HIV Disease Progression Research Articles

HIV disease progression among heterosexually-infected individuals before the introduction of universal ART in China: A linear mixed-effects model.

In 2016, China introduced universal antiretroviral therapy (ART) for all HIV-infected individuals regardless of CD4 cell count. However, the natural history and rate of CD4 count decline among heterosexually-infected individuals remain uncharacterized. Analyzing national surveillance data can address this gap and shed light on the pathogenesis of HIV in this population. We used a linear mixed-effects model to assess CD4 trajectory over time before ART initiation and estimated the median time from HIV seroconversion to reaching CD4 thresholds of < 500, < 350, and < 200 cell/mm3. From the Chinese HIV/AIDS Comprehensive Response Information Management System, 59,085 eligible individuals were identified, with 113 having data to estimate the date of HIV seroconversion. The linear mixed-effects models estimated an intercept of 23.64 (95% confidence interval [CI]: 22.41 to 24.87) and a slope of -1.32 (95% CI: -1.34 to -1.30) for males, and an intercept of 22.70 (95% CI: 21.00 to 24.40) and a slope of -1.29 (95% CI: -1.31 to -1.27) for females. The estimated median times from HIV seroconversion to reaching CD4 count thresholds of < 500, < 350, < 200 cells/mm3 were 0.97, 3.74, and 7.20 years for males, and 0.26, 3.09, and 6.48 years for females, respectively. Males consistently took longer to reach these CD4 count thresholds compared to females of the same age group. Older individuals (≥ 40 years) reached CD4 thresholds faster than younger individuals (15-29 years), indicating more rapid disease progression in older people living with HIV.

High rates of Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis co-infection in people with HIV: a systematic review and meta-analysis.

People living with HIV (PWH) experience a disproportionate burden of sexually transmitted infections (STIs), leading to more severe health outcomes and increasing the risk of HIV transmission. The presence of untreated STIs can accelerate HIV disease progression, while HIV infection can complicate STI diagnosis and treatment. Despite this interconnectedness, comprehensive data on the global prevalence of specific STIs among PWH remain limited. This systematic review aims to synthesize existing data to provide a more accurate picture of the prevalence of co-infection with Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis or Trichomonas vaginalis in PWH, while also identifying critical knowledge gaps and informing future research priorities. We searched databases for eligible studies reporting the prevalence of Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, or Trichomonas vaginalis among PWH, published from January 1, 2000, to February 1, 2023. From 22,290 identified articles, 127 independent studies meeting the inclusion criteria were included in this meta-analysis. The overall global co-infection prevalence of Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis in PWH, was 4.8% (95%CI: 4.7-5.0%), 0.8% (95%CI: 0.6-0.9%), 2.5% (95%CI: 2.2-2.7%), and 3.0% (95%CI: 2.7-3.3%), respectively. The global prevalence of these four STIs in PWH is high, especially in Africa and Southeast Asia and in MSM and TGW populations. Based on the subgroup analyses, we further found that there was a high prevalence of Treponema pallidum and Chlamydia trachomatis in Southeast Asia and a high infection of Trichomonas vaginalis in the whole of Africa. Treponema pallidum infection was more common in males than females, and Chlamydia trachomatis and Trichomonas vaginalis infections were more common in females than males. Besides, high infection rates of Treponema pallidum, Neisseria gonorrhoeae, and Chlamydia trachomatis were detected in men who have sex with men (MSM) + transgender women (TGW), while high infection rates of Trichomonas vaginalis were found in sex workers and pregnant women. The study confirmed high prevalence of four sexually transmitted pathogens in PWH, noting regional, gender, and subpopulation-specific differences. It offered insights for targeted interventions and healthcare strategies. The research underscored the necessity for enhanced data collection and expanded screening/treatment for vulnerable populations and regions.

