HIV-infected Participants Research Articles

Immunogenicity and Safety of the 9-Valent Human Papillomavirus Vaccine in Solid Organ Transplant Recipients and Adults Infected With Human Immunodeficiency Virus (HIV).

The burden of human papillomavirus (HPV) in human immunodeficiency virus (HIV)-infected persons and solid organ transplant (SOT) recipients is high. Clinical trials on HPV vaccines in persons living with HIV and particularly in SOT recipients have been sparse to date, included low numbers of participants, and none of them assessed the 9-valent HPV (9vHPV) vaccine. We investigated the immunogenicity with respect to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 and the safety of the 9vHPV vaccine in persons living with HIV and recipients of a kidney, lung, or heart transplant. This is a phase III investigator-initiated study in 100 persons living with HIV (age 18-45 years) and 171 SOT recipients (age 18-55 years). The 9vHPV vaccine was administered at day 1, month 2, and month 6. Primary outcome was seroconversion rates to the 9vHPV types at month 7. Secondary outcomes were geometric mean titers (GMTs) and frequency of adverse events (AEs). All HIV-infected participants seroconverted for all HPV types, but seroconversion ranged from 46% for HPV45 to 72% for HPV58 in SOT recipients. GMTs ranged from 180 to 2985 mMU/mL in HIV-positive participants and from 17 to 170 mMU/mL in SOT recipients, depending on the HPV type. Injection-site AEs occurred in 62% of participants but were mostly mild or moderate in intensity. None of the reported serious adverse events were deemed vaccine related. No patients died during the study. Immunogenicity of the 9vHPV vaccine is high in persons living with HIV but suboptimal in SOT recipients. The vaccine is safe and well tolerated in both groups.

The influence of haemodialysis on CD4+ T-cell counts in people living with human immunodeficiency virus with end-stage kidney disease.

BackgroundIn South Africa it is estimated that 7.9 million people are living with human immunodeficiency virus (HIV). HIV is associated with an increased risk of kidney disease. For people living with HIV (PLWH) who develop end-stage kidney disease (ESKD), access to renal replacement therapy can be difficult. Kidney transplantation is a cost-effective option, with improved overall survival and better quality of life. In Johannesburg, the eligibility criteria for kidney transplantation include a sustained CD4+ T-cell count of > 200 cells/μL and suppressed HIV replication.ObjectiveTo investigate the influence of haemodialysis on the lymphocyte subsets in PLWH with ESKD. In addition, all available %CD4+ T-cell counts, absolute CD4+ T-cell counts and viral load measurements were collected to assess the longitudinal trends of these measurements in PLWH with ESKD.MethodsThis was a cross-sectional study comparing two groups. The HIV-infected study participants (n = 17) and HIV-uninfected controls (n = 17) were recruited from renal dialysis centres in Johannesburg from 2017 to 2018. Demographic data and social data were collected from all the study participants (n = 17). Blood samples were collected from all the study participants (before and after a haemodialysis session), and the lymphocyte subsets were then measured. The available longitudinal data for the serial CD4+ T-cell counts and HIV viral loads were collected (n = 14).ResultsOur cohort showed a statistically significant increase in the post-dialysis percentage of CD4+ T cells (5%, p < 0.001) and the absolute CD4+ T-cell counts (21 cells/µL, p < 0.03). The longitudinal trend analysis for the percentage of CD4+ T cells revealed a significant increase in five participants (36%), and a single patient (7%) had a significant decrease in the longitudinal trend analysis for the absolute CD4+ T-cell counts. The longitudinal trend analysis for HIV viral load revealed the majority of our participants were not virologically suppressed.ConclusionThis study showed that haemodialysis does not have an immediate negative impact on CD4+ T-cell count, suggesting that immunologic recovery is not impeded by treatment of the underlying ESKD.

Prevalence and risk factors for bone mineral density changes in antiretroviral therapy-naive human immunodeficiency virus-infected adults: a Chinese cohort study.

