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Background Antiretroviral therapy (ART) for HIV infection has evolved substantially. The development of long-acting drugs, such as cabotegravir (CAB) and rilpivirine (RPV) might improve treatment satisfaction among people living with HIV (PLWH). The real-world effectiveness of long-acting ART and its effect on patient satisfaction needs to be assessed. This study investigated antiviral effectiveness and treatment satisfaction in PLWH who switched from conventional to long-acting ART (CAB + RPV). Methods This prospective cohort study included PLWH aged 18 years and older who switched to CAB + RPV and received the injections every 8 weeks between June 2022 and May 2023, after a 4-week oral lead-in phase. The eligibility criteria included viral suppression, absence of hepatitis B virus (HBV) DNA, and no prior RPV resistance mutations. Clinical data, including renal, lipid, and glucose biomarker levels, were monitored from the baseline to 44 weeks after switching. Treatment satisfaction was assessed using the HIV Treatment Satisfaction Questionnaire. A linear mixed-effects model was used to estimate changes in clinical data from baseline. Results Thirty-eight male participants were enrolled. Some participants had detectable levels of viral replication; however, all participants maintained viral suppression (HIV-RNA < 50 copies/mL) at 44 weeks and no cases of virological failure were detected. The creatinine level decreased by − 0.04 mg/dL (95% confidence interval [CI]: − 0.07 to − 0.01), lipid and glucose profiles remained stable, and treatment satisfaction increased by 6.6 points (95% CI: 2.4 to 10.8) after switching to CAB + RPV. Conclusions Long-acting ART provides effective viral suppression and enhances treatment satisfaction in PLWH switching from conventional ART. Long-acting ART can improve patient well-being; however, patient selection and monitoring to prevent HBV-related complications are important.

Introduction Long-acting injectable antiretroviral treatment (LAI-ART) has emerged as a novel alternative to the burden of daily oral pills. The bi-monthly intramuscular injectable containing cabotegravir and rilpivirine holds the promise of improving adherence to ART. The perspectives of potential users of LAI-ART, the majority of whom reside in Eastern and Southern Africa, are still largely unexplored. We set out to understand the experiences of people with HIV (PWH) who received LAI-ART at Fort Portal Regional Referral Hospital in mid-Western Uganda for at least 12 months. Methods This qualitative study, conducted between July and August 2023, was nested within a larger study. We conducted four focus groups with 32 (out of 69) PWH who received intramuscular injections of cabotegravir and rilpivirine. In-depth interviews were held with six health workers who delivered LAI-ART to PWH. Data were analyzed by thematic approach broadly modeled on the five domains of the Consolidated Framework for Implementation Research (CFIR). Results There was high acceptability of LAI-ART (30 /32 or 94%) participants requested to remain on LAI-ART even after the end of the 12-month trial. Adherence to ART was reportedly improved when compared to daily oral treatment. Participants credited LAI-ART with; superior viral load suppression, redemption from the daily psychological reminder of living with HIV, enhanced privacy in HIV care and treatment, reduced HIV-related stigma associated with taking oral pills and that it absolved them from carrying bulky medication packages. Conversely, nine participants reported pain around the injection site and a transient fever soon after administering the injection as side effects of LAI-ART. Missed appointments for receiving the bi-monthly injection were common. Providers identified health system barriers to the prospective scale-up of LAI-ART which include the perceived high cost of LAI-ART, stringent cold chain requirements, physical space limitations, and workforce skills gaps in LAI-ART delivery as potential drawbacks. Conclusion Overall, PWH strongly preferred LAI-ART and expressed a comparatively higher satisfaction with this treatment alternative. Health system barriers to potential scale-up are essential to consider if a broader population of PWH will benefit from this novel HIV treatment option in Uganda and other resource-limited settings. Trial registration Trial Registry Number PACTR ID PACTR202104874490818 (registered on 16/04/2021).