Magnitude of anemia and associated factors among HIV infected children on antiretroviral therapy in Awi zone health facilities, Northwest Ethiopia, 2023

BackgroundAnemia is a common complication of HIV infected children and it is enabling HIV disease progression, and decreasing survival. In Ethiopia, there is limited evidence on the prevalence of anemia and its associated factors among HIV infected children particularly in the Awi Zone. Therefore, this study aimed to assess the magnitude and associated factors of anemia among HIV infected children on ART aged from 6 months to 15 year-old in ART Clinic, Awi-Zone, Ethiopia.ObjectiveTo assess the magnitude and associated factors of anemia among HIV infected children on antiretroviral therapy in Awi zone health facilities, Northwest, Ethiopia, 2022.MethodsA facility based cross-sectional study design was conducted from October to December 2022. A simple random sampling method was used to select the study participants. Descriptive statistics, including frequencies and proportions was used to summarize the study variables and data had been entered in to Epi data 4.2 and exported to SPSS version 25. Bivariable logistic regression followed by multivariable logistic regression was performed. Degree of association between dependent and independent variables had been assessed using adjusted odds ratio with 95% CI at p value of ≤ 0.05.ResultFrom 346 participants in the selected sample 339 (97.9%) of them responded. Prevalence of anemia was 13.3% (n = 45) among which, majority (44.4%) of them had mild anemia, while about (42.2%,) had moderate anemia and around 13.3%, of them were severely anemic. Baseline CD4 count (AOR = 6.58, 95% CI: 2.85–15.22), WHO clinical stage III or IV (AOR = 8.42, 95% CI = 3.47, 20.45), hookworm infection (AOR = 5.06, 95% CI = 2.04, 12) and malaria infection (AOR = 4.92, 95% CI (2.19–11.02) were significantly associated with anemia among children on HAART.ConclusionThe prevalence of anemia among participants was relatively low in this study. However, a considerable proportion of participants had moderate to severe anemia. Lower CD4 count at enrolment, advanced HIV clinical stage, malaria and hookworm infection were significantly linked with anemia. Thus, it requires regular monitoring of anemia status in these patients for better clinical outcomes and quality of life improvements.

Alterations of the gut microbiome in HIV infection highlight human anelloviruses as potential predictors of immune recovery

BackgroundHIV-1 infection is characterized by a massive depletion of mucosal CD4 T cells that triggers a cascade of events ultimately linking gut microbial dysbiosis to HIV-1 disease progression and pathogenesis. The association between HIV infection and the enteric virome composition is less characterized, although viruses are an essential component of the gut ecosystem. Here, we performed a cross-sectional analysis of the fecal viral (eukaryotic viruses and bacteriophages) and bacterial microbiome in people with HIV (PWH) and in HIV-negative individuals. To gain further insight into the association between the gut microbiome composition, HIV-associated immunodeficiency, and immune recovery, we carried out a longitudinal study including 14 PWH who initiated antiretroviral therapy (ART) and were followed for 24 months with samplings performed at baseline (before ART) and at 2, 6, 12, and 24 months post-ART initiation.ResultsOur data revealed a striking expansion in the abundance and prevalence of several human virus genomic sequences (Anelloviridae, Adenoviridae, and Papillomaviridae) in stool samples of PWH with severe immunodeficiency (CD4 < 200). We also noted a decreased abundance of sequences belonging to two plant viruses from the Tobamovirus genus, a reduction in bacterial alpha diversity, and a decrease in Inoviridae bacteriophage sequences. Short-term ART (24 months) was linked to a significant decrease in human Anelloviridae sequences. Remarkably, the detection of Anellovirus sequences at baseline independently predicted poor immune recovery, as did low CD4 T cell counts. The bacterial and bacteriophage populations were unique to each PWH with individualized trajectories; we found no discernable pattern of clustering after 24 months on ART.ConclusionAdvanced HIV-1 infection was associated with marked alterations in the virome composition, in particular a remarkable expansion of human anelloviruses, with a gradual restoration after ART initiation. In addition to CD4 T cell counts, anellovirus sequence detection might be useful to predict and monitor immune recovery. This study confirms data on the bacteriome and expands our knowledge on the viral component of the gut microbiome in HIV-1 infection.3oR8qDfXoWY9s_P5ES648YVideo

Assessing the impact of COVID-19 on HIV care cascade for people living with HIV in Ethiopia: a retrospective longitudinal study.

