HIV People Research Articles

Transformation of brain myeloid cell populations by SIV in rhesus macaques revealed by multiomics.

The primary immune constituents in the brain, microglia and macrophages, are the target for HIV in people and simian immunodeficiency virus (SIV) in nonhuman primates. This infection can lead to neurological dysfunction, known as HIV-associated neurocognitive disorder (HAND). Given the gaps in our knowledge on how these cells respond in vivo to CNS infection, we performed single-cell multiomic sequencing, including gene expression and ATAC-seq, on myeloid cells from the brains of rhesus macaques with SIV-induced encephalitis (SIVE) as well as uninfected controls. We found that the myeloid cell populations were significantly changed by SIVE. In SIVE microglia-like cells express high levels of chemoattractants capable of recruiting highly activated CAM-like cells to the site of infection/inflammation. A unique population of microglia-like cells was found in which the chromatin accessibility of genes diverged from their RNA expression. Additionally, we observed a dramatic shift of upstream gene regulators and their targets in brain myeloid cells during SIVE. In summary, this study further uncovers the transcriptome, gene regulatory events and potential roles of different brain myeloid phenotypes in SIVE.

Two 5-year studies of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: a plain-language summary.

This is a plain-language summary of an article that reported on two studies of the medication bictegravir/emtricitabine/tenofovir alafenamide (shortened to B/F/TAF). B/F/TAF is a single pill containing three different drugs used to treat human immunodeficiency virus (known as HIV). The drugs work together to lower the levels of HIV (called viral load) in the body and make the virus undetectable in the blood. Researchers measured whether B/F/TAF was safe and effective when taken over 5years in over 400 people in 10 countries who had never taken HIV medication before. After 5years, almost all (99%) of the people who took B/F/TAF had an undetectable viral load. This does not mean that they were cured, but that the levels of HIV were so low that the tests used by researchers could not detect the virus in the blood. CD4 is a type of immune system cell. HIV causes CD4 cell numbers to decrease. On average, the number of CD4 cells increased by more than 300 cells per microliter (cells/μL) of blood over 5years. This means that the immune system was improving. HIV is able to change its genes to escape the effects of the drugs. This is known as HIV resistance to treatment. Nine people had a viral load high enough to suggest that the drugs might not be working, but no resistance to B/F/TAF was seen. Some people (less than one in three) experienced medical problems thought to be linked to B/F/TAF treatment, known as side effects. The most common side effects were headache, diarrhea, nausea, tiredness (fatigue), dizziness, and difficulty falling or staying asleep (insomnia). On average, people's body weight increased by 3kg in the first year of taking B/F/TAF. This might be because their general health improved after starting HIV treatment. Weight gained after that time was similar to the level of weight gain expected in the general population. Very few people (less than 1 in 100) stopped taking B/F/TAF because of side effects thought to have been caused by B/F/TAF. B/F/TAF was effective at treating HIV in people who had never taken HIV medication before. Most (70%) people were still taking B/F/TAF after 5years.Clinical Trial Registration: NCT02607930 (Study 1489); NCT02607956 (Study 1490) (ClinicalTrials.gov).

On the issue of treating HIV in people with syndemic mental-health and substance-use disorders.

People with HIV and comorbid substance use problems may be among those who benefit most from long-acting HIV antiretroviral treatment, but they are routinely excluded from Phase 3 clinical trials. Their inclusion would permit an examination of the clinical value of long-acting therapies for people with adherence problems and an exploration of syndemic interactions between HIV, mental health conditions, and substance use problems, which compound into a major challenge in the efforts to end the HIV epidemic.

Dual Infection of Different Clusters of HIV in People Living with HIV Worldwide: A Meta-Analysis Based on Next-Generation Sequencing Studies.

