HIV-uninfected Participants Research Articles

Immunogenicity and safety of SARS-CoV-2 recombinant spike protein vaccine in South African people living with and without HIV-1 infection: A phase 2 randomised trial

BackgroundResponse data for COVID-19 vaccines in immunosuppressed individuals are typically limited to standard dosing in small populations. Adjusting number or interval of doses may impact immune responses based on HIV status. MethodsThis phase 2 randomised, observer-blinded, placebo-controlled South African study (2019nCoV-505/NCT05112848) enrolled medically stable people living with HIV (PLWH) and HIV-uninfected participants aged 18–65 years. PLWH were randomised 1:1:1 to receive NVX-CoV2373 on day 0 (D0) and either D21 (2-DoseD0/D21) or D70 (2-DoseD0/D70), or on D0, D21, and D70 (3-Dose). HIV-uninfected participants were randomised 1:1 to each 2-Dose regimen. PLWH were stratified into well-controlled and less–well-controlled subgroups. The primary immunologic endpoint included serum IgG and neutralising antibody responses (per geometric mean fold rise [GMFR] in titre and seroconversion rate) to ancestral SARS-CoV-2 at D35 (2-DoseD0/D21) and D84 (2-DoseD0/D70 and 3-Dose). The primary safety endpoints were participants with an unsolicited adverse event through D84, at D120, and at D180, or reactogenicity ≤7 days post-vaccination. ResultsOf 288 PLWH, 98, 96, and 94 were randomised into the 2-DoseD0/D21, 2-DoseD0/D70, and 3-Dose groups, respectively; 96 HIV-uninfected participants were randomised to the 2-DoseD0/D21 (n=47) or 2-DoseD0/D70 (n=49) regimens. Most (>85%) of the population were SARS-CoV-2 positive at baseline. Ancestral anti-spike IgG GMFRs in PLWH and HIV-uninfected participants, respectively, were 12·4 and 12·9 (D35) and 12·2 and 13·6 (D84). Comparable outcomes occurred across dosing regimens and in well-controlled and less–well-controlled PLWH. Microneutralization GMFRs at D84 in PLWH and HIV-uninfected participants, respectively, were: 6·9 and 10·1 (2-DoseD0/D21), 11·0 and 11·3 (2-DoseD0/D70), and 17·2 (PLWH 3-Dose). Antibody responses against BA.1 trended similar to those against the ancestral virus. Safety outcomes were comparable among PLWH and HIV-uninfected participants. ConclusionThis study demonstrated that NVX-CoV2373 produced consistent immunogenicity responses to SARS-CoV-2 among PLWH and HIV-uninfected participants, with no new safety signals. FundingNovavax, Inc.

Self-reported cardiovascular disease risk factor screening among people living with HIV vs. members of the general population in Botswana: a community-based study.

Morbidity and mortality due to cardiovascular diseases (CVDs) are high and increasing in low- and middle-income countries. People living with HIV (PLWH) are more likely to experience CVD than members of the general population. Therefore, we aimed to assess whether PLWH were more likely to have previously been screened for cardiovascular disease risk factors (CVDRFs) than people without HIV. A population-based, cross-sectional study was conducted among individuals aged 16 to 68 years across 22 communities in Botswana from February to August 2017 as part of a larger community-based cluster randomized HIV treatment-as-prevention trial. Participants were asked if they had been screened for and counselled on cardiovascular disease risk factors (history of hypertension or blood pressure check, blood glucose and cholesterol measurements, weight check and weight control, tobacco smoking and cessation, alcohol use and physical activity) in the preceding 3 years. HIV testing was offered to those with an unknown HIV status. Multiple logistic regression analysis controlling for age and sex was used to assess the relationship between CVDRF screening and HIV status. Of the 3981 participants enrolled, 2547 (64%) were female, and 1196 (30%) were PLWH (93% already on antiretroviral therapy [ART]). PLWH were more likely to report previous screening for diabetes (25% vs. 19%, p < 0.001), elevated cholesterol (17% vs. 12%, p < 0.001) and to have had their weight checked (76% vs. 55%, p < 0.001) than HIV-uninfected participants. PLWH were also more likely to have received counselling on salt intake (42% vs. 33%, p < 0.001), smoking cessation (66% vs. 46%, p < 0.001), weight control (38% vs. 29%, p < 0.001), physical activity (46% vs. 34%, p < 0.001) and alcohol consumption (35% vs. 23%, p < 0.001) than their HIV-uninfected counterparts. Overall, PLWH were more likely to have received screening for and/or counselling on CVDRFs (adjusted odds ratio 1.84, 95% CI: 1.46-2.32, p < 0.001). PLWH were almost two times more likely to have been previously screened for CVDRFs than those without HIV, indicating a need for universal scale-up of integrated management and prevention of CVDs in the HIV-uninfected population.

