HIV-infected Adults Research Articles

Mortality and comorbidities in a Nationwide cohort of HIV-infected adults: comparison to a matched non-HIV adults' cohort, France, 2006-18.

Human immunodeficiency virus (HIV) remains a significant cause of morbidity and mortality worldwide. The aim of this study was to describe the mortality rate and associated comorbidities in a nationwide population-based cohort of persons living with HIV (PLWHIV) and to compare it with mortality in an age and gender-matched cohort of non-HIV individuals in France. Using data from the French national health data system, we identified and included 173712 PLWHIV (66.5% men) and 173712 non-HIV participants (66.5% men) matched for age and gender. PLHIV were identified based on ICD-10 HIV diagnoses, HIV-specific laboratory tests, and/or prescriptions for antiretroviral therapy specific to HIV. Hazard ratios (HRs) of mortality were assessed using multiple Cox regression models. During the 13 years of follow-up (2006-18), we observed 20018 deaths among PLWHIV compared with 6262 deaths among non-HIV participants (11.52% vs. 3.60%, P < 0.001). The over-mortality of PLWHIV was expressed by univariable HR = 2.135 (2.072-2.199), which remained significant after adjustment for region, Complementary Universal Health Insurance and AME, with multivariable HR = 2.182 (2.118-2.248). The results remained significant after adjusting for comorbidities, including infectious diseases [HR = 1.587 (1.538-1.638)]. Notably, PLWHIV were more importantly associated with mortality in women [HR = 2.966 (2.767-3.180)], compared in men [HR = 1.961 (1.898-2.027)]. Although the life expectancy of PLWHIV has globally increased, the causes of death should be prioritized in prevention policies and care management. Gender-specific policies should be highlighted, as we observed a higher impact of HIV mortality in women.

Comparison of short- and long-term humoral immune responses to pneumococcal polysaccharide and glycoconjugate vaccines in an HIV-infected population

Immunisation is recommended internationally to protect against pneumococcal infections in HIV-infected adults. However, vaccination schedule designs are mostly based on studies of initial rather than long-term antibody responses. This UK observational study investigated the short- and long-term antibody responses to polysaccharide and glycoconjugate pneumococcal vaccines in an adult HIV-infected cohort. We studied a subgroup of 152 of 839 participants from the AIR (Assessment of Immune Responses to Routine Immunisations in HIV-infected Adults, ISRCTN95588307) studythat had received pneumococcal vaccinationsand had blood samples collected pre- and post-vaccination, as well as at least annually for four subsequent calendar years. Patients received either Pneumovax-23 (PPV, N=89) or Prevenar-13 (PCV, N=63) as their primary vaccine, with immunity assessed by measuring IgG antibody concentrations for 12 pneumococcal polysaccharide serotypes (PnPS). The primary outcome was achieving IgG antibody concentrations above the recommended World Health Organisation (WHO) threshold of 0.35µg/mL for at least 8/12 of the PnPS assessed (WHO≥8/12PnPS). Patients who did not achieve WHO≥8/12PnPS after the primary vaccination were offered further vaccination with PCV; booster vaccinations with PCV were additionally offered to those where antibody levels subsequently fell below the WHO≥8/12PnPS threshold. Patients receiving PCV as their primary pneumococcal vaccine were significantly more likely to achieve WHO≥8/12PnPS after a single vaccine dose than those receiving PPV (54% vs. 33%, p=0.012). This difference persisted following booster vaccination with PCV, with cumulative rates of WHO≥8/12PnPS in those receiving PCV vs. PPV as the primary vaccine of 88% vs. 67% and 100% vs. 85% after receiving up to one and two booster vaccinations, respectively. Where WHO≥8/12PnPS was achieved, this persisted significantly longer in those receiving PCV as their primary vaccine compared to PPV (median: 23.5 vs. 11.1 months; p=0.010). Immunisation with PCV resulted in quantitatively greater antibody responses than immunisation with PPV in a cohort of HIV-infected UK adults. Individuals receiving PCV as their primary vaccine required fewer total pneumococcal vaccine doses to achieve WHO≥8/12PnPS and experienced greater duration of time above this threshold than those with PPV as the primary vaccine. However, the median longevity of both vaccine responses was relatively short, which supports the use of ongoing booster doses using high-valency glycoconjugate vaccines to sustain WHO≥8/12PnPS threshold antibody levels.