To understand the global dual HIV infection (DI) profiles comprehensively, the databases Cochrane Library, Embase, PubMed, and Web of Science were the data sources up to March 31, 2024 (PROSPERO: CRD42023388328). Stata and R-language software were used to analyze the extracted data. Publication bias was assessed using Egger's test. Sensitivity analysis was conducted to evaluate the stability of the combined effect values. Data from 17 eligible studies across four continents (Africa, Asia, Europe, and North America) with 1,475 subjects were used. The combined dual infection rate (DIR) was 10.47% (95% CI: 7.11%-14.38%) without a time trend (p = 0.105). The DIRs of target population groups differed significantly, with FSWs having the highest DIR (15.14%), followed by general population (12.08%), MSM (11.84%), and DUs (9.76%). The subtype profiles of 122 patients with dual infection were extracted, and the results showed that intrasubtype infections were predominant in coinfection (16/22, 72.73%) and superinfection (68/100, 68.00%) groups, with the subtype pattern B and B accounts for the largest proportion. The global dual infection rate may be underestimated, even though the data fluctuated around 10% and showed no time trend. The occurrence of DI indicated that individuals still do not acquire sufficient resistance to HIV even after primary infection, which could potentially compromise the patient's treatment effect and lead to the emergence of new subtypes, posing a significant challenge to HIV prevention, control, and treatment, suggesting that behavioral counseling and health education for all HIV-infected individuals are still crucial during the antiviral therapy.

Characteristics and rates of infection by HIV in people receiving non-occupational post-exposure prophylaxis (nPEP) against HIV

Introduction/objectivesThe use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary...

2675. Concurrent HIV and Sexually Transmitted Infections in People with Mpox in Guatemala City

Abstract Background High rates of HIV and sexually transmitted infections (STIs) among people with mpox have been reported. Guatemala has the highest number of mpox cases reported in Central America. Data on this topic in the region is lacking. We report the prevalence of STIs and HIV in people evaluated for mpox at Hospital Roosevelt in Guatemala City. Methods We conducted a cross-sectional analysis of confirmed mpox cases with outpatient care at our institution between July 2022 and January 2023. Sociodemographic and clinical data was retrospectively collected. This analysis includes new diagnoses of HIV, syphilis, chlamydia, gonorrhea, mycoplasma genitalium infection and herpes virus simplex (HSV) infection. Diagnoses were confirmed by serology or nucleic acid amplification tests. Rates of HIV/STIs were assessed and association with sociodemographic, behavioral and clinical characteristics was analyzed through non-parametric statistical tests. Results Sixty participants with mpox were included. All cis-gender male, 34 (56.6%) younger than 30 years old, 52 (86.6%) were residents of Guatemala City, 57 (95%) men who have sex with men (MSM), 51 (85%) had above secondary education, 36 (60%) with known HIV-positive status. Recent participation in group sex was reported in 9 (15%) participants and inconsistent or no condom use in 49 (81.6%). Among participants with known HIV-positive status 34 (94.4%) had CD4 count > 200/µL and 32 (88.9%) had a HIV viral load < 200 copies/ml. Two previously undiagnosed HIV infections were detected. Overall, 27 new STIs were found in 20 (33.3%) participants (5 had more than one STI). Comparisons between participants with concurrent STIs and those without are shown in Table 1. Nine cases of syphilis were detected. Eighteen STIs involved mucous membranes (oropharyngeal, genital or anorectal). Rates by site are shown in Table 2. Conclusion At least one STI was detected in a third of the mpox cases with syphilis being the most frequent. Almost half of STIs cases involved the anorectal site. People with previously known HIV-positive status had a significantly higher rate of STIs. HIV/STI care is key to an appropriate mpox management. Disclosures All Authors: No reported disclosures

Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence

Persistence of HIV in people living with HIV (PWH) on suppressive antiretroviral therapy (ART) has been linked to physiological mechanisms of CD4+ T cells. Here, in the same 37 male PWH on ART we measure longitudinal kinetics of HIV DNA and cell turnover rates in five CD4 cell subsets: naïve (TN), stem-cell- (TSCM), central- (TCM), transitional- (TTM), and effector-memory (TEM). HIV decreases in TTM and TEM but not in less-differentiated subsets. Cell turnover is ~10 times faster than HIV clearance in memory subsets, implying that cellular proliferation consistently creates HIV DNA. The optimal mathematical model for these integrated data sets posits HIV DNA also passages between CD4 cell subsets via cellular differentiation. Estimates are heterogeneous, but in an average participant’s year ~10 (in TN and TSCM) and ~104 (in TCM, TTM, TEM) proviruses are generated by proliferation while ~103 proviruses passage via cell differentiation (per million CD4). In simulations, therapies blocking proliferation and/or enhancing differentiation could reduce HIV DNA by 1-2 logs over 3 years. In summary, HIV exploits cellular proliferation and differentiation to persist during ART but clears faster in more proliferative/differentiated CD4 cell subsets and the same physiological mechanisms sustaining HIV might be temporarily modified to reduce it.

