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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. [ABSTRACT FROM AUTHOR]

Objective: Several cases of Fanconi syndrome (FS), a severe form of nephrotoxicity, have been reported in patients with HIV on tenofovir-containing antiretroviral therapy. A systematic review of the published literature on tenofovir-related FS in patients with HIV was conducted. Data Sources: PubMed and Embase were queried to identify articles in English published between January 2005 and June 2023, reporting tenofovir-related FS in adults with HIV. Preclinical studies, conference/poster abstracts, commentaries and responses, and review papers were excluded. Study Selection and Data Extraction: Of the 256 articles screened, 57 met the inclusion criteria. These comprised 37 case reports, 11 case series, 1 cross-sectional study, 1 case-control study, 4 cohort studies, 1 single-arm open-label clinical trial, 1 sub-analysis of clinical trials, and 1 pooled analysis of clinical trials. Data Synthesis: Among 56 cases on which information was abstracted, median age at FS diagnosis was 50 years, 51.8% were men, and duration of tenofovir use ranged from 6 weeks to 11 years. Ritonavir was co-prescribed in almost half the cases. In observational and interventional studies, incidence of FS was low. Many studies reported resolution of FS symptoms after tenofovir discontinuation. All FS occurrences were identified in those on tenofovir disoproxil fumarate (TDF), except for one patient on tenofovir alafenamide (TAF). Relevance to Patient Care and Clinical Practice: Continuous monitoring of signs and symptoms of renal and bone toxicity is essential for patients with HIV on tenofovir-containing therapy. Conclusions: Occurrence of FS is low in patients with HIV treated with tenofovir-based regimens. Concomitant use of ritonavir may increase risk of FS. TAF may be a safer alternative than TDF in terms of nephrotoxicity. [ABSTRACT FROM AUTHOR]

Background: Depression is a very common psychiatric disorder in worldwide. Globally, Human Immunodeficiency Virus (HIV) is highly prevalent among women, and are disproportionately affected by depression. Antiretroviral Therapy (ART) adherence which could highly be affected by depression is yet to be explored effectively. Depression affects overall poor HIV clinical outcomes, socioeconomic and social interactions. However, it is not well understood specifically how depression affects ART adherence in women living with HIV (WLWHIV). Investigating the effects of depression on ART adherence is critical in order to develop nuanced new evidence to address non-adherence in WLWHIV. Objective: To conduct a meta-analysis on the correlation between depression and adherence to antiretroviral therapy among women living with HIV in the globe. Method: Using population, exposed and outcome approach, we searched Scopus, PubMed, EMBASE, Cochrane Library, Psych info, Web of science and google scholar for cohort and cross-sectional studies globally. The search strategy was structured comprising terms associated with antiretroviral therapy and adherence, women living with HIV and depression. We evaluated the paper quality, using the Newcastle-Ottawa Scales (NOS). The fixed effect model was used to analysis the effect of depression on ART adherence. Result: A total of 8 articles comprise 6474 participants were included in this study. There were controversial findings related to the effect of depression to ART adherence. Among three cross-sectional study, one article demonstrating, depression was associated with ART adherence. Of the five cohort studies, four cohort studies reported association. The overall pooled estimated effect of depression on ART adherence was 1.02 [RR = 1.015 with 95% CI (1.004, 1.026)] with a p-value of 0.005. Conclusion and recommendation: Depression was the risk factor for ART adherence among women living with HIV. It is therefore, necessary for clinician to note this and perform screening for ART adherence. Trial registration: The review protocol was developed with prospero registration:CRD42023415935. [ABSTRACT FROM AUTHOR]

This paper tackles the complex interplay between Human Immunodeficiency virus (HIV-1) and Mycobacterium tuberculosis (M. tuberculosis) infections, particularly their contribution to immunosenescence, the age-related decline in immune function. Using the current literature, we discuss the immunological mechanisms behind TB and HIV-induced immunosenescence and critically evaluate the BCG (Bacillus Calmette-Guérin) vaccine's role. Both HIV-1 and M. tuberculosis demonstrably accelerate immunosenescence: M. tuberculosis through DNA modification and heightened inflammation, and HIV-1 through chronic immune activation and T cell production compromise. HIV-1 and M. tuberculosis co-infection further hastens immunosenescence by affecting T cell differentiation, underscoring the need for prevention and treatment. Furthermore, the use of the BCG tuberculosis vaccine is contraindicated in patients who are HIV positive and there is a lack of investigation regarding the use of this vaccine in patients who develop HIV co-infection with possible immunosenescence. As HIV does not currently have a vaccine, we focus our review more so on the BCG vaccine response as a result of immunosenescence. We found that there are overall limitations with the BCG vaccine, one of which is that it cannot necessarily prevent re-occurrence of infection due to effects of immunosenescence or protect the elderly due to this reason. Overall, there is conflicting evidence to show the vaccine's usage due to factors involving its production and administration. Further research into developing a vaccine for HIV and improving the BCG vaccine is warranted to expand scientific understanding for public health and beyond. [ABSTRACT FROM AUTHOR]

The Antiretroviral Therapy (ART) management system is a comprehensive software application designed to streamline and enhance the management and monitoring of patients undergoing antiretroviral treatment for HIV/AIDS. The system aims to improve the quality of care provided to ART patients, ensuring accurate treatment initiation, medication dispensing, clinical monitoring, appointment scheduling, adherence monitoring, side effects management, and reporting. By integrating various functionalities, the system enables healthcare providers to efficiently manage patient data, track treatment outcomes, and make informed decisions for optimal patient care. Additionally, the system prioritizes data security and privacy, complying with relevant regulations and employing measures to protect patient confidentiality. Through its integration capabilities, the system fosters interoperability with other healthcare information systems, promoting seamless data exchange and collaboration. Overall, the ART management system serves as a valuable tool in the comprehensive management of ART patients, ultimately contributing to improved health outcomes for individuals living with HIV/AIDS. [ABSTRACT FROM AUTHOR]

The HIV/AIDS pandemic is a global issue that has unequally affected several countries. Due to the complexity of this condition and the human drama it represents to those most affected by it, several fields have contributed to solving or at least alleviating this situation, and the information systems (IS) field has not been absent from these efforts. With the importance of antiretroviral therapy (ART) as a starting point, several initiatives in the IS field have focused on ways to improve the adherence and effectiveness of this therapy: mobile phone reminders (for pill intake and appointments), and mobile interfaces between patients and health workers are popular contributions. However, many of these solutions have been difficult to implement or deploy in some countries in the Global South, which are among the most affected by this pandemic. This paper presents one such case. Using a case‐study approach with an extreme‐case selection technique, the paper studies an m‐health system for HIV patients in the Kalangala region of Uganda. Using Heeks' design—reality gap model for data analysis, the paper shows that the rich interaction between social context and technology should be considered a central concern when designing or deploying such systems. [ABSTRACT FROM AUTHOR]

In this paper, we report the synthesis of a multi-template molecularly imprinted polymer (MIP) to target and extract naproxen, ibuprofen, diclofenac, emtricitabine, tenofovir disoproxil, and efavirenz from wastewater bodies. A bulk polymerization procedure was used to synthesize the MIP and non-imprinted polymer (NIP). The specific recognition sites for each target were obtained through the removal of the imprinted targeted compounds. The interaction of antiretroviral drugs (ARVs) and non-steroidal anti-inflammatory drugs (NSAIDs) compounds with the MIP was studied under various conditions such as pH, mass, concentration, and time factors. The results demonstrated the optimum conditions were 55 mg of MIP, pH 7.0, a concentration of 5 mg L−1, and a contact time of 10 min. For every compound studied, the extraction efficiencies for ARVs and NSAIDs in aqueous solutions was >96%. The adsorption capacity for the MIP was >0.91 mg·g−1. Adsorption obeys a second-order rate, and the Freundlich model explains the adsorption isotherm data. This study demonstrated that the synthesized multi-template MIP has huge potential to be employed for the removal of ARVs and NSAIDs from the environment as well as in drug purification or recovery processes. [ABSTRACT FROM AUTHOR]

