV and HIV-specific factors with CMR phenotypes in female participants enrolled in the Women's Interagency HIV Study's New York and San Francisco sites. Primary phenotypes included myocardial native (n) T1 (fibro-inflammation), extracellular volume fraction (ECV, fibrosis) and triglyceride content (steatosis). Associations were evaluated with multivariable linear regression, and results pooled or meta-analyzed across centers.ResultsAmong 261 women with HIV (WWH, total n = 362), 76.2% had undetectable viremia at CMR. For the 82.8% receiving continuous antiretroviral therapy (ART) in the preceding 5 years, adherence was 51.7%, and 71.3% failed to achieve persistent viral suppression (42.2% with peak viral load

BackgroundFacility HIV self-testing (HIVST) in outpatient departments can dramatically increase testing among adult outpatients. However, it is still unclear why populations opt out of facility HIVST and reasons for opt outing. Using data from a parent facility HIVST trial, we sought to understand individual characteristics associated with opting out of facility HIVST and reported reasons for not testing.MethodsExit surveys were conducted with outpatients aged ≥15 years at 5 facilities in Central and Southern Malawi randomized to the facility HIVST arm of the parent trial. Outpatients were eligible for our substudy if they were offered HIVST and eligible for HIV testing (ie, never previously tested HIV positive and tested ≥12 months ago or never tested). Summary statistics and multivariate regression models were used.ResultsSeven hundred seventy-one outpatients were included in the substudy. Two hundred sixty-three (34%) opted out of HIVST. Urban residency (adjusted risk ratios [aRR] 3.48; 95% CI: 1.56 to 7.76) and self-reported poor health (aRR 1.86; 95% CI: 1.27 to 2.72) were associated with an increased risk of opting out. Male participants had a 69% higher risk of opting out (aRR 1.69; 95% CI: 1.14 to 2.51), with risk being 38% lower among working male participants. Primary reasons for not testing were feeling unprepared to test (49·4%) and perceived low risk of HIV infection (30·4%)-only 2.6% believed that HIVST instructions were unclear, and 1.7% were concerned about privacy.ConclusionWorking, risky sexual behavior, rural residence, and good self-rated health were positively associated with opting out of HIVST among outpatients. Strategies to address internalized barriers, such as preparedness to test and perceived need to test, should be incorporated into facility HIVST interventions.

BackgroundElicitation of broad immune responses is understood to be required for an efficacious preventative HIV vaccine. This Phase 1 randomized controlled trial evaluated whether administration of vaccine antigens separated at multiple injection sites vs combined, fractional delivery at multiple sites affected T-cell breadth compared to standard, single site vaccination.MethodsWe randomized 90 participants to receive recombinant adenovirus 5 (rAd5) vector with HIV inserts gag, pol and env via three different strategies. The Standard group received vaccine at a single anatomic site (n = 30) compared to two polytopic (multisite) vaccination groups: Separated (n = 30), where antigens were separately administered to four anatomical sites, and Fractioned (n = 30), where fractions of each vaccine component were combined and administered at four sites. All groups received the same total dose of vaccine.FindingsCD8 T-cell response rates and magnitudes were significantly higher in the Fractioned group than Standard for several antigen pools tested. CD4 T-cell response magnitudes to Pol were higher in the Separated than Standard group. T-cell epitope mapping demonstrated greatest breadth in the Fractioned group (median 8.0 vs 2.5 for Standard, Wilcoxon p = 0.03; not significant after multiplicity adjustment for co-primary endpoints). IgG binding antibody response rates to Env were higher in the Standard and Fractioned groups vs Separated group.InterpretationThis study shows that the number of anatomic sites for which a vaccine is delivered and distribution of its antigenic components influences immune responses in humans.FundingNational Institute of Allergy and Infectious Diseases, NIH.

ObjectivesThis study investigates primary peer-referral engagement (PRE) strategies to assess which strategy results in engaging higher numbers of people with HIV (PWH) who are virally unsuppressed.DesignWe develop a modeling study that simulates an HIV epidemic (transmission, disease progression, and viral evolution) over 6 years using an agent-based model followed by simulating PRE strategies. We investigate two PRE strategies where referrals are based on social network strategies (SNS) or sexual partner contact tracing (SPCT).MethodsWe parameterize, calibrate, and validate our study using data from Chicago on Black sexual minority men to assess these strategies for a population with high incidence and prevalence of HIV. For each strategy, we calculate the number of PWH recruited who are undiagnosed or out-of-care (OoC) and the number of direct or indirect transmissions.ResultsSNS and SPCT identified 256.5 [95% confidence interval (CI) 234-279] and 15 (95% CI 7-27) PWH, respectively. Of these, SNS identified 159 (95% CI 142-177) PWH OoC and 32 (95% CI 21-43) PWH undiagnosed compared with 9 (95% CI 3-18) and 2 (95% CI 0-5) for SPCT. SNS identified 15.5 (95% CI 6-25) and 7.5 (95% CI 2-11) indirect and direct transmission pairs, whereas SPCT identified 6 (95% CI 0-8) and 5 (95% CI 0-8), respectively.ConclusionWith no testing constraints, SNS is the more effective strategy to identify undiagnosed and OoC PWH. Neither strategy is successful at identifying sufficient indirect or direct transmission pairs to investigate transmission networks.

BackgroundIncarceration is associated with drug-related harms among people who inject drugs (PWID). We trained >1800 police officers in Tijuana, Mexico on occupational safety and HIV/HCV, harm reduction, and decriminalization reforms (Proyecto Escudo). We evaluated its effect on incarceration, population impact and cost-effectiveness on HIV and fatal overdose among PWID.MethodsWe assessed self-reported recent incarceration in a longitudinal cohort of PWID before and after Escudo. Segmented regression was used to compare linear trends in log risk of incarceration among PWID pre-Escudo (2012-2015) and post-Escudo (2016-2018). We estimated population impact using a dynamic model of HIV transmission and fatal overdose among PWID, with incarceration associated with syringe sharing and fatal overdose. The model was calibrated to HIV and incarceration patterns in Tijuana. We compared a scenario with Escudo (observed incarceration declines for 2 years post-Escudo among PWID from the segmented regression) compared to a counterfactual of no Escudo (continuation of stable pre-Escudo trends), assessing cost-effectiveness from a societal perspective. Using a 2-year intervention effect and 50-year time horizon, we determined the incremental cost-effectiveness ratio (ICER, in 2022 USD per disability-adjusted life years [DALYs] averted).FindingsCompared to stable incarceration pre-Escudo, for every three-month interval in the post-Escudo period, recent incarceration among PWID declined by 21% (adjusted relative risk = 0.79, 95% CI: 0.68-0.91). Based on these declines, we estimated 1.7% [95% interval: 0.7%-3.5%] of new HIV cases and 12.2% [4.5%-26.6%] of fatal overdoses among PWID were averted in the 2 years post-Escudo, compared to a counterfactual without Escudo. Escudo was cost-effective (ICER USD 3746/DALY averted compared to a willingness-to-pay threshold of $4842-$13,557).InterpretationEscudo is a cost-effective structural intervention that aligned policing practices and human-rights-based public health practices, which could serve as a model for other settings where policing constitutes structural HIV and overdose risk among PWID.FundingNational Institute on Drug Abuse, UC MEXUS CONACyT, and the San Diego Center for AIDS Research (SD CFAR).

Background: Many clinical and population-based research studies pivoted from in-person assessments to phone-based surveys due to the COVID-19 pandemic. The impact of these transitions on survey response remains understudied, especially for people living with HIV. Given that there are gender-specific trends in alcohol and substance use, it is particularly important to capture these data for women.Objective: Identify factors associated with responding to an alcohol and substance use phone survey administered during the COVID-19 pandemic in the Women's Interagency HIV Study, a multicenter US prospective cohort of women living with and without HIV.Methods: We used multivariable logistic regression to assess for associations of pre-pandemic (April-September 2019) sociodemographic factors, HIV status, housing status, depressive symptoms, alcohol use, and substance use with response to an early-pandemic (August-September 2020) phone survey.Results: Of 1,847 women who attended an in-person visit in 2019, 78% responded to a phone survey during the pandemic. The odds of responding were lower for women of Hispanic ethnicity (aOR 0.47 95% CI 0.33-0.66, ref=Black/African American) and those who reported substance use (aOR 0.63 95% CI 0.41-0.98). By contrast, the odds were higher for White women (aOR 1.64 95% CI 1.02-2.70, ref=Black/African American) and those with stable housing (aOR 1.74 95% CI 1.24-2.43).Conclusions: Pivoting from an in-person to phone-administered alcohol and substance use survey may lead to underrepresentation of key subpopulations of women who are often neglected in substance use and HIV research. As remote survey methods become more common, investigators need to ensure that the study population is representative of the target population.