Electrocardiographic abnormalities and associated factors among HIV-infected adults on antiretroviral therapy.

Individuals living with HIV are at increased risk of developing cardiovascular diseases. This heightened vulnerability is influenced by various factors, including the direct impact of HIV infection, the side effects of HIV medications, and a higher presence of traditional cardiovascular risk factors. Detecting and managing cardiovascular diseases early in HIV-infected individuals is crucial for their overall health and well-being. Electrocardiography, a simple and non-invasive test, can provide valuable information in this regard. However, there is currently no published data on the prevalence of electrocardiographic abnormalities and the associated factors among HIV-infected adults in Ethiopia. This study was aimed at assessing the prevalence of ECG abnormalities and associated factors among HIV-infected adults on antiretroviral therapy. A hospital-based comparative cross-sectional study was conducted at Mettu Karl Specialized Hospital (MKSH), southwest Ethiopia, among 96 HIV-infected patients and 96 HIV-negative control groups. A systematic random sampling technique was used to select HIV-infected respondents, and HIV-negative respondents were purposively recruited from caregivers. A face-to-face interview with a semi-structured and pretested questionnaire was conducted to collect the socio-demographic and behavioral characteristics of the study participants. Electrocardiography was done for all study participants using a 12-lead electrocardiograph, interpreted by a cardiologist, and classified according to the Minnesota Code classification system. The data were entered into Epi-Data version 4.6 and exported to SPSS version 25 for analysis. Finally, descriptive statistics, chi-square, independent t-test, bivariable, and multivariable logistic regression analyses were done at a 5% significance level. The study found that 49% of HIV-infected and 19.8% of HIV-negative participants had at least one ECG abnormality. The proportion of coded ST-segment abnormalities, T-wave abnormalities, longer QT interval, and sinus tachycardia was significantly higher in HIV-infected respondents than in HIV-negatives. Being a smoker [AOR = 3.7, 95%CI: 1.03-13.6], being on Protease inhibitors [AOR = 3.6, 95%CI: 1.02-13.1] and having CD4 less than 350 cells/mm3 [AOR = 3.2, 95%CI: 1.22-8.49] were significantly associated with ECG abnormalities among HIV-infected respondents. Compared to HIV-negative participants, HIV-infected patients had a significantly higher prevalence of ECG abnormalities. Screening for ECG abnormalities is needed for the early detection of cardiac abnormalities and the reduction of future complications.

Subclinical atherosclerosis burden in carotid and femoral territories in HIV subjects: relationships with HIV and non-HIV related factors

BackgroundCardiovascular disease is a major cause of morbidity in an aging HIV population. However, risk estimation with the most frequent equations usually classifies HIV patients as having a low or moderate risk. Several studies have described a very high prevalence of subclinical atherosclerosis in a middle-aged, non-HIV population. There is insufficient body of knowledge to understand if this is the case in people living with HIV (PLWH). We aim to calculate the proportion of patients with subclinical atherosclerosis in a single site cohort of HIV-infected subjects.MethodsWe have analyzed chronically HIV infected adults (≥ 18 years) who were on active follow-up in an HIV unit specialized in the care of cardiovascular health. The most recent clinical visit and vascular ultrasonography were used to assess the objectives of our research. Our primary objective was to describe the proportion of participants with subclinical atherosclerosis (focal protrusion into the lumen > 0.5 mm or > 50% of the surrounding IMT or a diffuse thickness > 1.5 mm) in a single site cohort of PLWH. Carotid and iliofemoral territories were evaluated. As a secondary objective we have run a multivariate analysis to determine which HIV and non-HIV factors might be related with the presence of atherosclerotic plaques.FindingsWe included a total of 463 participants between November 2017 to October 2019. Subjects were predominantly male (84.2%) with a mean age of 48.8 years (SD 10.7). Hypercholesterolemia (36%) was the most prevalent comorbidity followed by Hypertension (18%) and Hypertriglyceridemia (16%). Mean duration of HIV infection is 12.3 years. Overall, participants had been receiving cART for a median of 9.5 years. Subclinical atherosclerosis was found in 197 subjects (42.5%; CI 95% [38.0–47.2]). The disease was found more frequently in the femoral arteries (37.8%) than in the carotid vascular bed (18.6%). Despite some HIV factors correlated with the presence of plaques in a univariate analysis (e.g., time with HIV-1 RNA > 50 copies/mL or time from HIV diagnosis), the only two explanatory factors that remained associated with the presence of atherosclerotic plaques in the multivariate analysis were smoking (OR 5.47, 95% CI 3.36 – 8.90) and age (OR 1.13, 95%CI 1.10 – 1.16).InterpretationWe have found a very high prevalence of subclinical atherosclerosis among our cohort of PLWH. Despite having analyzed several HIV factors, age and smoking have been found to be the only factors associated with the development of atherosclerotic plaques.