BackgroundStudies have reported that low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected patients; however, the factors that contribute to HIV-related BMD changes are yet to be fully understood. Due to the application of dual X-ray absorptiometry (DXA) among a select group of hospitals only, the prevalence and risk factors of low BMD in HIV-infected populations have not been intensively investigated in China. Thus, the aim of our study was to investigate the prevalence of and risk factors associated with BMD changes among antiretroviral therapy (ART)-naive HIV-positive patients in China.MethodsThe assessment of the prevalence of and risk factors associated with BMD changes was conducted among 156 ART-naive HIV-infected patients. Demographic and clinical data, as well as results of fasting blood tests were obtained from patients. Further, all patients underwent DXA scans to determine BMD, which was then used to classify patients with osteopenia/osteoporosis. The risk factors of reduced BMD were then evaluated using binary logistic regression.ResultsAmong the 156 ART-naive HIV-infected participants, osteopenia and osteoporosis were diagnosed in 48.7% (76/156) and 4.5% (7/156) of patients, respectively. The lumbar spine was most likely to have reduced BMD (49.4% [77/156]), and the proportion of osteopenia in the left hip (32.7% [51/156]) was higher than in the right hip (24.4% [38/156]). In the lumbar spine, bone loss rate in the L1 section (60.9% [95/156]) was the most significant (L2, 53.2% [83/156]; L3, 45.5% [71/156]; L4, 52.6% [82/156]). Further analysis showed that, compared with the neck (26.9% [42/156] in the left, 18.6% [29/156] in the right) and the interior (15.4% [24/156] in the left, 13.5% [21/156] in the right), the trochanter had the greatest probability of reduced BMD (46.2% [72/156] in the left, 28.8% [45/156] in the right). In the risk factor analysis, low body mass index (BMI: <18.5 kg/m2) was positively associated with reduced BMD (Exp (B) = 39.743, 95% confidence interval: 3.234–488.399, P = 0.004), and was specifically positively correlated with BMD values at three sites (r = 0.335 at right hip, r = 0.327 at left hip, r = 0.311 at lumbar spine).ConclusionReduced BMD was found in the majority of ART-naive HIV-infected patients and BMI was identified as an additional risk factor for reduced BMD. Our results show that BMD reduction was simultaneously present in the left hip, right hip, and lumbar spine among nearly one fifth of patients. Our work highlights the importance of closely monitoring BMD in ART-naive patients and provides a foundation for the clinical intervention of bone demineralization in them.

A study of pulmonary function tests in HIV infected children

Background: If untreated, HIV mortality will be high from the cause of acute respiratory infections in neonatal stage up to one year of age. Here, the study was conducted to determine the prevalence of spirometric abnormalities in HIV positive children. Methodology: A cohort of 20 children in the age group of 10 to18 years with a diagnosis of HIV was included. Spirometry measurements carried out to analyze the forced expiratory volume at one second (FEV1), forced vital capacity (FVC), FVC/FEV1 ratio, and forced expiratory flow 25% to 75% (FEF25-75) and pulse oximetry. The PFT data were analyzed in correlation with the age and blood parameters. Results: 20 HIV-infected participants with a mean age 15.5 years were recruited. 17 children were on antiretroviral therapy. The mean CD4 count was 496±235.22 (151-1088) cells/µl. Mean Hb% value observed was 9.96±2.5 and mean total leucocyte count was 3785±2087.37. We found mean FEV1 as 71.05±9.2, mean FVC as 71.6±8.5 and ratio FEV1/FVC as 98%±0.11. The total lung capacity was observed as 73%-117%. Conclusions: Clinicians evaluating HIV infected children with respiratory symptoms must first determine whether those symptoms are a result of common bacterial symptoms or opportunistic infections. Keywords: Antiretroviral therapy (ART); Chronic lung disease; HIV; Pulmonoray function test.

Apolipoprotein A-I mimetics attenuate macrophage activation in chronic treated HIV.

Despite antiretroviral therapy (ART), there is an unmet need for therapies to mitigate immune activation in HIV infection. The goal of this study is to determine whether the apoA-I mimetics 6F and 4F attenuate macrophage activation in chronic HIV. Preclinical assessment of the in-vivo impact of Tg6F and the ex-vivo impact of apoA-I mimetics on biomarkers of immune activation and gut barrier dysfunction in treated HIV. We used two humanized murine models of HIV infection to determine the impact of oral Tg6F with ART (HIV+ART+Tg6F+) on innate immune activation (plasma human sCD14, sCD163) and gut barrier dysfunction [murine I-FABP, endotoxin (LPS), LPS-binding protein (LBP), murine sCD14]. We also used gut explants from 10 uninfected and 10 HIV-infected men on potent ART and no morbidity, to determine the impact of ex-vivo treatment with 4F for 72 h on secretion of sCD14, sCD163, and I-FABP from gut explants. When compared with mice treated with ART alone (HIV+ART+), HIV+ART+Tg6F+ mice attenuated macrophage activation (h-sCD14, h-sCD163), gut barrier dysfunction (m-IFABP, LPS, LBP, and m-sCD14), plasma and gut tissue oxidized lipoproteins. The results were consistent with independent mouse models and ART regimens. Both 4F and 6F attenuated shedding of I-FABP and sCD14 from gut explants from HIV-infected and uninfected participants. Given that gut barrier dysfunction and macrophage activation are contributors to comorbidities like cardiovascular disease in HIV, apoA-I mimetics should be tested as therapy for morbidity in chronic treated HIV.