BackgroundThe syndemic of HIV, substance use (SU), and mental illness has serious implications for HIV disease progression among women. We described co-utilization of HIV care, SU treatment, and mental health treatment among women with or at risk for HIV.MethodsWe included data from women with or at risk for HIV (n = 2559) enrolled in all 10 sites of the Women's Interagency HIV Study (WIHS) from 2013 to 2020. Current SU was defined as self-reported, non-medical use of drugs in the past year, excluding use of only marijuana. Tobacco and alcohol were assessed separately. We described co-utilization of SU treatment, tobacco and alcohol use treatment, HIV care, and mental health care in the past year among women who were eligible for each service. We compared service utilization by those who did/did not utilize SU treatment using Wald Chi-square tests.ResultsAmong women with current SU (n = 358), 42% reported utilizing SU treatment. Among those with current SU+HIV (n = 224), 84% saw their HIV provider, and 34% saw a mental health provider. Among women with current SU+heavy alcohol use (n = 95), 18% utilized alcohol use treatment; among current SU+tobacco use (n = 276), 8% utilized tobacco use treatment. Women who utilized SU treatment had higher utilization of alcohol use treatment (59% vs. 5%; P

Ferroptosis is implicated in viral neuropathogenesis and may underlie HIV-associated neurocognitive impairment (NCI). Emerging data also suggest differences in brain iron transport by sex. We hypothesized that circulating ferritins that inhibit ferroptosis associate with neurocognitive function and NCI in people with HIV (PWH) in a sex-biased manner. Serum ferritin heavy-chain-1 (FTH1), ferritin light-chain (FTL), and urinary F2-isoprostanes (uF2-isoPs, specific lipid peroxidation marker) were quantified in 324 PWH (including 61 women) with serial global (NPZ-4) and domain-specific neurocognitive testing. Biomarker associations with neurocognitive test scores and NCIs were evaluated by multivariable regression; correlations with uF2-isoPs were also assessed. Higher FTL and FTH1 levels were associated with less NCI in all PWH (adjusted odds ratios 0.53, 95% confidence interval (95% CI) 0.36-0.79 and 0.66, 95% CI 0.45-0.97, respectively). In women, higher FTL and FTH1 were also associated with better NPZ-4 (FTL adjusted beta (β) = 0.15, 95% CI 0.02-0.29; FTL-by-sex βinteraction = 0.32, p = 0.047) and domain-specific neurocognitive test scores. Effects on neurocognitive performance persisted for up to 5 years. Levels of both ferritins correlated inversely with uF2-isoPs in women (FTL: rho = -0.47, p < 0.001). Circulating FTL and FTH1 exert sustained, sex-biased neuroprotective effects in PWH, possibly by protecting against iron-mediated lipid peroxidation (ferroptosis). Larger studies are needed to confirm the observed sex differences and further delineate the underlying mechanisms.

ObjectiveThis study investigated women living with HIV/AIDS (WLHA)'s practices and decision-making regarding disclosure of HIV status in healthcare settings in Vietnam. Introduction: Disclosure of HIV status in healthcare settings is under-studied.MethodsWe conducted in-depth interviews with 30 WLHA in Hanoi, Vietnam. Thematic analysis was conducted to investigate the patterns, considerations, and consequences of HIV disclosure. Results: Most participants chose a selective disclosure strategy based on the type of procedure and healthcare setting. They considered several factors: concerns about stigma/discrimination, risks of confidentiality breach, relevance to healthcare provision, and altruism towards protecting providers and other patients. Selective disclosure or non-disclosure often prevented participants from accessing comprehensive care. Conclusion: The study underscores the need to prepare WLHA to make informed decisions regarding disclosure and provide them with service navigations and support. It also highlights the necessity of reducing stigma and enhancing confidentiality protection to ensure safe disclosure in healthcare settings.

Neuropsychiatric complications such as neurocognitive impairment and depression are common in people with HIV despite viral suppression on antiretroviral therapy, but these conditions are heterogeneous in their clinical presentations and associated disability. Identifying novel biopsychosocial phenotypes that account for neurocognitive performance and depressive and functional symptoms will better reflect the complexities encountered in clinical practice and may have pathological and therapeutic implications. We classified 1580 people with HIV based on 17 features, including 7 cognitive domains, 4 subscales of the Beck depression inventory-II, 5 components of the patients assessment of own functioning inventory, and dependence in instrumental and basic activities of daily living. A two-stage clustering procedure consisting of dimension reduction with self-organizing maps and Mahalanobis distance-based k-means clustering algorithms was applied to cross-sectional data. Baseline demographic and clinical characteristics were compared between the phenotypes, and their prediction on the biopsychosocial phenotypes was evaluated using multinomial logistic regression. Four distinct phenotypes were identified. Participants in Phenotype 1 overall did well in all domains. Phenotype 2 had mild-to-moderate depressive symptoms and the most substance use disorders. Phenotype 3 had mild-to-moderate cognitive impairment, moderate depressive symptoms, and the worst daily functioning; they also had the highest proportion of females and non-HIV conditions that could affect cognition. Phenotype 4 had mild-to-moderate cognitive impairment but with relatively good mood, and daily functioning. Multivariable analysis showed that demographic characteristics, medical conditions, lifetime cocaine use disorder, triglycerides, and non-antiretroviral therapy medications were important variables associated with biopsychosocial phenotype. We found complex, multidimensional biopsychosocial profiles in people with HIV that were associated with different risk patterns. Future longitudinal work should determine the stability of these phenotypes, assess factors that influence transitions from one phenotype to another, and characterize their biological associations.

As a proposed mediator between stigma-related stressors and negative mental health outcomes, HIV-related shame has been predictive of increased rates of substance use and difficulties adhering to antiretroviral treatment among people with HIV. These downstream manifestations have ultimately impeded progress toward national goals to End the HIV Epidemic, in part due to limited success of conventional psychotherapies in addressing HIV-related shame. In a pilot clinical trial (N = 12), receipt of psilocybin-assisted group therapy was associated with a large pre-post decrease in HIV-related shame as measured by the HIV and Abuse Related Shame Inventory, with a median (IQR) change of - 5.5 (- 6.5, - 3.5) points from baseline to 3-months follow-up (Z = - 2.6, p = 0.009, r = - 0.75). A paradoxical exacerbation of sexual abuse-related shame experienced by two participants following receipt of psilocybin raises critical questions regarding the use of psilocybin therapy among patients with trauma. These preliminary findings carry potential significance for the future of HIV care.

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV pol gene sequences, but in many cases, investigators heuristically select other threshold parameters to better capture the underlying dynamics of the epidemic they are studying. Here, we present a general heuristic scoring approach for tuning a distance threshold adaptively, which seeks to prevent the formation of giant clusters. We prioritize the ratio of the sizes of the largest and the second largest cluster, maximizing the number of clusters present in the network. We apply our scoring heuristic to outbreaks with different characteristics, such as regional or temporal variability, and demonstrate the utility of using the scoring mechanism's suggested distance threshold to identify clusters exhibiting risk factors that would have otherwise been more difficult to identify. For example, while we found that a 0.015 substitutions/site distance threshold is typical for US-like epidemics, recent outbreaks like the CRF07_BC subtype among men who have sex with men (MSM) in China have been found to have a lower optimal threshold of 0.005 to better capture the transition from injected drug use (IDU) to MSM as the primary risk factor. Alternatively, in communities surrounding Lake Victoria in Uganda, where there has been sustained heterosexual transmission for many years, we found that a larger distance threshold is necessary to capture a more risk factor-diverse population with sparse sampling over a longer period of time. Such identification may allow for more informed intervention action by respective public health officials.

Reverse transcriptase inhibitors (RTIs) are currently broadly prescribed for the treatment of HIV infection but are also thought to prevent Alzheimer's disease (AD) progression by protecting against amyloidosis. Our study evaluates the hypothesis that reverse transcriptase inhibitors protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection. We compiled a case series of participants from a prospective study of the neurological consequences of HIV infection at the HIV Neurobehavioral Research Program (HNRP) who had serial neuropsychological and neurological assessments and were on RTIs. Two participants had gross and microscopic examination and immunohistochemistry of the brain at autopsy; one was assessed clinically for Alzheimer's disease by cerebrospinal fluid (CSF) analysis of phosphorylated-Tau, Total-Tau and Aβ42. Additionally, a larger cohort of 250 autopsied individuals was evaluated for presence of amyloid plaques, Tau, and related pathologies. Three older, virally suppressed individuals with HIV who had long-term treatment with RTIs were included in analyses. Two cases demonstrated substantial cerebral amyloid deposition at autopsy. The third case met clinical criteria for AD based on a typical clinical course and CSF biomarker profile. In the larger cohort of autopsied individuals, the prevalence of cerebral amyloidosis among people with HIV (PWH) was greater for those on RTIs. Our study showed that long-term RTI therapy did not protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection in these patients. Given the known toxicities of RTIs, it is premature to recommend them to individuals at risk or with Alzheimer's disease who do not have HIV infection.

