HIV Control Research Articles

Abstract 4113164: Central Arterial Stiffness in Young Adults with Perinatal HIV Exposure

Intro: Young adults with perinatally acquired HIV (YPHIV) have higher morbidity and mortality than uninfected persons. Antiretroviral therapy (ART) has extended life expectancy making adult CV disease a concern. Perinatal exposure to HIV increases inflammation which is associated with increased arterial stiffness which predicts CV disease. Aims: We compared arterial stiffness between YPHIV and young adults perinatally HIV exposed but uninfected (YPHEU), and evaluated the association of type and duration of ART regimens, HIV disease severity, and cardiac structure and function with arterial stiffness. Methods: In a substudy of the Pediatric HIV/AIDS Cohort Study, 150 participants (95 YPHIV, 55 YPHEU, mean 23.4 yrs, 60% female, 72% Black, 24% Hispanic) had echocardiography and pulse wave velocity (PWV) measured. We compared PWV between YPHIV and YPHEU, adjusting for covariates. Among YPHIV, we fit linear regression models to evaluate the association of current (within 1 year of PWV) and historical measures of HIV disease severity with PWV. We computed correlations between PWV and measures of left ventricular (LV) structure and function, overall and by HIV status. Results: Mean PWV and hemodynamic parameters did not differ between YPHIV and YPHEU (YPHIV 5.63 vs YPHEU 5.39 m/s; p=0.5). HIV control was good (82% with viral load <400 copies/ml), 91% used combination ART: integrase strand inhibitors (INSTIs; median duration 4.6 years), protease inhibitors (PIs 15.1 years), or non-nucleoside reverse transcriptase inhibitors (NNRTIs 5.2 years). Most participants had normal PWV compared to healthy controls but all values above 11.8 m/sec ( Figure , level associated with CV events in adults) were only in YPHIV. Only weak correlations were observed between PWV and echocardiographic measures (<0.20) in both YPHEU and YPHIV. Among YPHIV, HIV severity measures were not associated with PWV using either current or historical measures. Mean PWV was 1.68 (-0.36, 3.72) m/s higher among YPHIV with current PI use than those on INSTIs, and 1.58 (-0.94, 4.11) m/s higher than those on NNRTIs, although these differences were not significant. Conclusions: PWV was within normal ranges in most YPHIV and YPHEU although 5% YPHIV had elevated PWV. PWV may be higher with PI use due to cardiometabolic side effects. Successful HIV treatment and control of traditional CV risk factors may prevent premature vascular aging and subsequent cardiac compromise in YPHIV.

HIV replication and tuberculosis risk among people living with HIV in Europe: A multicohort analysis, 1983-2015.

HIV replication leads to a change in lymphocyte phenotypes that impairs immune protection against opportunistic infections. We examined current HIV replication as an independent risk factor for tuberculosis (TB). We included people living with HIV from 25 European cohorts 1983-2015. Individuals <16 years or with previous TB were excluded. Person-time was calculated from enrolment (baseline) to the date of TB diagnosis or last follow-up information. We used adjusted Poisson regression and general additive regression models. We included 272,548 people with a median follow-up of 5.9 years (interquartile range [IQR] 2.3-10.9). At baseline, the median CD4 cell count was 355 cells/μL (IQR 193-540) and the median HIV-RNA level 22,000 copies/mL (IQR 1,300-103,000). During 1,923,441 person-years of follow-up, 5,956 (2.2%) people developed TB. Overall, TB incidence was 3.1 per 1,000 person-years (95% confidence interval [CI] 3.02-3.18) and was four times higher in patients with HIV-RNA levels of 10,000 compared with levels <400 copies/mL in any CD4 stratum. CD4 and HIV-RNA time-updated analyses showed that the association between HIV-RNA and TB incidence was independent of CD4. The TB incidence rate ratio for people born in TB-endemic countries compared with those born in Europe was 1.8 (95% CI 1.5-2.2). Our results indicate that ongoing HIV replication (suboptimal HIV control) is an important risk factor for TB, independent of CD4 count. Those at highest risk of TB are people from TB-endemic countries. Close monitoring and TB preventive therapy for people with suboptimal HIV control is important.

Post-intervention control in HIV immunotherapy trials.