Etravirine (ETV) is an antiretroviral agent that belongs to the class of non-nucleoside reverse transcriptase inhibitors. This study explores the uptake and distribution of ETV in human aortic endothelial cells (HAECs) using Raman spectroscopy combined with chemometrics. The distinctive chemical structure of ETV facilitates tracking of its uptake by observing the Raman band at 2225 cm−1 in the Raman-silent region. The perinuclear distribution pattern in HAECs depends on drug concentration and incubation time. The uptake of ETV is observed within 5 minutes at a concentration of 10 μM, as evidenced by Raman images. Lower ETV concentrations, reflective of those found in human plasma, are detectable in HAECs by applying chemometric methods to Raman spectra from the perinuclear region. The ETV accumulation process is crucial in advancing our understanding of the drug's impact on biochemical alterations within endothelial cells. Additionally, ETV emerges as a promising Raman reporter for marking subcellular compartments, leveraging the 2225 cm−1 band in the cellular Raman silent region. This research contributes valuable insights into the behavior of ETV at the subcellular level, shedding light on its potential applications and impact on subcellular dynamics. [ABSTRACT FROM AUTHOR]

Background: Many children and adolescents living with HIV have ended up as orphans. Due to HIV taking away their parents leaves them deprived of their most important social network and support, which predisposes them to poor adherence to antiretroviral therapy (ART). Various studies have shown poor adherence to ART among orphaned children and adolescents. This systematic review and meta-analysis, therefore, aims to determine the level of ART adherence among orphaned children and adolescents living with HIV/AIDS. Methods: This PROSPERO registered review (CRD42022352867) included studies from PubMed, Google Scholar, Scopus, Web of Science, Africa Journal Online, and selected HIV/AIDS journals from data inception to June 01, 2022. We included articles published in all languages that report the prevalence of adherence to ART among children and adolescent orphans (single parent orphans and/or double orphans) living with HIV/AIDS. We excluded qualitative studies, case studies, opinion papers, and letters to editors. We used the random-effect model to calculate the pooled prevalence of ART adherence based on the highest prevalence provided by the various methods in a particular study. We used the Joanna Briggs Institute Appraisal tool for the prevalence study to evaluate for risk of bias in the included studies. The Egger's test was used to assess small study effects. Results: Out of 1087 publications identified from the various databases, six met the selection criteria. The included six studies had a total 2013 orphans living with HIV/AIDS. The pooled prevalence of ART adherence was 78∙0% (95% Confidence Interval: 67.4–87.7; I2 = 82.92%, p<0∙001) and ranged between 7∙6% and >95%, using one of the following methods: pill count, caregiver's self-report, clinical attendance, and nevirapine plasma levels (above three μg/mL). The factors associated with adherence were pill burden, caregiver involvement, stunting, and caregiver relationship. Limitation: There was a high level of heterogeneity in the finding. Conclusion: Approximately four fifth of orphan children and adolescents living with HIV/AIDS adhere to ART. Strategies to improve adherence among this group should be prioritized, especially among the double orphaned children and adolescents. [ABSTRACT FROM AUTHOR]

Introduction: Adverse drug reactions (ADRs) are harmful and unintended reactions to medicines given at standard doses through a proper route of administration for the purpose of prophylaxis, diagnosis, or treatment. Objective: The objective of this research paper was to assess median time to development of ADRs and associated factors among children HIV positive patients on antiretroviral treatment (ART) in North West Amhara Specialized Hospitals. Methods: The adverse drug effect survival time was estimated using the Kaplan–Meier survival method and log‐rank test curves was applied for analyze "time‐to‐event" data. Cox regression model was used to identify the associated factors. Adjusted hazard ratios with their respective 95% confidence intervals (CIs) were estimated and a value of p less than 0.05 was used to declare the presence of a significant association. Result: The overall incidence of ADRs was 0.67 (95% CI: 3.74–4.44) per 10,000 person‐year observation, with a median of 57 months. Adults are presenting with opportunistic Infections (OIs) experiences, baseline CD4 < 200 cells/µL counts, 1e, tenofovir disoproxil fumarate–lamivudine–efavirenz ART regimen, bedridden baseline functional status, World Health Organization (WHO) clinical stage II and III were notably associated with the incidence of ADRs development. Conclusion: ADRs were uncommon in this study. predictors, such as OIs experiences, a low CD4 count, ART regimen, an advanced WHO stage, and bedridden functional status were significantly associated with ADRs. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the use of antiretroviral treatment (ART) is effective in reducing the risk of HIV transmission to the foetus, there are concerns of possible adverse effects of in utero exposure on offspring's cardio-metabolic health. This paper systematically reviewed the effects of HIV/ART exposure during pregnancy on the cardio-metabolic health of offspring. Reports from 35 eligible studies showed that HIV-exposed uninfected (HEU) children's cardio-metabolic health was negatively impacted by in utero exposure to ART. A few studies showed direct cardiometabolic risk factors including increased blood pressure and lipids, reduced insulin, oxidative stress, cardiac damage and vascular and myocardial dysfunction among HEU children compared to their HIV-unexposed uninfected (HUU) children while most studies reported indirect cardiovascular risk factors including reduced head circumference, low birth weight, and altered mitochondrial content in HEU children. These findings suggest that in utero exposure of ART may affect foetal health predisposing them to cardiometabolic diseases later in life. Background: Antiretroviral treatment (ART) use during pregnancy continues to rise as it is known to decrease the likelihood of HIV transmission from mother to child. However, it is still unknown whether foetal exposure to (ART) may affect the foetal environment, predisposing the offspring to cardiometabolic risk. Therefore, the aim of this study was to systematically review the cardio-metabolic effects of in utero exposure to HIV/ART on offspring. Methods: We carried out a systematic review and obtained literature from the Google scholar, PubMed, ProQuest, Web of Science, and Scopus databases. Two independent reviewers evaluated the titles, abstracts, and full-length English contents. Data from the eligible studies were included. Results: The search yielded 7596 records. After assessing all of these records, 35 of the full-length articles were included in this systematic review. Several studies showed that low birth weight, small head circumference, and altered mitochondrial content were more common among HIV-exposed uninfected (HEU) children compared to HIV-unexposed uninfected children (HUU). A few studies demonstrated elevated triglyceride levels, lower levels of insulin, and increased blood pressure, oxidative stress, vascular dysfunction, cardiac damage, and myocardial dysfunction among HEU children compared with HUU children. Conclusion: Most findings showed that there were cardio-metabolic health risk factors among HEU children, indicating that maternal exposure to HIV and ART may negatively affect foetal health, which may lead to cardio-metabolic morbidity later in life. [ABSTRACT FROM AUTHOR]

Background: Optimum adherence to antiretroviral therapy (ART) is crucial in managing HIV. However, some people's religious beliefs can influence how they deal with HIV and the psychosocial factors influencing their adherence to ART, such as disclosure, acceptance of HIV status, belief in ART, and depression. In sub-Saharan Africa (SSA), the role of religious beliefs in ART adherence is underexplored. We aimed to identify and conceptualize the literature on religious beliefs concerning ART adherence among Pentecostal Christians living with HIV in SSA. Methods: We conducted a scoping review of the literature on religious beliefs and ART adherence. We searched papers from PubMed, Web of Science, Medline, Sabinet, Academic Search Complete, CINAHL Plus, Health Source/Nursing Academic, Scopus, and Google Scholar and published papers from conference proceedings and dissertations. Data were extracted according to a predetermined population, concept, context framework, and eligibility criteria for selecting or rejecting studies. We used a narrative synthesis to summarize the data on evidence and the impact of religious beliefs on ART adherence. Results: Seven papers published between January 2010 and February 2022 met the inclusion criteria. Nineteen aspects of religious beliefs were identified as negatively influencing ART adherence, while eight aspects facilitated optimal adherence. "Being saved" or "born again" enhanced coping strategies for optimal adherence through actions such as less alcohol use, fidelity to a sexual partner(s), disclosure, acceptance of HIV status, reduced depression, and facilitated PLHIV to access social support from church members or other institutions. Conclusion: Religious beliefs are integral to Pentecostal Christians living with HIV and affect their adherence to ART. While some Pentecostal Christians living with HIV on ART use their religious beliefs and practices to access psychosocial support from other church members or organizations and achieve good clinical outcomes, others apply their religious beliefs and practices differently and compromise their commitments to taking ART as prescribed, thus experiencing poor viral suppression and clinical outcomes. However, more research is required to understand and theorize how religious beliefs impact ART adherence among Pentecostals living with HIV to inform guidelines for practitioners. [ABSTRACT FROM AUTHOR]