The study aimed to investigate the impact of COVID-19 on the cascade of HIV care for people living with HIV (PLHIV) in Ethiopia. A retrospective longitudinal study. The study was conducted in North Showa Zone, Ethiopia, from pre-COVID-19 (January 2018-December 2019) and during COVID-19 (January 2020-December 2021). We identified 61901 records from 3925 PLHIV, of which 23 848 were recorded during the pandemic. We investigated indicators from four stages of the HIV care cascade, including HIV screening and diagnosis, HIV care, HIV treatment and HIV disease progression, according to a WHO framework. The indicator changes were assessed with incidence rate ratios (IRRs). For HIV screening and diagnosis, the monthly number of HIV tests experienced a 46% decline from 2520 to 1361 since the pandemic (IRR 0.553; 95% CI 0.546 to 0.561). For HIV care, the monthly number of consultations was reduced by 49.6% (from 1582 to 798) since the pandemic (IRR 0.591; 95% CI 0.581 to 0.601). Similarly, the monthly number of viral load tests was reduced by 42.8% (IRR 0.614; 95% CI 0.581 to 0.650). For HIV treatment, the number of antiretroviral therapy (ART) initiations was reduced by 27.8% and the number of ART adherence by 52.5% since the pandemic. For HIV disease progression, the monthly number of PLHIV achieving viral suppression was reduced by 61.6%, while HIV-related deaths doubled during the pandemic. The study highlights pandemic-induced disruptions in the cascade of care for PLHIV. Targeted interventions are necessary to protect PLHIV in public health emergencies.

Reconciling founder variant multiplicity of HIV-1 infection with the rate of CD4+ decline.

HIV-1 transmission precipitates a stringent genetic bottleneck, with 75% of new infections initiated by a single genetic variant. Where multiple variants initiate infection, recipient set point viral load (SpVL) and the rate of CD4+ T cell decline may be elevated, but these findings remain inconsistent. Here, we summarised the evidence for this phenomenon, then tested whether previous studies possessed sufficient statistical power to reliably identify a true effect of multiple variant infection leading to higher SpVL. Next, we combined models of HIV-1 transmission, heritability and disease progression to understand whether available data suggest a faster CD4+ T cell decline would be expected to associated with multiple variant infection, without an explicit dependency between the two. First, we found that most studies had insufficient power to identify a true significant difference, prompting an explanation for previous inconsistencies. Next, our model framework revealed we would not expect to observe a positive association between multiple variant infections and faster CD4+ T cell decline, in the absence of an explicit dependency. Consequently, while empirical evidence may be consistent with a positive association between multiple variant infection and faster CD4+ T cell decline, further investigation is required to establish a causal basis.

Impact of HLA allele-KIR partners on sexually transmitted HIV-1 infection.

HLA-I/KIR genotypes influence HIV-1 disease progression and viral load, but their role in primary infection is uncertain. Inconsistent results from previous studies suggest that the inoculum size and transmission route-parenteral vs. sexual-may influence this association. We conducted a GWAS in a population of people living with HIV-1 and HIV-1-exposed seronegative individuals exposed to the virus through the sexual route. Our data do not support any role of the HLA/KIR system in susceptibility to sexually transmitted HIV-1 infection. The genetics basis of HIV-1 viral load and disease progression are distinct from the genetics of HIV resistance, a paradox worth exploring.

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.

Genetic variants of IL-10 promoter influence susceptibility to HIV-1 infection and disease progression in the Polish population: IL-10 polymorphisms and HIV-1

The risk of HIV-1 infection and the rate of disease progression vary considerably among individuals and the genetic makeup of the host may be one of the possible reasons for this. We aimed to determine association of functional single nucleotide polymorphism (SNPs), −1082A/G (rs1800896), −819C/T (rs1800871), and −592C/A (rs1800872) in IL-10 gene, with the susceptibility to HIV-1 infection and clinical parameters expressed as a baseline CD4+ T cell count, CD8+ T cell count, and viral load. Therapy naïve HIV-1 infected individuals and HIV-1 seronegative controls from Poland were recruited for this study. Genotyping results revealed significantly higher frequency of −1082G/G genotype (28.1 % vs 16.1 %; p = 0.0019, OR=0.49) and −1082G allele (47.6 % vs 38.8 %; p = 0.0028, OR = 0.70) as well as lower frequency of −592 and −819 heterozygosity (45.0 % vs 34.4 %; p = 0.0266, OR = 1.47) in controls compared to seropositive subjects. High producing haplotype GCC was associated with increased risk of HIV-1 infection (p = 0.0018, OR = 1.52). Individuals possessing −592 and −819 minor allele had significantly higher CD8+ T cell count compared to the wild type allele carriers (p = 0.0303). Moreover, presence of −1082G allele was related with lower viral load as well as CD4+ and CD8+ T cells counts among patients infected with R5 HIV-1 variant. Thus, IL-10 gene promoter variants may be a risk factor for HIV-1 transmission and may modulate disease progression in the Polish population.