BackgroundElectronic health records (EHRs) are a cost-effective approach to provide the necessary foundations for clinical trial research. The ability to use EHRs in real-world clinical settings allows for pragmatic approaches to intervention studies with the emerging adult HIV population within these settings; however, the regulatory components related to the use of EHR data in multisite clinical trials poses unique challenges that researchers may find themselves unprepared to address, which may result in delays in study implementation and adversely impact study timelines, and risk noncompliance with established guidance.ObjectiveAs part of the larger Adolescent Trials Network (ATN) for HIV/AIDS Interventions Protocol 162b (ATN 162b) study that evaluated clinical-level outcomes of an intervention including HIV treatment and pre-exposure prophylaxis services to improve retention within the emerging adult HIV population, the objective of this study is to highlight the regulatory process and challenges in the implementation of a multisite pragmatic trial using EHRs to assist future researchers conducting similar studies in navigating the often time-consuming regulatory process and ensure compliance with adherence to study timelines and compliance with institutional and sponsor guidelines.MethodsEight sites were engaged in research activities, with 4 sites selected from participant recruitment venues as part of the ATN, who participated in the intervention and data extraction activities, and an additional 4 sites were engaged in data management and analysis. The ATN 162b protocol team worked with site personnel to establish the necessary regulatory infrastructure to collect EHR data to evaluate retention in care and viral suppression, as well as para-data on the intervention component to assess the feasibility and acceptability of the mobile health intervention. Methods to develop this infrastructure included site-specific training activities and the development of both institutional reliance and data use agreements.ResultsDue to variations in site-specific activities, and the associated regulatory implications, the study team used a phased approach with the data extraction sites as phase 1 and intervention sites as phase 2. This phased approach was intended to address the unique regulatory needs of all participating sites to ensure that all sites were properly onboarded and all regulatory components were in place. Across all sites, the regulatory process spanned 6 months for the 4 data extraction and intervention sites, and up to 10 months for the data management and analysis sites.ConclusionsThe process for engaging in multisite clinical trial studies using EHR data is a multistep, collaborative effort that requires proper advanced planning from the proposal stage to adequately implement the necessary training and infrastructure. Planning, training, and understanding the various regulatory aspects, including the necessity of data use agreements, reliance agreements, external institutional review board review, and engagement with clinical sites, are foremost considerations to ensure successful implementation and adherence to pragmatic trial timelines and outcomes.

ObjectiveMany persons with opioid use disorders (OUDs) have HIV disease and experience clinically significant stress after they enroll in abstinence-based treatment and undergo medically assisted withdrawal. We examined whether opioid withdrawal affects virologic control, inflammatory markers, cognition, and mood in persons with an OUD and HIV, and explored whether measures of withdrawal stress, such as activation of the HPA axis, contribute to alterations in immune function, cognition, and mood.Method and participantsStudy participants were 53 persons with HIV who were admitted for OUD treatment at the City Addiction Hospital in Saint Petersburg, Russian Federation. Participants were examined at admission, at the anticipated peak of withdrawal 3 to 7 days after the last day of a clonidine-based withdrawal process lasting 7 to 14 days, and 3 to 4 weeks after completing withdrawal. At these times, participants received medical exams and were evaluated for symptoms of withdrawal, as well as cognition and mood. Viral load, plasma cortisol, DHEA sulfate ester (DHEA-S), interleukin-6 (IL-6), and soluble CD14 (sCD14) were determined. Multivariable models examined the relationships between markers of HPA activation and the other parameters over time.ResultsHPA activation as indexed by cortisol/DHEA-S ratio increased during withdrawal, as did markers of immune activation, IL-6 and sCD14. There were no significant associations between viral load and indicators of HPA activation. In longitudinal analyses, higher cortisol/DHEA sulfate was related to worse cognition overall, and more mood disturbance. Increase in IL-6 was associated with worse cognitive performance on a learning task. There were no significant associations with sCD14.ConclusionsWorsening of cognition and measures of mood disturbance during withdrawal were associated with activation of the HPA axis and some measures of inflammation. Whether repeated episodes of opioid withdrawal have a cumulative impact on long-term HIV outcomes and neurocognition is a topic for further investigation.

BackgroundThere has been a longstanding effort to integrate behavioral health and HIV care for people with comorbid HIV and behavioral health needs, including those with severe mental illness (SMI). As this population frequents both behavioral health and HIV care settings, they were likely to experience new obstacles to the quality and availability of care during the COVID-19 pandemic. This study aims to describe how clinics for HIV services or behavioral healthcare-as well as co-located sites providing both-sought to rapidly shift protocols to maintain a standard of patient care for people with comorbid HIV and SMI while adapting to the unprecedented circumstances of the pandemic.MethodsWe interviewed HIV and behavioral healthcare providers, clinic leaders, and support service agencies that served clients impacted by both HIV and SMI. Seventeen key informants across three settings (HIV care settings, behavioral health care settings, and integrated or co-located care settings) were interviewed in 2022. Interviews focused on changes in clinical services, protocols, and care provision strategies during and at the onset of the COVID-19 pandemic. Interviews were transcribed and coded using thematic analysis.ResultsCommonly endorsed themes included both positive and negative changes in care and care provision during the pandemic. Negative impacts of the pandemic included the loss of physical space, exacerbated mental health needs and disengagement in HIV care, patient barriers to telehealth and the digital divide, and increased healthcare workforce burnout. Positive changes included improved healthcare delivery and care engagement through telehealth, new opportunities to provide a wide range of social services, paradoxical increases in engagement in HIV care for certain patients, and broad institution of workforce wellness practices.ConclusionsThough COVID-19 presented several complex barriers to care for providers serving patients with comorbid HIV and SMI, the increased flexibility afforded by telehealth and a greater focus on collaborative approaches to patient care may benefit this patient population in the future. Additionally, the focus on workforce wellness may serve to increase retention and avoid burnout among providers. The strategies and lessons learned through adapting to COVID-19 may be invaluable moving forward as healthcare systems respond to future pandemics.

Human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause significant neurologic disease. Central nervous system (CNS) involvement of HIV has been extensively studied, with well-documented invasion of HIV into the brain in the initial stage of infection, while the acute effects of SARS-CoV-2 in the brain are unclear. Neuropathologic features of active HIV infection in the brain are well characterized whereas neuropathologic findings in acute COVID-19 are largely non-specific. On the other hand, neuropathologic substrates of chronic dysfunction in both infections, as HIV-associated neurocognitive disorders (HAND) and post-COVID conditions (PCC)/long COVID are unknown. Thus far, neuropathologic studies on patients with HAND in the era of combined antiretroviral therapy have been inconclusive, and autopsy studies on patients diagnosed with PCC have yet to be published. Further longitudinal, multidisciplinary studies on patients with HAND and PCC and neuropathologic studies in comparison to controls are warranted to help elucidate the mechanisms of CNS dysfunction in both conditions.

There is growing evidence to support new modes of transmission for human monkeypox infection. As these methods are being explored, this report delineates the day-to-day clinical sequelae following the initial exposure in an HIV-positive man who had sexual intercourse with another man days preceding his infection. We describe atypical cutaneous manifestations involving widespread erythematous pustules with preceding anogenital ulcerations and concomitant bilateral inguinal lymphadenopathy. Clinicopathologic correlation is used to assist in the workup and establishing the diagnosis. Our case supports others reported in the literature that suggest sexual contact as a means of transmission. More research is needed that investigates the presence of infection in both men and women, including those who could act as carriers, to elucidate other pathways in this evolving yet evasive viral disease.

BackgroundInterleukin-17-producing CD4 T cells contribute to the control of Mycobacterium tuberculosis (Mtb) infection in humans; whether infection with human immunodeficiency virus (HIV) disproportionately affects distinct Th17-cell subsets that respond to Mtb is incompletely defined.MethodsWe performed high-definition characterization of circulating Mtb-specific Th17 cells by spectral flow cytometry in people with latent TB and treated HIV (HIV-ART). We also measured kynurenine pathway activity by liquid chromatography-mass spectrometry (LC/MS) on plasma and tested the hypothesis that tryptophan catabolism influences Th17-cell frequencies in this context.ResultsWe identified two subsets of Th17 cells: subset 1 defined as CD4+Vα7.2-CD161+CD26+and subset 2 defined as CD4+Vα7.2-CCR6+CXCR3-cells of which subset 1 was significantly reduced in latent tuberculosis infection (LTBI) with HIV-ART, yet Mtb-responsive IL-17-producing CD4 T cells were preserved; we found that IL-17-producing CD4 T cells dominate the response to Mtb antigen but not cytomegalovirus (CMV) antigen or staphylococcal enterotoxin B (SEB), and tryptophan catabolism negatively correlates with both subset 1 and subset 2 Th17-cell frequencies.ConclusionsWe found differential effects of ART-suppressed HIV on distinct subsets of Th17 cells, that IL-17-producing CD4 T cells dominate responses to Mtb but not CMV antigen or SEB, and that kynurenine pathway activity is associated with decreases of circulating Th17 cells that may contribute to tuberculosis immunity.