This discussion paper aimed to reflect on the development of relational connections in the context of a web-based, tailored, asynchronous nursing intervention (VIH-TAVIETM) aimed at empowering people living with HIV in taking their antiretroviral treatment. Our reflection culminates in the Relational Virtual Nursing Practice Model. This paper builds on nurse-researchers and people living with HIV's experiences, nursing theories, and cross-disciplinary work on relational engagement. The model shows the disciplinary principles underpinning VIH-TAVIETM, engagement processes used to create humanistic and supportive relational environment and people's relational experiences and it contributes to the development of conceptual nursing knowledge on how generating meaningful relational nursing care in virtual environments. [ABSTRACT FROM AUTHOR]

Introduction: Time from identification as people living with HIV/AIDS (PLWHA) to a confirmatory test followed by antiretroviral therapy (ART) initiation is critical to any HIV prevention and control program. Gaps persist in identifying and linking PLWHA with health system, making it necessary to continue looking for strategies to close this breach. Material and methods: AIDS Healthcare Foundation (AHF) has been working on linking recently diagnosed HIV patients in Peru, and this paper summarized the experiences and results obtained from our linkage to care program between 2016 and 2019. Methods utilized for linkage to care include telephone communication, accompaniment to health service, social support, multidisciplinary team assessment, and initiation of ART when indicated. Results: During 2014-2019 we identified 9,991 PLWHA, in which 8,491 (84.98%) had an initial contact (initial linkage to care), and 6,899 (69.05%) received highly active antiretroviral therapy (effective link to care). We observed a consecutive increase in attention, as in the number of effective linkages, growing from 566 (80.17%) in 2016 to 3,237 (85.39%) in 2019. Among genders, males had the higher ratios of effective linkage to care (85.69%), while transgender women had the lower (79.14%). Conclusions: We observed that linkage to care is a strategy that provides more opportunities for treatment of PLWHA, and it is helpful in low-income countries. [ABSTRACT FROM AUTHOR]

Failure to meet international targets set for the human immunodeficiency virus HIV pandemic suggests that more effective public health strategies are needed. New strategies informed by behavioural economics are now increasingly being tested, with promising results. However, the evidence base is diverse and challenging for policymakers to interpret. This paper aims to synthesise existing evidence by reporting results from a systematic review of behavioural economics-based interventions for addressing HIV prevention, testing and treatment. The reported study was a systematic review of randomized controlled trials. The search was conducted in four electronic medical literature databases, six trial registries, four grey literature sources and was not restricted to any country or region. Bias was assessed using criteria outlined in the Cochrane Handbook for Systematic Reviews; quality of evidence was assessed using GRADE methodology. Fifteen full text articles were included in the final analysis. The synthesis of these studies revealed that strategies involving opt-out defaults, active-choice defaults, and lottery incentives can potentially increase uptake of HIV testing. Lottery incentives also showed signs of effectiveness in improving HIV prevention, ART adherence and initiation. Despite the promising findings, the overall evidence was judged to be of moderate to very low quality. Behavioural economics-based interventions are promising behavioural change strategies, although more well-designed studies are needed to strengthen the evidence base. [ABSTRACT FROM AUTHOR]

Background Human immunodeficiency virus (HIV)/AIDS and tuberculosis (TB) continue to be a significant global burden, disproportionately affecting low- and middle-income countries (LMICs). While much progress has been made in treating these epidemics, this has led to a rise in liver complications, as patients on ARTs and anti-TBs are at an increased risk of drug-induced liver injury (DILI). Therefore, patients on these medicines require consistent screening of liver function. Due to logistical barriers, gold standard DILI screening fails to be executed at the point-of-care in LMICs. For this reason, we used cost-effectiveness analysis to gauge the efficacy of a paper-test that could be implemented in these settings. Methods We used a Markov Model to simulate HIV and TB coinfected patient care in LMICs using both publicly available data and data from Village Health Works in Burundi. We compared the cost-effectiveness of two screening interventions for liver function monitoring: 1. paper-based point-of-care testing, and 2. gold-standard laboratory testing. These interventions were compared against baseline clinical monitoring. Results The paper test showed a 56% increase in efficacy over clinical monitoring alone. The paper-test is more cost-effective than the gold-standard method, at a ceiling cost of $1.60 per test. Conclusions With this information, policy makers can be informed as to the large potential value of paper-based tests when gold standard monitoring is not achievable. Scientists and engineers should also keep these analyses in mind and while in development limit the cost of an ALT screening test to $1.60. [ABSTRACT FROM AUTHOR]

Introduction: Refugee HIV positive mothers experience significant obstacles in accessing, utilizing and adhering to antiretroviral therapy (ART). Identifying ART non-adherence can help in the development of interventions aimed at improving adherence and subsequently effectiveness of ART among the refugee mothers. We describe the use and the factors associated with non-adherence to ART among Refugee HIV positive pregnant mothers aged 18–49 years in Kyangwali Refugee Camp, Uganda. Methods: We conducted a cross-sectional study among HIV positive pregnant mothers aged 18–49 years in Kyangwali refugee camp between May and June 2023. Using a structured questionnaire, we collected data on use, and factors associated with non-adherence to ART. We used modified Poisson regression analysis to determine factors associated with non-adherence to ART. Results: Of the 380 participants enrolled, 192 (50.5%) were married, mean age 32.1 years. Overall, 98.7; 95% Confidence Interval (CI) [97.5–99.8%] were using ART and 27.4; 95% CI [22.9–31.9%] were non-adherent. Non-adherence was associated with: Initiating Prevention of Mother to Child Transmission (PMTCT) care in the third trimester of pregnancy (adjusted Prevalence ration(aPR): 2.06; 95% CI: 1.27–3.35), no need to get permission to seek PMTCT services aPR 1.61; 95% CI [1.07–2.42] and poor attitude of PMTCT providers aPR 1.90; 95% CI [1.20–3.01]. Conclusion and recommendations: Non-adherence to ART was generally high; therefore limiting the effectiveness of the PMTCT program in this setting. Refugee context specific education interventional programs aimed at early initiation into HIV care, strong social and psychological support from families, communities and health care providers are vital to improve adherence in this setting. [ABSTRACT FROM AUTHOR]

Despite advancements in antiretroviral therapy (ART) suppressing HIV-1 replication, existing antiviral drugs pose limitations, including lifelong medication, frequent administration, side effects and viral resistance, necessitating novel HIV-1 treatment approaches. CD4, pivotal for HIV-1 entry, poses challenges for drug development due to neutralization and cytotoxicity concerns. Nevertheless, Ibalizumab, the sole approved CD4-specific antibody for HIV-1 treatment, reignites interest in exploring alternative anti-HIV targets, emphasizing CD4's potential value for effective drug development. Here, we explore anti-CD4 nanobodies, particularly Nb457 from a CD4-immunized alpaca. Nb457 displays high potency and broad-spectrum activity against HIV-1, surpassing Ibalizumab's efficacy. Strikingly, engineered trimeric Nb457 nanobodies achieve complete inhibition against live HIV-1, outperforming Ibalizumab and parental Nb457. Structural analysis unveils Nb457-induced CD4 conformational changes impeding viral entry. Notably, Nb457 demonstrates therapeutic efficacy in humanized female mouse models. Our findings highlight anti-CD4 nanobodies as promising HIV-1 therapeutics, with potential implications for advancing clinical treatment against this global health challenge. In this study, Zhu et al. report Nb457, an alpaca-derived nanobody with broad-spectrum anti-HIV1 activity and show that Nb457 induces conformational changes in CD4, blocking viral entry and completely inhibiting HIV-1 in its trimeric form. [ABSTRACT FROM AUTHOR]