While post-treatment control following interruption of standard-of-care antiretroviral therapy (ART) is well described, post-intervention control following immunotherapy in HIV cure-related clinical trials is less well understood. We provide an overview of recent studies that have identified post-intervention controllers and review the mechanisms that may drive this biologically important phenotype. Post-intervention controllers have been identified in recent immunotherapy trials testing broadly neutralizing antibodies, immune modulators, modified T cells, checkpoint inhibitors, and gene therapy administered individually or in combination. Currently, there is substantial variability in how each trial defines post-intervention control, as well as in how the mechanisms underlying such control are evaluated. Such mechanisms include ongoing activity of both exogenous and autologous antibodies, as well as changes in HIV-specific T cell function. While no therapeutic strategy to date has succeeded in definitively inducing HIV control, many studies have identified at least a small number of post-intervention controllers. The field would benefit from a standardized approach to defining and reporting this phenotype, as well as standardization in the approach to assessment of how it is achieved. Such efforts would allow for comparisons across clinical trials and could help accelerate efforts toward an HIV cure.

Patterns of HIV-1 Drug Resistance Observed Through Geospatial Analysis of Routine Diagnostic Testing in KwaZulu-Natal, South Africa.

HIV-1 drug resistance (HIVDR) impedes treatment and control of HIV-1, especially in high-prevalence settings such as KwaZulu-Natal (KZN) province, South Africa. This study merged routine HIV-1 genotypic resistance test (GRT) data with Geographic Information Systems coordinates to assess patterns and geographic distribution of HIVDR in KZN, among ART-experienced adults with virological failure. We curated 3133 GRT records generated between 1 January 2018 and 30 June 2022, which includes the early phase of dolutegravir (DTG) rollout, of which 2735 (87.30%) had HIVDR. Of the 2735, major protease, nucleoside, and non-nucleoside reverse transcriptase inhibitor mutations were detected in 41.24%, 84.97% and 88.08% of GRTs, respectively. Additional genotyping of HIV-1 integrase for 41/3133 (1.31%) GRTs showed that 17/41 (41.46%) had integrase strand transfer inhibitor resistance. Notably, of 26 patients on DTG with integrase genotyping, 9 (34.62%) had DTG-associated resistance mutations. Dual- or triple-class resistance was observed in four of every five GRTs. The odds of HIVDR increased significantly with age, with ≥60 years having 5 times higher odds of HIVDR compared to 18-29 years (p = 0.001). We identified geospatial differences in the burden of HIVDR, providing proof of concept that this could be used for data-driven public health decision making. Ongoing real-time HIVDR surveillance is essential for evaluating the outcomes of the updated South African HIV treatment programme.

Impact of natural disasters on HIV risk behaviors, seroprevalence, and virological supression in a hyperendemic fishing village in Uganda.

Understanding the impact of natural disasters on the HIV epidemic in populations with high HIV burden is critical for the effective delivery of HIV control efforts. We assessed HIV risk behaviors, seroprevalence, and viral suppression in a high HIV prevalence Lake Victoria fishing community before and after COVID-19 emergence and lockdown and a severe lake flooding event, both of which occurred in 2020. We used data from the largest Lake Victoria fishing community in the Rakai Community Cohort Study, an open population-based HIV surveillance cohort in south-central Uganda. The data were collected both prior to (September-December 2018) and after (October-December 2021) COVID-19 emergence and a severe flooding event. Households impacted by flooding were identified via drone data and through consulting village community health workers. The entire study population was subject to extensive COVID-19-related lockdowns in the first half of 2020. Differences in HIV-related outcomes before and after COVID, and between residents of flooded and non-flooded households, were assessed using a difference-in-differences statistical modeling approach. A total of 1,226 people participated in the pre- and post-COVID surveys, of whom 506 (41%) were affected by flooding. HIV seroprevalence in the initial period was 37% in flooded and 36.8% in non-flooded households. After the COVID-19 pandemic and lockdown, we observed a decline in HIV-associated risk behaviors: transactional sex declined from 29.4% to 24.8% (p = 0.011), and inconsistent condom use with non-marital partners declined from 41.6% to 37% (p = 0.021). ART coverage increased from 91.6% to 97.2% (p<0.001). There was 17% decline in transactional sex (aPR = 0.83, 95% CI: 0.75-0.92) and 28% decline in the overall HIV risk score (aPR = 0.83, 95% CI: 0.75-0.92) among HIV-seronegative participants. We observed no statistically significant differences in changes of HIV risk behavior, seroprevalence, or viral suppression outcomes when comparing those affected by floods to those not affected by floods, in the periods before and after COVID-19, based on difference-in-differences analyses. Despite a high background burden of HIV, the COVID-19 pandemic, and severe flooding, we observed no adverse impact on HIV risk behaviors, seroprevalence, or virologic outcomes. This may be attributed to innovative HIV programming during the period and/or population resilience. Understanding exactly what HIV programs and personal or community-level strategies worked to maintain good public health outcomes despite extreme environmental and pandemic conditions may help improve HIV epidemic control during future natural disaster events.