Immunogenicity and safety of inactivated SARS-CoV-2 vaccines in people living with HIV: A longitudinal cohort study.

To clarify the characteristics in immunogenicity and safety of inactivated SARS-Cov-2 vaccines among HIV-infected individuals, a longitudinal cohort study was performed on HIV-infected and HIV-uninfected participants with no history of COVID-19 infection and COVID-19 vaccine inoculation. Participants information and adverse events were collected. Blood samples were collected on the same day before vaccination, 21 days after the first shot, 28 days after the second shot, 6 months after the second vaccination and 14 days after the third dose to test anti-receptor-binding domainIgG antibody, viral load, CD4+, CD8+ T cell count. Our result showed that although HIV-infected adults with low nadir CD4+ T cell count ≤ 350 cells/mm3 generate significantly lower immune response after three shots of vaccine compared with HIV-negative controls, 100% of all the HIV-infected and healthy controls were seroconverted after the third shot. Seroconversion ratio and antibody level of 190 days after two shots of vaccination for HIV-infected with nadir CD4+ T cell count ≤ 350 were significantly lower than that of healthy controls. No significant difference was found in viral load among blood samples collected at each time points. CD4 and CD4/CD8 ratio value were found increased greatly after each shot of inoculation in HIV-infected individuals with nadir CD4+ T cell count ≤ 350. Multiple logistic regression analysis showed that among HIV-infected individuals, PLWH with CD4+ T cell count ≤ 350 were less likely experience seroconversion 21 days after the first shot, and less likely maintained antibody immunity 6 months post 2nd dose. Adverse events after each inoculation were not serious and recovered within 1 week. In conclusion, inactivated COVID-19 vaccine was safe and effective in people living with HIV after three shots of vaccination. HIV-infected individuals with low nadir CD4+ T cell count ≤ 350 was associated with a nonoptimal antibody response. Further vaccination strategies could be developed for those with low CD4+ T cell counts.

Pulmonary function tests and their associated factors in people living with HIV at Jimma medical center; Ethiopia: a comparative cross-sectional study.

People living with HIV (PLHIV) have a greater risk of developing respiratory disorders. The problems are linked to poor socio-economic status, high viral load, low CD4 counts, and antiretroviral therapy. Despite the high prevalence of respiratory disorders, the association between HIV infection and pulmonary function status, as well as the associated factors, is not well established in resource-limited countries. A comparative cross-sectional study was conducted from September 24 to October 15 2020 at Jimma Medical Center among people living with HIV who were arranged into an age-sex-matched comparison group. Data were collected using a pretested structured questionnaire administered via face-to-face interviews. The collected data included socio-demographic, respiratory, HIV infection, and substance use variables. Pulmonary function tests were conducted using an SP10 spirometer. The collected data were entered and analyzed using SPSS version 26. Independent t-test and multiple linear regressions were carried out to identify factors associated with the pulmonary function status of the study participants. A total of 96 PLHIV and 96 matched control individuals participated in the study. The mean of pulmonary function test parameters among the PLHIV respondents was FVC (l) (67.35 ± 19.12, p0.003), FEV1s (l) (61.76 ± 16.04, p0.001), and PEFR (50.14 ± 23.32, p0.001), with a significant lowering in the study group. Female sex, respiratory symptoms, duration of HIV, duration of treatment, and khat chewing were associated with lowered FEV1s (l) (p < 0.05) in HIV-positive respondents. PLHIV had significantly lower mean lung function parameters than HIV-uninfected participants. As a result, health providers should screen HIV-positive patients with respiratory symptoms, prolonged duration of HIV infection, prolonged treatment, and khat chewing for non-infectious lung disorders while treating them.

Plasma galectin-3 is associated with decreased glomerular filtration rate in chronic HIV

Background People living with HIV (PLWH) have higher rates of chronic kidney disease (CKD) compared with HIV-uninfected individuals. The pathogenesis of CKD in HIV remains poorly understood but is likely from a combination of various factors, such as traditional comorbidities, prolonged antiretroviral therapy, immune dysregulation, and direct HIV effect on the kidneys. We evaluated plasma galectin-3 (Gal-3), a circulating marker of fibrosis, and its association with renal function. Methods Estimated glomerular filtration rate (eGFR) was assessed by CKD-EPI. Plasma galectin-3 was obtained from banked specimens by ELISA. Factors associated with eGFR were analyzed using step-wise multiple linear regression. Results A total of 45 PLWH and 58 HIV-uninfected participants were included with similar demographic parameters. Among PLWH, majority had undetectable plasma HIV RNA (82.2%). Gal-3 was significantly higher in PLWH than in HIV-uninfected participants (6.4 [IQR 4.0, 8.5] ng/mL and 4.5 [IQR 2.3, 6.5] ng/mL, respectively; p = 0.020) while a trend towards lower eGFR was found in PLWH compared to the HIV-uninfected cohort (86.8 [IQR 71.3, 91.8] and 89.0 [IQR 78.6, 97.4] mL/min/1.73 m2, respectively; p = 0.071). In univariable analysis, HIV status was marginally associated with decreased eGFR (β coefficient= −0.035, p = 0.051). In the final multivariable regression model adjusted for traditional risk factors of CKD, Gal-3 independently predicted a decrease in eGFR (unstandardized B= −0.008, p < 0.001) while HIV status did not demonstrate any significant association. Conclusion Gal-3 was higher in PLWH compared with HIV-uninfected participants. In multivariable adjusted analyses, Gal-3, but not HIV status, was associated with decreased eGFR. The role of Gal-3 as a biomarker of kidney function needs to be further elucidated.