While research involving pregnant women with HIV has largely focused on the antepartum and intrapartum periods, few studies in Nigeria have examined the clinical outcomes of these women postpartum. This study aimed to evaluate antiretroviral therapy retention, adherence, and viral suppression among postpartum women in Nigeria. This retrospective clinical data analysis included women with a delivery record at the antenatal HIV clinic at Jos University Teaching Hospital between 2013 and 2017. Descriptive statistics quantified proportions retained, adherent (≥95% medication possession ratio), and virally suppressed up to 24 months postpartum. Among 1535 included women, 1497 met the triple antiretroviral therapy eligibility criteria. At 24 months, 1342 (89.6%) women remained in care, 51 (3.4%) reported transferring, and 104 (7.0%) were lost to follow-up. The proportion of patients with ≥95% medication possession ratio decreased from 79.0% to 69.1% over the 24 months. Viral suppression among those with results was 88.7% at 24 months, but <62% of those retained had viral load results at each time point. In multiple logistic regression, predictors of loss to follow-up included having a more recent HIV diagnosis, higher gravidity, fewer antenatal care visits, and a non-hospital delivery. Predictors of viral non-suppression included poorer adherence, unsuppressed/missing baseline viral load, lower baseline CD4+ T-cell count, and higher gravidity. Loss to follow-up rates were lower and antiretroviral therapy adherence rates similar among postpartum women at our study hospital compared with other sub-Saharan countries. Longer follow-up time and inclusion of multiple facilities for a nationally representative sample would be beneficial in future studies. [ABSTRACT FROM AUTHOR]

Background: Anemia is common and associated with increased morbidity among people with HIV (PWH). Classification of anemia using the mean corpuscular volume (MCV) can help investigate the underlying causative factors of anemia. We characterize anemia using MCV among PWH receiving antiretroviral therapy (ART), and identify the risk factors for normocytic, macrocytic, and microcytic anemias. Methods: Including PWH with anemia (hemoglobin measure < 12.9 g/dL among men and < 11.9 g/dL among women) in the NA-ACCORD from 01/01/2007 to 12/31/2017, we estimated the annual distribution of normocytic (80–100 femtolitre (fL)), macrocytic (> 100 fL) or microcytic (< 80 fL) anemia based on the lowest hemoglobin within each year. Poisson regression models with robust variance and general estimating equations were used to estimate crude and adjusted prevalence ratios and 95% confidence intervals for risk factors for macrocytic (vs. normocytic) and microcytic (vs. normocytic) anemia stratified by sex. Results: Among 37,984 hemoglobin measurements that identified anemia in 14,590 PWH, 27,909 (74%) were normocytic, 4257 (11%) were microcytic, and 5818 (15%) were macrocytic. Of the anemic PWH included over the study period, 1910 (13%) experienced at least one measure of microcytic anemia and 3208 (22%) at least one measure of macrocytic anemia. Normocytic anemia was most common among both males and females, followed by microcytic among females and macrocytic among males. Over time, the proportion of anemic PWH who have macrocytosis decreased while microcytosis increased. Macrocytic (vs. normocytic) anemia is associated with increasing age and comorbidities. With increasing age, microcytic anemia decreased among females but not males. A greater proportion of PWH with normocytic anemia had CD4 counts ≤ 200 cells/mm3 and had recently initiated ART. Conclusion: In anemic PWH, normocytic anemia was most common. Over time macrocytic anemia decreased, and microcytic anemia increased irrespective of sex. Normocytic anemia is often due to chronic disease and may explain the greater risk for normocytic anemia among those with lower CD4 counts or recent ART initiation. Identified risk factors for type-specific anemias including sex, age, comorbidities, and HIV factors, can help inform targeted investigation into the underlying causes. [ABSTRACT FROM AUTHOR]

We examined the mediating role of depression and anxiety on the relationship between fear of disease progression (FoP) and antiretroviral therapy (ART) adherence and the moderating role of social support in the FoP-depression/anxiety-ART adherence relationship in persons with HIV/AIDS (PWHA). 202 PWHA completed self-report measures. Simple mediation and moderated mediation analyses were performed. FoP was directly and negatively associated with ART adherence, and the mediating role of depression in this relationship was significant. Indirect effect of FoP mediated by anxiety on ART adherence was not significant. The moderating effect of social support was significant in the FoP-depression pathway, while the indirect effect of FoP on ART adherence mediated by depression was greatest at a higher level of social support and lower level of FoP. The results suggest the relevance of high FoP and depression-mediated FoP in ART adherence and social support may attenuate the negative impact of FoP. [ABSTRACT FROM AUTHOR]

Using multiple pharmacies has been linked to negative outcomes including increased inappropriate drug use, toxicity, and mortality, yet up to half of all patients in the US use multiple pharmacies. A pilot survey was administered to measure pharmacy use in people living with HIV (PWH) and examine the associated attitudes and outcomes. In a midwestern HIV clinic, a convenience sample was surveyed based on using single (SPU) versus multiple pharmacies (MPU). One hundred forty-two subjects participated (69 SPU; 73 MPU): 75% male, 59% white, and > 70% being ≥ 40 years old. There was a trend towards increased recall of self-reported CD4 and viral load status for SPUs vs MPUs [OR 2.26 (95%, 0.91–5.64)]. SPU participants indicated acquiring all meds in one place [Likert Scale weighted average (LS WA) = 4.45], proximity (LS WA = 3.64), the identification of adverse effects (LS WA = 4.17), and concerns about missing potential drug-drug interactions (LS WA = 4.06) as reasons for preferring a single pharmacy. The desire to keep HIV status private (LS WA = 3.65) was noted as a significant reason for using a separate pharmacy specifically for acquiring antiretrovirals in MPU participants. Results indicate patients often have justifiable reasons for using single versus multiple pharmacies. [ABSTRACT FROM AUTHOR]

Most people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. Understanding the factors that determine whether viral rebound is likely after treatment interruption can enable the development of optimal treatment regimens and therapeutic interventions to potentially achieve a functional cure for HIV-1. We built upon the theoretical framework proposed by Conway and Perelson to construct dynamic models of virus-immune interactions to study factors that influence viral rebound dynamics. We evaluated these models using viral load data from 24 individuals following antiretroviral therapy interruption. The best-performing model accurately captures the heterogeneity of viral dynamics and highlights the importance of the effector cell expansion rate. Our results show that post-treatment controllers and non-controllers can be distinguished based on the effector cell expansion rate in our models. Furthermore, these results demonstrate the potential of using dynamic models incorporating an effector cell response to understand early viral rebound dynamics post-antiretroviral therapy interruption. Author summary: Most people living with HIV-1 experience rapid viral rebound once antiretroviral therapy is interrupted; however, a small fraction remain in viral remission for an extended duration. The factors that determine viral rebound dynamics after treatment interruption are not well understood. In this study, we built upon a previous theoretical framework to construct dynamic models of virus-immune interactions to study factors that influence viral rebound dynamics. We evaluated these models using viral load data from 24 individuals following antiretroviral therapy interruption. The best-performing model accurately captures the heterogeneity of viral dynamics and robustly shows that people who remain in viral remission for an extended duration after treatment interruption have a higher effector cell expansion rate compared to those who rapidly rebound. These results demonstrate the potential of using viral dynamic models incorporating an effector cell response to understand early viral rebound dynamics post-antiretroviral therapy interruption. [ABSTRACT FROM AUTHOR]

Introduction: HIV treating physicians in the Netherlands follow the guidelines of the Department of Health and Human Services (DHHS). Most of these recommended initial regimens are single-tablet regimens (STRs), which incur higher costs. By the end of 2017, generic NRTI backbones had become widely available, offering a potentially cheaper multi-tablet regimen. This study aimed to evaluate guideline compliance in people with HIV who started antiretroviral therapy (ART), the uptake of generic multi-tablet regimens (gMTRs), and associated medication costs. Methods: This retrospective cohort study used data from the Dutch HIV Monitoring Foundation to determine the proportion of treatment-naïve people entering care who initiated ART according to the DHHS and type of ART regimens prescribed between January 2016 and December 2020. We analyzed ART prescriptions, both at the national level and per individual HIV treatment centers. We calculated the monthly ART costs based on Dutch medicine prices listed on www.medicijnkosten.nl for each calendar year. Results: In 2016, an integrase inhibitor-containing regimen was initiated in 77.3% which increased to 87.8% in 2020. The compliance rate to DHHS-recommended initial regimens ranged from 82.8% in 2016 to 90.9% in 2020. Most patients received single-tablet regimens, 81.3% in 2016 to 60.3% in 2020. After the introduction the gMTRs showed a steady increase from 17.8% in 2018 to 37.8% in 2020. The cost of the first-line regimen per patient decreased by 22.9% in 2020 compared with 2017. The decrease was larger in centers where treatment-naïve individuals with HIV were preferentially initiated on a gMTR. Conclusions: There was a high compliance to the "DHHS-recommended initial regimens for most people with HIV" in the Netherlands. Most people who initiated ART received STRs, although the percentage of people who started on STRs gradually decreased over time. The use of gMTRs increased over time and was associated with lower medication costs. [ABSTRACT FROM AUTHOR]

