Examining barriers to antiretroviral therapy initiation in infants living with HIV in sub-Saharan Africa despite the availability of point-of-care diagnostic testing: a narrative systematic review.

INTRODUCTION: Antiretroviral therapy (ART) initiation in infants living with HIV before 12 weeks of age can reduce the risk of mortality by 75%. Point-of-care (POC) diagnostic testing is critical for prompt ART initiation; however, despite its availability, rates of ART initiation are still relatively low before 12 weeks of age. This systematic review describes the barriers to ART initiation in infants before 12 weeks of age, despite the availability of POC. METHODS: This systematic review used a narrative synthesis methodology. We searched PubMed and Scopus using search strategies that combined terms of multiple variants of the keywords "early infant initiation on antiretroviral therapy," "barriers" and "sub-Saharan Africa" (initial search 18th January 2023; final search 1st August 2023). We included qualitative, observational and mixed methods studies that reported the influences of early infant initiation on ART. We excluded studies that reported influences on other components of the Prevention of Mother to Child Transmission cascade. Using a deductive approach guided by the updated Consolidated Framework of Implementation Research, we developed descriptive codes and themes around barriers to early infant initiation on ART. We then developed recommendations for interventions for the identified barriers using the action, actor, target and time framework from the codes. RESULTS: Of the 266 abstracts reviewed, 52 full-text papers were examined, of which 12 papers were included. South Africa had most papers from a single country (n = 3) and the most reported study design was retrospective (n = 6). Delays in ART initiation beyond 12 weeks in infants 0-12 months were primarily associated with health facility and maternal factors. The most prominent barriers identified were inadequate resources for POC testing (including human resources, laboratory facilities and patient follow-up). Maternal-related factors, such as limited male involvement and maternal perceptions of treatment and care, were also influential. DISCUSSION: We identified structural barriers to ART initiation at the health system, social and cultural levels. Improvements in the timely allocation of resources for POC testing operations, coupled with interventions addressing social and behavioural barriers among both mothers and healthcare providers, hold a promise for enhancing timely ART initiation in infants. CONCLUSIONS: This paper identifies barriers and proposes strategies for timely ART initiation in infants.

Discrepancies between self-reported medication in adherence and indirect measurement adherence among patients undergoing antiretroviral therapy: a systematic review.

BACKGROUND: Given the critical importance of medication adherence in HIV/AIDS treatment, this study aims to compare medication adherence measured by self-report (SR) and indirect measurement among antiretroviral therapy (ART) patients, exploring the differences of adherence results measured by different tools. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library to identify all relevant literature published up to November 22, 2023, without language restrictions, reporting adherence to ART measured by both SR and indirect measurement methods, while also analyzing individual and group adherence separately. Discrepancies between SR and indirect measurement results were assessed using the Mann-Whitney U test or Wilcoxon signed-rank test, with correlations evaluated using the Pearson correlation coefficient. Following one-to-one comparisons, meta-epidemiological one-step analysis was conducted, and network meta-analysis techniques were applied to compare results obtained through specific adherence assessment tools reported in the identified articles. RESULTS: The analysis encompassed 65 original studies involving 13,667 HIV/AIDS patients, leading to 112 one-to-one comparisons between SR and indirect measurement tools. Statistically significant differences were observed between SR and indirect measurement tools regarding both individual and group adherence (P < 0.05), with Pearson correlation coefficients of 0.843 for individual adherence and 0.684 for group adherence. During meta-epidemiological one-step analysis, SR-measured adherence was determined to be 3.94% (95% CI: -4.48-13.44%) higher for individual adherence and 16.14% (95% CI: 0.81-18.84%) higher for group adherence compared to indirectly measured results. Subgroup analysis indicated that factors such as the year of reporting and geographic region appeared to influence the discrepancies between SR and indirect measurements. Furthermore, network meta-analysis revealed that for both individual and group adherence, the results obtained from most SR and indirect measurement tools were higher than those from electronic monitoring devices, with some demonstrating statistical significance (P < 0.05). CONCLUSIONS: The findings underscored the complexity of accurately measuring medication adherence among ART patients. Significant variability was observed across studies, with self-report methods showing a significant tendency towards overestimation. Year of reporting, geographic region, and adherence measurement tools appeared to influence the differences between SR and indirect measurements. Future research should focus on developing and validating integrated adherence measurements that can combine SR data with indirect measures to achieve a more comprehensive understanding of adherence behaviors.

