Attrition Rates in HIV Viral Load Monitoring and Factors Associated With Overdue Testing Among Children Within South Africa's Antiretroviral Treatment Program: Retrospective Descriptive Analysis.

BACKGROUND: Numerous studies in South Africa have reported low HIV viral load (VL) suppression and high attrition rates within the pediatric HIV treatment program. OBJECTIVE: Using routine laboratory data, we evaluated HIV VL monitoring, including mobility and overdue VL (OVL) testing, within 5 priority districts in South Africa. METHODS: We performed a retrospective descriptive analysis of National Health Laboratory Service (NHLS) data for children and adolescents aged 1-15 years having undergone HIV VL testing between May 1, 2019, and April 30, 2020, from 152 facilities within the City of Johannesburg, City of Tshwane, eThekwini, uMgungundlovu, and Zululand. HIV VL test-level data were deduplicated to patient-level data using the NHLS CDW (Corporate Data Warehouse) probabilistic record-linking algorithm and then further manually deduplicated. An OVL was defined as no subsequent VL determined within 18 months of the last test. Variables associated with the last VL test, including age, sex, VL findings, district type, and facility type, are described. A multivariate logistic regression analysis was performed to identify variables associated with an OVL test. RESULTS: Among 21,338 children and adolescents aged 1-15 years who had an HIV VL test, 72.70% (n=15,512) had a follow-up VL test within 18 months. Furthermore, 13.33% (n=2194) of them were followed up at a different facility, of whom 3.79% (n=624) were in a different district and 1.71% (n=281) were in a different province. Among patients with a VL of ≥1000 RNA copies/mL of plasma, the median time to subsequent testing was 6 (IQR 4-10) months. The younger the age of the patient, the greater the proportion with an OVL, ranging from a peak of 52% among 1-year-olds to a trough of 21% among 14-year-olds. On multivariate analysis, 2 consecutive HIV VL findings of ≥1000 RNA copies/mL of plasma were associated with an increased adjusted odds ratio (AOR) of having an OVL (AOR 2.07, 95% CI 1.71-2.51). Conversely, patients examined at a hospital (AOR 0.86, 95% CI 0.77-0.96), those with ≥2 previous tests (AOR 0.78, 95% CI 0.70-0.86), those examined in a rural district (AOR 0.63, 95% CI 0.54-0.73), and older age groups of 5-9 years (AOR 0.56, 95% CI 0.47-0.65) and 10-14 years (AOR 0.51, 95% CI 0.44-0.59) compared to 1-4 years were associated with a significantly decreased odds of having an OVL test. CONCLUSIONS: Considerable attrition occurs within South Africa's pediatric HIV treatment program, with over one-fourth of children having an OVL test 18 months subsequent to their previous test. In particular, younger children and those with virological failure were found to be at increased risk of having an OVL test. Improved HIV VL monitoring is essential for improving outcomes within South Africa's pediatric antiretroviral treatment program.

Adherence to antiretroviral therapy and determining factors in adults living with HIV receiving services at public health facilities amidst the COVID-19 crisis in Bahir Dar city, Northwest Ethiopia.

Background: The COVID-19 pandemic has presented new challenges to adhering to ART, and its influence on adherence and related factors has not been thoroughly studied. This study examines ART adherence and its associated factors during the COVID-19 pandemic. Methods: A cross-sectional study was conducted on HIV-positive individuals receiving care and treatment in public health facilities. A total of 612 participants were selected using a multi-stage sampling procedure. Data were collected through interviewer-administered questionnaires and chart reviews. We used Epi-data for data entry and Stata for data analysis. Results: Good adherence to antiretroviral therapy in this study was 76.5% (95% CI, 72.9, 79.7). Divorced marital status (AOR = 0.45,95%CI:0.22,0.90), regular follow-up (AOR = 3.01,95%CI:1.81,5.01), adherence counseling and information in the context of COVID-19 pandemic (AOR = 2.57,95%CI:1.63,4.08), and knowledge about ART (AOR = 1.81,95%CI:1.11,2.94) were significantly associated with adherence to antiretroviral therapy. Conclusion: The observed adherence rate in this study was lower than the World Health Organization recommendation and previous studies. The study highlighted the importance of addressing adherence to ART among HIV-positive adults during the COVID-19 pandemic and other upcoming emerging and reemerging outbreaks. Strategies to improve adherence should consider factors such as marital status, regular follow-up, provision of counseling and information, and enhancing knowledge about ART.

Factors associated with antiretroviral treatment adherence among people living with HIV in Guangdong Province, China: a cross sectional analysis.

