After Antiretroviral Therapy Initiation Research Articles

Survival analysis of PLWHA undergoing combined antiretroviral therapy: exploring long-term prognosis and influencing factors.

The survival time of human immunodeficiency virus (HIV)-infected individuals or patients with acquired immunodeficiency syndrome (AIDS) is influenced by multiple factors. Studying survival and influential factors after antiretroviral therapy (ART) contributes to improving treatment protocols, management strategies, and prognosis for people living with HIV/AIDS (PLWHA). This retrospective cohort study collected case data and follow-up records of PLWHA who received ART in Dazu District, Chongqing City, between 2007 and 2022. Cumulative survival rates were calculated using life tables. Survival curves were plotted using the Kaplan-Meier method. Uni-variable and multivariable Cox proportional hazards models analyzed factors influencing survival. The study included 5,237 PLWHA receiving ART. Within the first year of ART initiation, 146 AIDS-related deaths occurred, accounting for 29.49% (146/495) of total deaths. Cumulative survival rates at 1, 5, 10, and 15 years were 0.97, 0.90, 0.85, and 0.79, respectively. During the observation period, male patients who received ART had a 1.89 times higher risk of death compared to females (aHR, 1.89; 95%; CI, 1.50-2.37). Patients aged ≥60 years had a 3.44-fold higher risk of death than those aged <30 years (aHR, 3.44; 95% CI, 1.22-9.67). Injection drug users (aHR, 4.95; 95% CI, 2.00-12.24) had a higher risk of death than those with heterosexual (aHR, 1.60; 95% CI, 0.69-3.72) and homosexual transmission. Patients with a baseline CD4+ T lymphocyte count <200 cells/μL (aHR, 8.02; 95% CI, 4.74-13.57) and between 200 and 349 cells/μL (aHR, 2.14; 95% CI, 1.26-3.64) had a higher risk of death than those with ≥350 cells/μL. Patients with ART initiation at WHO clinical stage IV had a 2.48-fold higher risk of death than those at stage I (aHR, 2.48; 95% CI, 1.17-5.23). The first year following ART initiation is critical in HIV/AIDS treatment, emphasizing the need for intensified follow-up and monitoring to facilitate successful immune system reconstruction. Older age, male sex, injection drug use, baseline CD4+ T lymphocyte count <200 cells/μL, and WHO clinical stage IV are associated with an increased risk of death. Tailored treatment and management strategies should be implemented for patient populations at higher risk of mortality and with a poorer prognosis.

Incidence and Predicting Factors of Opportunistic Infections after Antiretroviral Therapy Initiation among Treatment-naïve Patients with HIV Infection: A Retrospective Cohort Study in A Tertiary Care Hospital.

To determine the incidence of opportunistic infections (OIs) and the predictive factors for the development of OIs after antiretroviral therapy (ART) initiation among treatment-naïve patients with HIV infection. Of 401 HIV-infected patients, 38 (9.5%) HIV-infected patients developed OIs after initiating ART, with an incidence rate of 25.6/1000 person-years. The median time (IQR) from ART initiation to OI occurrence was 26.5 (14-73) days. In multivariate Cox proportional hazard regression, body mass index ≤18.5 kg/m2 (adjusted hazard ratio [aHR] 2.28, 95% confidence interval [CI] 1.18-4.42, P = .015), symptoms at presentation (aHR 13.59, 95% CI 3.24-56.9, P < .001), serum glutamate-pyruvate transaminase >55 U/L (aHR 2.09, 95% CI 1.06-4.15, P = .035), and initiation of a dolutegravir-based regimen (aHR 4.39, 95% CI 1.54-12.48, P = .006) were significantly associated with OIs after ART initiation. OIs after ART initiation are common. Malnutrition, symptomatic presentation, abnormal liver enzymes, and DTG-based regimens are predictors of OI occurrence after ART initiation. Physicians must monitor and appropriately treat OIs after ART initiation.