Epidemiology and aetiology of moderate to severe diarrhoea in hospitalised patients ≥5 years old living with HIV in South Africa, 2018-2021: A case-control analysis.

Diarrhoea is a recognised complication of HIV-infection, yet there are limited local aetiological data in this high-risk group. These data are important for informing public health interventions and updating diagnostic and treatment guidelines. This study aimed to determine the pathogenic causes of diarrhoeal admissions in people living with HIV (PLHIV) compared to hospital controls between July 2018 and November 2021. Admitted diarrhoeal cases (n = 243) and non-diarrhoeal hospital controls (n = 101) ≥5 years of age were enrolled at Kalafong, Mapulaneng and Matikwana hospitals. Stool specimens/rectal swabs were collected and pathogen screening was performed on multiple platforms. Differences in pathogen detections between cases and controls, stratified by HIV status, were investigated. The majority (n = 164, 67.5%) of enrolled diarrhoeal cases with known HIV status were HIV-infected. Pathogens could be detected in 66.3% (n = 228) of specimens, with significantly higher detection in cases compared to controls (72.8% versus 50.5%, p<0.001). Amongst PLHIV, prevalence of Cystoisospora spp. was significantly higher in cases than controls (17.7% versus 0.0%, p = 0.028), while Schistosoma was detected more often in controls than cases (17.4% versus 2.4%, p = 0.009). Amongst the HIV-uninfected participants, prevalence of Shigella spp., Salmonella spp. and Helicobacter pylori was significantly higher in cases compared to controls (36.7% versus 12.0%, p = 0.002; 11.4% versus 0.0%, p = 0.012; 10.1% versus 0.0%, p = 0.023). Diarrhoeal aetiology differed by HIV status, with Shigella spp. (36.7%) and Salmonella spp. (11.4%) having the highest prevalence amongst HIV-uninfected cases and Shigella spp. (18.3%), Cystoisospora (17.7%), and Cryptosporidium spp. (15.9%) having the highest prevalence in cases amongst PLHIV. These differences should be considered for the development of diagnostic and treatment guidelines.

HIV infection in adult Ugandans with new-onset type 2 diabetes: exploring its influence on the anthropometric and metabolic profile

ObjectiveHIV infection increases the risk of type 2 diabetes and may influence its phenotypic profile. In this study, we aimed to compare the anthropometric and metabolic characteristics of HIV-infected and uninfected adult Ugandans with new-onset type 2 diabetes to evaluate the influence of HIV infection on specific surrogate markers of adiposity, insulin resistance, and pancreatic beta-cell function.MethodsWe consecutively recruited 500 HIV-infected and uninfected adult Ugandans with new-onset type 2 diabetes (diagnosed in < 3 months) from seven tertiary hospitals over a 20-month period and compared their anthropometric and metabolic characteristics to identify any significant differences.ResultsOf the 500 participants with new-onset type 2 diabetes, 59 (11.8%) had a self-reported history of HIV infection. Compared with HIV-uninfected participants with type 2 diabetes, participants with HIV infection and type 2 diabetes had a lower median (IQR) hip circumference (97.8 [91.0-106.0] cm vs. 104.0 [96.0-112.0], p = 0.002) and visceral fat level (8 [6–11] vs. 10 [7–12], p < 0.001) assessed using bioimpedance analysis. No statistically significant difference was noted with the markers of pancreatic beta-cell function (fasting, 30-minute, and 120-minute C-peptide concentrations, oral insulinogenic index, and homeostatic model assessment 2-beta cell function) and insulin resistance (homeostatic model assessment 2-insulin resistance) between both groups.ConclusionIn our study population, HIV infection was not associated with increased adiposity, pancreatic beta-cell function, and insulin resistance. Large prospective studies are needed to investigate the effect of HIV on the pathogenesis of type 2 diabetes in adult Ugandans.

Differences in epigenetic age by HIV status among patients with a non-AIDS defining cancer.