BACKGROUND: Understanding factors associated with antiretroviral treatment (ART) adherence is crucial for ART success among people living with HIV (PLHIV) in the "test and treat" era. Multiple psychosocial factors tend to coexist and have a syndemic effect on ART adherence. We aimed to explore factors associated with ART adherence and the syndemic effect of multiple psychosocial factors on ART adherence among PLHIV newly starting ART in Guangdong Province, China. METHODS: Newly diagnosed PLHIV from six cities in Guangdong Province were recruited between May 2018 and June 2019, and then followed up from May 2019 to August 2020. Baseline and follow-up data were collected from a questionnaire and the national HIV surveillance system, the follow-up data of which were analyzed in this study. A Center for Adherence Support Evaluation (CASE) index > 10 points was defined as optimal ART adherence, which was measured via participants' self-reported adherence during follow-up survey. Multivariable logistic regression was used to identify factors associated with ART adherence. Exploratory factor analysis (EFA) and multi-order latent variable structural equation modeling (SEM) were performed to explore the syndemic effect of multiple psychosocial factors on ART adherence. RESULTS: A total of 734 (68.53%) follow-up participants were finally included in this study among the 1071 baseline participants, of whom 91.28% (670/734) had self-reported optimal ART adherence. Unemployment (aOR = 1.75, 95%CI: 1.01-3.02), no medication reminder (aOR = 2.28, 95%CI: 1.09-4.74), low medication self-efficacy (aOR = 2.28, 95%CI: 1.27-4.10), low social cohesion (aOR = 1.82, 95%CI: 1.03-3.19), no social participation (aOR = 5.65, 95%CI: 1.71-18.63), and ART side effects (aOR = 0.46, 95%CI: 0.26-0.81) were barriers to optimal ART adherence. The EFA and second-order latent variable SEM showed a linear relationship (standardized coefficient = 0.43, P < 0.001) between ART adherence and the latent psychosocial (syndemic) factor, which consisted of the three latent factors of medication beliefs and self-efficacy (standardized coefficient = 0.65, P < 0.001), supportive environment (standardized coefficient = 0.50, P < 0.001), and negative emotions (standardized coefficient=-0.38, P < 0.01). The latent factors of medication beliefs and self-efficacy, supportive environment, and negative emotions explained 42.3%, 25.3%, and 14.1% of the variance in the latent psychosocial factor, respectively. CONCLUSIONS: About nine out of ten PLHIV on ART in Guangdong Province self-reported optimal ART adherence. However, more efforts should be made to address barriers to optimal ART adherence.

Plasma Levels of Secreted Cytokines in Virologically Controlled HIV-Infected Aging Adult Individuals on Long-Term Antiretroviral Therapy.

HIV-infected (HIV+) aging adult individuals who have achieved undetectable viral load and improved CD4 T cell counts due to long-term antiretroviral therapy (ART) may continue to experience inflammation and immunosenescence. Therefore, we evaluated the plasma levels of proinflammatory and anti-inflammatory cytokines in 173 HIV+ aging adult individuals with age ranging from 22 to 81 years on long-term ART with viral load mostly <20 HIV RNA copies/mL and compared with 92 HIV-uninfected (HIV- or healthy controls) aging individuals. We found that the median levels of TNF-α, IFN-γ, IL-1ß, IL-6, and IL-10 were higher (p < 0.001 to <0.0001) and IL-17 trended lower in HIV+ individuals than healthy controls. Increasing CD4 T cell counts in the HIV+ cohort did not significantly change the circulating cytokine levels, although levels of IL-1ß increased. However, IL-17 levels significantly decreased with increasing CD4 counts in the healthy controls and yet unchanged in the HIV+ cohort. Of note, the levels of circulating IL-17 were significantly reduced comparatively in the healthy controls where the CD4 count was below 500, yet once above 500 the levels of CD4, IL-17 levels were comparable with the HIV+ cohort. With increasing CD8 T cell counts, the levels of these cytokines were not significantly altered, although levels of TNF-α, IFN-γ, and IL-6 declined, whereas IL-1ß and IL-17 were slightly elevated. Furthermore, increasing age of the HIV+ cohort did not significantly impact the cytokine levels although a slight increase in TNF-α, IL-6, IL-10, and IL-17 was observed. Similarly, these cytokines were not significantly modulated with increasing levels of undetectable viral loads, whereas some of the HIV+ individuals had higher levels of TNF-α, IFN-γ, and IL-1ß. In summary, our findings show that HIV+ aging adult individuals with undetectable viral load and restored CD4 T cell counts due to long-term ART still produce higher levels of both proinflammatory and anti-inflammatory cytokines compared with healthy controls, suggesting some level of inflammation.

Risk of transmission of HIV to infants during breast/chest feeding when mothers/birthing parents living with HIV are on antiretroviral therapy: a protocol for a rapid review.