Prevalence and associated factors of low bone mineral density in people living with HIV: a cross-sectional study.

This study examined low bone mineral density (BMD) prevalence and associated factors among Chinese people living with HIV (PLWH), uncovering a persistent high BMD risk in older individuals, even after adjusting for age and body mass index (BMI). Notably, lopinavir/ritonavir (LPV/r) therapy was linked to reduced BMD, highlighting the imperative need for regular BMD monitoring and interventions in older PLWH. PURPOSE: HIV infection and antiretroviral therapy (ART) have been shown to contribute to lower BMD, resulting in an increased susceptibility to osteopenia and osteoporosis. However, there is limited knowledge about the prevalence of reduced BMD and its associated factors among Chinese PLWH. In this cross-sectional study, we aimed to investigate the prevalence and factors associated with low BMD among PLWH in China. METHODS: We retrospectively enrolled PLWH and non-HIV volunteers who underwent dual-energy X-ray absorptiometry (DXA) scans to measure bone density. Demographic information, laboratory test results, ART regimens, and treatment duration were collected. Univariate and multiple regression analyses were performed to identify factors influencing abnormal bone mass in PLWH. RESULTS: A total of 829 individuals were included in this study, comprising the HIV group (n = 706) and the non-HIV group (n = 123). The prevalence of low BMD among all PLWH was found to be 13.88% (98 out of 706). However, among PLWH aged 50 years and above, the prevalence increased to 65.32% (81 out of 124). In contrast, control subjects in the same age group had a prevalence of 38.21% (47 out of 123). After adjusting for age and BMI, older PLWH still demonstrated a higher prevalence of low BMD compared to the non-HIV group (68.24% vs 34.94%, P < 0.001). Multivariate analysis revealed that older age was strongly associated with a higher risk of low BMD among PLWH, with an odds ratio (OR) of 6.28 for every 10-year increase in age in the ART-naïve population (95% confidence intervals [CIs], 3.12-12.65; P < 0.001) and OR of 4.83 in the ART-experienced population (3.20-7.29, P < 0.001). Within the ART-experienced group, current LPV/r treatment was associated with an increased risk of low BMD (OR = 3.55, 1.24-10.14, P < 0.05), along with lower BMI (OR = 0.84, 0.75-0.95, P < 0.05), and elevated alkaline phosphatase (OR = 1.02, 1.01-1.03, P < 0.01). CONCLUSION: The prevalence of low BMD is higher among PLWH aged 50 years and above compared to non-HIV individuals. The use of LPV/r for ART is associated with reduced BMD. These findings emphasize the importance of regular monitoring of BMD in older PLWH and the need for appropriate interventions to mitigate the risks of osteopenia and osteoporosis in this population.

Predictors of Clinical Outcomes among People with HIV and Tuberculosis Symptoms after Rapid Treatment Initiation in Haiti.

Introduction: Few studies have evaluated baseline predictors of clinical outcomes among people with HIV starting antiretroviral therapy (ART) in the modern era of rapid ART initiation. Methods: We conducted a secondary analysis of a randomized controlled trial of two rapid treatment initiation strategies for people with treatment-naïve HIV and tuberculosis symptoms at an urban clinic in Haiti. We used logistic regression models to assess associations between baseline characteristics and (1) retention in care at 48 weeks, (2) HIV viral load suppression at 48 weeks (among participants who underwent viral load testing), and (3) all-cause mortality. Results: 500 participants were enrolled in the study 11/2017-1/2020. Eighty-eight (18%) participants were diagnosed with tuberculosis, and ART was started in 494 (99%). After adjustment, less than secondary education (adjusted odds ratio [AOR] 0.21, 95% CI 0.10-0.46), dolutegravir initiation (AOR 2.57, 95% CI 1.22-5.43), age (AOR 1.42 per 10-year increase, 95% CI 1.01-1.99), and tuberculosis diagnosis (AOR 3.92, 95% CI 1.36-11.28) were significantly associated with retention. Age (AOR 1.36, 95% CI 1.05-1.75), dolutegravir initiation (AOR 1.75, 95% CI 1.07-2.85), and tuberculosis diagnosis (AOR 0.50, 95% CI 0.28-0.89) were associated with viral suppression. Higher CD4 cell count at enrollment (unadjusted odds ratio [OR] 0.69, 95% CI 0.55-0.87) and anemia (OR 4.86, 95% CI 1.71-13.81) were associated with mortality. Conclusions: We identified sociodemographic, treatment-related, clinical, and laboratory-based predictors of clinical outcomes. These characteristics may serve as markers of sub-populations that could benefit from additional interventions to support treatment success after rapid treatment initiation.

