HIV Infection, Neurotoxicity, Inflammation, Premature Aging, and Therapeutic Challenges to PLWH: An Overview.

Global mental health and HIV care: gaps and research priorities.

Neurocognitive dysfunction remains prevalent among people living with HIV (PLWH), even after viral suppression on combination antiretroviral therapy (cART). We investigated associations between neuropsychological performance (NP) and patterns of circulating exosomal microRNA (exo-miRNA) expression in PLWH on cART. A cross-sectional examination of plasma exo-miRNA among PLWH on cART with systemic viral suppression and volunteers without HIV infection. Thirty-one PLWH who started cART during early infection (n = 19) or chronic infection (n = 12) participated in phlebotomy and an 11-test neuropsychological battery after >1 year on treatment. NP higher- or lower-performing participants were categorized based on normalized neuropsychological scores. Total RNA was extracted from purified exosomes of 31 PLWH and 5 volunteers without HIV and subject to small RNA sequencing. Differential expression of exo-miRNAs was examined and biological functions were predicted. Eleven exo-miRNAs were up-regulated in NP lower-performing (n = 18) relative to higher-performing PLWH (n = 13). A high proportion of the differentiating exo-miRNA target the axon guidance KEGG pathway and neurotrophin tyrosine receptor kinase signaling Gene Ontology pathway. Differential expression analysis of exo-miRNAs between NP lower- (n = 7) and higher-performing (n = 12) PLWH within the early infection group alone confirmed largely consistent findings. Plasma exo-miRNA content differed between NP higher- and lower-performing PLWH. Several differentially expressed exo-miRNAs were predicted to be involved in inflammation and neurodegeneration pathways. Exo-miRNA in plasma may indicate cross-talk between the circulation and central nervous system and thus may be clinically relevant for neurocognitive dysfunction in PLWH.

Adherence to antiretroviral therapy (ART) enables people living with HIV (PLWH) to reach and maintain viral suppression. As viral suppression significantly reduces risk for secondary transmission, this study aimed to examine sociodemographic factors associated with viral suppression among PLWH in South Carolina (SC). We analyzed cross-sectional data collected from 342 PLWH receiving HIV care from a large clinic in SC and provided complete information on most recent viral load, ART adherence, and sociodemographic factors. Bivariate analysis examined associations between key variables, and logistic regression was used to calculate the odds of viral suppression among select sociodemographic groups and adherence levels. Results indicated that approximately 82% of participants reported achieving viral suppression. PLWH who were older, male, and employed full-time had higher odds of being virally suppressed compared to those who were younger, female, and unemployed. PLWH with medium (adjusted Odds Ratio [aOR]: 3.79; 95% CI: 1.15–12.48) and high (aOR: 3.51; 95% CI: 1.21–10.24) levels of adherence were more likely to report viral suppression than those with low adherence. Targeted interventions are warranted for groups at-risk of low ART adherence, and healthcare providers should also be aware of contextual factors that serve as barriers to adherence for PLWH.

The role of antiretroviral therapy (ART) in HIV prevention has generated hope for an AIDS-free generation but also interest in behavioural outcomes of people living with HIV (PLHIV). This is from the knowledge that the benefits of ART in terms of enhancing PLHIV health outcomes and preventing HIV transmission depend on PLHIV’s behaviours including sexual risk, disclosure, treatment adherence and retention. The purpose of this study was to examine whether PLHIV in Nigeria who participate in support group activities have different behavioural outcomes than those who do not. A cross-sectional design was used to compare stigma, disclosure, sexual risk behaviors and ART adherence rates of PLHIV who participate in support group activities and those who do not. Respondents were adult PLHIV enrolled in ART from January 1, 2010 to December 31, 2012. Study sites and respondents were selected using multistage probability sampling. Data were collected using a self-administered questionnaire from 1,676 respondents between February and May 2014. Data were analysed using STATA. Univariate analysis was carried out to generate descriptive statistics while Chi-square tests were used to examine if there was any association between participation in support group activities and PLHIV selected behavioral outcomes. PLHIV who participated in support group activities differed from those who did not in terms of HIV-related stigma (p =< 0.001), positive HIV status disclosure (p = 0.005), ART adherence (p = 0.021), and sexual risk behaviors (p = 0.045). PLHIV who participated in support group activities were more likely to have less internal HIV-related stigma, disclose their positive HIV status, adhere to ART and live less risky sexual lives. These findings suggest that PLHIV who participate in support group activities are more likely to adopt positive behaviors than those who do not.