The burden of anemia among Chinese HIV-infected patients following the initiation of antiretroviral therapy in the treat-all era: a nationwide cohort study

BackgroundTo assess the prevalence of anemia before and after antiretroviral therapy (ART) initiation and to identify impact of anemia on mortality among HIV-infected patients in China during the Treat-All era.MethodsAll HIV-infected patients who newly initiated ART between January 1, 2017 and December 31, 2020 were enrolled and followed up to December 31, 2021 in China. We analyzed the prevalence of anemia before and after ART initiation. Generalized estimating equations were fitted to determine factors associated with anemia after ART. Time-dependent cox proportional hazards models were performed to estimate the effect of anemia on death.ResultsOf 436,658 patients at the baseline of ART initiation, the overall prevalence of anemia was 28.6%. During a median 2.65 (IQR: 1.80–3.51) years of follow-up after ART initiation, 376,325 (86.2%) patients had at least one Hb measurement (a total of 955,300 hemoglobin measurements). The annual prevalence of anemia after ART was 17.0%, 14.1%, 13.4%, 12.6% and 12.7%, respectively. Being anemic at the baseline of ART initiation (adjusted odds ratio, aOR = 6.80, 95% confidence interval (CI): 6.67–6.92) was the strongest factor associated with anemia after ART. Anemia status after ART showed a strong association with death after multivariable adjustment (mild anemia: adjusted hazard ratio (aHR) = 2.65, 95% CI: 2.55–2.76; moderate anemia: aHR = 4.60; 95% CI:4.40–4.81; severe anemia: aHR = 6.41; 95% CI:5.94–6.91).ConclusionsIn the era of ART universal access, pre-ART anemia was common among HIV-infected patients. Notably, a certain proportion of anemia still persisted after ART, and was significantly associated with death. We recommend strengthening the monitoring of patients at risk of anemia, especially in patients with baseline anemia or during the first year of ART, and timely treatment for correcting anemia.

Attrition one year after starting antiretroviral therapy before and after the programmatic implementation of HIV “Treat All” in Sub-Saharan Africa: a systematic review and meta-analysis

IntroductionEvidence on the real-world effects of “Treat All” on attrition has not been systematically reviewed. We aimed to review existing literature to compare attrition 12 months after antiretroviral therapy (ART) initiation, before and after “Treat All” was implemented in Sub-Saharan Africa and describe predictors of attrition.MethodsWe searched Embase, Google Scholar, PubMed, and Web of Science in July 2020 and created alerts up to the end of June 2023. We also searched for preprints and conference abstracts. Two co-authors screened and selected the articles. Risk of bias was assessed using the modified Newcastle–Ottawa Scale. We extracted and tabulated data on study characteristics, attrition 12 months after ART initiation, and predictors of attrition. We calculated a pooled risk ratio for attrition using random-effects meta-analysis.ResultsEight articles and one conference abstract (nine studies) out of 8179 screened records were included in the meta-analysis. The random-effects adjusted pooled risk ratio (RR) comparing attrition before and after “Treat All” 12 months after ART initiation was not significant [RR = 1.07 (95% Confidence interval (CI): 0.91–1.24)], with 92% heterogeneity (I2). Being a pregnant or breastfeeding woman, starting ART with advanced HIV, and starting ART within the same week were reported as risk factors for attrition both before and after “Treat All”.ConclusionsWe found no significant difference in attrition before and after “Treat All” one year after ART initiation. While “Treat All” is being implemented widely, differentiated approaches to enhance retention should be prioritised for those subgroups at risk of attrition.PROSPERO numberCRD42020191582.

Characteristics and short- and long-term direct medical costs among adults with timely and delayed presentation for HIV care in the Netherlands.