Understanding the audience in framing research: empirical evidence from three studies examining HIV framing in China.

Guided by framing theory, this three-phase mixed-methods study explored (a) how Chinese government-sponsored newspapers frame HIV and (b) framing effects on people's HIV beliefs. A content analysis of two government-sponsored newspapers and a survey of 210 readers showed discrepancies in frame and frame valence. In-depth follow-up interviews with 15 media and public health experts revealed that the discrepancies were related to people's attitudes toward the media and beliefs about HIV, which could further be explained by the political environment, media ecology, historical framing, and cultural identities in China. We discuss theoretical implications for framing theory and practical implications for HIV media coverage.

Lenacapavir: a twice-yearly treatment for adults with multidrug-resistant HIV infection and limited treatment options

Introduction Lenacapavir , the compoundreviewed in this paper, is a novel, potent, and long-acting first-in-classHIV-1 capsid inhibitor that was granted breakthrough therapy designation forHIV treatment by the U.S. Food and Drug Administration in May 2019. Lenacapavirwas subsequently approved, in combination with other antiretroviral agents, forthe treatment of multidrug-resistant HIV in people with HIV who have limitedtreatment options due to safety, intolerance and resistance considerations,based on clinical trial data which demonstrated its efficacy, tolerability, andsafety for that population. Areas Covered This review draws uponpublished and unpublished data of lenacapavir (GS-6207) to discuss itschemistry, mechanism of action, pharmacokinetic and pharmacodynamic properties,as well as efficacy and safety observed in clinical trials; and an expertopinion section discusses its clinical uses, advantages, limitations, andpotential future applications. Expert Opinion Lenacapavir should beused in combination with at least 1 or 2 additional fully active agents, wherepossible, and adherence support is critical for selected companion drugs(particularly if self-administered) to optimize efficacy and preventtreatment-emergent resistance to lenacapavir. Providers should pay attention todrug-drug interactions when initiating lenacapavir.

Efficacy and safety of long-acting cabotegravir versus oral tenofovir disoproxil fumarate-emtricitabine as HIV pre-exposure prophylaxis: A systematic review and meta-analysis.

WHO guidelines recommend daily oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) for pre-exposure prophylaxis (PrEP) of HIV in people at high risk of HIV infection. However, due to social, psychological and other reasons, the compliance with daily oral TDF-FTC in real life is low. Long-acting cabotegravir is currently the only long-acting drug approved by the U.S. Food and Drug Administration (FDA) for HIV PrEP. Due to the long dosing interval (8weeks), long-acting cabotegravir has low compliance requirements for people at high risk of HIV infection. We aimed to discuss the feasibility of long-acting cabotegravir to replace TDF-FTC as HIV PrEP based on efficacy and safety analyses. Randomized controlled trials were retrieved, and R software was used for meta-analysis after data extraction. and discussion: Results of the meta-analysis showed that compared with TDF-FTC, long-acting cabotegravir was associated with a lower risk of HIV infection (HR=0.22, 95% CI: 0.08-0.59, p<0.01), less decreased creatinine clearance (RR=0.96, 95% CI: 0.93-0.99, p<0.01), but more tolerated injection sites adverse events (p<0.01). No statistically significant differences were found between long-acting cabotegravir and oral placebo in non-injection-related adverse events (creatine phosphokinase, headache, nasopharyngitis, upper respiratory tract infection and gastroenteritis) (p>0.05). Long-acting cabotegravir has a manageable safety profile and is more effective than TDF-FTC in preventing HIV infection. Interestingly, decreased creatinine clearance occurred less frequently with long-acting cabotegravir than with TDF-FTC. Long-acting cabotegravir is very promising to replace TDF-TFC in the future, which requires more large-sample, high-quality RCTs to verify.

Prevalence of HIV in mental health service users: a retrospective cohort study

ObjectiveTo examine the prevalence of HIV in a cohort of people who have used secondary mental health services in the UK.DesignRetrospective cohort study.SettingRoutinely collected clinical data from secondary mental health...