Cross-cultural adaptation and validation of the 2021 Louisiana Needs Assessment Questionnaire for Arabic-speaking people living with HIV

BackgroundDespite the global decline in HIV infections and mortality worldwide, the HIV epidemic is still growing in the MENA region. In the region, People Living with HIV (PLWH) are facing many challenges related to cultural values, norms, and provided services which create significant obstacles to HIV prevention and control efforts. This study aimed to translate, culturally adapt, and validate the “2021 Louisiana Needs Assessment Questionnaire” for use among Egyptians and Arabic-speaking population.MethodsArabic translation and cultural adaptation of the questionnaire passed through five stages. The questionnaire was translated forward and backward then an expert committee reviewed the translated version. Another expert committee reviewed the developed version after modification to assess the content validity using the Content Validity Index (CVI). The last step included a cognitive interview of a convenient sample of 50 adult PLWH in five consecutive rounds to assess subjects’ understanding of questions and response items and their meanings.ResultsModifications were carried out all through the translation and adaptation process of the questionnaire including used words, nomenclature of services, adding or omitting response items, and ordering of questions and response items. The synthesized Arabic-adapted questionnaire has adequate content validity and all questions are clearly understood by the studied subjects. The calculated Content Validity Index of all questionnaire items ranged from 0.82 to 1.ConclusionThe developed culturally adapted questionnaire has adequate content validity/semantic appropriateness. It can be used to assess the needs of PLWH in the MENA region with minor adaptations to fit each country. It can also be used to follow the outcome and impact of implemented programs and services. Further research is recommended to assess its psychometric properties.

Energy demanding RNA and protein metabolism drive dysfunctionality of HIV-specific T cell changes during chronic HIV infection.

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

Pretreatment drug resistance among people living with HIV from 2018 to 2022 in Guangzhou, China.

The presence of pretreatment drug resistance (PDR) is posing an increasing threat to HIV control. Here we investigated drug resistance mutations (DRMs) and PDR among 6831 HIV-infected individuals from 2018 to 2022 in Guangzhou, China. DRMs were detected among 24.5% of the patients. The overall prevalence of PDR was 7.4%, with resistance rate to nucleotide reverse transcriptase inhibitor (NRTI) being 1.3%, nonnucleoside reverse transcriptase inhibitor (NNRTI) 4.8%, and protease inhibitor (PI) 1.4%. Abacavir (0.8%) resistance was the most common in NRTI, followed by resistance to emtricitabine (0.6%), lamivudine (0.6%), and tenofovir disoproxil fumarate (0.3%). In NNRTI, nevirapine (3.7%) resistance was the most common, followed by efavirenz (3.5%) and rilpivirine (3.4%). Among PI, resistance to tipranavir (0.8%), nelfinavir (0.6%), fosamprenavir (0.2%) and lopinavir (0.1%) was most frequent. Annual prevalence of PDR showed an increase trend from 2018 to 2022, although not significant. In the multivariable logistic regression model, hepatitis B surface antigen positivity, circulating recombinant form (CRF) 55_01B, CRF08_BC, CRF59_01B, and subtype B were demonstrated as associated risk factors for PDR. The overall prevalence of PDR in Guangzhou was moderate, with relatively severe NNRTI resistance. Therefore, it remains crucial to continue monitoring PDR among newly diagnosed HIV-infected individuals.

Demographic and clinical characteristics of New York City Health + Hospitals HIV Heart Failure (NYC4H cohort): cohort profile.