In Europe, half of people living with HIV (PLWH) present late to care, with associated higher morbidity and mortality. This study aims to assess short- and long-term costs of HIV-care based on time of presentation and identify other factors contributing to higher costs in the first and fifth year after antiretroviral therapy (ART) initiation. We included ATHENA cohort data which prospectively includes 98% of PLWH in the Netherlands. PLWH who initiated ART in 2013 were included and followed over five years. PLWH were divided in three categories based on CD4 cell-count at time of ART initiation: timely presentation (CD4>350cells/μL), late presentation (CD4 200-350cells/μL or >350cells/μL with AIDS-defining illness) and very late presentation (CD4<200cells/μL). The total HIV-care cost was calculated distinguishing ART medication and non-ART medication costs (hospitalization, outpatient clinic visits, co-medications, and HIV-laboratory tests). From 1,296 PLWH, 273 (21%) presented late and 179 (14%) very late. Nearly half of those who entered HIV-care in a very late stage were of non-Dutch origin, with 21% originating from sub-Saharan Africa. The mean cost per patient in the first year was €12,902 (SD€11,098), of which about two-thirds due to ART (€8,250 (SD€3,142)). ART costs in the first and fifth year were comparable regardless of time of presentation. During the first year on treatment, non-ART medication costs were substantially higher among those with late presentation (€4,749 (SD€8,009)) and very late presentation (€15,886 (SD€ 21,834)), compared with timely presentation (€2,407(SD€4,511)). Higher non-ART costs were attributable to hospitalization and co-medication. The total non-ART costs incurred across five years on treatment were 56% and 246% higher for late and very late presentation respectively as compared to timely presentation. Very late presentation is associated with substantial costs, with non-ART costs nearly seven times higher than for those presenting timely. Hospitalization and co-medication costs are likely to continue to drive higher costs for individuals with late presentation into the future. Programs that identify individuals earlier will therefore likely provide significant short- and long-term health cost savings.

Double-Negative T Cell Number and Phenotype Alterations Before and After Effective Antiretroviral Treatment in Persons Living with HIV.

Double-negative (DN) T cells represent a small and phenotypically heterogeneous population that display regulatory functions. In HIV infection, DN T cells are decreased in peripheral blood and have been negatively associated with T cell activation. This study was aimed at describing the dynamics and phenotypic characteristics of DN T cells in peripheral blood of people living with HIV (PLHIV) before and after antiretroviral therapy (ART) initiation. We included 41 newly diagnosed, ART-naive individuals with advanced HIV infection, who were followed up for 6 months after ART initiation. The control group included 34 people without HIV (PWHIV), on preexposure prophylaxis for HIV infection. DN T cells in peripheral blood were characterized by flow cytometry. The absolute counts of DN T cells were lower in PLHIV than in PWHIV (p = 0.0223), and were particularly low in individuals with advanced HIV disease (p = 0.0311). Activation of DN T cells before ART initiation was directly associated with viral load (VL) (p = 0.0081, r = 0.4083) and inversely associated with CD4+ T cell counts (p = 0.0004, r = -0.4041). Compared with PWHIV, DN T cells of PLHIV expressed higher levels of CD57 (p = 0.0019), Ki67 (p = 0.0065), PD-1 (p = 0.0187), and CD38/HLA-DR (p < 0.0001). After 6 months on ART, expression of Ki67, PD-1, and CD38/HLA-DR on DN T cells returned to similar levels to those observed in PWHIV (p > 0.05 in all cases). However, expression of CD57 decreased only in individuals that start ART with high VL (p = 0.0127). DN T cell counts are decreased in HIV infection. Low DN T cell counts remained despite ART-induced immune reconstitution and viremia control. DN T cell phenotype is altered during chronic untreated infection with a high proportion of proliferating, activated, exhausted, and senescent cells. Most markers return to levels similar to those observed in PWHIV after ART. The impact of altered phenotype of DN T and their regulatory functions warrants further exploration.

Rate, risk factors and estimations of time to develop severe acute malnutrition after children receiving antiretroviral therapy at selected health facilities in northwest Ethiopia.