Adverse drug reactions, adherence, and virologic outcomes in adult patients on dolutegravir-based antiretroviral therapy at a tertiary hospital, southeast Nigeria.

Objective: To assess the adherence, adverse drug reactions (ADR), and virologic outcomes of dolutegravir-based antiretroviral therapy. Design: This was a retrospective chart review. Setting: A tertiary health facility-based study in Abakaliki, Nigeria. Participants: Five hundred and fifteen (515) adult patients on dolutegravir were selected using a Random Number Generator. Demographic and clinical data were extracted from patients' case notes and analysed with IBM-SPSS version-25. Main outcome measures: Adherence to dolutegravir, ADRs, virologic outcome, and change in Body Mass Index (BMI) were estimated. Results: The mean age of the patients was 45.5±10.8 years; 68.2% of them were females; 97.1% of them had good self-reported adherence. The majority (82.9%) of them reported no ADRs and among those (17.1%) that did, headache (9.7%), body-itching (3.1%), and skin rash (2.7%) dominated. Most achieved viral suppression (94.4%) and did not have detectable viral particles (57.4%). There was a significant increase in the BMI of the patients with a mean weight increase of 0.9kg, a mean BMI increase of 0.3 kg/m2, and a 2.6% increase in the prevalence of overweight and obesity. Conclusions: Patients on dolutegravir reported low ADRs, good self-reported adherence, and a high viral suppression rate. However, dolutegravir is associated with weight gain. We recommend widespread use and more population-wide studies to elucidate the dolutegravir-associated weight gain. Funding: None declared.

Advances in HIV Management During Pregnancy and Infant Feeding.

Recent advances in human immunodeficiency virus (HIV) management during pregnancy and infant feeding encompass several key elements: expanded HIV testing guidance; growing evidence of safety, efficacy, and pharmacokinetic data favoring the use of preferred antiretroviral therapy (ART) during pregnancy and breastfeeding; increasing advocacy for the inclusion of pregnant individuals with HIV in clinical trials to expedite access to new ART; and updated guidelines supporting shared decision-making for choice of infant feeding methods in people with HIV.

Tenofovir-Associated Kidney Dysfunction and Bone Fracture: A Case Report and Literature Review.

Tenofovir is an integral part of antiretroviral therapy used to treat HIV. Long-term use of tenofovir has been associated with decreased glomerular filtration rate, leading to chronic kidney disease, as well as acidosis, electrolyte imbalances, and tubular dysfunction. Tenofovir can also disrupt bone health by decreasing renal phosphate absorption, contributing to osteomalacia. This leads to disruption in mineral metabolism, elevated parathyroid hormone levels, and ultimately, low bone mineral density. Replacing tenofovir with alternative antiretroviral therapy can improve kidney function if done early in the course of the disease. Here, we discuss a case of a 65-year-old woman with HIV who presented with advanced renal failure and hypophosphatemia-induced bone fracture attributed to long-term use of tenofovir. We conclude monitoring kidney function and considering alternative antiretroviral therapy is important to prevent and manage these side effects in patients on long-term tenofovir therapy.

Current syphilis infection in virally suppressed people living with HIV: a cross-sectional study in eastern China.