Prevalence of echocardiographic abnormalities in HIV-infected adults on long-term combination antiretroviral therapy.

Prevalence of echocardiographic abnormalities in HIV-infected adults on long-term combination antiretroviral therapy.

Antiretroviral adverse drug events reported among adult HIV patients in a Nigerian tertiary hospital: A retrospective study

Background: The use of Highly Active Antiretroviral Therapy (HAART) has changed HIV/AIDS from a near-certainly fatal illness to one that can be managed chronically. A significant constraint of HAART is the high prevalence of adverse drug events (ADE) among HIV patients taking them. Objectives: The study determined the frequency and severity of reported antiretroviral adverse events among HIV-infected adults (≥16 years) at the Institute of Human Virology (IHV) Clinic of Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, Nigeria, within five years. Antiretroviral therapies implicated in the reported adverse drug events were also determined. Method: Information on reported ADEs was extracted from the NAFDAC Pharmacovigilance forms in the Pharmacovigilance section of the IHV Clinic Pharmacy. The severity of ADEs was classified using the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) index for categorizing errors. Results: A hundred and nineteen (119) patients reported 161 ADEs within the 5-year study period (2017-2021). Most ADE reports came from females (74.53%) and patients 36-55 years old. Dizziness (31.1%), Rashes (14.3%), and Fatigue (13.0%) were prominent among all the ADE reports documented. TDF/3TC/EFV (57.8%) and AZT/3TC/NVP (11.8 %) combinations were the frequently implicated antiretroviral regimen. All the ADEs reported were mild (Category ‘E’). ADE reports appreciated in the second year and progressively declined afterwards. Conclusion: There is a need to improve the system for antiretroviral ADE reporting through sensitization and developing a specific tool that enhances ADE reports from patients and healthcare providers.

Food insecurity and its severity among adults receiving antiretroviral therapy in health facilities, northcentral Ethiopia: a multi-facility-based cross-sectional study.

Food insecurity plays a crucial role in predicting the spread of HIV due to the adverse effects of coping mechanisms adopted to mitigate it. However, there is a scarcity of context-specific evidence regarding food insecurity among HIV-infected adults. Therefore, this study aimed to assess the context-specific magnitude of food insecurity and associated factors among adults receiving antiretroviral therapy (ART) in health facilities in the North Shewa Zone, Ethiopia, ultimately contributing to the achievement of the 95-95-95 HIV treatment target in the local context. A multi-facility cross-sectional study was conducted among 865 HIV-infected adults receiving ART and being followed up for their treatment. We included health facilities that provide ART, including four hospitals and six health centers. A log-binomial regression model was fitted to identify the association between food insecurity and independent variables. Adjusted prevalence ratios (APRs) with a 95% confidence interval were computed to measure the strength of the association. In this study, 290 (33.7, 95% CI: 30.60, 36.91) of the HIV-infected adults studied had food insecurity during their treatment and follow-up, of which 152 (52.41, 95% CI: 46.64, 58.13) and 110 (37.93%, CI: 32.50, 43.68) of them were found to have severe and moderate forms of food insecurity, respectively. We found that being younger (APR = 2.27, 95% CI: 1.12, 4.60), being female (APR = 1.87, 95% CI: 1.03, 3.39), lacking formal education (APR = 10.79, 95% CI: 14.74, 24.58), having lower educational status (APR = 5.99, 95% CI: 2.65, 13.54), being a daily laborer (APR = 6.90, 95% CI: 2.28, 20.85), having low monthly income (APR = 1.89, 95% CI: 1.11, 3.22), advanced WHO clinical stage (APR = 2.34, 95% CI: 1.08, 5.10), and receiving ART for less than 4 years (AOR = 2.28, 95% CI: 1.09, 4.74) were significantly associated with a high proportion of food insecurity among HIV-infected adults. The magnitude of food insecurity among HIV-infected adults receiving ART was high, with an extremely high magnitude of severe food insecurity. The finding suggests the need for culture- and context-specific nutritional interventions to address the gender dynamics of food insecurity, attention to the early stage of ART, and the integration of strategies to improve educational status and enhance income-generation activities of HIV-infected adults. This requires an emphasis on the link between food insecurity and HIV in Ethiopia's national food and nutrition policy.