Persistence of monocyte activation under treatment in people followed since acute HIV-1 infection relative to participants at high or low risk of HIV infection.

BackgroundInterpretation of the increase in certain inflammatory markers in virally suppressed HIV-infected individuals must rely on an appropriate uninfected control group well characterized for non-HIV-related factors that contribute to chronic inflammation, e.g. smoking, alcohol consumption, or being overweight. We compared the inflammatory profiles of HIV-infected participants under long-term antiretroviral therapy (ART) with those of two HIV-uninfected groups with contrasting health behaviours.MethodsWe studied 150 HIV-infected participants (42 women, 108 men) under long-term ART (median, 6 years) followed in the ANRS PRIMO cohort since acute/early HIV-1 infection (AHI) diagnosis. Sex and age-matched controls were sampled from i) the ANRS IPERGAY pre-exposure prophylaxis trial among men at high risk for HIV infection and with high frequencies of non-HIV factors of inflammation ii) the ANRS COHVAC cohort of volunteers in vaccine trials with a low-risk profile for HIV infection. We measured the plasma levels of ten inflammatory markers.FindingsAfter adjusting for smoking, alcohol use and body mass index, both HIV-infected men and women had higher levels of sCD14, sCD163, sTNFRII and I-FABP than their high-risk IPERGAY and low-risk COHVAC counterparts. Hierarchical clustering showed a subset of 15 PRIMO participants to have an inflammatory profile similar to that of most HIV-negative participants. These participants already had favourable markers at AHI diagnosis.InterpretationLong-term ART, even when initiated at a low level of immunodeficiency, fails to normalize monocyte/macrophage activation and gut epithelial dysfunction. Persistent inflammation under treatment may be related to an increased inflammatory profile since AHI.FundingANRS and Paris-Saclay University.

Human immunodeficiency virus infection and syphilis among homeless people in a large city of Central-Western Brazil: prevalence, risk factors, human immunodeficiency virus-1 genetic diversity, and drug resistance mutations

Homeless people are at high risk for sexually transmitted infections (STIs), such as human immunodeficiency virus (HIV) infection and syphilis. We investigated the epidemiology of HIV-1 infection and syphilis among homeless individuals in a large city in Central-Western Brazil. In this cross-sectional study, we interviewed and tested 355 individuals from September 2014 to August 2015. Rapid test samples positive for syphilis were retested using the Venereal Disease Research Laboratory (VDRL) test. Blood samples from HIV-infected participants were collected for POL sequencing using HIV-1 RNA extracted from plasma, reverse transcription, and nested polymerase chain reaction. Anti-HIV-1-positive samples were subtyped by sequencing the nucleotides of HIV-1 protease and part of the HIV-1 reverse transcriptase genes. Transmitted and acquired drug resistance mutations and susceptibility to antiretroviral drugs were also analyzed. Anti-HIV was positive in 14 patients (3.9%; 95% confidence interval [CI]: 2.3–6.4). HIV-1 RNA was detected in 8 of the 14 samples. Two of the eight (25%) isolates showed HIV-1 drug resistance mutations. Furthermore, 78 (22%; 95% CI: 17.9–26.5) and 29 (8.2%; 95% CI: 5.6–11.4) homeless individuals tested positive for syphilis using the rapid test and VDRL test, respectively. Two individuals were anti-HIV-1 and VDRL test positive. Daily alcohol use (adjusted odds ratio [AOR]: 3.2, 95% CI: 1.0–10.4), sex with people living with HIV (PLWH) infection (AOR: 6.8, 95% CI: 1.9–25.0), and sex with people of the same sex (AOR: 5.4, 95% CI: 1.7–17.5) were predictors of HIV infection. Age ≤35 years (AOR: 3.8, 95% CI: 1.4–10.8), previous syphilis testing (AOR: 3.5, 95% CI: 1.4–8.4), history of genital lesions (AOR: 4.9, 95% CI: 1.3–19.1), and crack use in the last six months (AOR: 3.1, 95% CI: 1.3–7.6) were predictors of syphilis. Our findings highlight the importance of STI prevention and control strategies among the homeless.