Background: Antiretroviral therapy (ART) has been shown to reduce human immunodeficiency virus (HIV) viral replication and ultimately achieve viral suppression and eliminate HIV transmission. However, little is known about the impact of viral suppression on high-risk behaviors and sexually transmitted infections (STIs). Objective: This study aimed to assess the rates of current syphilis infection in virally suppressed people living with HIV (PLWH) and whether with the duration of ART can reduce the current syphilis infection in eastern China. Method: We conducted a cross-sectional survey of PLWH in Zhejiang Province, China, in 2022. PLWH who were on ART >6 months and were virally suppressed (viral load <50 copies/mL) were included in the study. Data were collected from the National Epidemiological Database of Zhejiang Province and all participants were tested for viral load and current syphilis. Multivariable logistic regression was used to identify risk factors associated with current syphilis infection. Result: A total of 30,744 participants were included in the analysis. 82.7% of participants were male, the mean age was 44.9 ± 14.1 years, 84.9% had received ART in a hospital setting, the mean time on ART was 5.9 ± 3.1 years and 5.6% of participants were infected with current syphilis. Multivariable logistic regression showed that being male [adjusted odds ratio (aOR): 2.12, 95% confidence interval (CI): 1.69-2.66], high level of education (aOR: 1.23, 95% CI: 1.02-1.49), homosexual route of HIV infection (aOR: 1.80, 95% CI: 1.60-2.04), non-local registered residence (aOR: 1.29, 95% CI: 1.11-1.51), had history of STIs before HIV diagnosis (aOR: 1.95, 95 % CI: 1.75-2.18) and treatment provided by a municipal hospital (aOR: 2.16, 95% CI: 1.31-3.55) were associated with increased risk of current syphilis infection. Being married (aOR: 0.67, 95% CI: 0.58-0.76) was associated with a decreased risk of current syphilis infection. Conclusion: Our findings revealed a high rate of current syphilis infection among virally suppressed PLWH in eastern China. Duration of ART did not reduce the prevalence of current syphilis infection. Targeted interventions to reduce current syphilis infection should be prioritized for subgroups at higher risk.

Explaining inequity in knowledge, attitude, and services related to HIV/AIDS: a systematic review.

BACKGROUND: Equitable service provision and coverage are important responses to end the threat of the HIV/AIDS pandemic. Understanding inequity supports policies and programmes to deliver tailored interventions. There is continuous evidence generation on inequity in HIV/AIDS services. However, there was a lack of evidence on the global picture of inequity in behavioural and biomedical services related to HIV/AIDS. This systematic review assessed inequities in knowledge, attitude, HIV testing, and ART coverage across individual-level social groups and multiple (dis)advantage categories. METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline, with a PROSPERO registration number CRD42024521247. The risk of bias was assessed by using Hoy et al's and Joanna Brigg's quality appraisal checklists for cross-sectional quantitative and qualitative studies, respectively. The search date was from inception to the final database search date (May 29, 2023). The included articles were either quantitative or qualitative studies. We used mixed-methods approach to analyse the data from the review articles. Quantitative descriptive analysis was conducted to estimate frequency of articles published from different countries around the world. Qualitative content analysis of the findings from the original studies was conducted using the PROGRESS plus framework which stands for: place of residence, occupation or employment status, gender, religion, education status, socioeconomic status, and social capital. RESULTS: Out of 6,029 articles that were accessed and screened, only 72 articles met the inclusion criteria. More articles on HIV-related equity in knowledge, attitude, testing, and ART were published in developed countries than in developing countries. Individuals from higher-income households had better knowledge about HIV/AIDS. Unfavourable attitudes towards people living with HIV and HIV/AIDS-associated stigma were common among women. HIV/AIDS service coverage (HIV testing or ART coverage) was higher among richer and urban residents. HIV/AIDS-associated stigma and lower levels of knowledge about HIV/AIDS were observed among multiple disadvantageous groups due to the intersection of two or more identities. CONCLUSIONS: The current review revealed that there have been disparities in HIV/AIDS services between social classes. Ending service disparity towards the global threat of HIV/AIDS demands tailored interventions based on socially disadvantaged groups (e.g., poor, rural dwellers, and women) and intersectional determinants. There is a need to understand the deep-rooted causes of inequity and the challenges that an equity-oriented system faces over time. More studies on inequity are needed, including intersectional inequity, which has been rarely studied in developing countries.

Utility of the Alcohol Use Disorder Inventory Test in determining caseness for alcohol use disorder among persons receiving antiretroviral therapy.