INTRODUCTION: HIV is a major public health issue affecting millions globally. Women and girls account for 46% of new HIV infections in 2022 and approximately 1.3 million females become pregnant every year. Vertical transmission of HIV from persons living with HIV (PLHIV) to infants may occur through different modalities, such as through breast/chest feeding. Notably, 82% of PLHIV who chose to breast/chest feed are on antiretroviral therapy (ART) when feeding their infants. Precise estimates of the risk of postpartum transmission to infants during breast/chest feeding at varying viral load levels remain a significant gap in the literature. METHODS AND ANALYSIS: A rapid systematic search of electronic databases will be conducted from January 2005 to the present, including Medline, Embase and Global Health. The objective of this rapid review is to explore and assess the available evidence on the effect of varying viral load levels on the risk of HIV transmission to infants during breast/chest feeding when the birthing or gestational parent living with HIV is on ART. Study characteristics will be summarised and reported to support the narrative summary of the findings. The focus will be on the absolute risk of HIV transmission from birthing parent to infant during chest/breast feeding. The findings will also be stratified by month, including the risk of HIV transmission for 6 months and greater than 6 months postpartum. We will ascertain the risk of bias using A Measurement Tool to Assess Systematic Reviews 2, Quality of Prognosis Studies and Downs and Black checklist for the appropriate study type. A summary score will not be calculated, rather the strengths and limitations of the studies will be narratively described. ETHICS AND DISSEMINATION: No human subjects will be involved in the research. The findings of this rapid review will inform a future systematic review and will be disseminated through peer-reviewed publications, presentations and conferences. PROSPERO REGISTRATION NUMBER: CRD42024499393.

Quality assessment of oral antimalarial and antiretroviral medicines used by public health systems in Sahel countries.

Malaria and Human Immunodeficiency Virus infections are among the top 10 causes of death in low income countries. Furthermore, many medicines used in these treatment areas are substandard, which contributes to the high death rate. Using a monitoring system to identify substandard and falsified medicines, the study aims to evaluate the quality of antimalarial and antiretroviral medicines in Sahel countries, assessing site conditions, compliance of medicines with pharmacopoeia tests, formulation equivalence with a reference medicine, and the influence of climate on quality attributes. Ultra Performance Liquid Chromatography methods for eight active pharmaceutical ingredients were validated following the International Conference for Harmonization guideline for its detection and quantification. Quality control consists of visual inspections to detect any misinformation or imperfections and pharmacopeial testing to determine the quality of pharmaceutical products. Medicines which complied with uniformity dosage units and dissolution tests were stored under accelerated conditions for 6 months. Artemether/Lumefantrine and Lopinavir/Ritonavir formulations failed uniformity dosage units and disintegration tests respectively, detecting a total of 28.6% substandard medicines. After 6 months stored under accelerated conditions (40 °C // 75% relative humidity) simulating climatic conditions in Sahel countries, some medicines failed pharmacopeia tests. It demonstrated the influence of these two factors in their quality attributes. This study emphasizes the need of certified quality control laboratories as well as the need for regulatory systems to maintain standards in pharmaceutical manufacturing and distribution in these countries, especially when medicines are transported to rural areas where these climatic conditions are harsher.

Parenteral platforms for tunable, long-acting administration of a highly hydrophobic antiretroviral drug.

GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound has demonstrated promising clinical results as an orally administered agent. Additionally, the compound's physical and pharmacological properties present opportunities for exploitation as long-acting parenteral formulations. Despite unique design constraints including solubility and dose of GSK8232, we report on three effective tunable drug delivery strategies: active pharmaceutical ingredient (API) suspensions, ionic liquids, and subdermal implants. Promising sustained drug release profiles were achieved in rats with each approach. Additionally, we were able to tune drug release rates through a combination of passive and active strategies, broadening applicability of these formulation approaches beyond GSK8232. Taken together, this report is an important first step to advance long-acting formulation development for critical HIV medicines that do not fit the traditional profile of suitable long-acting candidates.

Rapid antiretroviral therapy initiation following rollout of point-of-care early infant diagnosis testing, Uganda, 2018-2021.