Background The goal of antiretroviral therapy (ART) is to achieve a sustained HIV suppressed viral load. However, adolescents often present poor adherence to ART which is associated with lower rates of viral load suppression (VLS). The objective of this study was to determine the viral load suppression levels and the associated factors among adolescents living with HIV (ALHIV) and on ART in Eswatini. Methods We conducted cross-sectional analysis of data from 911 adolescents aged 10 to 19 living with HIV and on ART between the period January 2017 and September 2022. We collected data of demographic and clinical variables, using a standardized data abstraction tool. We defined viral load suppression as the latest viral load result of ≤ 1000 copies/ml. Univariable and bivariable logistic regression analysis was done to identify factors associated with VLS and factors with p  < 0.1 were included in the multivariable regression analysis to adjust for the confounding effect of other variables such as age, sex, and duration of ART. Factors with p  < 0.05 were considered statistically significant. Results Among the 911 participants, 60% (457) were female. The mean age of the participants was 16.3 years, with mean duration on ART of 1.8 years. Viral suppression was attained by 88.5% (806/911) of the participants. Residence in the Shiselweni region was an independent factor associated with viral load suppression (aOR 0.37; 95% CI 0.15–0.19; p˂0.027). Conclusion Low VLS is a risk factor for increased viral resistance and perpetuates HIV transmission within the population. Achieving viral suppression among ALHIV in Eswatini is challenging as data shows that VLS is way below the UNAIDS 95% cut off level among individuals on ART. This is particularly more problematic in the Shiselweni region, where viral suppression is lower than the other regions. Therefore, reinforcement of public health interventions is needed to improve treatment support for achieving sustained viral suppression among ALHIV in Eswatini.

Background Mother-to-child transmission is the primary cause of HIV cases among children. Antiretroviral therapy (ART) plays a critical role in preventing mother-to-child transmission and reducing HIV progression, morbidity, and mortality among mothers. However, after more than two decades of ART during pregnancy, the comparative effectiveness and safety of ART medications during pregnancy are unclear, and existing evidence is contradictory. This study aimed to assess the effectiveness and safety of different ART regimens among pregnant women living with HIV at preconception or during pregnancy. Methods We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. We included randomized trials that enrolled pregnant women living with HIV and randomized them to receive ART for at least four weeks. Pairs of reviewers independently completed screening for eligible studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Our outcomes of interest included low birth weight, stillbirth, preterm birth, mother-to-child transmission of HIV, neonatal death, and congenital anomalies. Network meta-analysis was performed using a random-effects frequentist model, and the certainty of evidence was evaluated using the GRADE approach. Results We found 14 eligible randomized trials enrolling 9,561 pregnant women. The median duration of ART uptake ranged from 6.0 to 17.4 weeks. No treatment was statistically better than a placebo in reducing the rate of neonatal mortality, stillbirth, congenital defects, preterm birth, or low birth weight deliveries. Compared to placebo, zidovudine (ZDV)/lamivudine (3TC) and ZDV monotherapy likely reduce mother-to-child transmission (odds ratio (OR): 0.13; 95% CI: 0.05 to 0.31, high-certainty; and OR: 0.50; 95% CI: 0.33 to 0.74, moderate-certainty). Moderate-certainty evidence suggested that ZDV/3TC was associated with decreased odds of stillbirth (OR: 0.47; 95% CI: 0.09 to 2.60). Conclusions Our analysis provides high- to moderate-certainty evidence that ZDV/3TC and ZDV are more effective in reducing the odds of mother-to-child transmission, with ZDV/3TC also demonstrating decreased odds of stillbirth. Notably, our findings suggest an elevated odds of stillbirth and preterm birth associated with all other ART regimens.

Background Long-acting injectable antiretroviral therapy (LAI ART) is a new, and innovative approach to HIV treatment, designed to address several challenges, including the adherence issues associated with daily oral ART. This review synthesizes existing literature on the barriers and strategies for implementing LAI ART in the sub-Saharan Africa region, while identifying key knowledge gaps and research priorities. Methods We performed a comprehensive literature search, encompassing electronic databases and grey literature sources. Our review included 18 studies published between 2014 and 2023, focusing on the acceptability, feasibility, effectiveness, and cost-effectiveness of LAI ART in SSA. A narrative synthesis approach was employed for reporting review findings. Results Our review revealed a high demand and acceptability of LAI ART among people living with HIV in SSA, particularly those facing stigma and discrimination. LAI ART can improve adherence, retention, and viral suppression while reducing pill burden and frequent clinic visits. Implementation challenges include lack of regulatory approval, high cost, limited supply chain, health system capacity, trained staff, and cold storage facilities. Further research on safety and efficacy, as well as efforts in advocacy, policy, and community engagement, are needed to ensure accessibility and equity. Conclusion This review highlights key knowledge gaps and research priorities essential for the successful implementation of LAI ART in sub-Saharan Africa. Addressing these gaps such as evaluating long-term outcomes, understanding drug resistance, and exploring the impact on sexual and reproductive health will be critical to ensuring the broader accessibility, effectiveness, and sustainability of LAI ART in the region. Further research on the experiences and preferences of different subgroups, as well as the interaction with other medications and co-infections, is also needed to inform tailored implementation strategies. Clinical trials number Not applicable.