We sought to determine the utility of the Alcohol Use Disorder Identification Test (AUDIT) in screening for alcohol use disorder (AUD) among 688 users of antiretroviral therapy (ART). We used the receiver operating characteristic (ROC) curve analysis to assess whether the AUDIT reliably detected AUD against the Structured Clinical Interview for the DSM (SCID). Of the samples, 22.09% (CI: 19.05% to 25.38%) of participants met the diagnostic criteria for AUD. Among men (n = 135) and women (n = 553), the prevalence estimates were 31.9% and 19.7%, respectively. For men, a cut-off score of 6 predicted AUD with 88.36% (95%CI: 74.92-96.11) sensitivity and 88.04% (95%CI: 79.61-93.88) specificity. For women, a cut-off score of 4 on the AUDIT yielded an optimal sensitivity of 92.66% (95% CI: 86.05%-96.78%) and a specificity of 93.24% (95% CI: 90.49-95.40%). For men, the AUDIT yielded a positive predictive value (PPV) of 75.55% (95% CI: 66.26%-85.87%) and a negative predictive value (NPV) of 91.49% (95% CI: 87.63-97.37%); for women the PPV and NPV were 77.09% (70.34%-82.68%) and 98.11% (96.37%-99.02%), respectively. The instrument's good sensitivity and specificity indicate it is likely to be useful for screening and referral of ART users who are probably cases of AUD.

Weight Gain and Antiretroviral Therapy.

Antiretroviral therapy (ART) agents as a determinant of body weight in ART-naïve and ART-experienced persons with human immunodeficiency virus (HIV) (PWH) has become a major focus area in research and clinical settings. Recent studies demonstrating weight-suppressing properties of efavirenz and tenofovir disoproxil fumarate led to re-evaluation of weight gain studies, and a reassessment of whether other agents are weight promoting versus weight neutral. In this review, the authors synthesize recent literature on factors related to obesity, clinical measurements of adiposity, weight gain in ART-naïve and ART-experienced PWH, metabolic consequences of ART and weight gain, and the clinical management of weight gain in PWH.

Influence of Stigma on Engagement in HIV Care and Adherence to Antiretroviral Therapy in Specialized HIV Clinics Targeting Men Who Have Sex with Men and Transgender Women in Lima, Peru.

HIV stigma is a social determinant of health that can influence multiple health outcomes, including adherence to antiretroviral therapy (ART), engagement in HIV care, and viral suppression levels in people with HIV (PWH). In Peru, where the HIV epidemic is concentrated in men who have sex with men (MSM) and transgender women (TGW), stigma may play an important role in healthcare engagement. To understand the relationship between stigma and two outcome variables, ART adherence and engagement in HIV care in 400 MSM and TGW, we assessed factors from the Behavioral Model for Vulnerable Populations at two HIV clinics that tailor services for sexual and gender minorities. While some predisposing, need, and enabling resource factors were associated with optimal (≥ 90%) ART adherence or engagement in HIV care, none of the stigma subscales were correlated, suggesting that when LGBTQ-affirming care is provided to MSM/TGW, stigma may not influence HIV-related outcomes.

RESUMEN: El estigma hacia el VIH es un determinante social de la salud que puede influir en múltiples desenlaces, incluyendo la adherencia a la terapia antirretroviral (TAR), el compromiso con la atención del VIH y los niveles de supresión viral en personas viviendo con VIH (PVV). En el Perú, donde la epidemia del VIH se concentra en hombres que tienen sexo con hombres (HSH) y mujeres transgénero (MT), el estigma puede desempeñar un papel importante en el compromiso con la atención médica. Para comprender la relación entre el estigma y dos variables de resultado, la adherencia al TAR y el compromiso con la atención del VIH en 400 HSH y MT, evaluamos factores del Modelo de Comportamiento para Poblaciones Vulnerables en dos clínicas de VIH que adaptan sus servicios para minorías sexuales y de género. Si bien algunos factores predisponentes, de necesidad y de recursos habilitantes se asociaron con una adherencia óptima (≥ 90%) al TAR o al compromiso con la atención del VIH, ninguna de las sub-escalas de estigma estuvieron correlacionadas, sugiriendo que cuando se brinda atención que afirma a la comunidad LGBTQ a HSH/MT, el estigma puede no influir en los desenlaces relacionados con el VIH.

The Current Pipeline of Antiretroviral Therapy: Expanding Options and Filling Gaps.