Factors Influencing Uptake of HIV/AIDS Care and Support Services among HIV Infected Adults in Baringo County, Kenya

Factors Influencing Uptake of HIV/AIDS Care and Support Services among HIV Infected Adults in Baringo County, Kenya

Fruits and vegetables dietary intake and its estimated consumption among adults receiving antiretroviral therapy in health facilities in Northcentral Ethiopia: a multi-facility cross-sectional study.

Despite the significant role of fruit and vegetables (FAVs) in preventing a variety of chronic diseases and their potential to bolster immune responses and slow the progression of HIV infection to AIDS, there is a lack of studies on the dietary intake of FAVs among HIV-infected adults in Africa, including Ethiopia. Hence, this study aimed to investigate the magnitude of FAV intake and estimated consumption among HIV-infected adults receiving antiretroviral therapy (ART) in northcentral Ethiopia. A multifacility cross-sectional study was conducted on the FAV intake among 865 HIV-infected adults receiving ART. A Poisson regression model with robust variance was used to identify factors associated with FAVs dietary intake. The study indicated that 655 (76.34%; 95% CI: 73.38, 79.07) HIV-infected adults reported consuming FAVs less than once per day, with 838 (97.67%, 95% CI: 96.41, 98.49) and 676 (78.79%, 95% CI: 75.92, 81.40) HIV-infected adults reporting consuming fruits and vegetables less than once per day, respectively. The median (IQR) total FAV intake was 271.3 (IQR: 92.5, 439.5) g/day, with the median (IQR) intake of fruits being 248.1 (IQR: 100.0, 400.0) g/day and vegetables being 273.78 (IQR: 82.44, 348.33) g/day, respectively. We found that being divorced (APR = 1.57, 95% CI: 1.16, 2.12), employed as a daily laborer (APR = 2.08, 95% CI: 1.36, 3.20), being employed (APR = 1.77, 95% CI: 1.10, 2.84), merchants (APR = 1.59, 95% CI: 1.03, 2.47), having children as caregivers (APR = 1.61, 95% CI: 1.02, 2.55), an advanced WHO clinical stage (APR = 1.32, 95% CI: 1.32(1.03, 1.69), and receiving ART for more than 8 years (APR = 1.78, 95% CI: 1.18, 2.67) were found to be independent predictors of FAV dietary intake among HIV-infected adults. From the findings, we understood that farmers were less likely to consume FAVs compared to employed individuals, daily laborers, and merchants. The finding indicated a very low level of FAV dietary intake among HIV-infected adults receiving ART, falling well-below the minimum recommendation for physically active adults. Despite living in areas with surplus production and producing these items, farmers are less likely to consume FAV. The study emphasizes the importance of focusing on the early stage of ART treatment for patients and family therapy, including counseling and guidance on consuming healthy diets such as FAVs, to enhance the role of children as caregivers for their families. Additionally, there is a need for comprehensive nutritional counseling to improve FAV consumption, with a particular emphasis on educating individuals about portion size estimation for the consumption of FAVs.

Population Pharmacokinetic Analysis of Dolutegravir in Treatment-Experienced Adults Living with HIV-1.

The World Health Organization has recommended the use of dolutegravir (DTG) for both first and second-line antiretroviral treatment in both adults and children down to 4 weeks of age. We developed a population pharmacokinetic(PopPK) model following oral administration of DTG 50 mg QD and 50 mg BID in HIV-infected treatment-experienced adults (607) based on pooled data from four phase 2/3 trials. DTG population pharmacokinetics are described by a one-compartment model with first-order absorption, absorption lag-time, and first-order elimination. The PopPK parameter estimates were apparent oral clearance (CL/F) = 1.00 L/h, apparent volume of distribution (V/F) = 18.9 L, absorption rate constant (Ka) = 1.99 per hour, and absorption lag time = 0.333 h, respectively. The final model included inter-individual and inter-occasion variability on apparent clearance (CL/F). Weight, smoking status, use of metabolic inducers as part of background antiretroviral therapy (ART) classified by their level of induction, use of atazanavir or atazanavir-ritonavir as part of background ART, and albumin level were predictors of CL/F; weight and albumin level were predictors of V/F; and sex and concomitant use of metal cation-containing vitamin/mineral supplements were predictors of relative bioavailability (F). The current model-based analysis suggests that the DTG dose adjustment is not required based on the demographics, laboratory values, smoking status, concomitant use of mild metabolic inducers or inhibitors in the background therapy, or use of metal cation-containing vitamin/mineral supplements because these covariate effects are not predicted to have a clinically relevant impact on safety and efficacy.