BACKGROUND: Uganda Ministry of Health (MOH) recommends a first HIV DNA-PCR test at 4-6 weeks for early infant diagnosis (EID) of HIV-exposed infants (HEI) and immediate return of results. WHO recommends initiating antiretroviral therapy (ART) ≤ 7 days from HIV diagnosis. In 2019, MOH introduced point-of-care (POC) whole-blood EID testing in 33 health facilities and scaled up to 130 facilities in 2020. We assessed results turnaround time and ART linkage pre-POC and during POC testing. METHODS: We evaluated EID register data for HEI at 10 health facilities with POC and EID testing volume of ≥ 12 infants/month from 2018 to 2021. We abstracted data for 12 months before and after POC testing rollout and compared time to sample collection, results receipt, and ART initiation between periods using medians, Wilcoxon, and log-rank tests. RESULTS: Data for 4.004 HEI were abstracted, of which 1.685 (42%) were from the pre-POC period and 2.319 (58%) were from the period during POC; 3.773 (94%) had a first EID test (pre-POC: 1.649 [44%]; during POC: 2.124 [56%]). Median age at sample collection was 44 (IQR 38-51) days pre-POC and 42 (IQR 33-50) days during POC (p < 0.001). Among 3.773 HEI tested, 3.678 (97%) had test results. HIV-positive infants' (n = 69) median age at sample collection was 94 (IQR 43-124) days pre-POC and 125 (IQR 74-206) days during POC (p = 0.04). HIV positivity rate was 1.6% (27/1.617) pre-POC and 2.0% (42/2.061) during POC (p = 0.43). For all infants, median days from sample collection to results receipt by infants' caregivers was 28 (IQR 14-52) pre-POC and 1 (IQR 0-25) during POC (p < 0.001); among HIV-positive infants, median days were 23 (IQR 7-30) pre-POC and 0 (0-3) during POC (p < 0.001). Pre-POC, 4% (1/23) HIV-positive infants started ART on the sample collection day compared to 33% (12/37) during POC (p < 0.001); ART linkage ≤ 7 days from HIV diagnosis was 74% (17/23) pre-POC and 95% (35/37) during POC (p < 0.001). CONCLUSION: POC testing improved EID results turnaround time and ART initiation for HIV-positive infants. While POC testing expansion could further improve ART linkage and loss to follow-up, there is need to explore barriers around same-day ART initiation for infants receiving POC testing.

Inhibition of caspase pathways limits CD4+ T cell loss and restores host anti-retroviral function in HIV-1 infected humanized mice with augmented lymphoid tissue.

The study of HIV infection and pathogenicity in physical reservoirs requires a biologically relevant model. The human immune system (HIS) mouse is an established model of HIV infection, but defects in immune tissue reconstitution remain a challenge for examining pathology in tissues. We utilized exogenous injection of the human recombinant FMS-like tyrosine kinase 3 ligand (rFLT-3 L) into the hematopoietic stem cell (HSC) cord blood HIS mouse model to significantly expand the total area of lymph node (LN) and the number of circulating human T cells. The results enabled visualization and quantification of HIV infectivity, CD4 T cell depletion and other measures of pathogenesis in the secondary lymphoid tissues of the spleen and LN. Treatment with the Caspase-1/4 inhibitor VX-765 limited CD4+ T cell loss in the spleen and reduced viral load in both the spleen and axillary LN. In situ hybridization further demonstrated a decrease in viral RNA in both the spleen and LN. Transcriptomic analysis revealed that in vivo inhibition of caspase-1/4 led to an upregulation in host HIV restriction factors including SAMHD1 and APOBEC3A. These findings highlight the use of rFLT-3 L to augment human immune system characteristics in HIS mice to support investigations of HIV pathogenesis and test host directed therapies, though further refinements are needed to further augment LN architecture and cellular populations. The results further provide in vivo evidence of the potential to target inflammasome pathways as an avenue of host-directed therapy to limit immune dysfunction and virus replication in tissue compartments of HIV+ persons.

Prevalence and factors associated with viral non-suppression in people living with HIV receiving antiretroviral therapy in sub-Saharan Africa: A systematic review and meta-analysis.

Despite advances in HIV treatment, the burden of viral non-suppression (VNS) remains a treatment success concern, particularly in Sub-Saharan African (SSA) countries. We determined the prevalence and factors associated with VNS for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). This review, registered with PROSPERO (CRD42023470234), conducted an extensive search for evidence, focusing on PLHIV living in SSA on ART from the year 2000 to 19th October 2023, across databases including PubMed/MEDLINE, Embase, Web of Science, and Scopus. A total of 2357 articles were screened, from which 32 studies met the criteria for the final analysis, involving 756,620 PLHIV of all ages. The pooled prevalance for VNS was found to be 20.0% (95% CI: 15.43%-25.52%, I2 = 100%, p-value <0.01) Children and adolescents demonstrated the highest prevalence of VNS (viral load ≥1000 copies/mL) at 27.98% (95% CI: 21.91%-34.97%, I2 = 94%, p-value <0.01). The study revealed various factors associated with increased odds (risk) of VNS, p-value <0.05. These factors encompassed socio-demographics such as sex, age, education level, and marital status. Additionally, aspects related to HIV care, such as the facility attended, HIV status disclosure and adherence exhibited higher odds of VNS. Suboptimal ART adherence, longer duration on ART, socio-economic factors, lack of family and social support, presence of co-morbidities, advanced WHO HIV clinical stage, ART regimens, lower CD4+ count, abnormal body mass index, history of treatment interruptions, and progression of HIV illness were associated with VNS. Furthermore, behavioural/psychological factors including depression, substance use, negative perceptions towards ART, experiences of abuse, alcohol use, stigma, and certain patterns of sexual behaviour were also identified as factors for VNS. The occurrence of two VNS to every ten PLHIV on ART poses a threat to the progress made towards reaching the third 95% UNAIDS target in SSA. Additionally, these findings highlight the intricate interplay of various factors, encompassing patient characteristics, behavioural patterns, sociocultural influences, and pharmacological factors, all impacting VNS among PLHIV. Recognising its multifaceted nature, we recommend designing and implementing high impact interventions to effectively address VNS in SSA.