We performed a systematic review and meta-analysis of hypertension in people living with human immunodeficiency virus (HIV) in sub-Saharan Africa (SSA). We searched the PubMed, Google Scholar, African Index Medicus, and Embase databases to identify studies published from January 1, 2010, to December 31, 2021. We used a random-effects model to estimate the pooled prevalence of hypertension and mean SBP/DBP level on a sex-specific basis. We included 48 studies reporting data on a pooled sample of 193,843 people living with HIV (PLW-HIV) in SSA. The pooled mean SBP/DBP level was 120 (95% CI 113–128)/77 (95%CI 72–82) mmHg, while the overall pooled prevalence of hypertension was 21.9% (95% CI 19.9–23.9%). Further meta-regression analyses suggested that the prevalence of hypertension was 1.33 times greater in males, 1.23 times greater in individuals receiving antiretroviral therapy (ART) and 1.45 times greater in those individuals with a CD4-count ≥ 200. This meta-analysis of the contemporary pattern of BP levels among PLW-HIV in SSA, suggests that around one in five of such individuals also have hypertension. Given the further context of greater access to ART and subsequently greater longevity, study findings support calls to integrate cardiovascular management into routine HIV care. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) has transformed HIV management, with various regimens available. Dolutegravir (DTG) plus lamivudine (3TC) dual therapy is now the one of the first line regimens. Methods: A retrospective, observational study included treatment naïve people living with HIV (PLWH) with baseline HIV RNA viral load (VL) greater than 500,000 copies/mL from March 2020 to June 2022. PLWH on DTG + 3TC were included in the 2DR group, while others on INSTI-based three-drug regimens were divided in the 3DR group. Viral suppression, immunological recovery, and safety were assessed. Results: The study included 52 PLWH, with no significant baseline differences. Virologic suppression rates at weeks 24 and 48 were similar in both groups, even with baseline HIV RNA VL greater than 1,000,000 copies/mL. CD4 + T cell counts improved rapidly. No serious adverse effects were reported. Conclusions: DTG + 3TC dual therapy demonstrates effectiveness in treatment naïve PLWH with high baseline HIV RNA VL, suggesting its potential as a first line regimen for all treatment naïve PLWH. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus (HIV) is a global public health problem, disproportionally affecting sub-Saharan African countries including Mozambique. In 2019, of 150,000 estimated HIV-infected children in Mozambique, only 95,080 were on antiretroviral treatment and 73% virally suppressed. The objective of this study was to determine the characteristics associated with viral suppression in children. A cross-sectional study was carried out using records of viral load samples from children aged 0 to 14 years old who underwent viral load tests in 2019 in Mozambique. Secondary analyses were conducted on data obtained from Data Intensive Systems and Applications (DISA) of children enrolled in health facilities who had viral load tests registered. Viral suppression was defined as the presence of less than 1,000 copies/ml of blood. Multivariate logistic regression analysis was used to evaluate the characteristics associated with viral suppression. Of the 33,559 viral load sample records analyzed, 53% (17,794/33,559) were female. The average patient age was 8 (sd ± 4) years old. About 44% (14,888/33,559) of the children had a suppressed viral load, with 55% (8,258/14,888) being female and 16% (2,319/14,888) belonging to the 1–4 years old age group. Characteristics associated with viral suppression were the age groups of 5–9 years [AOR = 1.73; 95% CI 1.34–2.23; p<0.001] and 10–14 years old [AOR = 1.92; 95% CI 1.50–2.48; p<0.001] versus < 1 year. Other factors such as living in Maputo City [AOR = 1.61; 95% CI 1.26–2.05; p <0.001] versus Tete Province were also associated with viral suppression. Factors such as being male [AOR = 0.83; 95% CI 0.80–0.87; p <0.001)], living in the provinces of Niassa [AOR = 0.75; 95% CI 0.56–0.99; p <0.003], Cabo Delgado [AOR = 0.77; 95% CI 0.60–0.99; p <0.045] and Zambezia [AOR = 0.72 (95% CI: 0.56–0.92, p<0.008)] versus Tete Province, or being on ART for 2–5 years [AOR = 0.72 (95% CI: 0.61–0.85, p<0.001)] versus 11–14 years were associated with not being virally suppressed. More than half of children did not achieve viral suppression. The odds of viral suppression were highest among children aged 5–14 years and among children living in Maputo city. Further research is needed to better understand the challenges in achieving viral suppression in children. [ABSTRACT FROM AUTHOR]

Background: Second-line HIV treatment failure has become increasing worldwide, mainly in sub-Sahara Africa including Ethiopia. Even though the problem becomes increasing, inadequate information was available about its magnitude and associated factors in the current study area. Objective: To assess the factors of second-line Anti-Retroviral Treatment virological failure among second-line ART users. Method and materials: Institutional-based unmatched case-control study design was conducted from September to December 2021 at Felege Hiowt and University of Gondar Comprehensive Specialized Hospitals; Amhara region, Northwest Ethiopia. A total of 216 patients (60 cases and 156 controls) were recruited by a simple random sampling technique with a 1:3 cases-to-controls ratio. Patients who had two viral load results >1000 copies/ml within a 3-month interval after taking ART drugs for at least 6 months were cases and those who had ≤1,000 copies/ mL were controls. The sample size was calculated by using Epi-Info version 7.2.4. Structured questionnaires were used to gather the required information. SPSS version 26 was used to summarize the findings. In bivariate logistic regression model, Variables with two-tailed P-value ≤ 0.25 at 95% confidence interval were transferred into multivariate binary logistic regression model and P value at ≤ 0.05 was set as statistically significant. Results: Out of 216 patients recruited, 212 have participated with a response rate of 98.2%. From these participants, 117(55.2%) were males and 187(88.2%) were urban dwellers. Among the total respondents, 208(98.1%) had age > 24 years, 200(94.3) were at HIV clinical stage I, 72(34%) had poor ART adherence and 112(52.8) did not disclose their HIV status. Likewise, most of the patients 147(69.37) didn't use condoms. The associated factors were not disclosing HIV status (AOR = 3.4, 95% CI: 1.52–7.79), medium adherence (AOR = 3.7, 95% CI = 1.3–10.7), poor adherence level (AOR = 5.27, 95% CI: 2.2–12.5), not using condoms (AOR = 4.47, 95% CI: 1.63–12.2) and Viral load (>150 copies/ml) when switched to second-line ART (AOR = 3.56, 95% CI: 1.5–8). Conclusion and recommendations: Non-disclosure, poor or medium adherence, not using condoms and high Viral load (>150 copes/ml) when switched to second-line ART were the main factors for second-line Anti-Retroviral Treatment virological failure. Disclosure about HIV status, using condoms and improving treatment adherence level are crucial to reduce second-line virological failure. [ABSTRACT FROM AUTHOR]

To assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women, we conducted a retrospective study comparing inflammatory biomarkers in participants' specimens collected before infection and after ≥2 years of effective ART. We measured biomarkers in four longitudinally collected plasma, including two specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression. Biomarkers were quantified by enzyme-linked immuno-assay or Meso Scale Discovery. When evaluating systematic variation in these markers over time, we found that multiple biomarkers consistently varied across participants' two pre-infection or two post-ART-suppression specimens. Additionally, we compared changes in biomarkers after vs before HIV acquisition. Across 47 participants, the levels of C-reactive protein (CRP), monocyte chemo-attractant protein-1, tumor necrosis factor-α and interferon gamma-induced protein-10 significantly increased while leptin and lipopolysaccharide binding protein (LBP) significantly decreased following HIV infection. Randomization to deferred-ART initiation was associated with greater increases in CRP and no decrease in LBP. Acquisition of HIV appeared to induce systemic inflammation, with elevation of biomarkers previously associated with infections and cardiovascular disease. Initiation of ART during the early weeks of infection tempered the increase in pro-inflammatory biomarkers compared to delaying ART for ~24 weeks after HIV diagnosis. These findings provide insight into potential mediators by which immediate-ART initiation improves health outcomes, perhaps because immediate-ART limits the size of the HIV reservoir or limits immune dysregulation that in turn trigger systemic inflammation. Author summary: A comparison of biomarkers of systemic inflammation were compared across 47 participants' specimens, two collected before infection and two after ≥2 years of effective ART. The levels of C-reactive protein, monocyte chemo-attractant protein-1, tumor necrosis factor-α and interferon gamma-induced protein-10 significantly increased while leptin and lipopolysaccharide binding protein significantly decreased following HIV infection. [ABSTRACT FROM AUTHOR]