Evaluation of viral suppression and medication-related burden among HIV-infected adults in a secondary care facility

BackgroundPeople living with HIV/AIDS (PLHIV) are prone to other health issues that may result from the disease or antiretroviral medicines. These persons experience other psychosocial aspects of the illness, which may negatively affect their quality of life and overall treatment outcomes. This study assessed the medication-related burden and virological response of adult PLHIV. MethodThis cross-sectional study involved 417 HIV-positive adults who had been on combined antiretroviral therapy for at least a year at the State Specialist Hospital Gombe. Nigeria. Patient medication experience was measured using the Living with Medication Questionnaire version-3 (LMQ-3). Virological suppression was assessed at viral loads <1000 copies/ml and 20 copies/ml for undetectable HIV RNA levels. The LMQ-3 scores were compared with the participants' characteristics using independent t-tests or one-way analysis of variance (ANOVA). Regression analyses was employed to identify the predictors of viral suppression and medication-related burden. P value <0.05 at 95% confidence interval was considered statistically significant. ResultsOf the 417 PLHIV included in this study, 271 (65%) were classified as WHO Stage 1 ART initiation, 93.8% achieved viral suppression with 291 (69.5%) whom were females. The majority of patients 382 (91.6%) were on a dolutegravir-based regimen, had no tuberculosis diagnosis at antiretroviral therapy (ART) initiation (82.5%) and were 6–10 years on ART (46.3%). Only 67.6% of the population had a moderate medication-related burden. Female sex (p < 0.0005), unsuppressed viral load (p = 0.01), second-line ART (p = 0.03), tuberculosis at ART initiation (p = 0.02), and employment (p = 0.003) were significantly associated with medication-related burden. The predictor of viral suppression was high degree of medication-related burden (AOR, 0.12; 95% CI, 0.02–0.59) while unsuppressed viral load (p = 0.01) and female gender (p = 0.002) were independent predictors of medication related burden. ConclusionThe findings from this study revealed that majority of the patients achieved viral suppression with moderate degree of medication-related burden. Targeted interventions should be directed toward younger patients, females and patients with unsuppressed viral loads.

The Comorbidity of HIV and Diabetes among HIV Patients Attending Katsina General Hospital, Katsina State, Nigeria

Study’s Novelty/Excerpt This study focuses on the prevalence of diabetes among HIV patients specifically attending the antiretroviral therapy (ART) center of Katsina General Hospital, providing localized insights previously unreported. Unlike broader studies, this research uniquely highlights the inadequacies in diabetes diagnosis within this specific ART center, emphasizing the need for more rigorous screening protocols. Additionally, the study’s identification of specific factors such as older age, higher BMI, higher viral load, alcohol use, and duration on antiretroviral therapy as increasing the odds of diabetes offers targeted avenues for improving patient care and outcomes in similar clinical settings. Full Abstract Assessing the magnitude of diabetes, a disease that accounts for increasing morbidity and mortality among HIV patients, would help reduce financial losses incurred in treating the disease, considering that the disease is mostly reported when acute and chronic complications are about to begin. This study was conducted to identify the prevalence of diabetes among patients attending the antiretroviral (ART) center of Katsina General Hospital. The study aimed to identify the prevalence of diabetes among HIV patients to identify whether new cases are always recorded or otherwise in the study center. Two hundred (200) HIV-infected adults (aged ≥ 18) who had been on antiretroviral therapy for at least six months in the hospital were recruited. Participants’ demographics, HIV characteristics, the presence of diabetes via self-report, clinic folders, and measurement of their plasma fasting glucose and insulin levels on the day of the interview were evaluated. The magnitude of diabetes comorbidity was 3%. There was a weak positive relationship between fasting plasma glucose and alcohol (r=0.004), age (r=0.04), low-density lipoprotein (r=0.01), cholesterol (r=0.01), and viral load (r=0.032). Therefore, these factors are associated with increased odds of having diabetes. Thus, older age, higher BMI, higher viral load, alcohol, and duration on antiretroviral therapy increase the odds of having diabetes among HIV-positive adults. A lower prevalence of diabetes in clinic folders was found, for instance, indicating inadequate diagnosis of the disease in the center. Screening for the incidences of diabetes, addressing modifiable risk factors, and providing integrated care in the center would help improve the quality of life of comorbid patients.