DeepARV: ensemble deep learning to predict drug-drug interaction of clinical relevance with antiretroviral therapy.

Drug-drug interaction (DDI) may result in clinical toxicity or treatment failure of antiretroviral therapy (ARV) or comedications. Despite the high number of possible drug combinations, only a limited number of clinical DDI studies are conducted. Computational prediction of DDIs could provide key evidence for the rational management of complex therapies. Our study aimed to assess the potential of deep learning approaches to predict DDIs of clinical relevance between ARVs and comedications. DDI severity grading between 30,142 drug pairs was extracted from the Liverpool HIV Drug Interaction database. Two feature construction techniques were employed: 1) drug similarity profiles by comparing Morgan fingerprints, and 2) embeddings from SMILES of each drug via ChemBERTa, a transformer-based model. We developed DeepARV-Sim and DeepARV-ChemBERTa to predict four categories of DDI: i) Red: drugs should not be co-administered, ii) Amber: interaction of potential clinical relevance manageable by monitoring/dose adjustment, iii) Yellow: interaction of weak relevance and iv) Green: no expected interaction. The imbalance in the distribution of DDI severity grades was addressed by undersampling and applying ensemble learning. DeepARV-Sim and DeepARV-ChemBERTa predicted clinically relevant DDI between ARVs and comedications with a weighted mean balanced accuracy of 0.729 ± 0.012 and 0.776 ± 0.011, respectively. DeepARV-Sim and DeepARV-ChemBERTa have the potential to leverage molecular structures associated with DDI risks and reduce DDI class imbalance, effectively increasing the predictive ability on clinically relevant DDIs. This approach could be developed for identifying high-risk pairing of drugs, enhancing the screening process, and targeting DDIs to study in clinical drug development.

Mortality and its predictors among human immunodeficiency virus-infected children younger than 15 years receiving antiretroviral therapy in Ethiopia: a systematic review and meta-analysis.

BACKGROUND: Despite antiretroviral treatment (ART), the human immunodeficiency virus (HIV) continues to pose a considerable health burden in resource-poor countries. This systematic review and meta-analysis aimed to determine the pooled incidence density of mortality and identify potential predictors among HIV-infected children receiving ART, from studies conducted in various parts of Ethiopia. METHODS: A comprehensive database search was made in Excerpta Medica, PubMed, Web of Science, African Journals Online, Google Scholar, and Scopus. We reported results following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020. Excel Spreadsheet and STATA Version 14 software were used for data abstraction and meta-analysis, respectively. Statistical heterogeneity among studies was assessed using I2 statistics. Meta-regression and subgroup analysis were performed to further explore the sources of statistical heterogeneity. Moreover, publication bias and a leave-out-one sensitivity analysis were performed. RESULTS: Twenty-two articles involving 8,731 participants met inclusion criteria and were included. The pooled incidence density of mortality was 3.08 (95% confidence interval (CI), 2.52 to 3.64) per 100 child years. Predictors of mortality were living in rural areas (hazard ratio (HR), 2.18 [95% CI, 1.20 to 3.98]), poor adherence to ART (HR, 2.85 [ 95% CI, 1.39 to 5.88]), failure to initiate co-trimoxazole preventive therapy (HR, 2.16 [95% CI, 1.52 to 3.07]), anemia (HR, 2.28 [95% CI, 1.51 to 3.45]), opportunistic infections (HR, 1.52 [ 95% CI, 1.15 to 2.00]), underweight (HR, 1.74 [95% CI, 1.26 to 2.41]), wasting (HR, 2.54 [95% CI, 1.56 to 4.16]), stunting (HR, 2.02 [95% CI, 1.63 to 2.51]), World Health Organization classified HIV clinical stages III and IV (HR, 1.71 [95% CI, 1.42 to 2.05]), and Nevirapine-based regimens (HR, 3.91 [95% CI, 3.09 to 4.95]). CONCLUSIONS: This study found that the overall mortality rate among HIV-infected children after ART initiation was high. Therefore, high-level commitment and involvement of responsible caregivers, healthcare providers, social workers, and program managers are of paramount importance to identify these risk factors and thus enhance the survival of HIV-infected children receiving ART.