Given advances in antiretroviral therapy, the mortality rate for HIV infection has dropped considerably over recent decades. However, people living with HIV (PLWH) experience longer life spans coupled with persistent immune activation despite viral suppression and potential toxicity from long-term antiretroviral therapy use. Consequently, PLWH face a cardiovascular disease (CVD) risk more than twice that of the general population, making it the leading cause of death among this group. Here, we briefly review the epidemiology of CVD in PLWH highlighting disparities at the intersections of sex and gender, age, race/ethnicity, and the contributions of social determinants of health and psychosocial stress to increased CVD risk among individuals with marginalized identities. We then overview the pathophysiology of HIV and discuss the primary factors implicated as contributors to CVD risk among PLWH on antiretroviral therapy. Subsequently, we highlight the functional evidence of premature vascular dysfunction as an early pathophysiological determinant of CVD risk among PLWH, discuss several mechanisms underlying premature vascular dysfunction in PLWH, and synthesize current research on the pathophysiological mechanisms underlying accelerated vascular aging in PLWH, focusing on immune activation, chronic inflammation, and oxidative stress. We consider understudied aspects such as HIV-related changes to the gut microbiome and psychosocial stress, which may serve as mechanisms through which exercise can abrogate accelerated vascular aging. Emphasizing the significance of exercise, we review various modalities and their impacts on vascular health, proposing a holistic approach to managing CVD risks in PLWH. The discussion extends to critical future study areas related to vascular aging, CVD, and the efficacy of exercise interventions, with a call for more inclusive research that considers the diversity of the PLWH population.

Selection of an antiretroviral regimen for people living with HIV (PLWH) involves various clinical considerations, such as comorbidities, archived drug resistance mutations, concomitant medications, and potential drug interactions and side effects. Alterations in the surface area and pH of the gastrointestinal tract following bariatric surgery may alter absorption, antiretroviral pharmacokinetics and viral suppression. Data on the efficacy of antiretroviral (ARV) therapy in PLWH who have undergone bariatric surgery are limited or lacking for new antiretrovirals, such as dolutegravir and bictegravir. This case series reports virologic outcomes and side effects in eight cases of PLWH receiving ARV therapy who underwent bariatric surgery. A systematic literature review was performed to review the available literature on the efficacy and safety of antiretroviral regimens in PLWH who have undergone bariatric surgery. Virologic suppression was not impacted for obese PLWH who underwent bariatric surgery following failure of life-style modifications and pharmacological therapy. There were no deleterious effects on HIV progression for PLWH that underwent bariatric surgery. More prospective research is required to validate the effects of bariatric surgery on immunologic and virologic function outcomes. Close involvement of HIV and surgical specialists is recommended to manage ARV therapy in patients undergoing bariatric surgery.

Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART. We performed a PubMed search using the term "Dolutegravir", last updated 18 December 2023, to estimate the prevalence of VF with emergent INSTI DRMs in people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART. Of 2131 retrieved records, 43 clinical trials, 39 cohorts, and 6 cross-sectional studies provided data across 6 clinical scenarios based on ART history, virological status, and co-administered ARVs: (1) ART-naïve PLWH receiving DTG plus two NRTIs; (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on a previous regimen receiving DTG plus two NRTIs; (4) ART-experienced PLWH with virological suppression receiving DTG plus two NRTIs; (5) ART-experienced PLWH with virological suppression receiving DTG and a second ARV; and (6) ART-experienced PLWH with virological suppression receiving DTG monotherapy. The median proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.5% for scenario 3 and 3.4% for scenario 6. In the remaining four trial scenarios, VF prevalence with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, whereas cross-sectional studies yielded prevalence data lacking denominator details. In clinical trials, the prevalence of VF with emergent INSTI DRMs in PLWH receiving DTG-containing regimens has been low. Novel approaches are required to assess VF prevalence with emergent INSTI DRMs in PLWH receiving DTG in real-world settings.