Background: Globally, Tuberculosis (TB) is the main cause of morbidity and mortality among infectious disease. TB and Human Immune Virus (HIV) are the two deadly pandemics which interconnected each other tragically, and jeopardize the lives of children; particularly in Sub-Saharan Africa. Therefore, this review was aimed to determine the aggregated national pooled incidence of tuberculosis among HIV- infected children and its predictors in Ethiopia. Methods: An electronic search engine (HINARI, PubMed, Scopus, web of science), Google scholar and free Google databases were searched to find eligible studies. Quality of the studies was checked using the Joanna Briggs Institute (JBI) quality assessment checklists for cohort studies. Heterogeneity between studies was evaluated using Cochrane Q-test and the I2 statistics. Result: This review revealed that the pooled national incidence of tuberculosis among children with HIV after initiation of ART was 3.63% (95% CI: 2.726–4.532) per 100-person-years observations. Being Anemic, poor and fair ART adherence, advanced WHO clinical staging, missing of cotrimoxazole and isoniazid preventing therapy, low CD4 cell count, and undernutrition were significant predictors of tuberculosis incidence. Conclusion: The study result indicated that the incidence of TB among HIV- infected children is still high. Therefore, parents/guardians should strictly follow and adjust nutritional status of their children to boost immunity, prevent undernutrition and opportunistic infections. Cotrimoxazole and isoniazid preventive therapy need to continually provide for HIV- infected children for the sake of enhancing CD4/immune cells, reduce viral load, and prevent from advanced disease stages. Furthermore, clinicians and parents strictly follow ART adherence. [ABSTRACT FROM AUTHOR]

HIV-associated neurocognitive disorders (HAND) persist under antiretroviral therapy as a complex pathology that has been difficult to study in cellular and animal models. Therefore, we generated an ex vivo human brain slice model of HIV-1 infection from surgically resected adult brain tissue. Brain slice cultures processed for flow cytometry showed >90% viability of dissociated cells within the first three weeks in vitro, with parallel detection of astrocyte, myeloid, and neuronal populations. Neurons within brain slices showed stable dendritic spine density and mature spine morphologies in the first weeks in culture, and they generated detectable activity in multi-electrode arrays. We infected cultured brain slices using patient-matched CD4+ T-cells or monocyte-derived macrophages (MDMs) that were exposed to a GFP-expressing R5-tropic HIV-1 in vitro. Infected slice cultures expressed viral RNA and developed a spreading infection up to 9 days post-infection, which were significantly decreased by antiretrovirals. We also detected infected myeloid cells and astrocytes within slices and observed minimal effect on cellular viability over time. Overall, this human-centered model offers a promising resource to study the cellular mechanisms contributing to HAND (including antiretroviral toxicity, substance use, and aging), infection of resident brain cells, and new neuroprotective therapeutics. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Noma is still around today and can be deadly if ignored. Prompt identification and comprehensive care are essential for averting permanent impairments and disfigurements. Noma is a rapid developing orofacial gangrene and a disabling disease that primarily affects young children who live in dangerous conditions. Underlying diseases such as HIV/AIDS and malnutrition can enhance the likelihood of Noma's emergence. This is a case of a 9‐year‐old girl patient who arrived malnourished and with an ulcerating communicating right mandibular soft tissue lesion as well as right hemiparesis which had an acute onset. The patient was likewise HIV positive discovered upon admission, possibly as a result of vertical transmission, and was an ART (antiretroviral therapy) treatment naive patient. A holistic treatment plan was installed and a positive clinical response was observed. Early treatment is key in Noma management. [ABSTRACT FROM AUTHOR]

The treatment of HIV infection has been revolutionized in recent years thanks to the advent of dual antiretroviral regimens, administered orally or as long-acting injectable formulations. Here, we provide an update on the usefulness of therapeutic drug monitoring (TDM) of antiretroviral drugs to optimize the management of people with HIV (PWH) in the current scenario. A MEDLINE PubMed search for articles published between January 2014 and January 2024 was completed matching the terms HIV, antiretrovirals and TDM. Moreover, additional studies were identified from the reference list of retrieved articles. Available antiretroviral treatments achieve a response rate of 90%–95%, making the routine TDM of antiretroviral drugs of limited clinical value. However, there are still some important applications of TDM in selected clinical conditions, such as assessing patient compliance or suspected drug–drug interactions (DDIs). Indeed, we are increasingly having to deal with polypharmacy and DDIs in the context of an aging patient with comorbidities that may potentially alter the pharmacokinetics of antiretroviral drugs. Finally, the role of pharmacogenetics, which is closely related to TDM, in influencing both the disposition of antiretrovirals and the course of DDIs should also be considered. [ABSTRACT FROM AUTHOR]

People with HIV are living longer due to advances in antiretroviral therapy. With improved life expectancy comes an increased lifetime risk of comorbid conditions – such as cardiovascular disease and cancer – and polypharmacy. Older adults, particularly those living with HIV, are more vulnerable to drug interactions and adverse effects, resulting in negative health outcomes. Antiretrovirals are involved in many potential drug interactions with medications used to treat common comorbidities and geriatric conditions in an aging population of people with HIV. We review the mechanisms and management of significant drug–drug interactions involving antiretroviral medications and non-antiretroviral medications commonly used among older people living with HIV. The management of these interactions may require dose adjustments, medication switches to alternatives, enhanced monitoring, and considerations of patient- and disease-specific factors. Clinicians managing comorbid conditions among older people with HIV must be particularly vigilant to side effect profiles, drug–drug interactions, pill burden, and cost when optimizing treatment. To support healthier aging among people living with HIV, there is a growing need for antiretroviral stewardship, multidisciplinary care models, and advances that promote insight into the correlations between an individual, their conditions, and their medications. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a leading infectious disease cause of mortality worldwide, especially for people living with human immunodeficiency virus (PLWH). Treating TB in PLWH can be challenging due to numerous drug interactions. This review discusses drug interactions between antitubercular and antiretroviral drugs. Due to its clinical importance, initiation of antiretroviral therapy in patients requiring TB treatment is discussed. Special focus is placed on the rifamycin class, as it accounts for the majority of interactions. Clinically relevant guidance is provided on how to manage these interactions. An additional section on utilizing therapeutic drug monitoring (TDM) to optimize drug exposure and minimize toxicities is included. Antitubercular and antiretroviral coadministration can be successfully managed. TDM can be used to optimize drug exposure and minimize toxicity risk. As new TB and HIV drugs are discovered, additional research will be needed to assess for clinically relevant drug interactions. [ABSTRACT FROM AUTHOR]

Introduction: Approval of the first long‐acting injectable antiretroviral therapy (LAI ART) medication heralded a new era of HIV treatment. However, the years since approval have been marked by implementation challenges. The "Accelerating Implementation of Multilevel Strategies to Advance Long‐Acting Injectable for Underserved Populations (ALAI UP Project)" aims to accelerate the systematic and equitable delivery of LAI ART. Methods: We coded and analysed implementation barriers according to the Consolidated Framework for Implementation Research (CFIR) domains, desired resources and programme goals from questionnaire short‐answer responses by clinics across the United States responding to ALAI UP's solicitation to participate in the project between November 2022 and January 2023. Results: Thirty‐eight clinics responded to ALAI UP's solicitation. The characteristics of LAI ART as an innovation (cost, complexity of procurement, dosing interval, limited eligibility) precipitated and interacted with barriers in other CFIR domains. Barriers included obtaining coverage for the cost of medication (27/38 clinics) (outer setting); need for new workflows and staffing (12/38) and/or systems to support injection scheduling/coordination (16/38), transportation and expanded clinic hours (13/38) (inner setting); and patient (10/38) and provider (7/38) education (individuals). To support implementation, applicants sought: technical assistance to develop protocols and workflows (18/38), specifically strategies to address payor challenges (8/38); additional staff for care coordination and benefits navigation (17/38); opportunities to share experiences with other implementing clinics (12/38); patient‐facing materials to educate and increase demand (7/38); and support engaging communities (6/38). Clinics' LAI ART programme goals varied. Most prioritized delivering LAI ART to their most marginalized patients struggling to achieve viral suppression on oral therapy, despite awareness that current US Food and Drug Administration approval is only for virally suppressed patients. The goal for LAI ART reach after 1 year of implementation ranged from ≤10% of patients with HIV on LAI ART (17/38) to ≥50% of patients (2/38). Conclusions: Diverse clinic types are interested in offering LAI ART and most aspire to use LAI ART to support their most vulnerable patients sustain viral suppression. Dedicated resources centred on equity and relevant to context and population are needed to support implementation. Otherwise, the introduction of LAI ART risks exacerbating, not ameliorating, health disparities. [ABSTRACT FROM AUTHOR]