People with HIV (PWH) are living longer and experiencing higher numbers of non-AIDS-defining cancers (NADC). Epigenetic aging biomarkers have been linked to cancer risk, and cancer is now a leading cause of death in PWH, but these biomarkers have not been investigated in PWH and cancer. In order to compare epigenetic age by HIV status, HIV-uninfected participants were matched to PWH by reported age, tumor site, tumor sequence number, and cancer treatment status. DNA from blood was assayed using Illumina MethylationEPIC BeadChip, and we estimated immune cell composition and aging from three epigenetic clocks: Horvath, GrimAge, and epiTOC2. Age acceleration by clock was computed as the residual from the expected value, calculated using linear regression, for each study participant. Comparisons across HIV status used the Wilcoxon rank sum test. Hazard ratios and 95% confidence intervals for the association between age acceleration and survival in PWH were estimated with Cox regression. Among 65 NADC participants with HIV and 64 without, biological age from epiTOC2 ( P < 0.0001) and GrimAge ( P = 0.017) was significantly higher in PWH. Biological age acceleration was significantly higher in PWH using epiTOC2 ( P < 0.01) and GrimAge ( P < 0.0001), with the difference in GrimAge remaining statistically significant after adjustment for immune cell composition. Among PWH, GrimAge acceleration was significantly associated with increased risk of death (hazard ratio 1.11; 95% confidence interval (CI) 1.04-1.18). We observed a higher epigenetic age in PWH with a NADC diagnosis compared with their HIV-uninfected counterparts, as well as a significant association between this accelerated biological aging and survival for patients diagnosed with a NADC.

Prevalence of dental caries and associated risk factors among People Living with HIV/AIDS and HIV uninfected adults at an HIV clinic in Kigali, Rwanda.

Dental caries is among the most frequent oral conditions in People Living with HIV/AIDS (PLWHA). There is a lack of baseline information on dental caries prevalence and associated risk factors among PLWHA in comparison to HIV uninfected people in Rwanda. This study was conducted to determine the prevalence of dental caries and associated risk factors among PLWHA and HIV uninfected adults at an HIV clinic of Kigali Teaching Hospital (CHUK) in Kigali, Rwanda. A comparative cross-sectional study was conducted among 200 PLWHA and 200 HIV uninfected adults aged 18 years and above attending an HIV clinic of CHUK. An oral examination was performed by a calibrated examiner. Dental caries were assessed using the WHO Decayed (D), Missing (M), and Filled Teeth (F) index (DMFT). Descriptive statistics, Chi-square, t-tests, and multiple binary logistic regression were used to analyze data. Overall, a higher prevalence (50.5%) of PLWHA had experienced dental caries (DMFT>0) compared to HIV uninfected counterparts (40.5%) (p = 0.045). The prevalence of Decayed teeth (D) was also higher (23.5%) among PLWHA compared to HIV uninfected persons (13.6%) (p = 0.011). The Mean(SD) DMFT scores among PLWHA and HIV uninfected participants were 2.28 (3.68) and 1.29 (2.21) respectively (p = 0.001). After performing multiple binary logistic regression analysis, the predictors of dental caries in PLWHA were being female (OR = 2.33; 95%CI = 1.14-4.75), frequent dental visits (OR = 4.50; 95% CI = 1.46-13.86) and detectable RNA viral load (OR = 4.50; 95% CI = 1.46-13.86). In HIV uninfected participants, the middle age range (36-45 years), and frequent dental visits were significantly associated with dental caries (OR = 6.61; 95%CI = 2.14-20.37) and (OR = 3.42; 95%CI: 1.337-8.760) respectively. The prevalence of dental caries was higher in PLWHA than in HIV uninfected counterparts. The reported higher prevalence of caries in PLWHA was associated with being female, detectable viral load, and frequent dental visits. Therefore, there is a need for effective oral health interventions specific to PLWHA in Rwanda to raise awareness of the risk of dental caries and provide preventive oral health services among this population. To ensure timely oral health care amongPLWHA, there is a need for an effort from policymakers and other stakeholders to integrate oral health care services within the HIV treatment program in Rwanda.

Neuropsychological Test Norms for the Assessment of HIV-Associated Neurocognitive Impairment Among South African Adults

Reliable and valid neurocognitive (NC) test batteries that assess multiple domains of cognitive functioning are vital tools in the early detection of HIV-associated NC impairment. The HIV Neurobehavioral Research Center’s International Neurobehavioral Battery (HNRC Battery) is one such diagnostic tool and has shown cultural validity in several international neuroHIV studies. However, no published norms are currently available for the full HNRC Battery in South Africa. To accurately interpret NC test results, appropriate reference norms are required. In light of this challenge, data were collected from 500 healthy, HIV-uninfected participants to develop demographically corrected South African norms. When demographically corrected United States of America (U.S.) norms were applied to the performance scores of our neurologically intact, HIV-negative sample, an impairment rate of 62.2% was observed compared to a 15.0% impairment rate when the newly generated South African norms were applied. These results reiterate the findings of other low- and middle-income countries, highlighting the need for localized, country-specific norms when interpreting NC performance.