Highly effective antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) care in the past 3 decades. 30 years ago, how many would have imagined that a single-tablet daily ART regimen containing different drug classes could achieve sustained HIV-1 suppression and halt disease progression to acquired immunodeficiency syndrome (AIDS)? Despite this remarkable achievement, challenges in HIV care remain that require further innovation for ART. In this review, we focus on newly approved antiretroviral agents and those undergoing phase 2/3 clinical trials. These new antiretrovirals hold great promise to expand treatment options and fill gaps in HIV care.

'I take the drugs to make the sickness to move out of me': key populations' and service provider perspectives about facilitators and barriers to ART adherence and retention in care in Nigeria.

BACKGROUND: Adherence to antiretroviral therapy (ART) has individual and public health benefits and is critical to improving life expectancy, achieving viral suppression, and reducing the risk of HIV transmission. This qualitative study explored the experience of receiving care as well as perceived facilitators and barriers of treatment initiation, retention in ART care, and adherence to treatment. METHODS: In-depth interviews were conducted among 28 men who have sex with men (MSM) and female sex workers (FSWs) receiving ART services in Lagos and Benue states. Key informant interviews were also conducted among 16 service providers engaged in counselling, clinical care, and ART treatment for MSM and FSWs. The Social Ecology Model guided the exploration of perceived barriers and facilitators of treatment initiation, retention in ART care and adherence to treatment. Qualitative data analysis was managed using NVIVO 11 software and themes were analysed using thematic analysis. RESULTS: We found that the key barriers to ART adherence were low motivation to comply with medication regimen, work commitments, socioeconomic factors, stigma, negative provider attitude and distance to health facilities. Facilitators of adherence identified include the desire to live a productive life, strong family support and participation in support group programs. Comprehensive adherence counselling, support group programs and an effective follow-up system were factors identified by service providers as key to facilitating adherence. CONCLUSION: To be effective, ART programs must address the unique challenges key populations face in accessing treatment and achieving optimal adherence regarding establishing a strong support system and follow-up. Community level interventions that support a stigma-free environment are critical to sustaining engagement in care.

The prevalence of HIV resistance mutations and their influence on the shedding of HIV-1 into peritoneal dialysis effluent.

HIV drug resistance mutations (HIVDRMs) are important determinants of therapeutic effects and outcomes even in end-stage kidney failure (ESKF) people living with HIV (PLWHIV). This study evaluated the prevalence of HIVDRMs and their effect on the shedding of HIV-1 into peritoneal dialysis (PD) effluents. This cross-sectional study of PLWHIV and having ESKF and managed with antiretroviral therapy (ART) and PD, collected enrolled patients' demographic information, clinical and laboratory data, and sequenced HIV-1 RNA in unsuppressed plasma and PD effluent samples. HIV viral load and HIVDRMs were determined using qualitative polymerase chain reaction (qPCR) and Stanford University HIVDRM Database, respectively. There were 60 participants recruited with a median age of 43.0 (interquartile range [IQR], 38.0-47) years and were predominantly on abacavir (88.3%), lamivudine (98.3%), and efavirenz (70%) for a median duration of 8 (IQR, 5-11) years. Among participants with detectable HIV-1 in PD effluents, the prevalence of HIVDRMs was 62.5% (5/8) compared to 7.7% (4/52) among those with undetectable HIV-1 (p = 0.001) with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations predominating. On Spearman's correlation analysis, high plasma HIV levels (ρ = 0.649, p < 0.001), T-cell CD4 count (ρ = -0370, p < 0.004), serum creatinine (ρ = -0.396, p < 0.002), and white blood cell count (ρ = -0.294, p < 0.023) levels were significant factors correlated with the detection of HIV-1 in PD effluents. Moreover, HIVDRMs presence (ρ = 0.504, p < 0.001) particularly NNRTI resistance (ρ = 0.504, p < 0.001) were also significantly correlated with detection of HIV-1 in PD effluents. The presence of HIVDRMs, high plasma HIV viral load, and T-cell CD4 count were correlated with HIV-1 shedding into PD effluents.

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

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

Association of comprehensiveness of antiretroviral care and detectable HIV viral load suppression among pregnant and postpartum women in the Democratic Republic of the Congo: a cross-sectional study.