Introduction: Assisted partner services (APS), or exposure notification and HIV testing for sexual partners of persons diagnosed HIV positive (index clients), is recommended by the World Health Organization. Most APS literature focuses on outcomes among index clients and their partners. There is little data on the benefits of providing APS to partners of partners diagnosed with HIV. Methods: We utilized data from a large‐scale APS implementation project across 31 facilities in western Kenya from 2018 to 2022. Females testing HIV positive at facilities were offered APS; those who consented provided contact information for all male sexual partners in the last 3 years. Male partners were notified of their potential HIV exposure and offered HIV testing services (HTS). Males newly testing positive were also offered APS and asked to provide contact information for their female partners in the last 3 years. Female partners of male partners (FPPs) were provided exposure notification and HTS. All participants with HIV were followed up at 12 months post‐enrolment to assess linkage‐to antiretroviral treatment (ART) and viral suppression. We compared HIV positivity, demographics and linkage outcomes among female index clients and FPPs. Results: Overall, 5708 FPPs were elicited from male partners, of whom 4951 received HTS through APS (87% coverage); 291 FPPs newly tested HIV positive (6% yield), an additional 1743 (35.2%) reported a prior HIV diagnosis, of whom 99% were on ART at baseline. At 12 months follow‐up, most FPPs were taking ART (92%) with very few adverse events: <1% reported intimate partner violence or reported relationship dissolution. FPPs were more likely than female index clients to report HIV risk behaviours including no condom use at last sex (45% vs. 30%) and multiple partners (38% vs. 19%). Conclusions: Providing HIV testing via APS to FPP is a safe and effective strategy to identify newly diagnosed females and achieve high linkage and retention to ART and can be an efficient means of identifying HIV cases in the era of declining HIV incidence. The high proportion of FPPs reporting HIV risk behaviours suggests APS may help interrupt community HIV transmission via increased knowledge of HIV status and linkage to treatment. [ABSTRACT FROM AUTHOR]

The primary obstacle to curing HIV-1 is a reservoir of CD4+ cells that contain stably integrated provirus. Previous studies characterizing the proviral landscape, which have been predominantly conducted in males in the United States and Europe living with HIV-1 subtype B, have revealed that most proviruses that persist during antiretroviral therapy (ART) are defective. In contrast, less is known about proviral landscapes in females with non-B subtypes, which represents the largest group of individuals living with HIV-1. Here, we analyze genomic DNA from resting CD4+ T-cells from 16 female and seven male Ugandans with HIV-1 receiving suppressive ART (n = 23). We perform near-full-length proviral sequencing at limiting dilution to examine the proviral genetic landscape, yielding 607 HIV-1 subtype A1, D, and recombinant proviral sequences (mean 26/person). We observe that intact genomes are relatively rare and clonal expansion occurs in both intact and defective genomes. Our modification of the primers and probes of the Intact Proviral DNA Assay (IPDA), developed for subtype B, rescues intact provirus detection in Ugandan samples for which the original IPDA fails. This work will facilitate research on HIV-1 persistence and cure strategies in Africa, where the burden of HIV-1 is heaviest. Most studies on HIV-1 proviruses that persist during antiretroviral therapy have focused on males with HIV-1 subtype B, even though the majority of people living with HIV globally have non-B subtypes. Here, the authors describe the proviral genetic landscape of HIV-1 subtypes A1 and D in Ugandan females and males using near-full-length proviral sequencing. The authors also describe a molecular assay for intact proviral quantification of these HIV-1 subtypes. [ABSTRACT FROM AUTHOR]

Raltegravir (RLT) is a human immunodeficiency virus integrase strand transfer inhibitor that is prescribed for the treatment of HIV-1 infection. The drug belongs to biopharmaceutics classification system (BCS) class II category and has poor aqueous solubility and chemical stability in acidic/basic medium. Polymorph screening was performed to search for an alternative solid form with improved drug attributes. By serendipity, this screening gave anhydrous RLT (form A) and two crystalline solid phases of impurity C. The RLT form A and impurity C were characterised using powder X-ray diffraction (XRD), thermal analysis (differential scanning calorimetry/thermogravimetric analysis) and vibrational spectroscopy (Fourier-transform infrared). The crystal structures of form A and impurity C were determined from the high resolution powder XRD patterns using Rietveld refinement, thus revealing their conformational and synthon differences. The crystal structure of impurity C1 (MeOH solvate) was solved from single crystal XRD and demonstrates the packing and conformational differences compared to parent phase C. The dissolution/solubility experiments confirmed that form A has a higher solubility than its hydrate in aqueous ethanol medium. Compared to the commercialized RLT potassium salt (RLT-K), form A did not offer improved chemical stability during acid hydrolysis (high-performance liquid chromatography data). Rather, impurity C exhibited higher thermal stability and aqueous stability compared to other RLT solid forms in an acidic medium. [ABSTRACT FROM AUTHOR]

Objective of this paper was to describe the various definitions for engagement used in HIV clinical trials. Methods: Articles were retrieved from CASCADE, a database of 298 clinical trials conducted to improve the HIV care cascade (https://hivcarecascade.com/), curated by income level, vulnerable population, who delivered the intervention, the setting in which it was delivered, the intervention type, and the level of pragmatism of the intervention. Studies with engagement listed as an outcome were selected from this database. Results: 13 studies were eligible, of which five did not provide an explicit definition for engagement. The remaining studies used one or more of the following: appointment adherence (n=6), laboratory testing (n=2), adherence to antiretroviral therapy (n=2), time specification (n=5), intervention adherence (n=5), and quality of interaction (n=1). Conclusion: This paper highlights the existing diversity in definitions for engagement in the HIV care cascade and categorize these definitions into appointment adherence, laboratory testing, adherence to antiretroviral therapy, time specification, intervention adherence, and quality of interaction. We recommend consensus on how to describe and measure engagement. [ABSTRACT FROM AUTHOR]

We report on the highlights ofthe 24th International AIDS Conference, held in Montreal in 2022. We address three main themes: human immunodeficiency virus (HIV) targets and cascades, HIV and sexually transmitted infection prophylaxis, and HIV treatment, including the use of antiretroviral therapy in pregnancy. [ABSTRACT FROM AUTHOR]

This paper investigates the effect of under-five mortality, child support grant (CSG) coverage and the rollout of antiretroviral therapy (ART) on fertility in South Africa. The study employs the quality-quantity trade-off framework to analyse the direct and indirect factors affecting fertility using the two stage least squares fixed effects instrumental variable approach. The analysis uses balanced panel data covering nine provinces from 2001–2016. This period was characterised by significant increases in the child support grant coverage and ART coverage. Furthermore, this period was characterised by a significant decline in the under-five mortality rate. We find no evidence to support the hypothesis that increases in the CSG coverage are associated with an increase in fertility. This finding aligns with previous literature suggesting that there are no perverse incentives for childbearing associated with the child support grant. On the other hand, results indicate that an increase in ART coverage is associated with an increase in fertility. Results also show that a decrease in under-five mortality is associated with a decline in fertility over the sample period. HIV prevalence, education, real GDP per capita, marriage prevalence and contraceptive prevalence are also important determinants of fertility in South Africa. Although the scale up of ART has improved health outcomes, it also appears to have increased fertility in HIV-positive women. The ART programme should therefore be linked with further family planning initiatives to minimise unintended pregnancies. [ABSTRACT FROM AUTHOR]