Prevalence and potential impact of human pegivirus-1 on HIV-1 disease progression among Indian PLHIV.

Human pegivirus-1 (HPgV-1) influences the pathogenesis and outcome of viral infections. We investigated the prevalence and impact of HPgV-1 due to the paucity of studies on Indian people living with HIV (PLHIV). Samples were collected from 347 treatment-naïve PLHIV; and 100 blood donors negative for HIV, HBV, and HCV. CD4+ T-cell and HIV-1 viral load were measured using flow-cytometry and quantitative polymerase chain reaction (qPCR), respectively. HPgV-1 was quantified and genotyped by qPCR and Sanger sequencing, respectively. HPgV-1 viremia in PLHIV and controls was 11% (38/347) and 1% (1/100), respectively. We found HPgV-1 genotype-2a in PLHIV and genotype-2b in controls. Male preponderance was seen in HIV-1 mono-infection and co-infection groups (166 vs. 143 and 33 vs. 5; p < 0.0001). The peak prevalence of HPgV-1 was at 31-50 years (p = 0.02). CD4+ T-cell count (245.5 vs. 240; p = 0.59) and HIV-1 log viral load (4.7 vs. 4.9; p = 0.50) were not significantly different between the HIV-1 mono-infected and coinfected individuals. However, a direct correlation existed between HpgV-1 viral load and CD4+ T-cell count (r = 0.27, p = 0.05) and an inverse correlation with HIV-1 viral load (r = -0.21, p = 0.10). This is the first study in India to estimate the HPgV-1 prevalence in PLHIV with the predominance of genotype-2a. HPgV-1 viremia had a moderate impact on CD4+ T-cells and HIV-1 viral load, which requires a longitudinal study to identify the beneficial influence on HIV-1 disease progression and outcome.

Advanced HIV disease and associated factors among young people aged 15—24 years at a tertiary hospital in Sierra Leone: a cross-sectional study

BackgroundAdvanced HIV disease (AHD) in young people living with HIV (PLHIV) is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many youths experience increased rates of HIV disease progression in sub-Saharan Africa. This study describes the burden, clinical manifestations, and factors for disease progression among young PLHIV aged 15 – 24 years seeking medical services at a major public hospital in Sierra Leone.MethodsWe performed a cross-sectional analysis of routinely collected data for PLHIV patients aged 15 to 24 seen at Connaught Hospital in Sierra Leone between September 2022 and March 2023. We estimated the proportion of AHD in young PLHIV and performed logistic regression modelling to explore predictors of AHD. The statistical significance level was set at 0.05 for all statistical tests.ResultsOf the 581 PLHIV that were reported, 238 (40.9%) were between the ages of 15 and 24 years, with a median age of 22 (20—24), and 151 (63.5%) were females. On review, 178 (74.8%) has initiated antiretroviral therapy regimen (ART); 117 (65.7%) were actively on ART for ≤ 6 months, while 114 (64%) had interruptions with their ART treatment. The overall prevalence of AHD was 41.6% (99/238); 46.7% (35/68) of young PLHIV at the HIV clinic, and 39.3% (64/163) of admission. Sex—Female (OR, 0.51; 95% CI, 0.28–0.94; p = 0.030), and Tertiary Education level (OR, 0.27; 95% CI, 0.10 – 0.78; p = 0.015) have significantly lower odds of AHD in the entire study population. While for inpatients, Age (young Adults) of PLHIV (OR, 1.23; 95% CI, 1.00–1.52; p = 0.047) had 1.23 times the odds of AHD compared to adolescents, and being female (OR, 0.27; 95% CI, 0.08–0.84; p = 0.024), Overweight—Body mass index (OR, 0.10; 95% CI, 0.01–0.77; p = 0.028), Tertiary Education level (OR, 0.08; 95% CI, 0.01–0.52; p = 0.008) have significantly lower odds of AHD. Common conditions reported for the AHD group in the medical wards are tuberculosis (13.58%), hepatitis B (6.13%), Kaposi sarcoma (3.07%), and oesophagal candidiasis (2.45%).ConclusionWe reported a high prevalence of advanced HIV among young patients in a tertiary Hospital in Sierra Leone. One in two young PLHIV aged 15 to 24 years reported AHD, emphasizing the need to strengthen public health measures that address access to and retention of HIV services.