Aging while living with HIV poses new challenges in clinical management, mainly due to the onset of multiple chronic comorbidities. Population-specific risk prediction indices considering comorbidities and other risk factors are essential to comprehensively characterise disease burden among PLWH. We developed and validated a mortality risk prediction index (MRPi) to predict the risk of one-year all-cause mortality among people living with HIV (PLWH). Participants were ≥18 years and had initiated antiretroviral therapy (ART) between 01/2001 and 12/2018, in British Columbia, Canada. The index date was randomly selected between one-year post-ART initiation and the end of the follow-up. Participants were followed for at least one year from the index date until 12/2019, the last contact date, or the date of death (all-cause), whichever came first. The MRPi included 18 physical/mental comorbidities, demographic and clinical variables, and ranged from 0 (no risk) to 100 (highest risk). The final model demonstrated the highest discrimination (c-statistic 0.8355, 95% CI: 0.8187-0.8523 in the training dataset and 0.7965, 95% CI: 0.7664-0.8266 in the test dataset). The comorbidities with the highest weights in the MRPi were substance use disorders, metastatic solid tumors and non-AIDs defining cancers. For example, for an MRPi of 30, the predicted one-year all-cause mortality was 0.2%, while an MRPi of 50 had a predicted mortality of 2.3%. The MRPi provides a promising tool to assess the risk of short-term mortality among PLWH in the modern ART era that can inform clinical practice and health policy decisions.

The widespread availability of antiretroviral therapy (ART) has dramatically reduced mortality and improved life expectancy for people living with HIV (PLWH). However, even with HIV-1 suppression, chronic immune activation and elevated inflammation persist and have been linked to a pro-inflammatory gut microbiome composition and compromised intestinal barrier integrity. PLWH in urban versus rural areas of sub-Saharan Africa experience differences in environmental factors that may impact the gut microbiome and immune system, in response to ART, yet this has not previously been investigated in these groups. To address this, we measured T cell activation/exhaustion/trafficking markers, plasma inflammatory markers, and fecal microbiome composition in PLWH and healthy participants recruited from an urban clinic in the city of Harare, Zimbabwe, and a district hospital that services surrounding rural villages. PLWH were either ART naïve at baseline and sampled again after 24weeks of first-line ART and the antibiotic cotrimoxazole or were ART-experienced at both timepoints. Although expected reductions in the inflammatory marker IL-6, T-cell activation, and exhaustion were observed with ART-induced viral suppression, these changes were much more pronounced in the urban versus the rural area. Gut microbiome composition was the most highly altered from healthy controls in ART experienced PLWH, and characterized by both reduced alpha diversity and altered composition. However, gut microbiome composition showed a pronounced relationship with T cell activation and exhaustion in ART-naïve PLWH, suggesting a particularly significant role for the gut microbiome in disease progression in uncontrolled infection. Elevated immune exhaustion after 24weeks of ART did correlate with both living in the rural location and a more Prevotella-rich/Bacteroides-poor microbiome type, suggesting a potential role for rural-associated microbiome differences or their co-variates in the muted improvements in immune exhaustion in the rural area. Successful ART was less effective at reducing gut microbiome-associated inflammation and T cell activation in PLWH in rural versus urban Zimbabwe, suggesting that individuals on ART in rural areas of Zimbabwe may be more vulnerable to co-morbidity related to sustained immune dysfunction in treated infection. Video Abstract.

Burden of subclinical carotid atherosclerosis and vascular risk factors among people living with HIV in Ghana

The estimated number of people living with HIV (PLHIV) in India in 2023 is 2.54 million (range 2.16-3.03 million). With the initiation of antiretroviral therapy (ART) and the "Test and Treat" policy, the life expectancy of PLHIV on ART has substantially increased, consequently leading to a higher rate of comorbidities among PLHIV. The Joint United Nations Programme on HIV/AIDS (UNAIDS) 2025 targets aim for about 90% of PLHIV to have access to integrated and comprehensive health care services, with a concerted effort to reach the End of AIDS by 2030. Hence, the National Integrated Bio-Behavioral Surveillance (IBBS) among PLHIV (IBBS-PLHIV) has been implemented for the first time in India to establish a baseline understanding of the prevalence of sexually transmitted infections (STIs), noncommunicable diseases (NCDs), and related risk behaviors among PLHIV. The primary aim of IBBS-PLHIV is to estimate the levels of HIV-related risk behaviors and the prevalence of other STIs and NCDs among PLHIV. The specific objectives are identifying the levels of HIV-related sexual and injecting risk behaviors; estimating the prevalence of STIs such as syphilis, hepatitis B virus, and hepatitis C virus; estimating the prevalence of NCDs such as diabetes and hypertension; understanding the lifestyle and behavioral risks associated with NCDs; and assessing the levels of violence, stigma, and discrimination experienced by PLHIV. IBBS-PLHIV will be a cross-sectional, biennial surveillance among PLHIV aged 15 years or older. The first round will be implemented at 120 ART centers across 28 states, accounting for approximately 95% of the total estimated PLHIV. Consenting, eligible PLHIV will be recruited through consecutive sampling. The overall sample size at each ART center is approximately 225, and the surveillance period is 3 months. Behavioral data on demographics, reproductive and sexual health, lifestyle and sexual behaviors, stigma, and discrimination will be collected. Blood samples will also be collected to test for STIs and NCDs. IBBS-PLHIV was initiated on January 1, 2024, in a phased manner. Data collection was carried out over 3 months and completed by June 2024 across all 120 sites. A total of 25,257 PLHIV were recruited for the surveillance, including 11,921 males, 11,855 females, and 1481 hijra/transgender individuals. Data entry, followed by data matching and validation of all records, was completed in December 2024. The data are currently being analyzed, and the final findings are expected to be disseminated by December 2025. Data collected through IBBS-PLHIV will help monitor the levels of HIV-related sexual and injecting risk behaviors among PLHIV. Additionally, it will provide estimates of the prevalence of NCD comorbidities and STI coinfections such as diabetes, hypertension, syphilis, and viral hepatitis. These findings will serve as a baseline and are expected to offer valuable insights for facilitating comprehensive HIV care and management through the effective integration of HIV and broader health service delivery. DERR1-10.2196/58252.