BACKGROUND: Emerging risk factors highlight the need for an updated understanding of cryptococcosis in the United States. OBJECTIVE: Describe the epidemiological trends and clinical outcomes of cryptococcosis in three patient groups: people with HIV (PWH), non-HIV-infected and non-transplant (NHNT) patients, and patients with a history of solid organ transplantation. METHODS: We utilized data from the Merative Medicaid Database to identify individuals aged 18 and above with cryptococcosis based on the International Classification of Diseases, Tenth Revision diagnosis codes from January 2017 to December 2019. Patients were stratified into PWH, NHNT patients, and transplant recipients according to Infectious Diseases Society of America guidelines. Baseline characteristics, types of cryptococcosis, hospitalization details, and in-hospital mortality rates were compared across groups. RESULTS: Among 703 patients, 59.7% were PWH, 35.6% were NHNT, and 4.7% were transplant recipients. PWH were more likely to be younger, male, identify as Black, and have fewer comorbidities than patients in the NHNT and transplant groups. Notably, 24% of NHNT patients lacked comorbidities. Central nervous system, pulmonary, and disseminated cryptococcosis were most common overall (60%, 14%, and 11%, respectively). The incidence of cryptococcosis fluctuated throughout the study period. PWH accounted for over 50% of cases from June 2017 to June 2019, but this proportion decreased to 47% from July to December 2019. Among the 52% of patients requiring hospitalization, 61% were PWH and 35% were NHNT patients. PWH had longer hospital stays. In-hospital mortality at 90 days was significantly higher in NHNT patients (22%) compared to PWH (7%) and transplant recipients (0%). One-year mortality remained lowest among PWH (8%) compared to NHNT patients (22%) and transplant recipients (13%). CONCLUSION: In this study, most cases of cryptococcosis were PWH. Interestingly, while the incidence remained relatively stable in PWH, it slightly increased in those without HIV by the end of the study period. Mortality was highest in NHNT patients.

Polygamy is the practice of marriage to multiple partners. Approximately 6-11% of households in Uganda and 4-11% of households in Kenya are polygamous. The complex families produced by polygamous marriage customs give rise to additional considerations for healthcare providers and public health messaging around HIV care. Using 27 in-depth, semi-structured qualitative interviews with participants in two studies in rural Kenya and Uganda, we analysed challenges and opportunities that polygamous families presented in the diagnosis, treatment and prevention of HIV, and provider roles in improving HIV outcomes in these families. Overall, prevention methods seemed more justifiable to families where co-wives live far apart than when all members live in the same household. In treatment, diagnosis of one member did not always lead to disclosure to other members, creating an adverse home environment; but sometimes diagnosis of one wife led not only to diagnosis of the other, but also to greater household support.

Human immunodeficiency virus (HIV) 1 infection is known to cause gut microbiota dysbiosis. Among the causes is the direct infection of HIV-1 in gut-resident CD4+ T cells, causing a cascade of phenomena resulting in the instability of the gut mucosa. The effect of HIV infection on gut microbiome dysbiosis remains unresolved despite antiretroviral therapy. Here, we show the results of a longitudinal study of microbiome analysis of people living with HIV (PLWH). We contrasted the diversity and composition of the microbiome of patients with HIV at the first and second time points (baseline_case and six months later follow-up_case, respectively) with those of healthy individuals (baseline_control). We found that despite low diversity indices in the follow-up_case, the abundance of some genera was recovered but not completely, similar to baseline_control. Some genera were consistently in high abundance in PLWH. Furthermore, we found that the CD4+ T-cell count and soluble CD14 level were significantly related to high and low diversity indices, respectively. We also found that the abundance of some genera was highly correlated with clinical features, especially with antiretroviral duration. This includes genera known to be correlated with worse HIV-1 progression (Achromobacter and Stenotrophomonas) and a genus associated with gut protection (Akkermansia). The fact that a protector of the gut and genera linked to a worse progression of HIV-1 are both enriched may signify that despite the improvement of clinical features, the gut mucosa remains compromised.

Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies demonstrated that DSP is associated with inflammatory cytokines in PWH. Adhesion molecules, essential for normal vascular function, are perturbed in HIV and other conditions linked to DSP, but the link between adhesion molecules and DSP in PWH is unknown. This study aimed to determine whether DSP signs and symptoms were associated with a panel of plasma biomarkers of inflammation (d-dimer, sTNFRII, MCP-1, IL-6, IL-8, IP-10, sCD14) and vascular I integrity (ICAM-1, VCAM-1, uPAR, MMP-2, VEGF, uPAR, TIMP-1, TIMP-2) and differed between PWH and people without HIV (PWoH). A cross-sectional study was conducted among 143 participants (69 PWH and 74 PWoH) assessed by studies at the UC San Diego HIV Neurobehavioral Research Program. DSP signs and symptoms were clinically assessed for all participants. DSP was defined as two or more DSP signs: bilateral symmetrically reduced distal vibration, sharp sensation, and ankle reflexes. Participant-reported symptoms were neuropathic pain, paresthesias, and loss of sensation. Factor analyses reduced the dimensionality of the 15 biomarkers among all participants, yielding six factors. Logistic regression was used to assess the associations between biomarkers and DSP signs and symptoms, controlling for relevant demographic and clinical covariates. The 143 participants were 48.3% PWH, 47 (32.9%) women, and 47 (33.6%) Hispanics, with a mean age of 44.3 ± 12.9 years. Among PWH, the median (IQR) nadir and current CD4+ T-cells were 300 (178-448) and 643 (502-839), respectively. Participants with DSP were older but had similar distributions of gender and ethnicity to those without DSP. Multiple logistic regression showed that Factor 2 (sTNFRII and VCAM-1) and Factor 4 (MMP-2) were independently associated with DSP signs in both PWH and PWoH (OR [95% CI]: 5.45 [1.42-21.00], and 15.16 [1.07-215.22]), respectively. These findings suggest that inflammation and vascular integrity alterations may contribute to DSP pathogenesis in PWH, but not PWoH, possibly through endothelial dysfunction and axonal degeneration.

BackgroundHIV or sexually transmitted infections remain a significant public health concern in the United States, with adolescents affected disproportionately. Adolescents engage in HIV/STI risk behaviors, including drug use and condomless sex, which increase the risk for HIV/STIs. At-risk adolescents, many of whom are racial minorities, experience HIV/STI disparities. Although at-risk adolescents are disproportionately affected by HIV/STI risk behaviors and infections and although the Centers for Disease Control and Prevention recommends routine HIV/STI testing for adolescents, relatively few adolescents report having ever been tested for HIV/STI. With expected increases in health clinic visits as a result of the Affordable Care Act combined with technological advances, health clinics and mobile health (mHealth), including apps, provide innovative contexts and tools to engage at-risk adolescents in HIV/STI prevention programs. Yet, there is a dearth of efficacious mHealth interventions in health clinics to prevent and reduce both condomless sex and drug use and increase HIV/STI testing for at-risk adolescents.ObjectiveTo address this gap in knowledge, we developed a theory-driven, culturally congruent mHealth intervention (hereon referred to as S4E [Storytelling 4 Empowerment]) that has demonstrated feasibility and acceptability in a clinical setting. The next step is to examine the preliminary efficacy of S4E on adolescent HIV/STI testing and risk behaviors. This goal will be accomplished by 2 aims: the first aim is to develop a cross-platform and universal version of S4E. The cross-platform and universal version of S4E will be compatible with both iOS and Android operating systems and multiple mobile devices, aimed at providing adolescents with ongoing access to the intervention once they leave the clinic, and the second aim is to evaluate the preliminary efficacy of S4E, relative to usual care control condition, in preventing or reducing drug use and condomless sex and increasing HIV/STI testing in a clinical sample of at-risk adolescents aged 14-21 years living in Southeast Michigan.MethodsIn this study, 100 adolescents recruited from a youth-centered community health clinic will be randomized via blocked randomization with random sequences of block sizes to one of the 2 conditions: S4E mHealth intervention or usual care. Theory-driven and culturally congruent, S4E is an mHealth adaptation of face-to-face storytelling for empowerment, which is registered with the Substance Abuse and Mental Health Services Administration's National Registry of Evidence-Based Programs and Practices.ResultsThis paper describes the protocol of our study. The recruitment began on May 1, 2018. This study was registered on December 11, 2017, in ClinicalTrials.gov. All participants have been recruited. Data analysis will be complete by the end of March 2024, with study findings available by December 2024.ConclusionsThis study has the potential to improve public health by preventing HIV/STI and substance use disorders.Trial registrationClinicalTrials.gov NCT03368456; https://clinicaltrials.gov/study/NCT03368456.International registered report identifier (irrid)DERR1-10.2196/47216.

BackgroundHuman Immunodeficiency Virus (HIV) remains a significant public health concern worldwide. Women living with HIV/AIDS (WLHA) have the additional and unique need to seek sexual and reproductive health services. WLHA's maternal health journeys can be shaped by the cultural norms and resources that exist in their society. This study sought to understand if and how WLHA's family planning, pregnancy, and motherhood experiences could be influenced by the patriarchal culture, gender roles, and HIV stigma in Vietnam, specifically.MethodsBetween December 2021 and March 2022, 30 WLHA with diverse socioeconomic backgrounds and childbirth experiences were interviewed in Hanoi, Vietnam. These semi-structured interviews covered topics including HIV stigma, gender norms, pregnancy experiences, and child-rearing challenges. Interviews were audio recorded, transcribed, and analysed using ATLAS.ti.ResultsQualitative analyses of participant quotes revealed how limited information on one's health prospects and reproductive options posed a significant challenge to family planning. Societal and familial expectations as well as economic circumstances also influenced reproductive decision-making. WLHA often encountered substandard healthcare during pregnancy, labor, and delivery. Stigma and lack of provider attentiveness resulted in cases where women were denied pain relief and other medical services. Communication breakdowns resulted in failure to administer antiretroviral therapy for newborns. Motherhood for WLHA was shadowed by concerns for not only their own health, but also the wellbeing of their children, as HIV stigma affected their children at school and in society as well. Many WLHA highlighted the constructive or destructive role that family members could play in their childbirth decision-making and care-giving experiences.ConclusionsOverall, this study underscores the complex ways that cultural expectations, family support, and stigma in healthcare impact WLHA. Efforts to educate and engage families and healthcare providers are warranted to better understand and address the needs of WLHA, ultimately improving their reproductive and maternal health.