Determinants of antiretroviral therapy adherence among transgender women in South Africa.

BACKGROUND:  Transgender women bear a huge burden of human immunodeficiency virus (HIV) in South Africa. However, they are not fully engaged in healthcare across the HIV continuum of care. In addition, transgender women face multiple facets of stigma and discrimination as well as socio-economic inequalities, which all have a negative impact on antiretroviral therapy (ART) adherence. OBJECTIVE:  The study aimed at exploring and describing the experiences of ART adherence of transgender women living with HIV in the Buffalo City Metro Municipality. METHODS:  The study employed an interpretative phenomenological analysis (IPA) design. Twelve participants were enrolled using a snowballing sampling technique. Data were collected using semi-structured interviews and analysed using an IPA framework. RESULTS:  While exploring determinants to ART adherence among transgender women living with HIV in Buffalo City Metro, two superordinate themes emerged: enablers to ART adherence and psychosocial factors promoting adherence. The study found that factors such as differentiated ART service delivery, ARV medicines-related factors, motivators for taking treatment and support systems facilitated ART adherence. CONCLUSION:  Emerging from this study is the need to scale up differentiated, person-centred ART service deliveries that will enhance access and adherence to treatment for transgender women.Contribution: This study provides unique insights on factors enhancing ART adherence among transgender women. There is a paucity of literature on access to HIV care services for key and vulnerable populations, and these findings will be shared in the country and in the region.

Experiences of patients living with HIV and AIDS on antiretroviral therapy in Accra, Ghana.

BACKGROUND:  The human immunodeficiency virus and acquired immunodeficiency syndrome (HIV and AIDS) pandemic has greatly affected Africa, particularly Ghana. The pandemic remains a public health concern, particularly in terms of accessing essential medication and improving quality of life for people living with the disease. OBJECTIVES:  This study aimed to explore and describe the experiences of persons diagnosed and living with HIV who are on antiretroviral therapy. METHOD:  A qualitative, exploratory, descriptive, and contextual design was used. The research population included persons diagnosed with HIV who were receiving antiretroviral therapy at three public hospitals in Ghana. Data saturation was achieved after conducting 15 semi-structured interviews. Creswell's six steps of data analysis were used to analyse the data, which resulted in the emergence of one main theme and six sub-themes. RESULTS:  The main theme identified by the researchers highlighted the participants' diverse experiences of being diagnosed and living with HIV. It was found that the study participants expressed shock, disbelief, surprise, and fear of death after being diagnosed with HIV. The participants also experienced stigmatisation, discrimination, and rejection. CONCLUSION:  There is a need for further research on the extent of discrimination and stigmatisation and the effect on optimal adherence to antiretroviral therapy. Continuous public education on HIV is required to limit the extent of discrimination and stigmatisation.Contribution: The study has highlighted the various emotions related to stigma and discrimination expressed by persons living with HIV (PLHIV). The findings will guide policy on eliminating discrimination and stigmatisation for people living with HIV.

Statistical analysis on the incidence and predictors of death among second-line ART patients in public hospitals of North Wollo and Waghemira Zones, Ethiopia, 2021.

Acquired immune deficiency virus, caused by the human immunodeficiency virus, is a significant global health concern. Sub-Saharan Africa particularly Ethiopia faces a high prevalence of human immunodeficiency virus. In low-income settings like Ethiopia, early mortality rates are elevated due to severe opportunistic infections and advanced disease at Anti-retroviral treatment initiation. Despite available treatments, delayed treatment initiation among Human Immunodeficiency Virus -infected individuals in Africa, including Ethiopia, leads to disease progression and increased mortality risk. This study aimed to identify the factors contributing to the death of HIV patients under treatment at second line regimen in public hospitals of North Wollo and Waghemira Zones. A retrospective cohort study with 474 patients was conducted in selected hospitals of North Wollo and Waghemira Zones. A parametric Weibull regression model was employed, and the adjusted hazard ratio served as the measure of association. Variables significantly affected the outcome of the study was determined at a p-value < 0.05, along with a 95% confidence interval for the variables. The patients were within the average age of 38.6(standard deviation ± 12.5) years and majority (45.57%) had no formal education. The overall death incidence rate among second-line anti-retroviral treatment patients was 1.98 per 100-person years [95% CI 1.4-2.9%]. Poor adherence to antiretroviral treatment, male gender, and being underweight significantly increased the hazard of death. Conversely, increased anti-retroviral treatment duration had a significant and negative impact, reducing the hazard of death among patients. The study reveals a high incidence of death among second line anti-retroviral treatment users. Independent predictors include poor adherence, male gender, and underweight status, all significantly increasing the risk of death. On the positive side, the hazard of death decreases with longer anti-retroviral treatment duration. A critical concern and counseling should be given for better ART adherence, to change their nutritional status and for males.