High Prevalence of Lower Extremity Medial Arterial Calcification in HIV-infected Patients With and Without Chronic Renal Disease: A Vascular Ultrasound Cross-sectional Study

Background: The association between HIV infection and increased risk of atherosclerotic peripheral artery disease (PAD) has been documented. Still, the relationship between HIV infection and lower extremity medial arterial calcification (MAC) is unknown. Objective: We performed a cross-sectional study to compare the frequency of MAC diagnosed by vascular ultrasound in PAD-asymptomatic people living with HIV (PLWH) with and without chronic kidney disease (CKD) compared to HIV-uninfected participants as a control group. Methods: MAC was defined as smooth, linear, and non-stenotic hyperechogenicity in the arterial wall compared to the surrounding tissues. We studied 191 patients: 50 PLWH (25 with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2 and 25 with an eGFR &lt;60 mL/min/1.73m2) and 141 HIV-uninfected patients (68 with eGFR&lt;60 ml/min/1.73m2). Results: MAC was most frequently found in PLWH with CKD (76%). The prevalence of MAC among PLWH was 54.0% (95% confidence interval [CI], 40.4-67.0%), whereas, in HIV-uninfected, it was 34.0% (95% CI, 26.7-42.2%, P=0.013). Age and CKD were consistently associated with MAC in our multivariable models, and there was also a sign that PLWH had higher odds of having MAC. Conclusion: We found a higher prevalence of MAC in PAD-asymptomatic PLWH compared to HIV-uninfected ones and provided evidence that HIV infection could be associated with MAC.

Burden of malaria in pregnancy among adolescent girls compared to adult women in 5 sub-Saharan African countries: A secondary individual participant data meta-analysis of 2 clinical trials.

BackgroundMalaria is among the top causes of death in adolescent girls (10 to 19 years) globally. Adolescent motherhood is associated with increased risk of adverse maternal and neonatal outcomes. The interaction of malaria, adolescence, and pregnancy is especially relevant in malaria endemic areas, where rates of adolescent pregnancy are high. However, data on burden of malaria among adolescent girls are limited. This study aimed at investigating whether adolescent girls were at a greater risk of experiencing malaria-related outcomes in pregnancy—parasitaemia and clinical disease—than adult women.Methods and findingsAn individual secondary participant-level meta-analysis was conducted using data from 5,804 pregnant women participating in 2 malaria prevention clinical trials in Benin, Gabon, Kenya, Mozambique, and Tanzania between 2009 and 2014. Of the sample, 1,201 participants were adolescent girls with a mean age of 17.5 years (standard deviation (SD) 1.3) and 886 (73.8%) of them primigravidae. Among the 4,603 adult women with mean age of 27.0 years (SD 5.4), 595 (12.9%) were primigravidae. Mean gestational age at enrolment was 20.2 weeks (SD 5.2) and 1,069 (18.4%) participants were HIV-infected. Women were followed monthly until the postpartum visit (1 month to 6 weeks after delivery). This study considered outcomes including clinical episodes during pregnancy, peripheral parasitaemia at delivery, and placental malaria. A 2-stage meta-analysis approach was followed by pooling single multivariable regression results into standard DerSimonian–Laird random-effects models. Adolescent girls were more likely than adult women to present with clinical malaria during pregnancy (incidence risk ratio (IRR) 1.70, 95% confidence interval (CI) 1.20; 2.39, p-value = 0.003, I2 = 0.0%, N = 4,092), peripheral parasitaemia at delivery (odds ratio (OR) 2.28, 95% CI 1.46; 3.55, p-value < 0.001, I2 = 0.0%, N = 3,977), and placental infection (OR 1.97, 95% CI 1.31; 2.98, p-value = 0.001, I2 = 1.4%, N = 4,797). Similar associations were observed among the subgroup of HIV-uninfected participants: IRR 1.72 (95% CI 1.22; 2.45, p-value = 0.002, I2 = 0.0%, N = 3,531) for clinical malaria episodes, OR 2.39 (95% CI 1.49; 3.86, p-value < 0.001, I2 = 0.0%, N = 3,053) for peripheral parasitaemia, and OR 1.88 (95% CI 1.06 to 3.33, p-value = 0.03, I2 = 34.9%, N = 3,847) for placental malaria. Among HIV-infected subgroups statistically significant associations were not observed. Similar associations were found in the subgroup analysis by gravidity. The small sample size and outcome prevalence in specific countries limited the inclusion of some countries in the meta-analysis. Furthermore, peripheral parasitaemia and placental malaria presented a considerable level of missing data—12.6% and 18.2% of participants had missing data on those outcomes, respectively. Given the original scope of the clinical trials, asymptomatic malaria infection was only assessed at the end of pregnancy through peripheral and placental parasitaemia.ConclusionsIn this study, we observed that adolescent girls in sub-Saharan Africa (SSA) are more prone to experience clinical malaria episodes during pregnancy and have peripheral malaria and placental infection at delivery than adult women. Moreover, to the best of our knowledge, for the first time this study disaggregates figures and stratifies analyses by HIV infection. Similar associations were found for both HIV-infected and uninfected women, although those for HIV-infected participants were not statistically significant. Our finding suggests that adolescent girls may benefit from targeted malaria prevention strategies even before they become pregnant.