Transgender women (TW) face inequities in HIV and unique barriers to PrEP, an effective biomedical intervention to prevent HIV acquisition. To improve PrEP retention among TW, we examined factors related to retention using a two-phase, sequential explanatory mixed methods approach. In Phase I, we used data from a trial of 170 TW who were provided oral PrEP to examine predictors of 24-week retention. In Phase II, we conducted 15 in-depth interviews with PrEP-experienced TW and used thematic analysis to explain Phase I findings. In Phase I, more participants who were not retained at 24 weeks reported sex work engagement (18% versus 7%) and substantial/severe drug use (18% versus 8%). In Phase II, participants reported drug use as a barrier to PrEP, often in the context of sex work, and we identified two subcategories of sex work. TW engaged in "non-survival sex work" had little difficulty staying on PrEP, while those engaged in "survival sex work" struggled to stay on PrEP. In Phase I, fewer participants not retained at 24 weeks reported gender-affirming hormone therapy (GAHT) use (56% versus 71%). In Phase II, participants prioritized medical gender affirmation services over PrEP but also described the bidirectional benefits of accessing GAHT and PrEP. TW who engaged in "survival sex work" experience barriers to PrEP retention (e.g., unstable housing, drug use) and may require additional support to stay in PrEP care.

Intimate partner violence (IPV) occurs at alarmingly high rates towards pregnant women in South Africa. Experiences of emotional, physical, and sexual IPV in pregnancy can adversely impact the health and safety of mother and fetus. Furthermore, IPV is associated with increased risk of HIV, exacerbating the public health impact of violence among pregnant women in this HIV endemic setting. In-depth understanding of cultural and contextual drivers of experiences of IPV is a critical precursor to development of interventions effectively addressing this issue among pregnant women in South Africa. The present study examines factors contributing to IPV among pregnant women to identify potential points of intervention. We conducted twenty in-depth interviews with postpartum women who used oral pre-exposure prophylaxis (PrEP) in pregnancy and reported recent experiences of IPV and/or ongoing alcohol use in a township near Cape Town, South Africa that experiences a heavy burden of both HIV and IPV. Interpretive thematic analysis was used. Several patterns of IPV during pregnancy were identified and violence was frequently described as co-occurring with male partner alcohol use. A majority of women referenced oral PrEP as their preferred method for HIV prevention, highlighting the agency and discretion it provided as beneficial attributes for women experiencing IPV. Fear of judgement from peers for remaining with an abusive partner and a lack of clear community messaging around IPV were identified as barriers to disclosure and support-seeking. Addressing the lack of social support received by women experiencing IPV during pregnancy in South Africa is essential to comprehensive IPV programming.

IntroductionErectile dysfunction (ED) has been established as a comorbidity among men living with HIV, but comparisons by HIV serostatus of ED incidence in a longitudinal follow-up cohort of men are lacking. We sought to evaluate the incidence of ED spanning a period of 12 years in a longitudinal cohort of sexual minority men (SMM) living with and without HIV.MethodsWe analyzed ED incidence data for 625 participants in the longitudinal Multicenter AIDS Cohort Study from visits spanning October 2006 to April 2019.ResultsSMM living with HIV were more likely to have incident ED compared with those living without HIV (rate ratio: 1.41; 95% CI: 1.14-1.75). Older age, current diabetes, cumulative cigarette use, and cumulative antidepressant use were associated with increased incidence of ED in the entire sample. Self-identifying as Hispanic, current diabetes, and cumulative antidepressant use were positively associated with ED incidence among SMM living with HIV. Cumulative cigarette use was positively associated with greater ED incidence only among SMM living without HIV.DiscussionIn summary, age (full sample/ with HIV), current diabetes (full sample/with HIV), cumulative cigarette use (full sample/without HIV), and cumulative antidepressant use (full sample/with HIV) were associated with increased ED incidence. Skillful management of diabetes and careful titration of antidepressants, along with smoking cessation practices, are recommended to mitigate ED in this population.

BackgroundAdolescent girls and young woman (AGYW) comprise a significant proportion of new HIV infections and unintended pregnancies in sub-Saharan Africa yet face many barriers to accessing family planning and reproductive health (FPRH) information and services. Developed via human-centered design, the Malkia Klabu ("Queen Club") program aimed to facilitate access to HIV self-testing (HIVST) and FPRH information and products at privately-owned drug shops. We sought to understand barriers and facilitators to program implementation in a 4-month pilot in Tanzania.MethodsForty semi-structured interviews were conducted with participants in a cluster randomized trial of the Malkia Klabu program from November 2019 through March 2020, including 11 with AGYW, 26 with drug shopkeepers, and three with counselors at health facilities to whom AGYW were referred. Interviews were audio-recorded, transcribed, coded, and analyzed to identify key themes. The Consolidated Framework for Implementation Research (CFIR) was used to assess barriers and facilitators to program implementation at multiple levels. CFIR considers the outer setting (e.g., culture and systemic conditions), the inner setting where the intervention is implemented (e.g., incentives, relationships, and available resources), the individuals involved, the innovation as it relates to stakeholder needs, and the implementation process.ResultsThe Malkia Klabu program reshaped and directed the role of drug shopkeepers as providers of information and resources rather than FPRH gatekeepers. Key implementation facilitators included the program's adaptability to a wide range of needs and stages of readiness among AGYW, ability to capitalize on AGYW social networks for driving membership, responsiveness to AGYW's need for privacy, and positive contributions to the income and community standing of drug shopkeepers. Components such as HIVST were highly acceptable to both AGYW and shopkeepers, and the introduction of the loyalty program and HIVST kits in shops opened doors to the provision of FPRH products and information, which was further facilitated by program tools such as videos, product displays, and symbol cards. Although some shopkeepers maintained beliefs that certain contraceptive methods were inappropriate for AGYW, most appeared to provide the products as part of the program.ConclusionsThe Malkia Klabu intervention's success was due in part to its ability to address key motivations of both AGYW and drug shopkeepers, such as maintaining privacy and increasing access to FPRH products for AGYW and increasing business for shops. Better understanding these implementation barriers and facilitators can inform the program's future adaptation and scale-up.Trial registrationclinicaltrials.gov #NCT04045912.

Herein, we develop an L -RNA aptamer, L -Apt.T8, for recognizing HIV-1 U3-III RNA G-quadruplex, and conjugate the L -Apt.T8 with DNA antisense (L -Apt.T8-10D) to enhance the binding affinity and selectivity. We demonstrate that L -Apt.T8-10D can inhibit HIV-1 U3-tRNA segment complementary binding and nucleocapsid interaction, and interrupt in vitro HIV-1 minus strand transfer. [ABSTRACT FROM AUTHOR]

Objective Method Results Conclusions Our objective was to evaluate antiretroviral therapy (ART) prescription rates over time among US Medicare enrolees with HIV and to describe disparities in ART prescription and associated factors.We constructed successive cross‐sectional cohorts including adult enrollees with HIV and fee‐for‐service coverage and Part D enrolment in US Medicare between 2007 and 2019. We calculated the percentage of receipt of any ART prescription (ART%) in a calendar year by sex, age, and original Medicare entitlement and calculated age–sex standardized ART% over time. We used multivariable logistic regression to assess the association between ART prescription and sociodemographic factors and chronic conditions by age strata (<65, ≥65 years) in 2019.ART% increased over time and was highest among people with HIV aged 50–64 years in 2019: 95% in males and 92% in females. Multivariable analysis showed that female sex was associated with less ART%, with odds ratios (ORs) of 0.65 (95% confidence interval [CI] 0.60–0.70) and 0.34 (95% CI 0.30–0.39), than male sex in those aged <65 and ≥65 years, respectively. The youngest and oldest enrollees had lower ART use (e.g., OR 0.43 [95% CI 0.34–0.54] for 18–29 vs. 50–64 years; OR 0.34 [95% CI 0.30–0.39] for ≥80 vs. 65–69 years). The top conditions associated with less ART included dementia and alcohol use disorder. Other factors included no Part D low‐income subsidy, non‐Hispanic white race, and Midwest residence.ART use increased over time in US Medicare enrollees. Non‐Hispanic white, female, and the youngest and oldest enrollees received less ART. Multimorbidity, substance use, and dementia were associated with less ART use. Research to overcome these disparities is needed. [ABSTRACT FROM AUTHOR]