Background Long-acting Cabotegravir and Rilpivirine (LA CAB + RPV) shows potential advantages in heavily comorbid and even in viremic people with HIV (PWH). We assessed LA CAB + RPV durability in a cohort of PWH with a high comorbidity burden and adherence issues. Methods Retrospective observational study in two Italian outpatient settings enrolling PWH who switched to LA CAB + RPV from February 2021 to January 2024 in presence of exclusion criteria enlisted in registrational trials or with other worrisome clinical risks. Kaplan-Meier (KM) was used to assess the probability of CAB/RPV discontinuation. Cox regression analysis was used to evaluate potential predictors of discontinuation. Results We enrolled 74 PWH, with a median of 7 injections (IQR 5–9), a median age of 53 years (IQR 45–61), median time of exposure to antiretrovirals of 11 years (IQR 8–18) and median time from HIV diagnosis of 11.8 years (IQR 6.6–18.2). Eleven (14.9%) discontinued LA CAB + RPV mainly for injection-site pain. Of 53 PWH who were undetectable before switch, 37 maintained viral suppression at week 52. We registered only one virological failure at week 12. Twenty-one started injections with unsuppressed viral loads (median 66 cps/ml, IQR 40–215) and 10 (47.6%) achieved viral suppression. Overall probability of discontinuation was 14.9% at week 52. Younger age was protective against discontinuation (HR 0.93, 95%CI 0.88–0.99, p  = 0.048). Conclusions Our results support the potential advantages in using LA CAB + RPV in PWH with adherence issues and comorbidities.

Background Early prediction of mortality in individuals with HIV (PWH) has perpetually posed a formidable challenge. With the widespread integration of machine learning into clinical practice, some researchers endeavor to formulate models predicting the mortality risk for PWH. Nevertheless, the diverse timeframes of mortality among PWH and the potential multitude of modeling variables have cast doubt on the efficacy of the current predictive model for HIV-related deaths. To address this, we undertook a systematic review and meta-analysis, aiming to comprehensively assess the utilization of machine learning in the early prediction of HIV-related deaths and furnish evidence-based support for the advancement of artificial intelligence in this domain. Methods We systematically combed through the PubMed, Cochrane, Embase, and Web of Science databases on November 25, 2023. To evaluate the bias risk in the original studies included, we employed the Predictive Model Bias Risk Assessment Tool (PROBAST). During the meta-analysis, we conducted subgroup analysis based on survival and non-survival models. Additionally, we utilized meta-regression to explore the influence of death time on the predictive value of the model for HIV-related deaths. Results After our comprehensive review, we analyzed a total of 24 pieces of literature, encompassing data from 401,389 individuals diagnosed with HIV. Within this dataset, 23 articles specifically delved into deaths during long-term follow-ups outside hospital settings. The machine learning models applied for predicting these deaths comprised survival models (COX regression) and other non-survival models. The outcomes of the meta-analysis unveiled that within the training set, the c-index for predicting deaths among people with HIV (PWH) using predictive models stands at 0.83 (95% CI: 0.75–0.91). In the validation set, the c-index is slightly lower at 0.81 (95% CI: 0.78–0.85). Notably, the meta-regression analysis demonstrated that neither follow-up time nor the occurrence of death events significantly impacted the performance of the machine learning models. Conclusions The study suggests that machine learning is a viable approach for developing non-time-based predictions regarding HIV deaths. Nevertheless, the limited inclusion of original studies necessitates additional multicenter studies for thorough validation.