Elite controllers microbiome: unraveling the mystery of association and causation.

To unravel the current knowledge and possible link between the gut microbiome and HIV-1 virological control in elite controllers (EC), who can suppress viral replication in the absence of antiretroviral therapy. In addition, to discuss the limitations of current research and propose future research directions. EC possess a different gut bacterial microbiota profile in composition and functionality from that of treatment-naive HIV-1 viremic progressors (VP). Specifically, EC have a richer bacterial microbiota as compared to VP, which closely resembles the microbiota in HIV-1 negative healthy controls (HC). Differentially abundant bacteria are found between EC and VP or HC, though results vary among the few existing studies. These data imply that the gut microbiome could contribute to the natural suppression of HIV-1 infection. An association between the gut microbiome and HIV-1 virological control is evidenced by recent studies. Yet, there are substantial knowledge gaps, and the underlying mechanism of how the microbiome influences the EC phenotype is far from clarified. Future research should consider diverse microbial communities, the complex microbe-host interactions, as well as yet-unidentified causal links between microbiome alterations and HIV-1 disease progression.

Immune restoration by TIGIT blockade is insufficient to control chronic SIV infection.

TIGIT is a negative immune checkpoint receptor associated with T cell exhaustion in cancer and HIV. TIGIT upregulation in virus-specific CD8+ T cells and NK cells during HIV/SIV infection results in dysfunctional effector capabilities. In vitro studies targeting TIGIT on CD8+ T cells suggest TIGIT blockade as a viable strategy to restore SIV-specific T cell responses. Here, we extend these studies in vivo using TIGIT blockage in nonhuman primates in an effort to reverse T cell and NK cell exhaustion in the setting of SIV infection. We demonstrate that in vivo administration of a humanized anti-TIGIT monoclonal antibody (mAb) is well tolerated in both cynomolgus macaques and rhesus macaques. Despite sustained plasma concentrations of anti-TIGIT mAb, we observed no consistent improvement in NK or T cell cytolytic capacity. TIGIT blockade minimally enhanced T cell proliferation and virus-specific T cell responses in both magnitude and breadth though plasma viral loads in treated animals remained stable indicating that anti-TIGIT mAb treatment alone was insufficient to increase anti-SIV CD8+ T cell function. The enhancement of virus-specific T cell proliferative responses observed in vitro with single or dual blockade of TIGIT and/or PD-1 highlights TIGIT as a potential target to reverse T cell dysfunction. Our studies, however, reveal that targeting the TIGIT pathway alone may be insufficient in the setting of viremia and that combining immune checkpoint blockade with other immunotherapeutics may be a future path forward for improved viral control or elimination of HIV.IMPORTANCEUpregulation of the immune checkpoint receptor TIGIT is associated with HIV-mediated T cell dysfunction and correlates with HIV disease progression. Compelling evidence exists for targeting immune checkpoint receptor pathways that would potentially enhance immunity and refocus effector cell efforts toward viral clearance. In this report, we investigate TIGIT blockade as an immunotherapeutic approach to reverse immune exhaustion during chronic SIV/SHIV infection in a nonhuman primate model of HIV infection. We show that interfering with the TIGIT signaling axis alone is insufficient to improve viral control despite modest improvement in T cell immunity. Our data substantiate the use of targeting multiple immune checkpoint receptors to promote synergy and ultimately eliminate HIV-infected cells.

Neurocognitive Impairment among HIV-Infected Participants on Methadone for IV-Heroin use in Yunnan, China Relates to AIDS Status and Depression Severity, not Patterns of Substance use

We used a comprehensive and culturally normed battery of Neurocognitive (NC) tests to evaluate NC impairment (NCI) in 406 adults with prior IV heroin use who were in a government-supervised methadone maintenance program in Yunnan province, China. Participants included 202 without HIV infection, 57 with AIDS, and 147 HIV+ without AIDS (“nonAIDS group”). The AIDS group had higher proportions of individuals with global NCI (38.6%) relative to nonAIDS (15.7%) and HIV- participants (17.3%; ps &lt; 0.01). The AIDS group performed worse than the non AIDS group globally (&lt; 0.001), and in the domains of executive functioning (ps = 0.001), learning (ps = 0.035), and speeded information processing (ps = 0.0002). Despite the lack of difference in prevalence of NCI between non AIDS and HIV- groups, the non AIDS group showed impairment in memory and complex motor domains relative to the HIV- group (p = 0.03). In People With HIV (PWH), NCI was associated with more severe depression symptoms and HIV disease characteristics (duration of illness, CD4 nadir, AIDS status). Nearly all participants were HCV infected. Alcohol use disorder diagnoses, non-invasive indications of liver fibrosis, and characteristics of prior heroin use were not associated with NCI. PWH with NCI had worse daily functioning, as indexed by unemployment (ps = 0.016) and reported increased cognitive difficulties in daily life (ps = 0.016). These results highlight the importance of early HIV diagnosis and treatment to avoid HIV disease progression, particularly among IV drug users, with the goal of protecting NC abilities, everyday functioning, and life quality in infected individuals.