Multifunctional anti-HIV Fc-fusion proteins aim to tackle HIV efficiently through multiple modes of action. Although results have been promising, these recombinant proteins are hard to produce. This study explored the production and characterization of anti-HIV Fc-fusion proteins in plant-based systems, specifically Nicotiana benthamiana plants and tobacco BY-2 cell suspension. Fc-fusion protein expression in plants was optimized by incorporating codon optimization, ER retention signals, and hydrophobin fusion elements. Successful transient protein expression was achieved in N. benthamiana , with notable improvements in expression levels achieved through N -terminal hydrophobin fusion and ER retention signals. Stable expression in tobacco BY-2 resulted in varying accumulation levels being at highest 2.2.mg/g DW. The inclusion of hydrophobin significantly enhanced accumulation, providing potential benefits for downstream processing. Mass spectrometry analysis confirmed the presence of the ER retention signal and of N -glycans. Functional characterization revealed strong binding to CD64 and CD16a receptors, the latter being important for antibody-dependent cellular cytotoxicity (ADCC). Interaction with HIV antigens indicated potential neutralization capabilities. In conclusion, this research highlights the potential of plant-based systems for producing functional anti-HIV Fc-fusion proteins, offering a promising avenue for the development of these novel HIV therapies. • Production of anti-HIV Fc-fusion proteins in plant-based systems was successful. • N-terminal hydrophobin & ER retention improved expression in Nicotiana benthamiana. • Stable expression in tobacco BY-2 resulted in varying accumulation levels. • Plant-based anti-HIV Fc-fusion proteins had good binding to CD64 & CD16a receptors. [ABSTRACT FROM AUTHOR]

Introduction: Mother-to-child transmission (MTCT) of HIV accounts for over 90% of annual HIV infections among children under the age of 15. Despite the introduction of the Option B+ strategy in Ethiopia in 2013, the rate of MTCT of HIV at 18 months was 15% in 2020. This study aimed to identify determinants of HIV infection among HIV-exposed infants (HEIs) in the context of prevention of MTCT (PMTCT) care in southern Ethiopia. Methods: We conducted a retrospective facility-based study of 299 mother-baby pairs (HIV-infected women and their HEIs up to 18 months) enrolled in PMTCT care at three health facilities in Wolaita Sodo town, southern Ethiopia, from September 2015 to October 2021. Data was collected from medical charts and PMTCT registers. Logistic regression was used to identify determinants of HIV infection among HEIs. Results: At enrolment into PMTCT care, most women were already on ART (75.3%) and in clinical stage I (89.6%) according to the World Health Organization's algorithm. Overall, 13 (4.3%, 95% CI: 2.5%–7.4%) HEIs were HIV-infected; the level was higher among HEIs born at home (17.9% (95% CI: 7.6%–36.5%). Being born to HIV-positive women with late WHO clinical stage (III and IV) of HIV (AOR = 9.1, 95%CI: 2.4, 34.5), being born at home (AOR = 4.8, 95%CI: 1.1–20.7), being born to women newly diagnosed with HIV (AOR = 4.8, 95%CI: 1.3–17.4), and low infant adherence to cotrimoxazole prophylaxis (AOR = 5.4, 95%CI: 1.4–20.4) increased the odds of MTCT. Conclusion: HIV infection levels among breastfeeding HEIs in PMTCT care was <5%, meeting the WHO transmission rate targets. Strengthening PMTCT care to expand community-based PMTCT interventions such as improving women's and communities' awareness of HIV, PMTCT and promoting male involvement would reduce reduce HIV infection among children to reach the 95–95–95 targets to end HIV in Ethiopia. [ABSTRACT FROM AUTHOR]

Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) represent a global public health challenge that has persisted for decades. While significant advancements have been made in treatment and prevention, HIV/AIDS continues to have a devastating impact on millions of lives worldwide. Long-Acting Antiretrovirals (LAARVs) have emerged as a crucial way to reduce the progression of HIV as well as suppressing its replication. Despite this, the disease seems to be a global health challenge, especially in Sub-Saharan Africa. This review revealed several challenges hindering the widespread implementation of LAARVs. These challenges include a lack of accurate information about LAARVs, persistent societal stigma surrounding HIV, and concerns about their perceived high cost. Additionally, long travel distances, financial constraints, inconvenient clinic appointments, and queues impede regular clinic attendance also play a significant role in the constraints faced by people in Sub-Saharan Africa. Long-Acting Anti-retroviral drugs represent a significant advancement in the management of HIV. This perspective review discusses the potential implications. We briefly highlight the mechanism of action and efficacy, showing its potential to reduce the burden of HIV in Sub-Saharan Africa. This review also aims to inform healthcare providers, researchers, general public, and the government about the opportunities and hurdles of integrating this group of medication into the already existing standard, ultimately controlling HIV and improving the outcomes for people living with HIV in Sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Background: The burden of pediatric HIV/AIDS, mother-to-child transmission rate, and unintended pregnancy among HIV-positive women remain high in sub-Saharan Africa, including Ethiopia. Provision of contraceptives is an undeniable strategy to overcome the risks. However, pooled data to provide informed decisions on modern contraceptive use among HIV-positive women attending ART clinics in Ethiopia are meager. Hence, this review aimed to estimate the magnitude of modern contraception, and revisable long act contraceptives methods (RLCM) use and associated factors among HIV positive ART clinic attending women. Methods: A systematic review and meta-analysis was conducted using PubMed, Google, Cochrane library, Web of Science, Google Scholar, and Scopus database. A funnel plot and Egger's regression test were used to assess publication bias. Heterogeneity of studies was assessed using I-square statistics and the Joanna Briggs Institute (JBI) quality assessment tool was applied to ensure the quality of the included articles. We employed a random-effect model to pool the national utilization of modern contraceptives and the effect size of associated factors. We conducted sub-group analysis by regions to control heterogeneity and to detect variation. Results: A total of 21 studies were included in the meta-analysis. The magnitude of pooled utilization of modern contraceptive and RLCM was 60% [95% CI: 52–68] and 11%, [95% CI: 8–14], respectively. In the random effect model, young women [OR = 2.36, 95% CI: 1.78–3.13], attending secondary school and above [AOR = 1.34, 95% CI: 1.06–1.69], having two or more live children [AOR = 1.84, 95% CI: 1.46–2.34], discussion with a husband [AOR = 2.92, 95% CI: 2.39–3.57], CD4 > 250cells/mm3 [AOR = 1.59, 95% CI: 1.08–2.33], and using HAART [AOR = 1.71, 95% CI: 1.35–2.15] increased odds of modern contraceptive methods utilization. Conclusion: Overall the utilization of RLCM among modern contraceptive users HIV positive women is low. Therefore, to improve the uptake of RLCM among modern contraceptive users HIV positive women, policymakers and program designers need to take into account age and educational levels of women and programs which enhance reproductive health consultation habit between couples. Moreover, integration of family planning services to ART clinics needs to be strengthened. [ABSTRACT FROM AUTHOR]

Background: The HIV epidemic in Kenya remains a significant public health concern, particularly among gay, bisexual, and other men who have sex with men (GBMSM), who continue to bear a disproportionate burden of the epidemic. This study's objective is to describe HIV phylogenetic clusters among different subgroups of Kenyan GBMSM, including those who use physical hotspots, virtual spaces, or a combination of both to find male sexual partners. Methods: Dried blood spots (DBS) were collected from GBMSM in Kisumu, Mombasa, and Kiambu counties, Kenya, in 2019 (baseline) and 2020 (endline). HIV pol sequencing was attempted on all seropositive DBS. HIV phylogenetic clusters were inferred using a patristic distance cutoff of ≤ 0.02 nucleotide substitutions per site. We used descriptive statistics to analyze sociodemographic characteristics and risk behaviors stratified by clustering status. Results: Of the 2,450 participants (baseline and endline), 453 (18.5%) were living with HIV. Only a small proportion of seropositive DBS specimens were successfully sequenced (n = 36/453; 7.9%), likely due to most study participants being virally suppressed (87.4%). Among these sequences, 13 (36.1%) formed eight distinct clusters comprised of seven dyads and one triad. The clusters mainly consisted of GBMSM seeking partners online (n = 10/13; 76.9%) and who tested less frequently than recommended by Kenyan guidelines (n = 11/13; 84.6%). Conclusions: Our study identified HIV phylogenetic clusters among Kenyan GBMSM who predominantly seek sexual partners online and test infrequently. These findings highlight potential unmet HIV prevention, testing, and treatment needs within this population. Furthermore, these results underscore the importance of tailoring HIV programs to address the diverse needs of GBMSM in Kenya across different venues, including both physical hotspots and online platforms, to ensure comprehensive prevention and care strategies. [ABSTRACT FROM AUTHOR]