Studies have elucidated that heart failure (HF) in people living with HIV manifests differently when compared with HF cases in the general population. This cohort aimed to examine the mortality risk factors, including biological and social factors, as well as suitable medical interventions to prevent death in this population. The New York City Health+Hospitals HIV Heart Failure (NYC4H) cohort encompassed records from 11 major hospital sites. Adult individuals with confirmed HIV and HF were recruited from either inpatient or clinic hospital visits between July 2017 and June 2022. The first follow-up period began on the date of the first clinical encounter until June 2023, and the second follow-up period extended between July 2022 and October 2023. In total, 1044 patients were enrolled in the study. The cohort comprised 657 (62.9%) males and 387 (37.1%) females. The average age was 61.6 years at baseline and the average follow-up time was 3.8 years. Overall, a total of 259 (24.8%) deaths were identified, of which 193 occurred in the first follow-up period (enrolling date to June 2022) and 66 during the second follow-up period (June 2022 to October 2023). The most common comorbidities within this population were hypertension (75.3%), chronic obstructive pulmonary disease (39.2%), type II diabetes mellitus (40%) and hyperlipidaemia (35.7%). The most common social adversities were polysubstance use (31.13%), mental health-related issues (20.7%) and lack of family support (14.5%). 601 (57.6%) patients had encountered at least one and more than one social adversity in their lifetime. Currently, nutritional notes from licensed dietitians and right and left heart catheterisation reports are under review. We are scheduled to complete the data collection for the comprehensive third follow-up period, which includes follow-up psychosocial evaluations, by the end of 2025. In addition, we intend to conduct annual follow-ups for specific high-risk groups, such as individuals with pulmonary hypertension, those facing higher social adversities and participants with poor HIV control.

Soluble markers of viral rebound and post-treatment HIV control.

We focus on the different classes of biological molecules measurable in easily accessible bodily fluids that have the potential to serve as biomarkers for the HIV post-treatment controller (PTC) phenotype and/or the timing of viral rebound after stopping antiretroviral therapy (ART). Various viral components and host factors measurable in body fluids can play crucial roles in understanding and predicting the PTC phenotype. We review recent findings linking viral components, the quantitative and qualitative features of antibodies (including autologous HIV-specific antibodies), markers of inflammation and tissue damage, other host proteins (including hormones such as sex hormones), as well as metabolites, extracellular vesicles, and cell-free DNA to HIV control post-ART interruption. Several of these molecules can or have the potential to predict the time and probability of viral rebound after stopping ART and are biologically active molecules that can directly or indirectly (by modulating immune pressures) impact the size and activity of HIV reservoirs during and post-ART interruption. A comprehensive model combining multiple markers is needed to predict the PTC phenotype. This model can be leveraged to predict and understand the PTC phenotype, which can guide novel curative interventions to replicate this phenotype in post-treatment non-controllers.

NKG2C and NKG2A coexpression defines a highly functional antiviral NK population in spontaneous HIV control.

Elite controllers (ECs), a unique group of people with HIV (PWH), exhibit remarkable control of viral replication in the absence of antiretroviral therapy. In this study, we comprehensively characterized the NK cell repertoire in ECs after long-term viral control. Phenotypic profiling of NK cells revealed profound differences compared with other PWH, but marked similarities to uninfected individuals, with a distinctive prevalence of NKG2C+CD57+ memory-like NK cells. Functional analyses indicated that ECs had limited production of functional molecules upon NK stimulation and consequently reduced natural cytotoxicity against non-HIV target cells. Importantly, ECs showed an exceptional ability to kill primary HIV-infected cells by the antibody-dependent cell cytotoxicity adaptive mechanism, which was achieved by a specific memory-like NK population expressing CD16, NKG2A, NKG2C, CD57, and CXCR3. In-depth single-cell RNA-seq unveiled a unique transcriptional signature in these NK cells linked to increased cell metabolism, migration, chemotaxis, effector functions, cytokine secretion, and antiviral response. Our findings underscore a pivotal role of NK cells in the immune control of HIV and identify specific NK cells as emerging targets for immunotherapies.

Knowledge, attitudes and practices related to AIDS amongst transgender women in Chongqing, China: a cross-sectional study