Severe acute malnutrition (SAM) affects up to 50 % of children with HIV, especially those who reside in resource-constrained healthcare setting like Ethiopia. During subsequent follow-up of children factors related to incidence of SAM after antiretroviral therapy (ART) is set on, however, there is no prior evidence. An institution-based retrospective cohort study was employed among 721 HIV-positive children from 1 January to 30 December 2021. Data were entered using Epi-Data version 3.1 and exported to STATA version 14 for analysis. Bi-variable and multivariable Cox-proportional hazard models were employed at 95 % confidence intervals to identify significant predictors for SAM. According to this result, the overall mean (±sd) age of the participants was found to be 9⋅83 (±3⋅3) years. At the end of the follow-up period, 103 (14⋅29 %) children developed SAM with a median time of 30⋅3 (13⋅4) months after ART initiation. The overall incidence density of SAM was found to be 5⋅64 per 100 child (95 % CI 4⋅68, 6⋅94). Children with CD4 counts below the threshold [AHR 2⋅6 (95 % CI 1⋅2, 2⋅9, P = 0⋅01)], disclosed HIV status [AHR 1⋅9 (95 % CI 1⋅4, 3⋅39, P = 0⋅03)] and Hgb level ≤10 mg/dl [AHR 1⋅8 (95 % CI 1⋅2, 2⋅9, P = 0⋅03)] were significant predictors for SAM. Significant predictors of acute malnutrition were having a CD4 count below the threshold, children who had previously reported their HIV status, and having haemoglobin <10 mg/dl. To ensure better health outcomes, healthcare practitioners should improve earlier nutritional screening and consistent counselling at each session of care.

Longitudinal decline of plasma neurofilament light levels after antiretroviral initiation in people living with HIV.

This retrospective follow-up study aims to investigate the dynamic longitudinal change of plasma neurofilament light (NfL) levels after antiretroviral therapy (ART) initiation in a cohort of people living with human immunodeficiency virus (HIV) (PWH). We tested a convenience sample of 116 patients from the NORTHIV study. Plasma NfL levels-measured using Single molecule array (Simoa) technology-as well as other laboratory parameters were collected at baseline, weeks 4, 48, 96, and 144. Linear mixed-effects models were estimated to evaluate longitudinal change over time. Baseline CD4+ T-cell levels, CDC classification, and HIV RNA levels were considered. Models were adjusted by age, sex, treatment regimen, and baseline serum creatinine levels. Plasma NfL levels were higher at baseline and also declined faster during the follow-up for participants with CD4+ count <100 cells/µl compared with >100 cells/µl. No significant difference was found between the CD4+ strata 100-199 and 200-499/µl. Participants with CDC classification stages B and C had higher levels of plasma NfL at baseline, as well as faster decline compared with participants with stage A. No significant main effects or change over time was found in baseline HIV RNA levels, treatment regimen, or sex. Plasma NfL is a sensitive biomarker to assess ongoing central nervous system injury in PWH. Plasma NfL concentrations decline relatively fast following ART initiation and then stabilize after 48 weeks. Plasma NfL concentrations are associated with CD4+ count and stage of HIV disease. No correlations were seen with different ART regimens.

How soon should patients be eligible for differentiated service delivery models for antiretroviral treatment? Evidence from a retrospective cohort study in Zambia

ObjectivesPatient attrition is high the first 6 months after antiretroviral therapy (ART) initiation. Patients with <6 months of ART are systematically excluded from most differentiated service delivery (DSD) models, which...

Association Between Body Mass Index Variation and Early Mortality Among 834 Ethiopian Adults Living with HIV on ART: A Joint Modelling Approach.