Plasma vesicular miR-155 as a biomarker of immune activation in antiretroviral treated people living with HIV.

People living with HIV (PLWH), despite suppression of viral replication with antiretroviral therapy (ART), have high morbidity and mortality due to immune activation and chronic inflammation. Discovering new biomarkers of immune activation status under ART will be pertinent to improve PLWH quality of life when the majority will be treated. We stipulate that plasma large and small extracellular vesicle (EVs) and their microRNA content could be easily measured biomarkers to monitor immune activation in PLWH. Venous blood samples from n = 128 ART-treated PLWH with suppressed viral load (≤ 20 copies/mL) and n = 60 HIV-uninfected participants were collected at five testing or treatment centers of PLWH in Burkina Faso. Large and small plasma EVs were purified, counted, and the mature miRNAs miR-29a, miR-146a, and miR-155 were quantified by RT-qPCR. Diagnostic performances of large and small EVs miRNAs level were evaluated by receiver operating characteristic (ROC) curve analysis and principal component analysis (PCA). Among the EVs microRNA measured, only large EVs miR-155 copies distinguished PLWH with immune activation, with AUC of 0.75 for CD4/CD8 < 1 (95% CI: 0.58–0.91, P = 0.0212), and 0.77 for CD8 T cells ≥ 500/µL (95% CI: 0.63–0.92, P = 0.0096). In addition, PCA results suggest that large EVs miR-155 copies may be a biomarker of immune activation. Since miR-155 may influence immune cell function, its enrichment in large EV subpopulations could be a functional biomarker of immune activation in PLWH on ART. This measure could help to monitor and diagnose the immune activation with more accuracy.

Proinflammatory and cardiovascular biomarkers are associated with echocardiographic abnormalities in children with HIV taking antiretroviral therapy.

Children with perinatally acquired HIV (PHIV) and taking antiretroviral therapy (ART) have a high prevalence of subclinical cardiac disease. We hypothesized that cardiac disease may be a consequence of dysregulated systemic immune activation driven by HIV infection. We examined cardiovascular and proinflammatory biomarkers and their association with echocardiographic abnormalities in children with PHIV. Cross-sectional analysis of soluble biomarkers from a prospective cohort of children aged 6-16 years with PHIV and age-matched HIV-uninfected comparison group. Cryopreserved plasma samples were used to measure seven soluble biomarkers using multiplex bead assay (Luminex). Multivariable logistic regression assessed how biomarker levels related to cardiac abnormalities. A total of 406 children participated in this study (195 PHIV and 211 HIV-uninfected). Mean [standard deviation (SD)] ages of PHIV and HIV-uninfected participants were 10.7 (2.6) and 10.8 (2.8) years, respectively. Plasma levels of CRP, TNF-α, ST2, VCAM-1 and GDF-15 were significantly higher in the PHIV group compared with uninfected control ( P < 0.001). Among children with PHIV, with one-unit representing one SD in biomarker level, a one-unit increase in CRP and GDF-15, was associated with increased odds of having left ventricular (LV) diastolic dysfunction [adjusted odds ratio (aOR), 1.49 (1.02-2.18; P < 0.040)] and [aOR 1.71 (1.18-2.53; P = 0.006)], respectively. Each one unit increase in GDF-15 was associated with increased odds of LV hypertrophy [aOR 1.84 (95% CI 1.10-3.10; P < 0.021)]. Children with PHIV had higher levels of proinflammatory and cardiovascular biomarkers compared with HIV-uninfected children. Increased CRP and GDF-15 were associated with cardiac abnormalities in children with PHIV.

Four-Year Trajectories of Internal Strengths and Socioemotional Support Among Middle-Aged and Older Adults with HIV

Positive psychological attributes are associated with better health outcomes, yet few studies have identified their underlying constructs and none have examined their temporal trajectories in clinical vs. non-clinical samples. From data collected over 4 years from people with HIV (PWH) and HIV-uninfected (HIV−) participants, we identified two latent factors (internal strengths; socioemotional support) based on responses to seven positive psychological attributes. Internal strengths increased over 4 years for PWH, but not for HIV− comparisons. Socioemotional support did not change significantly in either group. Lower internal strengths and worse socioemotional support were related to greater depressive symptoms. We speculate that improvement in internal strengths in PWH could reflect their being in care, but this requires further study to include PWH not in care. Given the apparent malleability of internal strengths and their association with improved health outcomes, these attributes can serve as promising intervention targets for PWH.