Quality of life (QoL) is recognized as an essential end point in the disease management of chronic conditions such as HIV with calls to include good QoL as a 'fourth 90' in the 90-90-90 testing and treatment targets introduced by World Health Organization in 2016. Cognitive impairments impact a broad spectrum of experiences and are a common issue effecting people living with HIV (PLWH). Despite this, few studies have examined QoL in PLWH who also have a cognitive disorder. This study aimed to synthesize and describe what is known about QoL in those living with HIV-associated neurocognitive disorders (HAND). A scoping review of peer-reviewed literature was conducted to identify how QoL has been investigated and measured in PLWH with HAND, and how PLWH with HAND report and describe their QoL. We searched PsychInfo, Medline, Scopus, and Web of Science along with hand-searching reference lists from relevant studies found. Included studies were those published in English after 1st January 2003 which included PLWH with cognitive impairment not due to other pre-existing conditions. Fifteen articles met criteria for inclusion. Two studies measured QoL as a primary aim, with others including QoL assessment as part of a broader battery of outcomes. The MOS-HIV and SF-36 were the most commonly used measures of overall QoL, with findings generally suggestive of poorer overall QoL in PLWH with HAND, compared to PLWH without cognitive impairment. Studies which examined dimensions of QoL focused exclusively on functionality, level of independence, and psychological QoL domains. There is a considerable dearth of research examining QoL in PLWH with HAND. The initiatives which advocate for healthy aging and improved QoL in PLWH must be extended to include and understand the experiences those also living with cognitive impairment. Research is needed to understand the broad experiential impacts of living with these two complex, chronic conditions, to ensure interventions are meaningful to patients and potential benefits are not missed.

Objectives Despite the advances in antiretroviral treatment (ART), persistent inflammation remained a challenge. We analyzed the inflammatory-score changes through 2-years in people living with HIV (PLWH) treated with different antiretroviral regimes. Methods This study was conducted in Hacettepe University HIV/AIDS Treatment and Research Center. PLWH diagnosed between 2014-2020 were included. Inflammatory and metabolic markers (CD4/CD8 ratio, C-reactive protein (CRP), Systemic Inflammatory Index (SII), Neutrophil-Lymphocyte Ratio (NLR), Mean Platelet Volume (MPV), Platecrite (PCT), and Low-Density Lipoprotein/High-Density Lipoprotein (LDL/HDL), Platelet-to-Lymphocyte Ratio (PLR)) and ARTs were captured from database through 2-years from the diagnosis. The 2-year change (Δ) in markers was calculated and compared by ART type (backbone and 3rd agent). Mann-Whitney-U test and T-test were used for statistical analysis. Results This study included 205 PLWH; 175 (85.4%) were male, and the mean age was 38.98 (±10.88) years. The number of PLWH with suppressed viremia (<40 HIV-RNA copies/ml) was 164 (80%) at the end of the second year. MPV increased significantly higher among PLWH receiving ABC/3TC compared to PLWH receiving TDF/FTC (p<0.05). The CD4:CD8 ratio increased, and SII, NLR, LDL/HDL ratios decreased significantly among PLWH treated with integrase strand transfer inhibitors (INSTI) compared with protease inhibitors (PI) and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) (p<0.05). Conclusions : Integrase inhibitor treatment is related to favorable inflammatory marker profile among PLWH in the 2-year follow-up. A favorable inflammatory profile may, in turn, contribute to the prevention of non-communicable diseases (NCD) among PLWH. This study showed that simple, easy-to-calculate markers could be implemented to define ongoing inflammation among PLWH under suppressive ART.