Body mass index (BMI) is a simple and cost-effective tool for monitoring the clinical responses of patients living with human immunodeficiency virus (HIV) after antiretroviral therapy (ART) initiation, especially in resource-limited settings where access to laboratory tests are limited. Current evidence on the association between longitudinal BMI variation and clinical outcomes among adults living with HIV receiving ART is essential to inform clinical guidelines. Therefore, this study examines the association between BMI variation and premature mortality in adults living with HIV on ART. An institution-based retrospective cohort study was conducted among 834 adults living with HIV receiving ART from June 2014 to June 2020 at Debre Markos Comprehensive Specialized Hospital in Northwest Ethiopia. We first identified predictors of mortality and BMI variation using proportional hazards regression and linear mixed models, respectively. Then, the two models were combined to form an advanced joint model to examine the effect of longitudinal BMI variation on mortality. Of the 834 participants, 49 (5.9%) died, with a mortality rate of 4.1 (95% CI 3.1, 5.4) per 100 person-years. A unit increase in BMI after ART initiation corresponded to an 18% reduction in mortality risk. Patients taking tuberculosis preventive therapy (TPT), mild clinical disease stage, and changing ART regimens were at lower risk of death. However, patients with ambulatory/bedridden functional status were at higher risk of death. Regarding BMI variation over time, patients presenting with opportunistic infections (OIs), underweight patients, patients who started a Dolutegravir (DGT)-based ART regimen, and those with severe immunodeficiency had a higher BMI increase over time. However, patients from rural areas and overweight/obese patients experienced a lower BMI increase over time. BMI improvement after ART initiation was strongly associated with a lower mortality risk, regardless of BMI category. This finding implies that BMI may be used as a better predictor tool for death risk in adults living with HIV in Ethiopia. Additionally, patients who took a DGT-based ART regimen had a higher BMI increase rate over time, which aligns with possible positive effects, such as weight gain, of the DGT-based ART regimen in developing countries.

Obesity-Related Single-Nucleotide Polymorphisms and Weight Gain Following First-Line Antiretroviral Therapy.

We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH). Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models. A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020). Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.

Improvement of liver metabolic activity in people with advanced HIV after antiretroviral therapy initiation.

Objective:Evaluating hepatic metabolic changes in people with HIV (PWH) with advanced disease, before and after antiretroviral therapy (ART) initiation, using [18F]-fluorodeoxyglucose (FDG) PET-computed tomography (PET/CT). FDG PET/CT noninvasively quantifies glucose metabolism in organs.Design/methods:Forty-eight viremic PWH (CD4+ cell counts <100 cells/μl) underwent FDG PET/CT at baseline and approximately 6 weeks after ART initiation (short-term). Twenty-seven PWH participants underwent follow-up scans 2 years after treatment (long-term). FDG PET/CT scans from 20 healthy controls were used for comparison. Liver FDG uptake was quantified from the PET/CT scans. Imaging findings as well as clinical, laboratory, and immune markers were compared longitudinally and cross-sectionally to healthy controls.Results:Liver FDG uptake was lower at baseline and short-term in PWH compared with controls (P < 0.0001). At the long-term scan, liver FDG uptake of PWH increased relative to baseline and short-term (P = 0.0083 and 0.0052) but remained lower than controls’ values (P = 0.004). Changes in FDG uptake correlated negatively with levels of glucagon, myeloperoxidase, sCD14, and MCP-1 and positively with markers of recovery (BMI, albumin, and CD4+ cell counts) (P < 0.01). In multivariable analyses of PWH values across timepoints, BMI and glucagon were the best set of predictors for liver FDG uptake (P < 0.0001).Conclusion:Using FDG PET/CT, we found decreased liver glucose metabolism in PWH that could reflect hepatocytes/lymphocytes/myeloid cell loss and metabolic dysfunction because of inflammation. Although long-term ART seems to reverse many hepatic abnormalities, residual liver injury may still exist within 2 years of treatment initiation, especially in PWH who present with low nadir CD4+ cell counts.