Blood Pressure and Body Composition During First Year of Antiretroviral Therapy in People With HIV Compared With HIV-Uninfected Community Controls.

Body composition changes may explain the rapid increase in blood pressure (BP) in people with HIV (PWH) during the first year of antiretroviral therapy. We analyzed data from a cohort of PWH and HIV-uninfected adults from the same communities in Mwanza, Tanzania. Blood pressure (BP, mm Hg) and body composition data were collected at baseline and 12-month follow-up. We used multivariable linear regression to compare BP changes in PWH and HIV-uninfected adults, and the relationship between changes in body composition and changes in BP. BP data were available for 640 PWH and 299 HIV-uninfected adults. Sixty-four percent were women and the mean age was 38 years. In PWH, systolic BP (SBP) increased (114-118) whereas SBP decreased (125-123) in HIV-uninfected participants. Fat mass increased by 1.6 kg on average in PWH and was strongly associated with the change in BP (P < 0.001). The greater increase in SBP in PWH was partly explained by the lower baseline SBP but PWH still experienced a 2.2 (95% CI: 0.3-4.2) greater increase in SBP after adjustment. Weight gain partially mediated the relationship between HIV and SBP increase in PWH; a 1-kg increase in fat mass accounted for 0.8 (95% CI: 0.6-1.1) increase in SBP. Weight and fat mass increase rapidly in PWH during the first 12 months of antiretroviral therapy and contribute to a rapid increase in SBP. Interventions to prevent excessive increase in fat mass are needed for PWH.

Effect of aging on immune cells in male HIV-infected and -uninfected healthy individuals.

HIV induces immunologic dysfunction in T cells of infected individuals. However, the impact of aging on T cell phenotypes in HIV-infected individuals receiving antiretroviral therapy (ART) has not been fully delineated. We evaluated the relationship between aging and the expression of immune activation and exhaustion markers on CD8 + T cells of age-matched HIV-infected and -uninfected male participants. Levels of immune activation and exhaustion markers on peripheral blood CD8 + T cells of HIV-infected and -uninfected participants were examined. 110 HIV-infected aviremic male participants receiving ART and 146 HIV-uninfected male participants were studied. The levels of TIGIT, PD-1, CD38, and CD226 on CD8 + T cells of the study participants were determined by flow cytometry. The level of TIGIT on CD8 + T cells was higher in aviremic HIV-infected compared to uninfected participants ( P < 0.0001). In contrast, no significant differences were found in the levels of PD-1 and CD38 on CD8 + T cells between the two groups. Statistically significant correlations were observed between age and the levels of TIGIT + and CD38 + CD8 + T cells in both groups; however, no correlation was found between age and the level of PD-1 + CD8 + T cells in HIV-infected participants. Age-stratification of HIV-infected and -uninfected groups did not show any significant differences in the level of PD-1 expression on CD8 + T cells. The findings of our study highlight the role of aging in the expression of immune markers on CD8 + T cells and have important implications for therapies that target immune checkpoints in HIV-infected individuals.

Effects of HIV Infection in Plasma Free Fatty Acid Profiles among People with Non-Alcoholic Fatty Liver Disease.

Despite its high prevalence, the mechanisms underlying non-alcoholic fatty liver disease (NAFLD) in people living with HIV (PLWH) are still unclear. In this prospective cohort study, we aim to evaluate differences in plasma fatty acid profiles between HIV-infected and HIV-uninfected participants with NAFLD. We included participants diagnosed with NAFLD, both HIV-infected and HIV-uninfected. Fatty acid methyl esters were measured from plasma samples. Ratios ([product]/[substrate]) were used to estimate desaturases and elongases activity. We used linear regression for adjusted analyses. We included 31 PLWH and 22 HIV-uninfected controls. We did not find differences in the sum of different types of FA or in FA with a greater presence of plasma. However, there were significant differences in the distribution of some FA, with higher concentrations of ALA, trans-palmitoleic, and behenic acids, and a lower concentration of lignoceric acid in PLWH. PLWH had lower C24:0/C22:0 and C16:0/C14:0 ratios, which estimates the activity of elongases ELOVL1 and ELOVL6. Both groups had similar fatty acid distribution, despite differences in traditional risk factors. PLWH had a lower proportion of specific ratios that estimate ELOVL1 and ELOVL6 activity, which had been previously described for other inflammatory conditions, such as psoriasis.