Abstract 15507: Trajectories of Point of Care B-type Natriuretic Peptide (bnp) and Its Role as a Predictor of All-cause Mortality Among Hiv and Non-hiv Heart Failure Patients in Uganda

Introduction: The usefulness of serial measurement of BNP to reduce hospitalization or mortality in patients with HIV and heartfailure is unknown. Hypothesis: We sought to describe changes in B-type natriuretic peptide (BNP) and estimate the effect of HIV on BNP over a week of observation in an acute heart failure cohort of 40 HIV-infected adults (≥18 years) on antiretroviral therapy (ART) and 175 HIV-uninfected hospitalized patients in Uganda. Methods: We measured BNP using i-STAT BNP (Abbott point of care, Princeton, New Jersey) and compared changes by HIV serostatus, and evaluated BNP as a predictor of all-cause mortality at 30 days from hospitalization using multilevel mixed and competitive risk regression models respectively. Results: Overall HIV-infected participants had a higher mean BNP than HIV-uninfected counterparts. After initial declines in BNP in both groups between day 0 and day 3, BNP moderately increased among the HIV-infected on day 7 and continued to decline in the HIV-uninfected group. Each 1 pg/mL increase in baseline BNP from 400 pg/mL increased the risk of all-cause mortality within 30 days by 1% (adjusted standardized hazard ratio (aSHR) 1.01, 95%CI 1.01, 1.01). Other predictors of increased 30-day all-cause mortality included smoking (aSHR 1.99, 95%CI 1.04, 3.84), hypotension (aSHR 1.69, 95%CI 1.26, 2.26) and renal failure stage 3 (aSHR 2.06, 95%CI 1.34, 3.18), and renal failure stage 5 (aSHR 2.02, 95%CI 1.30, 3.13). We found a lower risk of 30-day all-cause mortality of 38% (95%CI 20%, 73%) for those receiving loop diuretics and 74% (95%CI 56%, 99%) for antiplatelet agents. Conclusions: Over a week of observation, HIV-infected people hospitalized with acute heart failure in Uganda have higher BNP levels than HIV-uninfected counterparts. Increases in BNP above the upper bound of the normal predicted heightened risk of all-cause mortality within 30 days of hospitalization.

Performance of a simple flow cytometric assay in diagnosing active tuberculosis

A flow cytometric assay measuring Mycobacterium tuberculosis-specific CD4 T-cell responses using co-expression of CD25/CD134 (OX40 assay) was explored as a diagnostic tool for active tuberculosis (TB) in a Thai population with and without HIV infection. Peripheral blood mononuclear cells (PBMC) obtained from 133 participants at TB diagnosis were cryopreserved. Seventy-six participants had a clinical diagnosis of TB which were confirmed by a positive culture. CD4 T-cell responses were measured after stimulation with a pool of overlapping peptides covering RD-1 antigens: CFP-10 + ESAT-6. The performance of the assay was also compared to the Xpert MTB/RIF assay. The overall sensitivity of the OX40 assay was 94.7% (95%CI 87.1–98.5); its specificity was 71.9% (95%CI, 58.5–83). The sensitivity of the OX40 assay among HIV-infected participants was 100% (95%CI, 88.8–100) with a specificity of 92.9% (95%CI, 66.1–99.8). OX40 assay performed particularly well in those with active TB and HIV infection.

Single nucleotide polymorphisms in LCAT may contribute to dyslipidaemia in HIV-infected individuals on HAART in a Ghanaian population

Highly active antiretroviral therapy (HAART) is known to cause lipid abnormalities such as dyslipidaemia in HIV-infected individuals. Yet, dyslipidaemia may not independently occur as it may be worsened by single nucleotide polymorphisms (SNPs) in lecithin cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). This case–control study was conducted in three-selected hospitals in the Northern part of Ghana. The study constituted a total of 118 HIV-infected participants aged 19–71 years, who had been on HAART for 6–24 months. Dyslipidaemia was defined based on the NCEP-ATP III criteria. HIV-infected individuals on HAART with dyslipidaemia were classified as cases while those without dyslipidaemia were grouped as controls. Lipid profile was measured using an automatic clinical chemistry analyzer and genomic DNA was extracted for PCR (GeneAmp PCR System 2700). Overall, the prevalence of dyslipidaemia was 39.0% (46/118). High levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and reduced levels of high-density lipoprotein cholesterol (HDL-C) were observed in all cases. A total of 256 selected PCR amplicons comprising 137 LPL (exons 3, 5 and 6) and 119 LCAT (exons 1, 4, and 6) were sequenced in 46 samples (Inqaba Biotech). Six (6) clinically significant SNPs were identified in exons 1 and 4 for LCAT whereas 25 non-clinically significant SNPs were identified for LPL in exons 5 and 6. At position 97 for LCAT exon 1, there was a deletion of the nucleotide, ‘A’ in 32.5% (13/40) of the sampled population while 67.5% (27/40) of the sample population retained the nucleotide, ‘A’ which was significantly associated with dyslipidaemic outcomes in the study population (p = 0.0004). A total of 25 SNPs were identified in exons 5 and 6 of LPL; 22 were substitutions, and 3 were insertions. However, none of the 25 SNPs identified in LPL exon 5 and 6 were statistically significant. SNPs in LCAT may independently contribute to dyslipidaemia among Ghanaian HIV-infected individuals on HAART, thus, allowing genetic and/or functional differential diagnosis of dyslipidaemia and creating an opportunity for potentially preventive options.