Introduction: Worldwide, over two-thirds of people living with HIV are on antiretroviral therapy (ART). Despite increased ART access, high virological suppression prevalence remains out of reach. Few studies consider the quality of ART services and their impact on recipients' viral suppression. We assessed the association between ART service readiness and HIV viral load suppression among pregnant and breastfeeding women living with HIV (WLH) receiving ART in maternal and child health (MCH) clinics in Kinshasa, Democratic Republic of Congo. Methods: We performed a cross-sectional analysis leveraging data from a continuous quality improvement intervention on WLH's long-term ART outcomes. From November 2016 to May 2020, we enrolled WLH from the three largest clinics in each of Kinshasa'Ls 35 health zones. We measured clinic's readiness using three WHO-identified ART care quality indicators: relevant guidelines in ART service area, stocks of essential ART medicines, and relevant staff training in ≥24 months, scoring clinics 0-3 based on observed indicators. We defined viral load suppression as ≤1,000 cp/ml. Multilevel mixed-effect logistic models were used to estimate prevalence odds ratios (ORs) measuring the strength of the association between ART service readiness and viral suppression. Results: Of 2,295 WLH, only 1.9% received care from a clinic with a score of 3, 24.1% received care from a 0-scoring clinic, and overall, 66.5% achieved virologically suppression. Suppression increased from 65% among WLH receiving care in 0-scoring clinics to 66.9% in 1-scoring clinics, 65.8% in 2-scoring clinics, and 76.1% in 3-scoring clinics. We did not observe a statistically significant association between ART service readiness score and increased viral suppression prevalence, however we did find associations between other factors, such as the location of the health center and pharmacist availability with suppressed viral load. Discussion: A lack of comprehensive ART care underscores the need for enhanced structural and organizational support to improve virological suppression and overall health outcomes for women living with HIV..

Risk Factors Associated with Osteopenia/Osteoporosis in Antiretroviral Therapy Naive HIV Patients Maltepe University, Turkey.

INTRODUCTION/OBJECTIVES: Different ART (antiretroviral therapy) options may affect the risk of osteopenia/osteoporosis in people living with HIV (PLWH) having increased life expectancy. Current guidelines recommend bone mineral density (BMD) measurement only in patients at risk. In our study, we investigated the prevalence of osteopenia/osteoporosis and associated risk factors in naive patients not receiving ART. METHODS: This study included 116 newly diagnosed, ART naive HIV-positive patients who were studied retrospectively. Vitamin D level, BMD measurement, CD4 and CD8 count, CD4/CD8 ratio, HIV RNA level, body mass index and other risk parameters of ART naive patients were included in our study. RESULTS: Of 116 patients, 103 were male and 13 female. 47.4% (osteoporosis in 4.3%, osteopenia in 43.1%) of patients had osteopenia/osteoporosis. The patients with osteopenia/osteoporosis had older age (39.2±11.0 vs 32.0±8.6, p=0.0001), lower vitamin D levels (16.0±5.0 vs 24.4±6.3, p=0.0001), lower BMI (body mass index) (23.0±4.0 vs 24.6±4.6 p<0.05), lower CD4 and CD8 counts (405.1±885.0 vs 467.3± 695.1; 849.9570.4 vs 1012.0±629.4 respectively, p<0.05). 41.8% had CD4 count ≤200/µL (vs 18.0%, p=0.005). No statistically significant differences were observed in terms of gender distribution, smoking, alcohol and drug use, comorbidities and, additional drug use and HIV RNA >100 000 copies/ml. In multivariate analysis, age and vitamin D level were significant and independent (p<0.05) risk factors with osteoporosis/osteopenia. CONCLUSION: Being over 40 years of age, CD4 count ≤200/µL, vitamin D level <20 ng/mL and low BMI are the most important risk factors for osteopenia/osteoporosis in ART naive patients. Among these parameters, age and vitamin D level were significant and independent risk factors. These factors may guide the determination of the need for dual-energy x-ray absorptiometry (DXA) testing in ART naive patients and drug choices in the treatment plan.

Factors associated with incomplete adherence to integrase strand transfer inhibitor-containing single-tablet regimen among Japanese people living with HIV.