A Heavy Burden: Preexisting Physical and Psychiatric Comorbidities and Differential Increases Among Male and Female Participants After Initiating Antiretroviral Therapy in the HIV Outpatient Study, 2008-2018.

Attention to non-AIDS comorbidities is increasingly important in the HIV care and management in the United States. We sought to assess comorbidities before and after antiretroviral therapy (ART) initiation among persons with HIV (PWH). Using the 2008-2018 HIV Outpatient Study (HOPS) data, we assessed changes in prevalence of physical and psychiatric comorbidities, by sex, among participants initiating ART. Cox proportional hazards models were fit to investigate factors associated with the first documented occurrence of key comorbidities, adjusting for demographics and other covariates, including insurance type, CD4+ cell count, ART regimen, and smoking status. Among 1,236 participants who initiated ART (median age 36 years, CD4 cell count 375 cells/mm3), 79% were male, 66% non-white, 44% publicly insured, 53% ever smoked, 33% had substance use history, and 22% had body mass index ≥30 kg/m2. Among females, the percentages with at least one condition were: at ART start, 72% had a physical and 42% a psychiatric comorbidity, and after a median of 6.1 years of follow-up, these were 87% and 63%, respectively. Among males, the percentages with at least one condition were: at ART start, 61% had a physical and 32% a psychiatric comorbidity, and after a median of 4.6 years of follow-up, these were 82% and 53%, respectively. In multivariable Cox proportional hazards analyses, increasing age and higher viral loads (VL) were associated with most physical comorbidities, and being a current/former smoker and higher VL were associated with all psychiatric comorbidities analyzed. HOPS participants already had a substantial burden of physical and psychiatric comorbidities at the time of ART initiation. With advancing age, PWH who initiate ART experience a clinically significant increase in the burden of chronic non-HIV comorbidities that warrants continued surveillance, prevention, and treatment.

A nomogram for predicting paradoxical immune reconstitution inflammatory syndrome associated with cryptococcal meningitis among HIV-infected individuals in China

BackgroundCryptococcal meningitis (CM) associated immune reconstitution inflammatory syndrome (CM-IRIS) is the second most common complication in HIV-infected individuals with cryptococcal meningitis, with a reported mortality rate ranging from 8 to 30%. Given the devastating consequences of CM-IRIS related intracranial neuroinflammation and its challenging in diagnosis, we conducted a study to explore the risk factors and the occurrence of paradoxical CM-IRIS in HIV-infected patients, which is of great value for prevention and clinical management.MethodsWe conducted a retrospective cohort study to identify the indicators associated with paradoxical CM-IRIS among 86 HIV-infected patients with CM using univariate and multivariate cox analysis. A nomogram was constructed using selected variables to evaluate the occurrence of paradoxical CM-IRIS at 6 months and 12 months after ART initiation. The discrimination and calibration of the nomogram were assessed by concordance index (C-index) and calibration plots. Decision curves analysis (DCA) were used to evaluate clinical effectiveness of the nomogram. Subsequently, to help clinicians recognize patients at high risk faster, patients were divided into high-risk and low-risk groups according to the best cutoff point identified by X-tile.ResultsOf 86 AIDS patients with CM, 22.1% experienced paradoxical CM-IRIS at a median of 32 days after antiretroviral therapy (ART) initiation. The occurrence of paradoxical CM-IRIS was associated with age, ART initiation within 4 weeks of antifungal treatment, a four-fold increase in CD4 T cell counts, C-reactive protein levels, and hemoglobin levels independently. These five variables were further used to construct a predictive nomogram. The C-index (0.876) showed the favorable discriminative ability of the nomogram. The calibration plot revealed a high consistency between the predicted and actual observations. DCA showed that the nomogram was clinically useful. Risk stratification based on the total score of the nomogram showed well-differentiated in the high-risk and low-risk groups. Clinicians should pay attention to patients with total points high than 273.ConclusionsWe identified the predictive factors of paradoxical CM-IRIS and constructed a nomogram to evaluate the occurrence of paradoxical CM-IRIS in 6 months and 12 months. The nomogram represents satisfactory performance and might be applied clinically to the screening and management of high-risk patients.