Twelve-Month Outcomes of Community-Based Differentiated Models of Multimonth Dispensing of ART Among Stable HIV-Infected Adults in Lesotho: A Cluster-Randomized Noninferiority Trial.

Lesotho adopted the test-and-treat approach for HIV treatment in June 2016, which increased antiretroviral treatment (ART) clinic volume. We evaluated community-based vs. facility-based differentiated models of multimonth dispensing of ART among stable HIV-infected adults in Lesotho. Thirty facilities were randomized to 3 arms, facility 3-monthly ART (3MF) (control), community ART groups (3MC), and 6-monthly community distribution points (6MCD). We estimated risk differences (RDs) between arms using population-averaged generalized estimating equations, controlling for baseline imbalances and specifying for clustering. The primary outcome was retention in ART care by intention-to-treat and virologic suppression as a secondary outcome (ClinicalTrials.gov: NCT03438370). A total of 5,336 participants were enrolled, with 1898, 1558, and 1880 in 3MF, 3MC, and 6MCD, respectively. Retention in ART care was not different across arms and achieved the prespecified noninferiority limit (-3.25%) between 3MC vs. 3MF (control); 6MCD vs. 3MF; and 6MCD vs. 3MC, adjusted RD = -0.1% [95% confidence interval (CI): -1.6% to 1.5%], adjusted RD = -1.3% (95% CI: -3.0% to 0.5%), and adjusted RD = -1.2% (95% CI: -2.9% to 0.5%), respectively. After 12 months, 98.6% (n = 1503), 98.1% (n = 1126), and 98.3% (n = 1285) were virally load (VL) suppressed in 3MF, 3MC, and 6MCD, respectively. There were no differences in VL between 3MC vs. control and 6MCD vs. control, risk ratio (RR) = 1.00 (95% CI: 0.98 to 1.01) and RR = 1.00 (95% CI: 0.98 to 1.01), respectively. There were no differences in retention and VL suppression for stable HIV-infected participants receiving multimonth dispensing of ART within community-based differentiated models when compared with the facility-based standard-of-care model.

The association of household food insecurity and HIV infection with common mental disorders among newly diagnosed tuberculosis patients in Botswana

To determine the association between food insecurity and HIV infection with depression and anxiety among new tuberculosis (TB) patients. Our cross-sectional study assessed depression, anxiety and food insecurity with Patient Health Questionnaire (PHQ-9), Zung Anxiety Self-Assessment Scale (ZUNG) and Household Food Insecurity Access Scale, respectively. Poisson regression models with robust variance were used to examine correlates of depression (PHQ-9 ≥ 10) and anxiety (ZUNG ≥ 36). Gaborone, Botswana. Patients who were newly diagnosed with TB. Between January and December 2019, we enrolled 180 TB patients from primary health clinics in Botswana. Overall, 99 (55·0 %) were HIV positive, 47 (26·1 %), 85 (47·2 %) and 69 (38·5 %) indicated depression, anxiety and moderate to severe food insecurity, respectively. After adjusting for potential confounders, food insecurity was associated with a higher prevalence of depression (adjusted prevalence ratio (aPR) = 2·30; 95 % CI 1·40, 3·78) and anxiety (aPR = 1·41; 95 % CI 1·05, 1·91). Prevalence of depression and anxiety was similar between HIV-infected and HIV-uninfected participants. Estimates remained comparable when restricted to HIV-infected participants. Mental disorders may be affected by food insecurity among new TB patients, regardless of HIV status.

Risk factors associated with HIV and hepatitis C virus co-infection among people who inject drugs in Cambodia

BackgroundGlobally, research on the co-infection of the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) among people who inject drugs is growing. However, studies in resource-poor countries remain limited. Therefore, we conducted this study to explore factors associated with HIV/HCV co-infection among people who inject drugs in Cambodia. MethodsThis national survey was conducted in 2017 in the capital city and 11 provinces. We used a ‘peer-based social network recruitment’ method to recruit 286 participants for face-to-face interviews and HIV and HCV testing. A modified Cox proportional hazard model was used to identify risk factors associated with HIV/HCV co-infection. ResultsThe prevalence of HIV and HCV was 15.4% and 30.4%, respectively. Of the total, 9.4% of the participants were HIV/HCV co-infected, and 61.4% of the HIV-infected participants were co-infected with HCV. About half (56.8%) of the participants tested HIV positive were aware of their HIV status; of whom, 83.3% were on antiretroviral therapy. Only 11.5% of the participants with HCV antibody positivity were aware of their HCV infection status; of whom, 50.0% were on HCV treatment. The adjusted prevalence ratio (APR) of HIV/HCV co-infection was significantly higher among women than among men and among participants who lived on the streets than among those living with their family or relatives. The APR of HIV/HCV co-infection was also significantly higher among participants who had received methadone maintenance therapy than those who had not received it. ConclusionsThe prevalence of HIV/HCV co-infection among people who inject drugs in Cambodia was considerably high. Intervention programs are required to increase access to harm-reduction interventions among most marginalized people who inject drugs to prevent HIV and HCV infection. HCV screening services should be expanded in this key population, given its small population size and the availability of directly-acting antiviral agents in the country.