BackgroundTransgender women (TGWs) constitute one of the key populations for HIV prevention and control and constitute a high-risk group due to a lack of health services. The aim of this study was to investigate knowledge, attitudes and practices (KAPs) related to HIV and knowledge access and needs amongst transgender women in Chongqing, China.MethodsA cross-sectional study was conducted from October 2022 to March 2023. A total of 128 self-identified TGWs were recruited in Chongqing, China, via snowball sampling, and a KAP-related questionnaire was completed via Questionnaire Star.ResultsFor the 128 TGWs surveyed effectively, the total knowledge of AIDS-related knowledge was 82.03%, with significant differences in age, education level, marital status, occupation and average monthly income (p < 0.05). Significant differences were obtained in terms of personal attitudes toward AIDS and place of domicile and literacy (p < 0.05) and subjective norms in terms of literacy (p < 0.05). No significant difference was observed between the groups in terms of HIV-related practices. The corresponding values were assigned to knowledge, attitudes or practices. The total scores of the three aspects were 6.77 ± 1.47 (95% confidence interval [CI]: 3.89–9.65) (range: 0–8), 14.22 ± 2.37 (95% CI: 9.57–18.87) (range: 0–18) and 6.66 ± 1.79 (95% CI: 3.16–10.17) (range: 0–9), respectively. The main approaches for TGWs to acquire AIDS knowledge are ‘Internet/smartphone’ (81.68%), ‘TV/radio’ (49.62%) and ‘special education on AIDS prevention in schools’ (48.09%). TGW is more inclined to accept promotional activities such as ‘WeChat push’ (58.02%), ‘peer education’ (44.27%) and ‘mobile app management’ (37.40%). AIDS knowledge indicates that TGW needs to strengthen publicity, including ‘transmission routes’ (71.76%), ‘voluntary counselling and testing knowledge’ (67.94%) and ‘virus-related knowledge’ (64.89%).ConclusionsFirst, the knowledge rate of AIDS amongst TGWs in Chongqing, China, still has room for improvement, and there is a gap between knowledge and behavior. Second, TGWs are tolerant of AIDS and people living with AIDS and have a strong awareness of AIDS prevention. Third, the health department should attach importance to the group of TGW over 35 years old, low-income, and low-educated, and promote social organizations and network platforms to further strengthen the health education and publicity of AIDS from the perspectives of knowledge acquisition and needs.

Immune checkpoint inhibitors in infectious disease.

Following success in cancer immunotherapy, immune checkpoint blockade is emerging as an exciting potential treatment for some infectious diseases, specifically two chronic viral infections, HIV and hepatitis B. Here, we will discuss the function of immune checkpoints, their role in infectious disease pathology, and the ability of immune checkpoint blockade to reinvigorate the immune response. We focus on blockade of programmed cell death 1 (PD-1) to induce durable immune-mediated control of HIV, given that anti-PD-1 can restore function to exhausted HIV-specific T cells and also reverse HIV latency, a long-lived form of viral infection. We highlight several key studies and future directions of research in relation to anti-PD-1 and HIV persistence from our group, including the impact of immune checkpoint blockade on the establishment (AIDS, 2018, 32, 1491), maintenance (PLoS Pathog, 2016, 12, e1005761; J Infect Dis, 2017, 215, 911; Cell Rep Med, 2022, 3, 100766) and reversal of HIV latency (Nat Commun, 2019, 10, 814; J Immunol, 2020, 204, 1242), enhancement of HIV-specific T cell function (J Immunol, 2022, 208, 54; iScience, 2023, 26, 108165), and investigating the effects of anti-PD-1 and anti-CTLA-4 in vivo in people with HIV on ART with cancer (Sci Transl Med, 2022, 14, eabl3836; AIDS, 2021, 35, 1631; Clin Infect Dis, 2021, 73, e1973). Our future work will focus on the impact of anti-PD-1 in vivo in people with HIV on ART without cancer and potential combinations of anti-PD-1 with other interventions, including therapeutic vaccines or antibodies and less toxic immune checkpoint blockers.

Identification of a Clade-Specific HLA-C*03:02 CTL Epitope GY9 Derived from the HIV-1 p17 Matrix Protein.

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02 CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope potentially restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

Effectiveness and safety of tildrakizumab in individuals with HIV and psoriasis: A case series.

Psoriasis, a chronic inflammatory skin disease, presents unique challenges when co-occurring with HIV. Tildrakizumab, an IL-23p19 inhibitor, has demonstrated efficacy in treating moderate-to-severe psoriasis. This retrospective case series reports three individuals living with HIV and psoriasis treated with tildrakizumab. Clinical outcomes, including Psoriasis Area and Severity Index (PASI) and HIV viral load, were recorded over a year. All three patients achieved significant clinical improvements with tildrakizumab, with PASI scores improving by over 95%. No adverse effects were reported, and HIV viral loads remained undetectable. Tildrakizumab appears to be a safe and effective treatment option for psoriasis in individuals living with HIV, providing significant benefits without compromising HIV control.

HIV-1 control in vivo is related to the number but not the fraction of infected cells with viral unspliced RNA.