Background Chronic kidney disease (CKD) is a common condition among people living with HIV worldwide, but it is more common in patients from Africa. Both opportunistic infections and chronic illnesses are responsible for a large proportion of people living with HIV in low-resource settings like Ethiopia, which are linked to higher rates of morbidity and mortality. Further, as CKD is acknowledged as a major global public health issue affecting productivity, health, and healthcare costs, the goal of this systematic review and meta-analysis was to ascertain the pooled prevalence of CKD among people living with HIV in Ethiopia. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria were followed by us when we carried out a systematic review and meta-analysis. Electronic databases like PubMed, Google Scholar, African Journal Online, Science Direct, Embase, Research Gate, Scopus, and Web of Sciences were searched in order to find pertinent articles. Domain-based assessment was used to evaluate the listed studies' quality. Stata version 14.0 software was used to conduct the statistical analysis. We used the Cochran's Q test and I 2 statistics to assess heterogeneity. Using Egger's test and a funnel plot analysis, publication bias was evaluated. Using a random effect model, the pooled prevalence was calculated. Sub-group and sensitivity studies were also carried out. Results This systematic review and meta-analysis included 12 articles from Ethiopia, and 3364 People living with HIV were included. The overall pooled prevalence of chronic kidney disease (CKD) among People living with HIV in Ethiopia was 18.10% (95% CI: 14.17–22.03). According to the CKD calculation, the pooled prevalence of CKD was 18.06 (95% CI: 10.62–25.49) by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula and 18.38 (95% CI: 15.75–21.02) by using the Modification of Diet in Renal Diseases (MDRD) formula. Using random-effect model, the I 2 test result showed high heterogeneity I 2  = 89.7% and P  < 0.001. Additionally, Egger’s test of publication bias P -value was 0.017. Conclusion People living with HIV had a high prevalence of CKD, according to this systematic review and meta-analysis. Consequently, frequent CKD diagnosis at baseline, antiretroviral therapy follow-up and screening improves the quality of life for People living with HIV. Systematic review registration: PROSPERO (2023: CRD42023431245).

Background Long-acting antiretroviral therapy (LA-ART) is an emerging alternative to daily oral ART pills that may improve HIV treatment adherence. We studied preference heterogeneity for LA-ART among people with HIV (PWH) in western Washington State and Atlanta, Georgia to determine how preference heterogeneity was related to individual characteristics. Methods We recruited 699 PWH to complete a survey including 17 choice-tasks, each of which included two hypothetical LA-ART alternatives and current daily oral therapy. Each hypothetical alternative was defined by mode (long-acting [LA] oral pills, subcutaneous injections, intramuscular injections, and implants), frequency, treatment location (home, clinic, or pharmacy), injection pain, pre-treatment time undetectable, pre-treatment reaction testing, and late-dose leeway. We fitted a latent class model to the data and investigated associations between class membership and individual characteristics. Results Our sample had three classes which were defined by their treatment preferences. Two classes preferred LA-ART over current treatment: the LA-Implant class (29%) and the LA-Oral-or-Injection class (35%). In contrast, the Daily-or-LA-Oral class (36%) preferred current treatment or LA oral pills taken at home. Compared to the third class, participants from the other two were younger, more educated, less adherent to current ART, and less averse to injections. Further, LA-Implant participants were less likely to be virally suppressed and had easier clinic access. LA-Oral-or-Injection participants had a higher prevalence of psychotic disorders. Conclusion These results provide a deeper understanding of the preference landscape for LA-ART and can aid in the development of interventions better aligned with individual preferences.

Monitoring chronic diseases, particularly kidney disorders, in people living with HIV (PLWH) is of paramount importance. Here, a systematic search was conducted across electronic search engine and databases like PubMed, Scopus, and Google Scholar, from date of inception until December 2023, to identify pertinent studies reporting on any association between inflammation and kidney function in PLWH. Only six clinical studies in peer-reviewed journals met the inclusion criteria, involving 1467 participants aged 37 to 51, with approximately 17% being females. The report emphasizes the potential impact of highly active antiretroviral therapy (HAART) on kidney function in PLWH, highlighting the significance of monitoring inflammation markers as indicators of kidney function, even when HAART is effective. Acknowledging study limitations, particularly the scarcity of relevant research, the findings highlight a need for more research to inform on clinical guidance to optimize HIV management, particularly regarding kidney health and HAART regimens. Although very limited studies were evaluated, the study lays an important foundation for future research to uncover the complex relationship between HAART, inflammation markers, and kidney health in PLWH.