Assessment of Diabetic and Inflammatory Markers in HIV Infected Adults with and without Diabetes Mellitus in NAUTH, Nnewi, Nigeria

Assessment of Diabetic and Inflammatory Markers in HIV Infected Adults with and without Diabetes Mellitus in NAUTH, Nnewi, Nigeria

Biomarkers of mortality in adults and adolescents with advanced HIV in sub-Saharan Africa

One-third of people with HIV in sub-Saharan Africa start antiretroviral therapy (ART) with advanced disease. We investigated associations between immune biomarkers and mortality in participants with advanced HIV randomised to cotrimoxazole or enhanced antimicrobial prophylaxis in the Reduction of Early Mortality in HIV-Infected Adults and Children Starting Antiretroviral Therapy (REALITY) trial (ISRCTN43622374). Biomarkers were assayed using ELISA and Luminex. Associations between baseline values and all-cause 24-week mortality were analysed using Cox models, and for cause-specific mortality used Fine & Gray models, including prophylaxis randomisation, viral load, CD4, WHO stage, age, BMI, and site as covariates; and weighted according to inverse probability of selection into the substudy. Higher baseline CRP, IFN-γ, IL-6 and IP-10 were associated with higher all-cause mortality; and higher IL-23, IL-2 and RANTES with lower all-cause mortality. Associations varied by cause of death: tuberculosis-associated mortality was most strongly associated with higher CRP and sST2, and cryptococcosis-associated mortality with higher IL-4 and lower IL-8. Changes in I-FABP (p = 0.002), faecal alpha-1 antitrypsin (p = 0.01) and faecal myeloperoxidase (p = 0.005) between baseline and 4 weeks post-ART were greater in those receiving enhanced versus cotrimoxazole prophylaxis. Our findings highlight how the immune milieu shapes outcomes following ART initiation, and how adjunctive antimicrobials can modulate the gut environment in advanced HIV.

Highly active antiretroviral therapy is necessary but not sufficient. A systematic review and meta-analysis of mortality incidence rates and predictors among HIV-infected adults receiving treatment in Ethiopia, a surrogate study for resource-poor settings

BackgroundOwing to the introduction of highly active antiretroviral therapy (HAART), the trajectory of mortality and morbidity associated with human immunodeficiency virus (HIV) infection has significantly decreased in developed countries. However, this remains a formidable public health challenge for people living with HIV in resource-poor settings. This study was undertaken to determine the pooled person-time incidence rate of mortality, analyze the trend, and identify predictors of survival among HIV-infected adults receiving HAART.MethodsQuantitative studies were searched in PubMed, Embase, Scopus, Google Scholar, African Journals Online, and Web of Science. The Joana Briggs Institute critical appraisal tool was used to assess the quality of the included articles. The data were analyzed using the random-effects Dersimonian-Laird model.ResultsData abstracted from 35 articles involving 39,988 subjects were analyzed. The pooled person-time incidence rate of mortality (all-cause) was 4.25 ([95% uncertainty interval (UI), 3.65 to 4.85]) per 100 person-years of observations. Predictors of mortality were patients aged ≥ 45 years (hazard ratio (HR), 1.70 [95% UI,1.10 to 2.63]), being female (HR, 0.82 [95% UI, 0.70 to 0.96]), history of substance use (HR, 3.10 [95% UI, 1.31 to 7.32]), HIV positive status non disclosure (HR, 3.10 [95% UI,1.31 to 7.32]), cluster of differentiation 4 + T cell - count < 200 cells/mm3 (HR, 3.23 [95% UI, [2.29 to 4.75]), anemia (HR, 2.63 [95% UI, 1.32 to 5.22]), World Health Organisation classified HIV clinical stages III and IV (HR, 3.02 [95% UI, 2.29 to 3.99]), undernutrition (HR, 2.24 [95% UI, 1.61 to 3.12]), opportunistic infections (HR, 1.89 [95% UI, 1.23 to 2.91]), tuberculosis coinfection (HR, 3.34 [95% UI, 2.33 to 4.81]),bedridden or ambulatory (HR,3.30 [95% UI, 2.29 to 4.75]), poor treatment adherence (HR, 3.37 [95% UI,1.83 to 6.22]), and antiretroviral drug toxicity (HR, 2.60 [95% UI, 1.82 to 3.71]).ConclusionDespite the early introduction of HAART in Ethiopia, since 2003, the mortality rate has remained high. Therefore, guideline-directed intervention of identified risk factors should be in place to improve overall prognosis and increase quality-adjusted life years.