In the absence of antiretroviral therapy (ART), a subset of individuals, termed HIV controllers, have levels of plasma viremia that are orders of magnitude lower than non-controllers (NC) who are at higher risk for HIV disease progression. In addition to having fewer infected cells resulting in fewer cells with HIV RNA, it is possible that lower levels of plasma viremia in controllers are due to a lower fraction of the infected cells having HIV-1 unspliced RNA (HIV usRNA) compared with NC. To directly test this possibility, we used sensitive and quantitative single-cell sequencing methods to compare the fraction of infected cells that contain one or more copies of HIV usRNA in peripheral blood mononuclear cells (PBMC) obtained from controllers and NC. The fraction of infected cells containing HIV usRNA did not differ between the two groups. Rather, the levels of viremia were strongly associated with the total number of infected cells that had HIV usRNA, as reported by others, with controllers having 34-fold fewer infected cells per million PBMC. These results reveal that viremic control is not associated with a lower fraction of proviruses expressing HIV usRNA, unlike what is reported for elite controllers, but is only related to having fewer infected cells overall, maybe reflecting greater immune clearance of infected cells. Our findings show that proviral silencing is not a key mechanism for viremic control and will help to refine strategies toward achieving HIV remission without ART.

Evolving molecular HIV clusters revealed genotype-specific dynamics in Guangzhou, China (2008-2020)

ObjectivesThis study investigated the genotype-specific dynamics of molecular HIV clusters (MHCs) in Guangzhou, China, aiming to enhance HIV control. MethodsHIV pol sequences from people with HIV (PWH) in Guangzhou (2008-2020) were obtained for genotyping and molecular network creation. MHCs were identified and categorized into three types: emerging, growing, or stable. Clustering rates, proportions of cluster types, and members within each type were calculated and their trends were assessed using joinpoint regression. ResultsAmong 8395 PWH, the most prevalent HIV-1 genotypes were CRF07_BC (39.7%) and CRF01_AE (32.6%). The genotype composition has been stable since 2012 (Ps > 0.05). The overall clustering rate was 43.3%, with significant variations across genotypes (P < 0.001), indicating genotype-specific transmission fitness. Significant declines in overall and genotype-specific clustering rates toward the end of 2020 (Ps < 0.05), potentially offer support for HIV control efforts in reducing local infections. The continuously increasing proportions of stable clusters and the gradually decreasing proportions of emerging and growing clusters (either Ps < 0.05 or Ps > 0.05) suggest a trend toward stable molecular network structure. However, growing clusters exhibited CRF55_01B, CRF07_BC, and CRF59_01B dominance that indicate their priority for interventions. ConclusionThe evolving MHCs highlight the genotype-specific cluster dynamics, providing fresh insights for enhanced prevention and control strategies.

The unsung heroes in the fight to end HIV: The role of nurses in Indonesia

HIV new cases are continuing to be reported in Indonesia. Although progress in HIV prevention and control has been made, Indonesia continues to face significant challenges in its fight against HIV. Continued efforts to expand treatment, reduce stigma, and strengthen prevention initiatives by involving health care workers and all stakeholders are essential to controlling the epidemic and improving the lives of those affected by HIV in the country. As a healthcare worker, nurses are central to the country's efforts to control and eventually end the HIV epidemic. Their roles are diverse and impactful, ranging from direct patient care to community outreach, education, and policy advocacy. As Indonesia continues to face challenges in its HIV response, the contributions of nurses will remain essential in overcoming these barriers and improving the lives of those affected by HIV.

Sexually transmitted infections and migration in Uganda: a population-based study

ObjectivesMigration is associated with increased risk of HIV infection in Africa, but evidence about non-HIV sexually transmitted infection (STI) burden among African migrants is limited.MethodsWe used data from the Sexually...

Public T cell clonotypes are selected in HLA-B∗57:01+/HIV+ patients independently of the viral load

HIV controllers can control viral replication and remain healthy, but the mechanism behind this control is unknown. Despite human leukocyte antigen (HLA) diversity in the population, almost 50% of HIV controllers express the HLA-B∗57:01 molecule, which presents, among others, the Gag-derived epitope TW10. Given TW10's presentation in early infection, TW10-specific Tcells could participate in the control of HIV. Here, we study the strength and functionality of TW10-specific Tcells from HLA-B∗57:01+/HIV+ controller and non-controller individuals. We determine the TW10-specific Tcell receptor (TCR) repertoire, revealing a bias in TCR gene usage with the presence of a public TCR. We determine that the Tcell response is polyfunctional regardless of the viral load, despite the low affinity of TW10-specific TCRs. We solve the crystal structure of HLA-B∗57:01-TW10 in complex with a TCR, providing the basis of recognition that underpins the strong TRBV5 bias observed in TW10-specific clonotypes.