Unbiased Profiling Reveals Compartmentalization of Unconventional T-Cells Within the Intestinal Mucosa Irrespective of HIV Infection.

The intestinal mucosa is enriched for unconventional T-cells, including mucosal associated invariant T-cells (MAIT), invariant natural killer T-cells (iNKT) and γδ T-cells. These cells are activated by bacterial metabolites, lipid antigens and cytokines, and are important for intestinal barrier integrity. The loss of gut homeostasis observed in HIV infection is central to disease pathogenesis, and studies have highlighted impairment of particular unconventional T-cell subsets within a specific gut compartment. However, although the small and large intestine are distinct niches, the overall impact of HIV on unconventional T-cells across the gut mucosal has not been well-studied. We hypothesized that compartment specific differences in the unconventional T-cell repertoire would exist between the small and large intestine, due to increasing bacterial loads and microbial diversity; and that the impact of HIV infection might differ depending on the compartment examined. We used mass cytometry, flow cytometry and unbiased T-cell receptor profiling to quantify unconventional T-cells in blood and tissue from the small (duodenum) and large (colon) intestine in HIV infected and uninfected participants undergoing examination for a range of intestinal conditions. Overall, we find distinct compartmentalisation of T-cells between blood, duodenum and colon, with iNKT cells significantly enriched in the duodenum and δ-1 expressing γδ T-cells in the colon. In addition, we observe greater clonal expansion of conventional TCRs in the duodenum, suggestive of stronger adaptive immunity in this compartment. Conversely, we find evidence of an expanded unconventional TCR repertoire in the colon, which contained far more overlapping “donor unrestricted” sequences than the duodenum. Twelve of these TCRs were highly “MAIT-like” and 3 were unique to the colon, suggesting an enrichment of donor unrestricted T-cells (DURTs) in this compartment. Unexpectedly, however, no significant impact of HIV infection on any of the unconventional T-cell subsets measured was observed in either mucosal site in terms of frequency or TCR repertoire. Further studies are required to investigate the importance of these unconventional T-cell subsets to intestinal homeostasis within the different gut compartments and determine if they are functionally impaired during HIV infection.

Prevalence of hepatitis B surface antigen and serological markers of other endemic infections in HIV-infected children, adolescents and pregnant women in Sierra Leone: A cross-sectional study

ObjectiveTo assess the prevalence of serological markers of HBV and endemic acute and chronic infections (HAV, HCV, CMV, HTLV-1/2 and syphilis) in HIV-infected children, adolescents and pregnant women in Sierra Leone. MethodWe conducted a cross-sectional study at the national children’s and women’s hospitals in Freetown. Logistic regression was used to assess predictors of HBsAg positivity. Results183 HIV-infected participants were enrolled, comprising children (n = 88), adolescents (n = 47) and pregnant women (n = 48). All participants (100%) were CMV IgG-positive, while 56.8%, 93.6% and 100% of children, adolescents and pregnant women, respectively, were HAV IgG-positive. The prevalence of HCV, HTLV-1/2 and syphilis were <4%. HBV markers were distributed as follows—children: HBsAg (2.3%), HBeAg (0%), anti-HBc (5.7%); adolescents: HBsAg (17.0%), HBeAg (6.4%), anti-HBc (27.7%); and pregnant women: HBsAg (18.8%), HBeAg (4.2%), anti-HBc (77.1%). Age >10 years, i.e., being born pre-2009 before implementation of routine hepatitis B immunization (aOR 5.05 [1.18−21.28]; p = 0.029) and CD4 count <350 cells/mm3 (aOR 3.97 [1.07−14.71]; p = 0.039) predicted HBsAg positivity. ConclusionA high burden of chronic HBV and other endemic infections was observed among HIV-infected patients born pre-2009 before implementation of routine HBV immunization in Sierra Leone, warranting targeted screening and immunization of this high-risk population.

Successes and gaps in the HIV cascade of care of a high HIV prevalence setting in Zimbabwe: a population-based survey.