Challenges and support experienced by family caregivers seeking antiretroviral therapy services for children living with HIV/AIDS: a phenomenological study in Ghana.

BACKGROUND: Family caregivers of children living with HIV/AIDS in most cases are found to be overwhelmed and under-resourced, yet they are believed to be the primary source of support for children living with HIV/AIDS. Family caregivers experience different challenges that affect their children's antiretroviral therapy (ART) adherence. AIM: This study explored the lived experiences of family caregivers of children living with HIV/AIDS who sought ART services for these children at the St Joseph's Hospital of Jirapa, Ghana. METHOD: Using a qualitative phenomenology design and a semistructured in-depth interview guide and using purposive sampling, data were gathered from 13 family caregivers of children living with HIV/AIDS receiving ART treatment at St Joseph's Hospital, Jirapa following ethical approval. All interviews were audio-taped and transcribed verbatim. Reflexive thematic analysis was used to analyse the transcribed data. FINDINGS: Six themes were generated: five challenges and one support. Family caregivers of children living with HIV/AIDS experienced: (1) Financial challenges, (2) Human-related challenges, (3) Challenges at HIV testing and counselling (HTC) centres, (4) Challenges with transportation, (5) Challenges in disclosing children's HIV status to them and (6) Support received from HTC and their family members. CONCLUSION AND RECOMMENDATION: Family caregivers of children living with HIV/AIDS experience daunting challenges in their quest to care for their children. Governmental and non-governmental HIV/AIDS programme support should include small business skills training and acquisition including capital to help set up small-scale businesses for such caregivers to reduce their financial challenges. Access to ART at clinics closer to caregivers is also key to promoting adherence. Family and community support has been recognised as key to enhancing ART adherence. Education of caregivers on policy regarding disclosure of the HIV/AIDS status of children, the need to work to reduce the time spent by caregivers at HTC, and ensuring privacy by limiting access to HTCs to only caregivers and their children, are important to enhancing adherence.

Acceptability of a pilot motivational interviewing intervention at public health facilities to improve the HIV treatment cascade among people who inject drugs in Indonesia.

BACKGROUND: HIV-positive people who inject drugs (PWID) experience challenges in initiating and adhering to antiretroviral treatment (ART). Counselling using motivational interviewing (MI) techniques may help them formulate individualised strategies, and execute actions to address these challenges collaboratively with their providers. We evaluated the acceptability of MI from a pilot implementation at three public health facilities in Indonesia. METHODS: Adapting the acceptability constructs developed by Sekhon (2017) we assessed the acceptability to HIV-positive PWID clients (n = 12) and providers (n = 10) in four synthesised constructs: motivation (attributes that inspire engagement); cost consideration (sacrifices made to engage in MI); learned understanding (mechanism of action); and outcomes (ability to effect change with engagement). We included all providers and clients who completed ≥ 2 MI encounters. Qualitative analysis with an interpretive paradigm was used to extract and categorise themes by these constructs. RESULTS: In motivation, clients valued the open communication style of MI, while providers appreciated its novelty in offering coherent structure with clear boundaries. In cost consideration, both groups faced a challenge in meeting MI encounters due to access or engagement in other health care areas. In learned understanding, clients understood that MI worked to identify problematic areas of life amenable to change to support long-term ART, with reconciliation in family life being the most targeted change. By contrast, providers preferred targeting tangible health outcomes to such behavioural proxies. In outcomes, clients were confident in their ability to develop behaviours to sustain ART uptakes, whereas providers doubted the outcome of MI on younger PWID or those with severe dependence. CONCLUSIONS: There is broad acceptability of MI in motivating engagement for both actors. Relative to providers, clients were more acceptable in its mechanism and had greater confidence to perform behaviours conducive to ART engagement. Design innovations to improve the acceptability of MI for both actors are needed.

Improving Adherence to the Target Window for Cabotegravir + Rilpivirine Long-Acting Injections Through the CHORUS™ App and Web Portal: A Cluster Randomized Trial.