Weight change after antiretroviral therapy initiation among adults living with HIV in Northwest Ethiopia: a longitudinal data analysis

ObjectivesThe first objective was to explore weight change in the first 2 years after antiretroviral therapy (ART) initiation in adults living with HIV. The second objective was to identify the...

Treatment outcomes 12 months after antiretroviral therapy initiation in Oman: a nationwide study from the Middle East

ABSTRACT We used routinely collected programme data on people living with HIV in Oman who started ART in 2014–2018 to assess retention on ART, viral suppression, attrition (mortality or loss to follow-up [LTFU]) and treatment failure (attrition or HIV viral load of > 1000 copies/mL) 12 months after antiretroviral therapy (ART) initiation. We identified 726 patients; 72% were male. Overall, 12 months retention on ART and viral suppression (intention-to-treat [ITT] analysis) were 85.7% and 74.5%, respectively. Attrition occurred in 14.3% (mortality of 7% and LTFU of 7.3%). Retention increased from 78.8% (93/118) to 90.6% (144/159) among patients who started ART in 2014 and 2018, respectively. Similarly, ITT and on-treatment analyses revealed that viral suppression 12 months after ART initiation increased from 57.6% (68/118) and 73.1% (68/93) among patients who initiated therapy in 2014–80.5% (128/159) and 88.8% (128/144) among patients started treatment in 2018, respectively. On multivariate analysis, older age, having “Other” as an HIV risk factor (compared to heterosexual) and receiving HIV care outside the capital Muscat independently predicted both attrition and treatment failure. Our findings have been useful in identifying factors at the individual and programme level that influenced the risk of attrition and treatment failure.

Evidence of HIV-1 Genital Shedding after One Year of Antiretroviral Therapy in Females Recently Diagnosed in Bamako, Mali.

Little is known about the dynamic of HIV-1 shedding and resistance profiles in the female genital reservoir after antiretroviral therapy (ART) initiation in resource-limited countries (RLCs), which is critical for evaluating the residual sexual HIV-1 transmission risk. The present study aimed to evaluate the efficacy of 1 year duration ART at blood and genital levels in females newly diagnosed for HIV-1 from three centers in Bamako, Mali. Seventy-eight consenting females were enrolled at the time of their HIV-1 infection diagnosis. HIV-1 RNA loads (Abbott Real-Time HIV-1 assay) were tested in blood and cervicovaginal fluids (CVF) before and 12 months after ART initiation. Primary and acquired resistances to ART were evaluated by ViroseqTM HIV-1 genotyping assay. The vaginal microbiota was analyzed using IonTorrentTM NGS technology (Thermo Fisher Scientific). Proportions of primary drug resistance mutations in blood and CVF were 13.4% and 25%, respectively. Discrepant profiles were observed in 25% of paired blood/CVF samples. The acquired resistance rate was 3.1% in blood. At month 12, undetectable HIV-1 RNA load was reached in 84.6% and 75% of blood and CVF samples, respectively. A vaginal dysbiosis was associated with HIV RNA shedding. Our findings emphasize the need of reinforcing education to improve retention in care system, as well as the necessity of regular virological monitoring before and during ART and of implementing vaginal dysbiosis diagnosis and treatment in RLCs.

Ten-year attrition and antiretroviral therapy response among HIV-positive adults: a sex-based cohort analysis from eight West African countries.

IntroductionSex differences have already been reported in sub‐Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow‐up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults.MethodsWe used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no‐follow‐up and 10‐year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively.ResultsA total of 71,283 patients (65.8% women) contributed to 310,007 person‐years of follow‐up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10‐year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow‐up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10‐year attrition throughout the 10‐year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/μL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/μL in their sixth year of follow‐up, whereas men failed to reach it even at the end of the 10‐year follow‐up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%).ConclusionsIn West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex‐adapted are needed for patients in care to monitor attrition, detect early high‐risk groups so that they can stay in care with a durably controlled infection.