The Public Debates Regarding the Use of the Contraceptive Pill and PrEP: What can the Arguments Used Tell Us About Attitudes Surrounding Sexual and Reproductive Rights in Norway?

The introduction of pre-exposure prophylaxis (PrEP) in 2012 in the US ushered in new technology for preventing HIV in people who are seen as at risk of contracting HIV. However, the rollout of PrEP has been filled with various debates and controversies ranging from concerns about effectiveness, adherence levels, cost-effectiveness, and moral responsibility for HIV prevention. In this context, some commentators have noted the uncanny similarities between this debate on PrEP and the debates that surrounded the launch of the oral contraceptive pill (the Pill) some 50 years ago. In this article, we provide the first to our knowledge analysis that compares how debates surrounding the launch of the Pill and debates which emerged concerning the launch of PrEP. Our analytical setting is the launch of the Pill in Norway in the 1960s and the launch of PrEP in 2016. Moreover, we wanted to focus on how both pharmaceuticals were framed in news media in Norway. We argue that such an analysis can tell us something about how the pharmaceuticalization of sex and sexuality often becomes dominated by discourses of morality and pivots around various issues of responsibility, in particular when it comes to female and gay sexualities.

Evaluation of an inner city HIV pre-exposure prophylaxis service tailored to the needs of people who inject drugs.

HIV prevention strategies including pre-exposure prophylaxis (PrEP) must reach all in need to achieve elimination of transmission by 2030. Mainstream provision may inadvertently exclude key populations. Incidence of HIV in people who inject drugs (PWID) in Glasgow, Scotland's largest city, is increasing, partly due to sexual transmission. Scotland provides publicly funded oral PrEP for individuals at sexual risk of HIV through sexual health services; however, uptake by PWID has been negligible. We developed a tailored outreach PrEP service based in the local homeless health centre. We used active case finding, flexibility of assessment location, supervised community daily dispensing and active follow-up to optimise uptake and adherence. We describe a two-year service evaluation. We reviewed the case records of all PWID identified by the outreach team as being at higher risk of sexual acquisition for whom PrEP was considered between November 2018 and November 2020. Evaluation focused on PrEP uptake, adherence and monitoring. We conducted a descriptive statistical analysis. Of 41 PWID assessed as eligible, 32 (78.0%) commenced PrEP. The proportion of PrEP-covered days was 3320/3400days (97.6%); 31/32 (96.9%) had regular HIV serology monitoring. The service was feasible to run, but it relied on outreach provision and liaison with other services. Tailored PrEP services can reach PWID effectively. Uptake and adherence were high but the model was resource-intensive. Appropriately tailored PrEP delivery may be required to meet the needs of this and other key populations who experience barriers to accessing mainstream services.

The RNA-Binding Proteins SRP14 and HMGB3 Control HIV-1 Tat mRNA Processing and Translation During HIV-1 Latency.

HIV-1 Tat protein is essential for virus production. RNA-binding proteins that facilitate Tat production may be absent or downregulated in resting CD4+ T-cells, the main reservoir of latent HIV in people with HIV (PWH) on antiretroviral therapy (ART). In this study, we examined the role of Tat RNA-binding proteins on the expression of Tat and control of latent and productive infection. Affinity purification coupled with mass spectrometry analysis was used to detect binding partners of MS2-tagged tat mRNA in a T cell-line model of HIV latency. The effect of knockdown and overexpression of the proteins of interest on Tat transactivation and translation was assessed by luciferase-based reporter assays and infections with a dual color HIV reporter virus. Out of the 243 interactions identified, knockdown of SRP14 (Signal Recognition Particle 14) negatively affected tat mRNA processing and translation as well as Tat-mediated transactivation, which led to an increase in latent infection. On the other hand, knockdown of HMGB3 (High Mobility Group Box 3) resulted in an increase in Tat transactivation and translation as well as an increase in productive infection. Footprinting experiments revealed that SRP14 and HMGB3 proteins bind to TIM-TAM, a conserved RNA sequence-structure in tat mRNA that functions as a Tat IRES modulator of tat mRNA. Overexpression of SRP14 in resting CD4+ T-cells from patients on ART was sufficient to reverse HIV-1 latency and induce virus production. The role of SRP14 and HMGB3 proteins in controlling HIV Tat expression during latency will be further assessed as potential drug targets.