Pediatric immunotherapy and HIV control.

Highlighting opportunities/potential for immunotherapy by understanding dynamics of HIV control during pediatric HIV infection with and without antiretroviral therapy (ART), as modeled in Simian immunodeficiency virus (SIV) and Simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and observed in clinical trials. This review outlines mode of transmission, pathogenesis of pediatric HIV, unique aspects of the infant immune system, infant macaque models and immunotherapies. During the earliest stages of perinatal HIV infection, the infant immune system is characterized by a unique environment defined by immune tolerance and lack of HIV-specific T cell responses which contribute to disease progression. Moreover, primary lymphoid organs such as the thymus appear to play a distinct role in HIV pathogenesis in children living with HIV (CLWH). Key components of the immune system determine the degree of viral control, targets for strategies to induce viral control, and the response to immunotherapy. The pursuit of highly potent broadly neutralizing antibodies (bNAbs) and T cell vaccines has revolutionized the approach to HIV cure. Administration of HIV-1-specific bNAbs, targeting the highly variable envelope improves humoral immunity, and T cell vaccines induce or improve T cell responses such as the cytotoxic effects of HIV-1-specific CD8+ T cells, both of which are promising options towards virologic control and ART-free remission as evidenced by completed and ongoing clinical trials. Understanding early events during HIV infection and disease progression in CLWH serves as a foundation for predicting or targeting later outcomes by harnessing the immune system's natural responses. The developing pediatric immune system offers multiple opportunities for specific long-term immunotherapies capable of improving quality of life during adolescence and adulthood.

Genetic Variation in Toll-Like Receptors (TLRs) 2, 4, and 9 Influences HIV Disease Progression Toward Active TB and AIDS.

Toll-like receptors (TLRs) are identified as one of the key components of the innate immune system. The objective of this study was to explore the influence of genetic variability in these TLRs on human immunodeficiency virus (HIV) disease progression with and without tuberculosis (TB) co-infection. This prospective, cross-sectional, and longitudinal study included 373 HIV-positive patients without TB infection. This study aimed to examine the genetic variation in TLRs (TLR2, TLR4, and TLR9) between patients with HIV-1 infection and those who progressed to active TB during the two years of follow-up. During the two year follow-up of 373 positive patients, 98 patients progressed to active TB/AIDS (acquired immunodeficiency syndrome). When comparing 98 HIV patients who developed active TB/AIDS to 275 HIV patients who did not, it was discovered that the frequency of the A allele in TLR9 was considerably higher (p <0.001) in HIV patients progressed to active TB/AIDS. Ninety eight HIV individuals who advanced to active TB/AIDS showed a significantly higher frequency of the AA genotype in TLR9 than did in HIV patients who had no TB/AIDS (p <0.001). The increased association of the AA genotype of TLR9 in HIV patients who progressed to active TB during follow-up suggests that HIV-positive patients with the AA genotype of TLR9 have increased susceptibility towards TB during the disease progression.

Loneliness, Methamphetamine Use, and Cardiovascular Risk Factors Among Sexual Minority Men in the COVID-19 Era.