Comparison of HIV-Infected and Noninfected Patients Undergoing Bariatric Surgery: The ObeVIH Study.

The aim of this study was to compare clinical characteristics and adipose/liver tissue histology analysis in HIV-infected and HIV-uninfected subjects undergoing bariatric surgery. This was a cross-sectional study of HIV-infected subjects undergoing single-port sleeve gastrectomy with prospective enrolment and frequency age (±5 years), sex, and body mass index (BMI, ± 5 kg/m2) matched on HIV-uninfected subjects. This study was conducted at a single clinical site at Pitié-Salpêtrière hospital-Paris-France comprising 19 HIV-uninfected and 21 HIV-infected subjects with plasma VL < 20 copies/mL, all with a BMI > 40 kg/m2 or >35 kg/m2 with comorbidities. Histology of subcutaneous and visceral abdominal adipose tissue (SCAT/VAT) and liver biopsies was collected during single-port sleeve gastrectomy. Outcomes included anthropometric characteristics, comorbidities, cardiovascular parameters, adipose tissue, and liver histology. The age of HIV-infected participants was (median, interquartile range IQR) 48 y (42-51), with 76.2% females, a BMI of 41.4 kg/m2 (37.3-44.4), an antiretroviral duration of 16 y (8-21), current integrase strand transfer inhibitor (INSTI)-based regimen in 15 participants and non-INSTI regimen in 6 participants, and a CD4 count of 864/mm3 (560-1066). The age of controls was 43 y (37-51), with 78.9% females and a BMI of 39.2 kg/m2 (36.3-42.6). Anthropometric characteristics, comorbidities, and cardiovascular parameters did not differ according to HIV status and INSTI treatment. The number of macrophage crown-like structures in SCAT was lower in INSTI-treated participants than in HIV-uninfected participants (P = 0.02) and non-INSTI-treated HIV-infected subjects (P = 0.07). Hepatic steatosis and liver disease severity global score were lower in INSTI-treated participants than in non-INSTI-treated HIV-infected participants (P = 0.05 and P = 0.04, respectively). HIV-infected and HIV-uninfected subjects undergoing bariatric surgery presented a similar profile regarding anthropometric measures, cardiovascular parameters, and comorbidities. However, INSTI-treated participants presented milder SCAT and liver alterations than non-INSTI-treated participants.

Serum Ferritin Is Associated With Elevated ALT Among People Living With HIV and HIV-Seronegative Individuals in the Miami Adult Studies on HIV Cohort

ObjectivesIt has been shown that people living with HIV (PLWH) are vulnerable to liver inflammation and damage. Elevated serum ferritin has been associated with higher incidence of liver damage. This study examined the relationship between serum ferritin levels and liver damage in PLWH.MethodsA cross-sectional analysis of data from participants in the Miami Adult Studies on HIV (MASH) cohort. Informed consent, demographics, Alcohol Use Disorder Identification Test (AUDIT) for hazardous drinking (≥8), and fasting blood samples were collected by trained personnel. HIV status, HIV Viral Load (VL, copies/ml) was abstracted from medical charts with the participants’ consent. LabCorp (Burlington, NC) determined serum ferritin and serum alanine aminotransferase (ALT). Opioid use was analyzed by urinalysis (American Bio Medica Corp; Kinderhook, NY). Statistical analyses were performed using SPSS 26 and included T-test, linear and logistic regression. Elevated serum ferritin levels were defined as ≥150 ng/mL and elevated ALT as ≥5 IU/L.ResultsParticipants’ mean age was 54.6 ± 7.9 years (n = 1,026), 57.9% were male, and 61.2% wereBack; 46.8% were PLWH, 90.9% had an undetectable viral load. Males had significantly higher ALT (29.6 ± 36.2 vs. 20.8 ± 16.4 IU/L) and serum ferritin (156.1 ± 223.0 vs. 98.7 ± 114.9 ng/mL) than females (P < 0.001). Ferritin (148.3 ± 203.3 vs. 117.5 ± 171.1 ng/mL; P = 0.009), but not ALT (25.6 ± 32.078 vs. 26.1 ± 27.7 IU/L; P > 0.05), was significantly higher in PLWH than HIV-uninfected participants. In a linear model, elevated ALT was positively associated with higher serum ferritin levels after adjusting for sex, age, HIV status, and opioid use (β = 163.75 SE = 14.579, p = 0.001). Individuals with elevated ALT had 4.55 greater odds of having elevated ferritin levels (CI: 3.203–6.460, P < 0.001) after adjusting for age, sex and opioid use.ConclusionsAlanine aminotransferase seems to be a good predictor of serum ferritin levels in PLWH. Elevated levels of ferritin have been associated with liver inflammation, chronic kidney disease, acute infections, and therefore deleterious health consequences in PLWH that warrant further examination.Funding SourcesNational Institute on Drug Abuse.