Redistribution of brain glucose metabolism in people with HIV after antiretroviral therapy initiation.

We evaluated brain glucose metabolism in people living with HIV (PWH) with [18F]-Fluoro-Deoxyglucose (FDG) PET/computed tomography (CT) before and after antiretroviral therapy (ART) initiation. We conducted a longitudinal study wherein ART-naive late-presenting untreated PWH with CD4+ cell counts less than 100 cells/μl were prospectively assessed for FDG uptake at baseline and at 4-8 weeks (n = 22) and 19-26 months (n = 11) following ART initiation. Relative uptake in the subcortical regions (caudate, putamen and thalamus) and cortical regions (frontal, parietal, temporal and occipital cortices) were compared across time and correlated with biomarkers of disease activity and inflammation, in addition to being compared with a group of uninfected individuals (n = 10). Before treatment initiation, putaminal and caudate relative FDG uptake values in PWH were significantly higher than in uninfected controls. Relative putaminal and thalamic uptake significantly decreased shortly following ART initiation, while frontal cortex values significantly increased. FDG uptake changes correlated with changes in CD4+ cell counts and viral load, and, in the thalamus, with IL-6R and sCD14. Approximately 2 years following ART initiation, there was further decrease in subcortical relative uptake values, reaching levels below those of uninfected controls. Our findings support pretreatment basal ganglia and thalamic neuroinflammatory changes in PWH, which decrease after treatment with eventual unmasking of long-term irreversible neuronal damage. Meanwhile, increased frontal cortex metabolism following ART initiation suggests reversible cortical dysfunction which improves with virologic control and increased CD4+ cell counts. Early initiation of treatment after HIV diagnosis and secondary control of inflammation are thus necessary to halt neurological damage in PWH.

Immune recovery after antiretroviral therapy initiation: a challenge for people living with HIV in Brazil.

Immune recovery reflects health conditions. Our goal was to estimate the time it takes to achieve immune recovery and its associated factors, in people living with HIV (PLHIV), after antiretroviral therapy (ART) initiation. A historical cohort study was performed among PLHIV (> 18 years-old) in Minas Gerais State, Brazil, using data from healthcare databases. Patients initiating ART between 2009-2018, with T-CD4+ lymphocytes and viral load recorded before and after antiretroviral therapy were included. The outcome is achievement of immune recovery, defined as the first T-CD4+ > 500 cells/µL after ART initiation. Explanatory variables were age, gender, place of residence, year of ART initiation, baseline viral load and T-CD4+, viral load status, and adherence to ART at follow-up. Descriptive analysis, cumulative, and person-time incidences of immune recovery were estimated. Median-time to immune recovery was estimated using Kaplan-Meier method. Factors associated with immune recovery were assessed by Cox regression. Among 26,430 PLHIV, 8,014 (30%) were eligible. Most were male (67%), mean age 38.7 years, resided in non-central region, median-baseline T-CD4+ = 228 cells/µL (< 200 cells/µL = 43%) and viral load median-baseline = 4.7 log10 copies/mL (detectable viral load = 99%). Follow-up time = 15,872 person-years. Cumulative and incidence rate were 58% (95%CI: 57-58) (n = 4,678) and 29.47 cases/100 person-years, respectively. Median-time to immune recovery was of 22.8 months (95%CI: 21.9-24.0). Women living with HIV, younger than 38 years of age, with T-CD4+ baseline > 200 cells/µL, detectable viral load (baseline), antiretroviral therapy-adherence and undetectable viral load (follow-up) were independently associated with immune recovery. Time to immune recovery remains long and depends on early treatment and antiretroviral therapy-adherence.