BACKGROUND: We evaluated the impact of the CHORUS™ app on adherence to the cabotegravir and rilpivirine long-acting injectable (CAB + RPV LAI) monthly injections schedule. METHODS: Healthcare centers (HCCs) were randomized to access CHORUS™ CAB + RPV LAI features (intervention) or not (control) from 01OCT2021-31JAN2022. Target window adherence (maintenance injections ≤7 days before/after target day) was assessed with multivariate logistic regression (generalized estimating equations). RESULTS: CAB + RPV LAI was administered to 188 and 79 individuals at intervention and control HCCs, respectively. Intervention was not associated with improved target window adherence (adjusted odds ratio: 0.61 [95% CI: 0.30-1.25]). However, app use was associated with increased odds of adherence compared to no app use among all intervention HCCs (2.98 [1.26-7.06]) and at smaller HCCs (3.58 [1.31-9.80]). CONCLUSIONS: While access to CHORUS™ CAB + RPV LAI features did not improve target window adherence, app use did, especially at smaller HCCs which may not have established LAI management procedures. TRIAL REGISTRATION: https://clinicaltrials.gov/show/NCT04863261.

Evaluation of a mobile app and web portal to help with the timely injections of cabotegravir + rilpivirine long-acting injectionsCabotegravir + rilpivirine long-acting injectable (CAB+RPV LAI) is the first long-acting regimen for HIV treatment, which was approved in the US in 2021. CAB+RPV LAI should be administered ≤7 days before/after the target date. We conducted a trial to evaluate the impact of the CHORUS™ app and web portal on the timing of monthly CAB+RPV injections. The intervention clinics had access to features designed to help with CAB+RPV LAI management, including flagging delayed/missed injections and appointment scheduling status. Control clinics did not have access to these features and managed CAB+RPV LAI administration on their own. Access to the app and web portal features for intervention clinics had no impact on timing of injections compared to control clinics. However, intervention clinics who actively used the app were close to three times more likely to give injections on-time than intervention clinics who did not use the app. The effect of app use was seen specifically among smaller clinics caring for <1000 people with HIV: smaller clinics that actively used the app were 3.58 times more likely to give injections on-time than those who did not use the app. In conclusion, while access to CHORUS™ CAB+RPV LAI features in the app and the web portal did not improve the likelihood of on time injections, actively using the app did make a difference, especially at smaller clinics which may not have established injection management procedures.

The association between HIV pretreatment drug resistance and virological outcomes in children and adults in sub-Saharan Africa: A systematic review and meta-analysis.

INTRODUCTION: Pretreatment drug resistance (PDR) could occur in antiretroviral treatment (ART) naïve individuals, those previously exposed to ART, or individuals re-initiating ARV after a long period of interruption. Few studies have shown its association with virological outcomes, although inconsistent. The objective of this review was to provide a synthesis of the association between PDR and virological outcomes (virological failure or suppression). METHODS: This report is presented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The method was subdivided into three main phases: record identification, screening, and report inclusion. Record identification consisted of an initial search with search term "HIV pretreatment drug resistance". Another search was done using terms "Pretreatment drug resistance OR pre-treatment drug resistance OR Pretreatment drug resist* OR pre-treatment drug resist* OR pretreatment antiretroviral resistance OR pretreatment medic* OR pretreatment medic* resist*" and a list of all the countries in sub-Saharan Africa. After the electronic search, studies were screened from full list based on their title and abstract and then full articles retrieved and studies were assessed based on set criteria. Inclusion criteria involved observational studies that report the association between PDR and virological failure. Data from trials that reported the association were also included. Published articles like modelling studies and reviews, and studies with data that had been previously included in the review were excluded. The Mantel Haenszel method with odds ratios was used for synthesis (meta-analyses) with the weights of each study which depends on the number of events and totals. RESULTS: A total of 733 records(studies) were obtained from all database search of which 74 reported on PDR, virological outcomes in sub-Saharan Africa (SSA). Out of the 74 articles, 11 were excluded and 26 did not explicitly report data needed, and 5 did not meet the inclusion criteria. Of the remaining 32 studies, 19 studies that had complete data on the number of participants with PDR and no PDR according to virological failure (VF) were included in the metanalyses. The pooled results from eleven (13) of these studies showed those with PDR had higher odds of virological failure compared to those without PDR OR 3.64[95% CI 2.93, 4.52]. The result was similar when stratified in adults and in children. In six (6) studies that had Virological suppression (VS) as outcome, there was a reduction in the odds of VS in those with PDR compared to those without PDR, OR 0.42 (95% CI 0.30, 0.58). CONCLUSION: In conclusion, this systematic review indicates that PDR increases the risk of virological failure in sub-Saharan Africa. The risk could be reduced by PDR monitoring for NNRTIs and INSTIs.