ОГЛЯД ПРОГРАМИ ЗАМІСНОЇ ПІДТРИМУВАЛЬНОЇ ТЕРАПІЇ ЯК ЗАСІБ СОЦІАЛЬНОЇ ПРОФІЛАКТИКИ ВІЛ ДЛЯ ЛЮДЕЙ, ЯКІ ВЖИВАЮТЬ ІН'ЄКЦІЙНІ НАРКОТИКИ В УКРАЇНІ

Currently, the prevalence of HIV in people who inject drugs in Ukraine is over 22 %. Medication-assisted treatment (MAT) is an effective evidence-based means of HIV prevention in people who inject drugs (PWID). The objective of this article was to present the overview of medication-assisted program in Ukraine. Descriptive statistics were used to summarize the open-access official data as well as the results of most recent studies in the field of research to analyze and describe the current state of MAT program for PWID. Presented results summarize demographic, clinical data and access to psycho-social support of PWID on MAT in Ukraine as well as present effective approaches for program scale up for prevention of HIV transmission in people who inject drugs in Ukraine.

Brief Report: HIV Incidence Among Older Adults in a Rural South African Setting: 2010-2015.

Introduction:In South Africa, evidence shows high HIV prevalence in older populations, with sexual behavior consistent with high HIV acquisition and transmission risk. However, there is a dearth of evidence on older people's HIV incidence.Methods:We used a 2010–2011 cohort of HIV-negative adults in rural South Africa who were 40 years or older at retest in 2015–2016 to estimate HIV incidence over a 5-year period. We used Poisson regression to measure the association of HIV seroconversion with demographic and behavioral covariates. We used inverse probability sampling weights to adjust for nonresponse in 2015, based on a logistic regression with predictors of sex and age group at August 2010.Results:HIV prevalence increased from 21% at baseline to 23% in the follow-up survey. From a cohort of 1360 individuals, 33 seroconverted from HIV negative at baseline, giving an overall HIV incidence rate of 0.39 per 100 person-years [95% confidence interval (CI): 0.28 to 0.57]. The rate for women was 0.44 (95% CI: 0.30 to 0.67), double than that for men, 0.21 (95% CI: 0.10 to 0.51). Incidence rate ratios (IRRs) again show women's risk of seroconverting double than that of men (IRR = 2.04, P value = 0.098). In past age 60, the IRR of seroconversion was significantly lower than that for those in their 40s (60–69, IRR = 0.09, P value = 0.002; 70–79, IRR = 0.14, P value = 0.010).Conclusions:The risk of acquiring HIV is not zero for people older than 50 years, especially women. Our findings highlight the importance of acknowledging that older people are at high risk of HIV infection and that HIV prevention and treatment campaigns must take them into consideration.

Treating HIV in People with HIV/TB Coinfection

In people with HIV/tuberculosis (TB) coinfection, antiretroviral therapy (ART) should be started soon after anti-TB therapy is initiated. Dolutegravir

Global systematic review and ecological analysis of HIV in people who inject drugs: National population sizes and factors associated with HIV prevalence

BackgroundPeople who inject drugs (PWID) are at elevated risk of HIV infection. Data on population sizes of PWID living with HIV are needed to inform the implementation of prevention, treatment and care programs. We estimated national population sizes of people who recently (past 12 months) injected drugs living with HIV and evaluated ecological associations with HIV prevalence in PWID. MethodsWe used national data on the prevalence of injecting drug use and of HIV among PWID, derived from systematic reviews, to estimate national population sizes of PWID living with HIV. Uncertainty was estimated using Monte Carlo simulation with 100,000 draws. We extracted data on sample characteristics from studies of HIV prevalence among PWID, and identified national indicators that have been observed or hypothesised to be associated with HIV prevalence in PWID. We used linear regression to evaluate associations between these variables and HIV prevalence in PWID. ResultsFour countries comprised 55% of the estimated global population of PWID living with HIV: Russia (572,500; 95% uncertainty interval (UI) 235,500–1,036,500); Brazil (462,000; 95% UI 283,500–674,500); China (316,500; 95% UI 171,500–493,500), and the United States (195,500; 95% UI 80,000–343,000). Greater anti-HCV prevalence and national income inequality were associated with greater HIV prevalence in PWID. ConclusionThe countries with the largest populations of PWID living with HIV will need to dramatically scale up prevention, treatment and care interventions to prevent further increases in population size. The association between anti-HCV prevalence and HIV prevalence among PWID corroborates findings that settings with increasing HCV should implement effective interventions to prevent HIV outbreaks. The association between income inequality and HIV among PWID reinforces the need to implement structural interventions alongside targeted individual-level strategies.