Background: With access to and uptake of pre-exposure prophylaxis (PrEP), the United States can prevent new HIV infections. To end the HIV epidemic, health insurance plans must facilitate access to comprehensive preventive care benefits. Since plan benefit designs vary considerably by plan, it is difficult to systematically determine plans that facilitate and restrict preventive services for PrEP. Methods: We applied an unsupervised machine learning method to cluster 17,061 Qualified Health Plans offered to individuals. We examined the clusters to draw conclusions about the types of benefits insurance companies tend to group together in plans. Then we analyzed the geographic distribution of those clusters across the United States to assess geographic inequities in access to HIV preventive care. Results: Our method uncovered three cohesive clusters of plans. Plans in Cluster 1: the least restrictive cluster, facilitate access to preventive care using copays over coinsurance on almost all benefits; Cluster 2: the moderately restrictive cluster, plans cover HIV prevention benefits with copays but restrict access to general health benefits with coinsurance; and Cluster 3: the most restrictive cluster, plans cover almost all benefits using coinsurance. Overall, increased prior authorization requirements tend to accompany reductions in out-of-pocket costs. Examining the geographic plan distribution, states with at least one rating area where at least 75% of plans offered are in the most restrictive cluster included: Georgia, Illinois, Missouri, Oklahoma, Texas, Virginia, and Wyoming. Conclusions: Insurance plan design is complex. To address the ambitious call to end the HIV epidemic in this country, plans should also take into account both public health and health equity factors to create plan designs that ensure access to critical preventive services for people who need them most. Addressing the growing disparities in PrEP access along racial and ethnic lines should be a national priority, and federal and state insurance regulators as well as insurance plans themselves should be part of the conversation about how to ensure people who would benefit from PrEP can access it. Better state/federal regulation of plan design to ensure access is consistent, equitable, and based on clinical recommendations will reduce the variability across plan designs. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusions The survival rate of people with HIV admitted to intensive care units (ICUs) is approaching that of people without HIV. We conducted a matched‐cohort study of people with and without HIV admitted to ICU at a large hospital to compare short‐term mortality, during 2000–2019.People with HIV were matched to people without HIV (1:2) on age, sex, admission year and Acute Physiology and Chronic Health Evaluation (APACHE)‐II score. Applying logistic regression models fitted using independence estimating equations, we describe population‐averaged associations of HIV with short‐term (in‐ICU, in‐hospital) mortality during a patient's first admission to ICU, and explore whether these varied by year.A total of 177 people with HIV were matched to 354 people without HIV (71.2% vs. 71.2% male; median age: 47 vs. 48 years, median APACHE‐II: 18 vs. 17, median admission year: 2013 vs. 2013). Among people with HIV, 73.4% were on antiretroviral therapy, 51.2% had HIV‐RNA ≤50 copies/mL and median CD4 T‐cell count was 132 cells/μ$$ \upmu $$L. People with HIV had higher in‐ICU (24.3% vs. 15.3%) and in‐hospital (31.6% vs. 20.1%) mortality. People with HIV had 1.69‐fold higher odds (95% confidence interval: 1.03–2.76) of in‐ICU mortality and 1.86 (1.19–2.91) higher odds of in‐hospital mortality than people without HIV, adjusted for age, sex, year and APACHE‐II. There was no evidence that these associations varied by year (p‐interaction‐in‐ICU = 0.90; p‐interaction‐in‐hospital = 0.46).Our findings suggest that although outcomes have improved over time, people with HIV continue to have higher short‐term in‐ICU and in‐hospital mortality following ICU admission compared with people without HIV with similar characteristics. [ABSTRACT FROM AUTHOR]

Although HIV infection can be managed with antiretroviral drugs, there is no cure and therapy has to be taken for life. Recent successes in animal models with HIV-specific broadly neutralising antibodies (bNAbs) have led to long-term virological remission and even possible cures in some cases. This has resulted in substantial investment in human studies to explore bNAbs as a curative intervention for HIV infection. Emerging data are encouraging, but suggest that combinations of bNAbs with other immunomodulatory agents may be needed to induce and sustain long-term viral control. As a result, a number of clinical trials are currently underway exploring these combinations. If successful, the impact for the millions of people living with HIV could be substantial. Here, we review the background to the use of bNAbs in the search for an HIV cure and how different adjunctive agents might be used together to enhance their efficacy. [ABSTRACT FROM AUTHOR]

Background: Renal dysfunction (RD) is more prevalent among people living with HIV (PLHIV) in sub-Saharan Africa (SSA) due to factors such as co-infections, hypertension, diabetes, and nephrotoxic antiretroviral drugs like tenofovir. Early detection of RD is critical but limited by resource constraints in many SSA countries, including Tanzania. Point-of-care (POC) tests, such as the Stat-Sensor Creatinine test by Nova Biomedical, present a cost-effective and non-invasive option for early detection. This study will evaluate the diagnostic performance of the Stat-Sensor creatinine test in detecting renal dysfunction in HIV care and treatment clinics (CTCs) in Tanzania. It will be conducted for a period of six months, from November 2024 to April 2025. Methodology: The study will measure point-of-care creatinine using a rapid creatinine dipstick against the standard serum creatinine test. The diagnostic performance and agreement to diagnose renal dysfunction will be assessed using a standardized statistical approach: Bland-Altman analysis and linear mixed-effects models to test agreement between creatinine dipstick tests with serum creatinine. Receiver operating characteristics (ROC) statistics will be used to test the diagnostic performance of the creatinine dipstick test to diagnose renal dysfunction. Discussion: We hypothesize that POC creatinine testing will show strong diagnostic performance, providing a reliable, rapid, and cost-efficient alternative for RD detection, leading to better patient outcomes and integration of POC tests into routine HIV care. Ethical clearance: The study protocol was reviewed and approved by the Muhimbili University of Health and Allied Sciences Research and Publication committee in June 2024 with reference number, MUHAS-REC-05-2024-2275. [ABSTRACT FROM AUTHOR]

Although Western biomedical treatment has dramatically increased across sub-Saharan African health systems, traditional medicine as a form of healing and beliefs in supernatural powers as explanations for disease remain prevalent. Research in this region has identified HIV in particular as a disease located within both the traditional African and Western medical paradigms, whilst mental illness is ascribed to primarily supernatural causes. Within this context, this study sought to understand and explore the perceptions of HIV and mental illness among a population of rural women in Limpopo, South Africa. 82 in-depth interviews were conducted between January and December, 2022. Interviews were transcribed and translated into English. Data were managed using NVivo 11 software and thematically analyzed. The majority of participants identified HIV as a Western illness requiring biomedical treatment with an origin largely attributed to biological mechanisms. A traditional form of HIV only cured using traditional treatments was also denoted. Unlike for HIV, the majority of respondents felt that there was no biological or behavioral cause for mental illness but rather the illness was conceptualized supernaturally thus likely impacting patient care pathways. Further research to study HIV and mental health perceptions among a larger sample in different regions of sub-Saharan Africa is warranted. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion Our aim was to examine mortality trends in the era of antiretroviral therapy, among people who inject drugs (PWID) who are living with HIV. The study objectives were to assess and quantify mortality among PWID diagnosed with HIV over time in Scotland, in the context of a recent outbreak of HIV and rise in drug‐related mortality.This was a retrospective cohort study of those diagnosed with HIV in Scotland between January 2000 and February 2020, with acquisition related to injecting drug use, linked to mortality data. Factors associated with all‐cause mortality were examined using Cox proportional hazards regression.Among 430 individuals with 3143 person‐years (py) of follow‐up, 88 (20.5%) died. Drug‐related deaths accounted for 45.5% of all deaths, rising to 60% among those diagnosed in 2015–2020. The crude all‐cause mortality was 28.00 per 1000 py overall and 37.62 per 1000 py within 5 years of diagnosis. Mortality risk was markedly higher among PWID diagnosed in 2015–2020 [adjusted hazard ratio (aHR) = 3.53], relative to those diagnosed in 2000–2004. Among those diagnosed in 2015–2020 (as part of the HIV outbreak), the mortality risk was higher among those not on, compared with those on, opioid agonist therapy (aHR = 3.87).Mortality among PWID living with HIV in Scotland has risen substantially in the 21st century. Our findings highlight the important role of opioid‐agonist therapy, alongside other prevention and treatment measures to address high levels of drug‐related mortality for PWID living with HIV, including within HIV outbreaks in this population group. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis, since its discovery has become a global health burden, continuously spreading across the nations of the earth with increased mortality. Its effect on human immunodeficiency virus (HIV) progression and immune cell deterioration cannot be overlooked. The widespread use of traditional and molecular TB diagnostic methods has been hindered by several factors. Nonetheless, the development of a rapid, sensitive, timely, non-invasive diagnostic protocol could revolutionise the diagnostic era and halt the spread of this infectious agent. It could also help in the early diagnosis of the infection in poorly developed areas. The detection efficacy of urine lipoarabinomannan assay as a prospect in tuberculosis diagnosis in HIV-positive patients was assessed in this study. Urine samples were collected into a wide-mouthed universal container from HIV-positive patients with signs and symptom of tuberculosis and HIV advanced disease. Alere determine urine lateral flow—LAM test was used for the detection of LAM antigen in urine samples of HIV-positive patients. The CD4 count of the HIV-positive patients was also documented. Results: A total of 85 HIV-positive subjects were included in the analysis based on the inclusion criteria. Urinary LAM was reactive in 29 (34.1%) of 85 HIV-positive patients and non-reactive in 56 (69.1%). The majority of the participants had a CD4+ count < 200 cells/µL 60 (70.6%), while others had CD4+ count ≥ to 200 cells/µL 25 (29.4%). There was no statistically significant difference between CD4 count and LAM positivity. Most of the affected age groups in the study were 31–45 years, and females had preponderance in comparison to male subjects. Conclusions: The use of urinary LAM in HIV-positive patients is a helpful tool for TB screening. It also has a promising ability for early TB diagnosis in the study group and other TB-associated disease conditions in resource-deprived settings. For the general populace, further research is required to certify its sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Skin cancer, the most common cancer in the United States, has been well-described in the literature to be associated with environmental factors including ultraviolet (UV) radiation. However, the effect of chronic viral infections on risk of skin cancer development, particularly in individuals co-infected with Human Immunodeficiency Virus (HIV) and Hepatitis B or C Viruses (HBV/HCV), has yet to be elucidated. This systematic review aims to be one of the first to consolidate existing literature and examine the relationship between skin cancer and HIV/HBV and HIV/HCV co-infections. We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching MEDLINE, Embase, Cochrane CENTRAL, and Web of Science databases for studies published from inception to March 26, 2024. Inclusion criteria for studies included only those reporting on HBV and/or HCV in people living with HIV (PLWH). Five studies were ultimately included for analysis. The review identified multiple non-melanoma skin cancers (NMSC) and cutaneous adnexal carcinomas in HIV/HCV or HIV/HBV co-infected patients. Notably, Pilomatrical carcinomas were observed in co-infected individuals. Sarcomas including Kaposi sarcoma and low-grade fibroblastic sarcoma were also linked to HIV/HCV or HIV/HBV infections. However, the studies primarily focused on specific types of cancers without elucidating the underlying mechanisms for the association between HIV/HCV/HBV infection and sarcoma development. In summary, this review suggests a potential link between HIV/HCV and HIV/HBV co-infection and certain types of skin cancer, namely adnexal carcinomas. Further research is crucial to determine the underlying mechanisms, explore the association with different skin cancer types, and identify effective prevention and treatment strategies for co-infected individuals. [ABSTRACT FROM AUTHOR]