ABSTRACTStudies on immune reconstitution inflammatory syndrome (IRIS) in people living with HIV (PLWH) and presenting with interstitial pneumonitis (IP) are limited in the era of rapid antiretroviral therapy (ART) initiation, particularly with integrase strand-transfer inhibitor (INSTI)-containing regimens. Adult PLWH presenting with IP in whom ART was initiated within 30 days of IP diagnosis between 2015 and 2021 were retrospectively identified. The primary outcome was the occurrence of IRIS within 30 days after admission. Of 88 eligible PLWH with IP (median age, 36 years; CD4 count, 39 cells/mm3), Pneumocystis jirovecii and cytomegalovirus (CMV) DNA were detected via polymerase-chain-reaction assay in 69.3% and 91.7% of respiratory specimens, respectively. 22 PLWH (25.0%) had manifestations that met French’s IRIS criteria for paradoxical IRIS. There were no statistically significant differences in terms of the all-cause mortality (0.0% versus 6.1%, P = 0.24), the occurrence of respiratory failure (22.7% versus 19.7%, P = 0.76), and pneumothorax (9.1% versus 7.6%, P = 0.82) between PLWH with and those without paradoxical IRIS. In a multivariable analysis, the factors associated with IRIS were the decline of the 1 month plasma HIV RNA load (PVL) with ART (adjusted hazard ratio [aHR] per 1 log decrease, 3.45; 95% CI, 1.52 to 7.81), a baseline CD4-to-CD8 ratio of <0.1 (aHR, 3.47; 95% CI, 1.16 to 10.44), and the rapid initiation of ART (aHR, 7.95; 95% CI, 1.04 to 60.90). In conclusion, we found a high rate of paradoxical IRIS among PLWH with IP in the era of rapid ART initiation with INSTI-containing ART and this was associated with immune depletion at baseline, a rapid decline of PVL, and an interval of <7 days between the diagnosis of IP and the initiation of ART.IMPORTANCE Our study of PLWH who presented with IP mainly due to Pneumocystis jirovecii demonstrates that a high rate of paradoxical IRIS and a rapid decline of PVL with the initiation of ART, a CD4-to-CD8 ratio of <0.1 at baseline, and a short interval (<7 days) between the diagnosis of IP and the initiation of ART were associated with paradoxical IP-IRIS in PLWH. Paradoxical IP-IRIS was not associated with mortality or respiratory failure with heightened awareness among the HIV-treating physicians, rigorous investigations to exclude the possibilities of concomitant infections, or the malignancies and adverse effects of medications, including the cautious use of corticosteroids.

BackgroundUnderstanding the current status of low-level viremia (LLV) is necessary for controlling the spread of HIV globally. However, the existing data on LLV prevalence during antiretroviral therapy (ART) and LLV risk contributing to subsequent virologic failure (VF) is still scant in China.MethodsA large sample size, retrospective cohort study was conducted in Hubei province, China between January 1, 2011 and October 30, 2023. The LLV incidence was evaluated according to the first viral load of each year. The risk factors associated with LLV and subsequent VF among people living with HIV (PLWH) were accessed.ResultsTotally, 25,607 PLWH managed by Hubei province Center for Disease Control and Prevention were screened, and 19,930 PLWH were eligible for the study. Of them, 18,052 received the first line ART, 1103 received the second line ART, and 963 received the third line ART. 2497 (13.8%) PLWH on first line, 189 (17.1%) PLWH on second line and 100 (10.4%) PLWH on third line ART experienced LLV, respectively.The LLV level between 51 and 199 copies/ml was the most common in both three groups. CD4 count < 200 cells/µL and older age at ART initiation were associated with higher risk of LLV among all PLWH and PLWH receiving the first line ART, and protease inhibitors (PIs) using was associated with the higher risk of LLV among all PLWH. Both LLV level among 51–199, 200–399 and 400–999 copies/mL were risk factors leading to VF occurrence.ConclusionsClose surveillance of HIV-VL is imperative among PLWH with CD4 count < 200 cells/µL, older age and PIs use for avoiding LLV occurrence. Clinical strategies should be strengthened among PLWH with LLV, given the increased vulnerability to subsequent VF.