IntroductionGutu, a rural district in Zimbabwe, has been implementing comprehensive HIV care with the support of Médecins Sans Frontières (MSF) since 2011, decentralizing testing and treatment services to all rural healthcare facilities. We evaluated HIV prevalence, incidence and the cascade of care, in Gutu District five years after MSF began its activities.MethodsA cross‐sectional study was implemented between September and December 2016. Using multistage cluster sampling, individuals aged ≥15 years living in the selected households were eligible. Individuals who agreed to participate were interviewed and tested for HIV at home. All participants who tested HIV‐positive had their HIV‐RNA viral load (VL) measured, regardless of their antiretroviral therapy (ART) status, and those not on ART with HIV‐RNA VL ≥ 1000 copies/mL had Limiting‐Antigen‐Avidity EIA Assay for cross‐sectional estimation of population‐level HIV incidence.ResultsAmong 5439 eligible adults ≥15 years old, 89.0% of adults were included in the study and accepted an HIV test. The overall prevalence was 13.6% (95%: Confidence Interval (CI): 12.6 to 14.5). Overall HIV‐positive status awareness was 87.4% (95% CI: 84.7 to 89.8), linkage to care 85.5% (95% CI: 82.5 to 88.0) and participants in care 83.8% (95% CI: 80.7 to 86.4). ART coverage among HIV‐positive participants was 83.0% (95% CI: 80.0 to 85.7). Overall, 71.6% (95% CI 68.0 to 75.0) of HIV‐infected participants had a HIV‐RNA VL < 1000 copies/mL. Women achieved higher outcomes than men in the five stages of the cascade of care. Viral Load Suppression (VLS) among participants on ART was 83.2% (95% CI: 79.7 to 86.2) and was not statistically different between women and men (p = 0.98). The overall HIV incidence was estimated at 0.35% (95% CI 0.00 to 0.70) equivalent to 35 new cases/10,000 person‐years.ConclusionsOur study provides population‐level evidence that achievement of HIV cascade of care coverage overall and among women is feasible in a context with broad access to services and implementation of a decentralized model of care. However, the VLS was relatively low even among participants on ART. Quality care remains the most critical gap in the cascade of care to further reduce mortality and HIV transmission.

High microbial translocation limits gut immune recovery during short-term HAART in the area with high prevalence of foodborne infection

BackgroundIndividuals residing in areas with high prevalence of foodborne infection could have a higher risk of gut microbial translocation which may affect monocyte activation, gut immune recovery and intestinal epithelial cell damage. We aimed to measure alterations in microbial translocation, monocyte activation, gut immune recovery, and intestinal epithelial cell damage in HAART treated individuals. MethodsA prospective, single-arm, longitudinal, cohort study was conducted among antiretroviral naïve HIV-1 infected Thai participants. All participants were in chronic stage of HIV-1 infection before starting HAART. Data and samples were collected prior to initiation of HAART and then after 24 and 48 weeks of HAART. Plasma biomarkers for microbial translocation (16S rDNA and LBP), monocyte activation (sCD14) and intestinal epithelial cell damage (I-FABP) were evaluated. We measured circulating gut-homing CD4+ T cells and circulating gut-homing Th17 cells to assess recoveries of gut immunity and gut immunity to microbial pathogens. ResultsThe kinetic studies showed no reduction in the levels of plasma 16S rDNA, sCD14 or I-FABP, significant decrease of plasma LBP level, and slow but significant increases in the frequencies of circulating gut-homing CD4+ T cells and circulating gut-homing Th17 cells during 48 weeks of HAART. Dividing participants into low and high microbial translocation (low and high MT) groups at baseline, both groups showed persistent plasma levels of 16S rDNA, sCD14 and I-FABP, and significantly decreased plasma level of LBP. The low MT group had significantly increased frequencies of circulating gut-homing CD4+ T cells and circulating gut-homing Th17 cells during 48 weeks of HAART but this was not observed in the high MT group. ConclusionsWe demonstrated persistent high microbial translocation, monocyte activation and intestinal epithelial cell damage with slow gut immune recovery during successful short-term HAART. Additionally, gut immune recovery was apparently limited by high microbial translocation. Our findings emphasize the adverse impact of high microbial translocation on gut immune recovery and the necessity of establishing a novel therapeutic intervention to inhibit microbial translocation.