Determinants of longitudinal changes of CD4 cell count and survival time to death of HIV/AIDS patients treated at Yabelo General Hospital, the case of pastoralist area: Using joint modelling approach.

HIV/AIDS is a chronic disease that challenges public health worldwide and causes morbidity and mortality in humans. The main purpose of this study was to investigate the determinants of longitudinal changes in CD4 cell count and survival time to death among HIV/AIDS patients as adults from January 2016 to December 2019 at Yabelo General Hospital. The intellectual gap in this study was focused on the study area, which means that the study related to joint modeling doesn't exist in the pastoralist community of Borena. This study involved 293 adult HIV-infected adults that could be collected from the recorded patient chart data, and the study design is a retrospective cohort design. The study used a Cox proportional hazard model, a linear mixed effect model, and a joint model, which is the combination of both model processes. The joint model showed that longitudinal CD4 cell count is significantly associated with survival time (p-value = 0.0253). Covariates such as visiting time, age, weight, educational status, ART adherence, and functional status were statistically significant factors associated with mean changes in the CD4 cell count of HIV patients. WHO stage, educational status, place of residence, TB, family history, and opportunistic infection disease had a significant effect on the survival time of HIV patients. The estimated association parameter is a negative value, which indicates both outcomes are negatively associated, and higher values of the CD4 cell count are associated with better survival.

Chronic immune activation and accelerated immune aging among HIV-infected adults receiving suppressive antiretroviral therapy for at least 12 years in an African cohort

BackgroundHIV-associated alterations innate and adaptive immune cell compartments are reminiscent of the process of immune aging. ObjectivesWe described immune aging phenotypes among ART-treated HIV-infected adults relative to age-matched HIV-negative counterparts. MethodsIn a cross-sectional comparative study of HIV-infected adults with CD4≥500 cells/μl after at least 12 years of suppressive ART and age-and-gender-matched HIV-negative individuals, immune activation and immune aging phenotypes were measured, using multi-color flowcytometry. ResultsART-treated HIV-infected individuals had higher body mass index (P = 0.004), waist-hip circumference (P = 0.041), hip circumference (P < 0.001), and diastolic blood pressure (P = 0.012) and immune activation (CD4+CD38+HLADR+; median 4.15,IQR(1.030,14.6)] relative to the HIV-negative age-matched individuals [median 3.14,IQR(1.030, 6.68)]; P=0.0034. Immune aging markers [CD4+CD57+T-cells; median 13.00 IQR (0.45,64.1)] were higher among HIV-infected ART-treated adults<50 years relative to HIV-negative<50 years[median 8.020,IQR(0.004,21.2)]; P=0.0010. Naïve CD4 T-cells, Central memory CD4 T-cells, Terminal Effector Memory T cells (TEMRA: CD27−CD45RA + CCR7-) and immune senescence CD4/CD8+CD28-/CD57+ T-cells were similar among ART-treated HIV-infected individuals<45 years relative to 60 years-and-older HIV-negative counterparts≥; p = 0.0932, p = 0.05357, p = 0.0950 and p = 0.5714 respectively. ConclusionART-treated adults are immunologically two decades older than their HIV-negative counterparts. Accelerated immune aging among individuals aging with HIV underscores the need for an HIV cure to avert the unprecedented complications of accelerated immune senescence and the associated NCD risk in African settings with protracted exposure to endemic co-infections.

Antiretroviral Therapy Switch in HIV-Infected Adults from a Regional HIV/AIDS Center in NE Romania.