Important gaps exist in our understanding of loneliness and biobehavioral outcomes among sexual minority men (SMM), such as faster HIV disease progression. At the same time, SMM who use methamphetamine are approximately one-third more likely than non-users to develop cardiovascular disease. This study examined associations of loneliness, stimulant use, and cardiovascular risk in SMM with and without HIV. Participants were enrolled from August 2020 to February 2022 in a 6-month prospective cohort study. The study leveraged self-report baseline data from 103 SMM, with a subset of 56 SMM that provided a blood sample to measure markers of cardiovascular risk. Loneliness showed negative bivariate associations with total cholesterol and LDL cholesterol in the cardiometabolic subsample (n = 56). SMM with methamphetamine use (t(101) = 2.03, p < .05; d = .42) and those that screened positive for a stimulant use disorder (t(101) = 2.07, p < .05; d = .46) had significantly higher mean loneliness scores. In linear regression analyses, negative associations of loneliness with LDL and total cholesterol were observed only among SMM who used methamphetamine. We observed lower cholesterol in SMM reporting loneliness and methamphetamine use. Thus, in addition to the observed associations of loneliness with cholesterol, there are important medical consequences of methamphetamine use including cardiovascular risk, higher HIV acquisition risk and progression, as well as stimulant overdose death. This cross-sectional study underscores the need for clinical research to develop and test interventions targeting loneliness among SMM with stimulant use disorders.

Adherence of HIV/AIDS patients to clinical outcome in Semarang City

Background: The success of HIV therapy can be measured by clinical, immunological, and virological monitoring. Meanwhile, low adherence to antiretroviral therapy (ART) contributes significantly to the disease progression and emergence of drug-resistant HIV. Objective: This study aimed to determine the correlation between the adherence of HIV/AIDS patients to clinical outcomes in Semarang. Method: This was an observational and cross-sectional approach. The instrument used the Simple Medication Adherence Questionnaire (SMAQ), which was validated and distributed to 50 respondents. The data were analyzed using chi-square (p &lt; 0.05), and the results showed a statistically significant relationship. Result: Respondents were male (96%), aged 26-45 years (76%), high school graduates (24%), working (88%), single (86%), without comorbidity (86%), length of treatment more than 12 months (80%), and general treatment (50%). A total of 31 respondents (62%) adhered to treatment with the combination regimen of Tenofovir/Lamivudine/Efavirenz (20%). There was a significant relationship (p = 0.006) between the length of treatment and patient adherence. The adherence results were not significantly related (p &gt; 0.05) to virological outcomes. Conclusion: There is no significant relationship between the adherence of HIV/AIDS patients and clinical outcomes.

The electrostatic landscape of MHC-peptide binding revealed using inception networks

Predictive modeling of macromolecular recognition and protein-protein complementarity represents one of the cornerstones of biophysical sciences. However, such models are often hindered by the combinatorial complexity of interactions at the molecular interfaces. Exemplary of this problem is peptide presentation by the highly polymorphic major histocompatibility complex class I (MHC-I) molecule, a principal component of immune recognition. We developed human leukocyte antigen (HLA)-Inception, a deep biophysical convolutional neural network, which integrates molecular electrostatics to capture non-bonded interactions for predicting peptide binding motifs across 5,821 MHC-I alleles. These predictions of generated motifs correlate strongly with experimental peptide binding and presentation data. Beyond molecular interactions, the study demonstrates the application of predicted motifs in analyzing MHC-I allele associations with HIV disease progression and patient response to immune checkpoint inhibitors. A record of this paper's transparent peer review process is included in the supplemental information.

Persistence of a Skewed Repertoire of NK Cells in People with HIV-1 on Long-Term Antiretroviral Therapy.

HIV-1 infection greatly alters the NK cell phenotypic and functional repertoire. This is highlighted by the expansion of a rare population of FcRγ- NK cells exhibiting characteristics of traditional immunologic memory in people with HIV (PWH). Although current antiretroviral therapy (ART) effectively controls HIV-1 viremia and disease progression, its impact on HIV-1-associated NK cell abnormalities remains unclear. To address this, we performed a longitudinal analysis detailing conventional and memory-like NK cell characteristics in n = 60 PWH during the first 4 y of ART. Throughout this regimen, a skewed repertoire of cytokine unresponsive FcRγ- memory-like NK cells persisted and accompanied an overall increase in NK surface expression of CD57 and KLRG1, suggestive of progression toward immune senescence. These traits were linked to elevated serum inflammatory biomarkers and increasing Ab titers to human CMV, with human CMV viremia detected in approximately one-third of PWH at years 1-4 of ART. Interestingly, 40% of PWH displayed atypical NK cell subsets, representing intermediate stages of NK-poiesis based on single-cell multiomic trajectory analysis. Our findings indicate that NK cell irregularities persist in PWH despite long-term ART, underscoring the need to better understand the causative mechanisms that prevent full restoration of immune health in PWH.