BACKGROUND: People living with human immunodeficiency virus (PLWH) require high rates of medication adherence to antiretroviral therapy (ART) for a successful treatment outcome. Understanding the factors associated with incomplete adherence among those receiving integrase strand transfer inhibitor-containing single-tablet regimens (INSTI-STRs) is crucial for improving treatment outcomes. This study aimed to identify the factors contributing to incomplete ART adherence among Japanese PLWH receiving INSTI-STRs. METHODS: This multicenter cross-sectional study was conducted at 11 Japanese institutions as an anonymous survey. ART adherence was assessed using a self-reported questionnaire. We defined incomplete ART adherence as missing ≥ 1 dose of antiretroviral drugs (ARVs) over the past month. The factors associated with incomplete ART adherence were assessed using logistic regression analysis. Additionally, we investigated the associations between patients' satisfaction score with and need for ARVs and their adherence to ART. RESULTS: The final analysis included data of 387 patients who were treated with INSTI-STRs. Multivariate logistic regression demonstrated significant association of younger age (adjusted odds ratio [aOR], 0.79; 95%confidence interval [CI]: 0.64-0.99 for each 10-year increment) with incomplete ART adherence. Additionally, female sex (aOR, 3.98; 95%CI: 1.36-11.60); depressive symptoms (mild depression: aOR, 1.68; 95%CI: 1.001-2.82, moderate depression: aOR, 2.98; 95%CI: 1.35-6.53, and severe depression: aOR, 8.73; 95%CI: 1.38-55.00 vs. minimal depression); were also significantly associated with incomplete ART adherence when compared with the reference categories. Concomitant medication usage was significantly associated with a lower rate of incomplete ART adherence (1-4 medications: aOR, 0.53; 95%CI: 0.31-0.89 and ≥ 5 medications: aOR, 0.30; 95%CI: 0.13-0.70 vs. no concomitant medication usage). In the incomplete ART adherence group, satisfaction scores for various aspects were significantly lower. Furthermore, a lower proportion of patients in the incomplete ART adherence group preferred the option of "taking tablets daily and visiting the hospital every 3 months," compared to those in the complete ART adherence group (p = 0.008). CONCLUSIONS: This study demonstrated that factors associated with incomplete ART adherence include younger age, female sex, no concomitant medication, and depressive symptoms. Despite ART simplification, incomplete adherence among PLWH receiving INSTI-STRs, remains a challenge, requiring additional actions.

Virologic Failure and Drug Resistance After Programmatic Switching to Dolutegravir-based First-line Antiretroviral Therapy in Malawi and Zambia.

BACKGROUND: People with human immunodeficiency virus (PWH) on first-line, nonnucleoside reverse-transcriptase inhibitor-based antiretroviral therapy (ART) were routinely switched to tenofovir-lamivudine-dolutegravir. We examined virologic outcomes and drug resistance in ART programs in Malawi, where switching was irrespective of viral load, and Zambia, where switching depended on a viral load <1000 copies/mL in the past year. METHODS: We compared the risk of viremia (≥400 copies/mL) at 1 and 2 years by viral load at switch and between countries using exact methods and logistic regression adjusted for age and sex. We performed HIV-1 pol Sanger sequencing on plasma samples with viral load ≥1000 copies/mL. RESULTS: A total of 2832 PWH were eligible (Malawi 1422, Zambia 1410); the median age was 37 years, and 2578 (91.0%) were women. At switch, 77 (5.4%) were viremic in Malawi and 42 (3.0%) in Zambia (P = .001). Viremia at switch was associated with viremia at 1 year (adjusted odds ratio (OR), 6.15; 95% confidence interval [CI], 3.13-11.4) and 2 years (7.0; 95% CI, 3.73-12.6). Viremia was less likely in Zambia than in Malawi at 1 year (OR, 0.55; 0.32-0.94) and 2 years (OR, 0.33; 0.18-0.57). Integrase sequencing was successful for 79 of 113 eligible samples. Drug resistance mutations were found in 5 PWH (Malawi 4, Zambia 1); 2 had major mutations (G118R, E138K, T66A and G118R, E138K) leading to high-level dolutegravir resistance. CONCLUSIONS: Restricting switching to dolutegravir-based ART to PWH with a viral load <1000 copies/mL may reduce subsequent viremia and, consequently, the emergence of dolutegravir drug resistance mutations. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov (NCT04612452).