Effects of Highly Active Antiretroviral Treatment on Liver and Kidney Functions

Aim: This study assesses the effects of HAART on liver and renal functions in HIV infected individuals on HAART.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Methods: This study was conducted in Tamale, Ghana from August, 2015 to November 2017.&#x0D; Methodology: A total of 300 HIV infected participants with ages ranging from 19 to 79 years who have been administered with HAART for at least 6 months were recruited. Pre-HAART administration (baseline) demographic and clinical information, with initial liver and renal function test results were retrieved from the medical records of the participants present at the ART center. Post HAART administration blood sample (5 mLs) was taken from each participant into a gel separated vacutainer tube, allowed to clot and spun at 3000 rpm for 3 minutes to produce serum. The product (serum) was used for liver and renal function test analysis using a fully automated chemistry analyser (Vital Scientific Selectra Flexor XL).&#x0D; Results: Of the study population, 72% were administered with AZT/3TC/EFV, 13% with AZT/3TC/NVP, 6.7% with TDF/3TC/LPV/r and TDF/3TC/NVP, 1% with AZT/3TC/EFV while 0.7% were administered with TDF/FTC/EFV. The following parameters were significantly increased post HAART administration; ALT (25.53 ± 16.90 to 30.87 ± 19.28 U/L), ALP (163.7 ± 141.0 to 215.2 ± 143.4 U/L), GGT (37.27 ± 25.21 to 53.19 ± 41.71 U/L), Total protein (73.97 ± 17.08 to 82.31 ± 11.62 g/L), Albumin (38.02 ± 9.331 to 41.01 ± 7.471 g/L), Globulin 38.02 ± 15.71 to 42.79 ± 25.20 (g/L). There were however significant reductions in Total bilirubin (12.13 ± 10.85 to 9.434 ± 4.560 µmol/L), Direct bilirubin (6.616 ± 5.770 to 4.184 ± 2.806 µmol/L), (Creatinine 73.19 ± 36.13 to 63.14 ± 27.14 µmol/L) and Urea (3.515 ± 2.552 to 3.011±1.274 mmol/L).&#x0D; Conclusion: HAART improves renal function, induces elevation in liver enzymes, stimulates the production of plasma proteins and reduces serum bilirubin concentration.

Vascular function and cardiovascular risk in a HIV infected and HIV free cohort of African ancestry: baseline profile, rationale and methods of the longitudinal EndoAfrica-NWU study

BackgroundPeople living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world’s largest ART programme.The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa.MethodsIn this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free.ResultsAt baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m2) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (all p < 0.047) in PLHIV.ConclusionDespite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV.

High-Risk Human Papillomavirus Persistence and Anal Microbiota Among Nigerian Men Who Have Sex With Men Living With or At Risk for HIV

PURPOSE Noninvasive therapies, such as probiotics that promote local immunity and reduce persistence of high-risk human papillomavirus (HR-HPV), would circumvent challenges in implementing anal cancer screening where same-sex behavior is stigmatized and criminalized. We describe the persistence of HR-HPV and its relationship with the anal microbiota among Nigerian men who have sex with men (MSM). METHODS Anal swabs from HIV-uninfected and -infected MSM who were enrolled in the TRUST/RV368 cohort were HPV genotyped at enrollment and at 3 and 12 months. Participants who presented with the same type(s) of HR-HPV across all visits were categorized as having persistent infections. The anal microbiota composition at baseline of HR-HPV–positive individuals was evaluated. Unsupervised K-means clustering of the 15 most abundant bacterial taxa identified 2 microbial clusters (MC-1 and MC-2). Unadjusted associations of 12-month HR-HPV persistence was evaluated by MC membership and HIV status using χ2 tests and logistic regression. RESULTS One hundred nine HIV-infected and 41 HIV-uninfected participants—contributing 284 baseline HR-HPV infections—were observed for a median of 12 months (interquartile range, 11.5-12.6 months). MC-1 was dominated by Prevotella and MC-2 consisted of a diverse set of anaerobic bacteria ( Finegoldia, Corynebacterium, Peptoniphilus, and Anerococcus). At 12 months, 45% (67 of 150) of MSM had 86 persistent HR-HPV and 55% (83 of 150) cleared all baseline HR-HPV. HPV16 (21%), HPV45 (13%), and HPV51 (12%) were the most persistent. Persistence of any HR-HPV was nonsignificantly higher in MC-1 (odds ratio [OR], 1.6; 95% CI, 0.8 to 3.1). Persistent HPV16 was more abundant in MC-2 versus MC-1 (OR, 3.9; 95% CI, 1.2 to 12.0), whereas HPV45 and HPV51 were similarly distributed across both MCs. Compared with HIV-uninfected, persistence (OR, 1.6; 95% CI, 0.8 to 3.3) and MC-2 membership (OR, 1.3; 95% CI, 0.8 to 2.0) were nonsignificantly higher among HIV-infected participants. CONCLUSION Anal HPV16 has the highest annual persistence and is associated with a low Prevotella anal microbiota, a potentially modifiable cofactor.