Identifying priorities for HIV-associated tuberculosis research through the WHO guidelines process.

Guidelines developed by the WHO aim to provide recommendations to support best practice in health delivery, with a focus on low-income and middle-income countries. As part of the guideline development process, critical knowledge gaps are identified and one of the core functions of WHO guidelines is to set forth priorities for future research. A review of research priorities identified through the WHO guideline development has recently been promoted as one approach to building an overarching priority research agenda in a given area. This paper outlines priorities for HIV-associated TB research identified in WHO HIV and TB guidelines published since 2015. Nine guidelines were reviewed and 29 priority research questions were identified. Research priorities were identified for prevention of HIV-associated TB (11 questions), screening of latent and active TB in people living with HIV (six questions), treatment of drug sensitive (four questions), and drug-resistant (two questions) TB, and treatment of HIV in people coinfected with TB (three questions). Multiple approaches to defining priority research questions for health research exist. Research priorities that arise from the WHO guideline development process are limited to those areas for which guidelines are developed. One strength of this approach is that it takes as a starting point a desire to make actionable recommendations for policy makers. WHO is working to further refine the formulation of research questions within the guideline development process.

Comparing risk environments for HIV among people who inject drugs from three cities in Northern Mexico

BackgroundA large body of research has investigated the rise of injection drug use and HIV transmission in Tijuana and Ciudad Juarez (CJ). However, little is known about the dynamics of injecting in Hermosillo. This study compares drug-related behaviors and risk environment for HIV of people who inject drugs (PWID) across Tijuana, CJ, and Hermosillo to identify factors that could explain differences in HIV prevalence.MethodsData from Tijuana belong to a prospective study (El Cuete IV). Data from Hermosillo and Ciudad Juarez belong to a cross-sectional study. Both studies collected data in places where PWID spend time. All participants completed quantitative behavioral and serological testing for HIV. Datasets were merged using only comparable variables. Descriptive statistics tests were used to compare sociodemographic and behavioral characteristics of people who inject drugs PWID sampled in each city. A logistic regression model was built to identify factors independently associated with the likelihood of reporting receptive syringe sharing in the past 6 months.ResultsA total of 1494 PWID provided data between March 2011 and May 2012. HIV prevalence differed significantly between participants in Tijuana (4.2%), CJ (7.7%), and Hermosillo (5.2%; p < 0.05). PWID from Hermosillo reported better living conditions, less frequency of drug injection, and lower prevalence of syringe sharing (p < 0.01). PWID from CJ reported a higher prevalence of syringe sharing and confiscation by police (p < 0.01). In a multivariable logistic regression model, living in Hermosillo compared to Tijuana (adjusted odds ratio [AOR] = 0.42, 95% confidence interval [CI] 0.29–0.61) and being female (AOR = 0.61, 95% CI 0.45–0.83) were protective against syringe sharing. Having used crystal meth (AOR = 1.62, 95% CI 1.24–2.13, p = 0.001), having experienced syringe confiscation by police in the last 6 months (AOR = 1.78, 95% CI 1.34–2.40), and lower perception of syringe availability (AOR = 2.15, 95% CI 1.59–2.91) were significantly associated with syringe sharing (p < 0.05).ConclusionsDifferences in HIV prevalence across cities reflect mainly differences in risk environments experienced by PWID, shaped by police practices, access to injection equipment, and dynamics of drug markets. Findings highlight the importance of ensuring sterile syringe availability through harm reduction services and a human rights approach to drug harms in northern Mexico and to generate better understanding of local dynamics and contexts of drug use for designing proper harm reduction programs.