Architect-HIV Ag/Ab combo chemiluminescence assay is globally recognized for its sensitivity but has a notable false-positive rate. In this study, we aim to evaluate the performance of a new cost-effective screening alternative, the chemiluminescence Ag/Ab combo assay (CL-900i-HIV) from Mindray, China. We selected 195 archived samples categorized according to the INNO-LIA™ HIV I/II, the gold standard confirmatory assay. These samples included true positive (n = 38; positive by Architect-HIV & INNO-LIA-HIV), true negative (n = 101; negative by Architect-HIV & INNO-LIA-HIV), false positive (n = 20; positive by Architect-HIV & negative by INNO-LIA-HIV), and indeterminate results (n = 26). We tested all samples using the Mindray CL-900i-HIV and all positive Architect-HIV samples (n = 80) were confirmed by PCR. Compared to INNO-LIA™ HIVI/II line immunoassay confirmatory assay, Mindray CL-900i-HIV demonstrated a sensitivity of 100% (95% CI 90.7–100), specificity of 100% (95% CI 97.0–100), overall percent agreement (OPA) of 100% (95% CI 97.7–100.0), and perfect agreement with the INNO-LIA confirmatory assay (κ = 1.00). Additionally, Mindray's CL-900i-HIV exhibited a significantly lower false-positive rate (8.75%) compared to Architect-HIV's (55%). Mindray CL900i demonstrated high sensitivity and very low false-positive rate, thus, has the potential to serve as an excellent, cost-effective surrogate for HIV screening, overcoming the limitations of existing automated assays. [ABSTRACT FROM AUTHOR]

Background Central nervous system (CNS) compartmentalization provides opportunity for human immunodeficiency virus (HIV) persistence and resistance development. Differences between cerebrospinal fluid (CSF) and cerebral matter regarding HIV persistence are well described. However, CSF is often used as surrogate for CNS drug exposure, and knowledge from solid brain tissue is rare. Methods Dolutegravir, tenofovir, lamivudine, and efavirenz concentrations were measured across 13 CNS regions plus plasma in samples collected during autopsy in 49 Ugandan decedents. Median time from death to autopsy was 8 hours (interquartile range, 5–15 hours). To evaluate postmortem redistribution, a time course study was performed in a mouse model. Results Regions with the highest penetration ratios were choroid plexus/arachnoid (dolutegravir and tenofovir), CSF (lamivudine), and cervical spinal cord/meninges (efavirenz); the lowest were corpus callosum (dolutegravir and tenofovir), frontal lobe (lamivudine), and parietal lobe (efavirenz). On average, brain concentrations were 84%, 87%, and 76% of CSF for dolutegravir, tenofovir, and lamivudine, respectively. Postmortem redistribution was observed in the mouse model, with tenofovir and lamivudine concentration increased by 350% and efavirenz concentration decreased by 24% at 24 hours postmortem. Conclusions Analysis of postmortem tissue provides a unique opportunity to investigate CNS antiretroviral penetration. Regional differences were observed paving the way to identify mechanisms of viral compartmentalization and/or neurotoxicity. [ABSTRACT FROM AUTHOR]

In the recent mpox outbreak, people with human immunodeficiency virus (PWH) were at high risk both for contracting infection and for a more severe disease course. We studied cellular and humoral immune responses elicited by mpox infection (n = 5; n = 3 PWH) or smallpox vaccination (n = 17; all PWH) in a cohort of men who have sex with men. All PWH were successfully treated, with stable CD4 counts and undetectable HIV viral loads. Eleven of 17 vaccinated individuals had received childhood smallpox vaccination. In this group of individuals, both 2-dose modified vaccinia Ankara (MVA) vaccination and natural infection evoked mpox-specific immune responses mediated by B cells as well as CD4 and CD8 T cells. This study improves our understanding of smallpox vaccination-mediated cross-reactivity to other orthopox viruses, and long-lasting durability of childhood smallpox vaccination-mediated immune responses, including in PWH. [ABSTRACT FROM AUTHOR]

Background: Following the 2018 World Health Organization's (WHO) guidelines on HIV treatment and management, the Zimbabwean government has embraced dolutegravir (DTG)‐based regimens as the preferred first‐line treatment for people living with HIV (PLWH). Despite this implementation, there remains a paucity of knowledge on the potential associations between DTG‐based regimens, body weight and blood lipid levels among PLWH in Zimbabwe. Thus, the aim of this study was to investigate variances in body weight and blood lipid levels at two distinct timepoints—baseline and 6‐month post‐DTG initiation. Methods: We conducted this study between November 2021 and April 2023 among ART‐naïve individuals initiating a DTG‐based regimen. Participants were recruited from a tertiary clinic in Zimbabwe. Body weight, standing height and blood lipid levels were measured at baseline and 6‐month post‐DTG. Changes in weight, body mass index (BMI) and lipids levels were assessed using the paired Student's t‐test and Wilcoxon signed rank test. Multivariable logistic and linear regression analysis was used to assess risk factors associated with changes in weight, BMI and lipid levels. Results: A cohort comprising 130 study participants, characterised by a mean (±SD) age of 40.0 (±11.0) years at baseline, was subjected to a 6‐month regimen of DTG‐based therapy. The outcomes revealed statistically significant alterations in various physiological parameters. Specifically, post the DTG‐based intervention, there were substantial increases observed in body weight (p < 0.001), BMI (p = 0.003), total cholesterol (TC) levels (p = 0.002) and high‐density lipoprotein cholesterol (HDL‐C) levels (p < 0.001) in comparison to their baseline values. Intriguingly, the corresponding triglyceride (TG) levels exhibited a noteworthy decrease (p < 0.001). Notably, individuals aged 40 years or older exhibited a positive association (p = 0.022) with increased TC levels and concurrent weight gain. Furthermore, current employment emerged as another factor positively linked to increased TC levels and weight gain. Conclusions: Upon the initiation of DTG, discernible elevations were observed in body weight, BMI and lipid levels. This study represents the first comprehensive assessment of lipid profiles and weight gain among this population in Zimbabwe, filling a critical gap in the existing literature. These findings, while indicative of short‐term effects, underscore the imperative for further investigative efforts aimed at elucidating the prolonged consequences associated with DTG‐induced weight gain and increased lipid levels and its underlying mechanisms. [ABSTRACT FROM AUTHOR]

AbstractSyphilis is a systemic infection caused by the spirochete Treponema pallidum. It is transmitted during pregnancy or through sexual contact. Signs and symptoms vary depending on the clinical stage of the disease. Syphilis has been well-studied, and the introduction of penicillin has resulted in a decline in the number of new cases and deaths. Recently, however, there has been a surge in new cases in young people, especially those with human immunodeficiency virus (HIV). This epidemiological shift has been attributed to increased sexual activity, risky sexual behaviors, and immunodeficiency. There is a paucity of data on gastrointestinal (GI) manifestations of syphilis owing to its rarity and lack of physician awareness. T. pallidum can seed to any part of the GI tract, resulting in esophagitis, gastritis, hepatitis, pancreatitis, or proctocolitis. Depending on the affected part of the GI tract, syphilis can present with nausea, vomiting, painless esophageal ulcers, dysphagia, abdominal pain, weight loss due to early satiety, diarrhea, melena, hematochezia, dyschezia, or anorectal ulcers. Given its indolent clinical course and vague presentation, GI syphilis can mimic other GI disorders, which can delay diagnosis and treatment. A detailed medical history, physical examination, serological tests, and endoscopy can provide a definitive diagnosis. Syphilis and its GI complications are usually treated with long-acting intramuscular penicillin benzathine, and rarely with a 14-day course of intravenous penicillin. Herein, we describe the clinical features, etiopathogenesis, diagnosis, and treatment of GI syphilis. This primer should aid clinicians in timely diagnosis and treatment of various presentations of GI syphilis. [ABSTRACT FROM AUTHOR]