Background and Objectives: Antiretroviral therapy (ART) has revolutionized the management of HIV infection, transforming it from a once-debilitating disease to a chronic, manageable condition. However, challenges such as treatment resistance, medication side effects, and long-term tolerability persist, prompting the exploration of novel therapeutic approaches. We aimed to highlight the characteristics and related comorbidities of HIV/AIDS cases in which the antiretroviral therapy was modified. Material and Methods: A cross-sectional clinical investigation was conducted on adults diagnosed with HIV/AIDS who were hospitalized at the "St. Parascheva" Clinical Hospital of Infectious Diseases in Iasi in the Northeastern region of Romania. The timeframe under investigation was 1 January 2023 to 30 June 2023. Results: In the Northeastern part of Romania, from a total of 1692 patients in the active records, there were a total of 148 recorded cases of antiretroviral therapy switch in HIV-infected patients. The main reason for the ART switch was the simplification of the ART regimen (82 cases, 55.40%), viro-immunological failure (16 cases, 10.66%), other disturbances correlated to the ART regimen, dyslipidemia (34 cases 22.97%), depression (3 cases, 2.02%), suicide attempt (1 case, 0.67%), new situations, including the appearance of pregnancy (3 cases 2.02%), and tuberculosis (9 cases, 6.08%). ART before the switch was represented by protease inhibitors that accounted for 84 cases (56.75%) of the ART switch. Following the therapy switch, integrase inhibitor-based ART single-tablet regimens accounted for 43.91% (65 cases) of all changeovers, with non-nucleoside reverse transcriptase inhibitor regimens coming in second, in 63 cases, 42.66%. Conclusions: ART switch as an experimental therapy offers a promising approach to optimizing HIV treatment outcomes. By focusing on viral suppression and immune reconstitution, addressing treatment challenges, and exploring novel ARV agents, ART switch strategies aim to improve the overall health and well-being of individuals living with HIV.

Bridging dolutegravir clinical viral response across doses and formulations using model-based exposure-response analysis in pediatrics.

Dolutegravir (DTG) is a once-daily HIV-1 integrase inhibitor approved for the treatment of HIV-1 infection in adults and children from 4 weeks of age. The posology of DTG in children has been driven by exposure-matching relative to the adult dose for efficacy and safety. However, higher variability in pediatric exposures raises concern that efficacy may not be reliably extrapolated from adult trials. Therefore, we evaluated the relationship between DTG exposure and virologic response in children. A population exposure-response analysis using logistic regression for virologic response was undertaken based on DTG exposure and covariate data from 146 pediatric participants with HIV-1 from age at least 4 weeks to less than 18 years treated for up to 48 weeks with DTG in IMPAACT P1093 study. None of the DTG exposure metrics were predictive of virologic response over the range of exposures in this analysis. Of the covariates tested, viral load at least 100 000 copies/ml at enrolment was a significant predictor of virologic response showing a lower probability of achieving a virologic response of HIV-1 RNA less than 50 copies/ml compared with participants with viral load less than 100 000 copies/ml at enrolment. Baseline viral load was also a significant predictor at week 48 whereby the probability of achieving a virologic response at week 48 decreased with increasing baseline viral load. This exposure-response analysis suggests that DTG exposures in children are all above the plateau of the exposure-response relationship. These results suggest that matching pediatric pharmacokinetic exposure parameters to those in adults is a reasonable approach for dose determination of DTG-containing formulations in pediatrics.

Rapid decrease in IL-1Ra and IP-10 plasma levels following tuberculosis treatment initiation

ObjectivesMonitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation. MethodsANRS12394-LILAC-TB was a proof-of-concept prospective study: adults with a rifampicin-susceptible TB who are HIV-negative and HIV-infected documented by a positive Xpert MTB/RIF test were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interferon-γ–induced protein-10 and clusters of differentiation (CD) (scavenging CD163) were measured by commercial enzyme-linked immunosorbent assay kits. A Wilcoxon test for paired data was used for longitudinal comparisons. ResultsA total of 55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10 of 13 participants with HIV: 53 cells/mm3). Overall, 83% were considered in TB treatment success. Compared with baseline, the IL-1Ra plasma levels significantly decreased as soon as week (W) 1, independent of HIV status (−71% in HIV-positive vs −33% in HIV-negative; P <0.001). The IP-10 plasma levels significantly decreased at W1 and W2 compared with baseline (P <0.0001); however, that decrease was less marked in participants with HIV. ConclusionsOur findings suggest that measuring IL-1Ra plasma levels with a standard enzyme-linked immunosorbent assay technique at baseline and then 1 week after TB treatment onset could help clinicians to quickly assess TB treatment response.