Background: The number of elderly people living with HIV (EPLHIV) has increased significantly as a result of antiretroviral treatment (ART) and this has brought about a variety of psychosocial challenges that have an impact on their quality of life (QoL). Various psychosocial interventions have been tried or implemented in Sub-Saharan Africa (SSA) to improve QoL of EPLHIV. However, there is paucity of data on the types and effectiveness of these interventions. This systematic review, therefore, aims to explore available psychosocial interventions in SSA and their effectiveness in improving the QoL of EPLHIV. Methods: We will search PubMed, PsycINFO, LILACS, Cochrane Library, Google Scholar, HINARI, Africa Journals Online, Scopus and Web of Science to retrieve publications on psychosocial interventions implemented to improve QoL of EPLHIV from inception of the identified databases to 31st December 2023 without language restrictions. Also, supplementary sources such as conference proceedings, preprint repositories, databases of dissertations, as well as WHO and governmental databases can be explored for additional studies. For unpublished studies, trial registries and experts would be contacted, and reference lists of retrieved papers will be manually searched. Retrieved studies will be deduplicated using Mendeley and exported to Rayyan. At least two reviewers will independently select studies, extract data and assess the quality of the included studies using validated tools. Dichotomous outcomes data will be assessed and reported as odds ratio (OR) or risk ratio (RR) and for continuous outcomes, mean difference (MD) will be used; all reported with their 95% confidence interval (CI). Heterogeneity will be explored graphically by inspecting the overlapping of CIs and assessed quantitatively using the I2 statistic. Expected outcomes: This systematic review will be the first to rigorously identify psychosocial intervention on QoL of EPLHIV in SSA and assess their effectiveness with the aim to provide regional and country- specific data that will inform the selection and implementation of appropriate and socially acceptable policies across countries in SSA. Key findings of the review are expected to contribute critical evidence on availability, types and effectiveness of psychosocial interventions for improving quality of life of vulnerable elderly persons in SSA living with HIV. Furthermore, the review will explore any variation and possible correlates of psychosocial interventions by age, sex, CD4 count (if available), setting and geographic location within SSA that will provide healthcare professionals with reliable evidence, with the ultimate goal of inspiring countries in SSA to adopt innovative interventions to improve HIV care. Trial registration: Systematic review registration: The systematic review protocol has been registered in the International Prospective Register for Systematic Reviews (PROSPERO), with registration ID CRD42021278218. [ABSTRACT FROM AUTHOR]

Background: Nigeria is one of six countries with half the global burden of youth living with HIV. Interventions to date have been inadequate as AIDS-related deaths in Nigeria's youth have remained unchanged in recent years. The iCARE Nigeria HIV treatment support intervention, a combination of peer navigation and SMS text message medication reminders to promote viral suppression, demonstrated initial efficacy and feasibility in a pilot trial among youth living with HIV in Nigeria. This paper describes the study protocol for the large-scale trial of the intervention. Methods: The iCARE Nigeria-Treatment study is a randomized stepped wedge trial of a combination (peer navigation and text message reminder) intervention, delivered to youth over a period of 48 weeks to promote viral suppression. Youth receiving HIV treatment at six clinical sites in the North Central and South Western regions of Nigeria were recruited for participation. Eligibility criteria included registration as a patient at participating clinics, aged 15–24 years, on antiretroviral therapy for at least three months, ability to understand and read English, Hausa, Pidgin English, or Yoruba, and intent to remain a patient at the study site during the study period. The six clinic sites were divided into three clusters and randomized to a sequence of control and intervention periods for comparison. The primary outcome is plasma HIV-1 viral load suppression, defined as viral load ≤ 200 copies/mL, in the intervention period versus the control period at 48 weeks of intervention. Discussion: Evidence-based interventions to promote viral load suppression among youth in Nigeria are needed. This study will determine efficacy of a combination intervention (peer navigation and text message reminder) and collect data on potential implementation barriers and facilitators to inform scale-up if efficacy is confirmed. Trial registration: ClinicalTrials.gov number, NCT 04950153, retrospectively registered July 6, 2021, https://clinicaltrials.gov/. [ABSTRACT FROM AUTHOR]

Analytic treatment interruption (ATI) is scientifically necessary in HIV‐remission ("cure") studies to test the effects of new interventions. However, stopping antiretroviral treatment poses risks to research participants and their sexual partners. Ethical debate about whether and how to conduct such studies has largely centered on designing risk‐mitigation strategies and identifying the responsibilities of research stakeholders. In this paper, we argue that because the possibility of HIV transmission from research participants to partners during ATI cannot practicably be eliminated—that is, it is ineliminable—the successful conduct of such trials ultimately depends on relationships of trust and trustworthiness. We describe our experiences with conducting and studying HIV‐remission trials with ATI in Thailand to examine the strengths, complexities, and limitations of the risk‐mitigation and responsibility approaches and to explore ways in which the building of trust—and trustworthiness—may help enhance the scientific, practical, and ethical dimensions of these trials. [ABSTRACT FROM AUTHOR]

Purpose: This paper reports a review of couple-based behavioral HIV interventions conducted by the Social Intervention Group (SIG); and addresses gaps, future directions, and implications for couple-based HIV interventions. Method: We performed a literature review for SIG research on intervention and prevention studies involving couples/partners. Results: We identified nine couple-based interventions. Outcomes included reduced sexual and substance use-related risk behaviors and improved use of anti-retroviral treatment. We conducted these studies in diverse venues, including needle/syringe exchange programs, primary care clinics, and criminal justice settings. Conclusions: The findings of this review provide strong evidence for the efficacy of couple-based HIV interventions in reducing sexual HIV risks and linkage to HIV and substance-use treatment. SIG has advanced couple-based HIV intervention research science by improving study design, intervention core components, conceptual models, and implementation strategies; which have informed scientific directions and transformed couple-based HIV prevention research. [ABSTRACT FROM AUTHOR]

HIV/AIDS remains one of the most significant global health challenges, affecting millions of people worldwide. Since the inception of the disease, various global response strategies have been devised and implemented, aiming to mitigate its impact and ultimately eradicate it. While these strategies have yielded remarkable progress, there are still key barriers impeding the global fight against the disease. This paper, thus, delves into the key global response strategies employed in response to the HIV/AIDS epidemic since its inception, examines the impediments to their successful implementation, and outlines the trajectory towards a world without AIDS. To continue the momentum in the fight against HIV/AIDS, it is imperative to adopt a multifaceted approach that addresses the existing barriers. One pivotal aspect of this approach involves intensifying efforts to improve the uptake of HIV testing. Encouraging individuals to get tested is a critical step, as it not only aids in identifying more cases of HIV infection but also facilitates the linkage of those affected to appropriate care and support services. [ABSTRACT FROM AUTHOR]

Introduction: With effective antiretroviral therapy (ART), many persons living with HIV (PLHIV) live to old age. Caring for aged PLHIV necessitates the engagement of caregivers and patients to establish agreed-upon goals of treatment. However, there is limited literature on friendly and centered models of care for elderly PLHIV. We explored strategies to improve care in HIV clinics among PLHIV aged 50 years and above in Uganda. Methods: We conducted 40 in-depth interviews in two hospitals with elderly PLHIV aged 50 years and above who had lived with HIV for more than ten years. We explored strategies for improving care of elderly PLHIV at both health facility and community levels. The in-depth interviews were audio-recorded and transcribed verbatim. The thematic approach guided data analysis. Results: The elderly PLHIV suggested the following strategies to improve their care: creating geriatric clinics; increasing screening tests for non-communicable diseases in the ART clinics; community and home-based ART delivery; workshops at health facilities to provide health education on aging effectively; creating community support groups; financial assistance for the elderly PLHIV and advances in science. Conclusions: There is need to improve community HIV care especially for the elderly and social and economic support in the community. Involving the elderly PLHIV in developing strategies to improve their health goes a long way to improve the patients' quality of care. There is a need to incorporate the raised strategies in HIV care or older adults. [ABSTRACT FROM AUTHOR]

Background: South Africa recently adopted HIV self-test technology (HIVST) to improve HIV testing and encourage earlier treatment initiation in working populations with a low uptake of conventional testing approaches. This study investigates the impact of HIVST on testing outcomes, focusing on both frequent and infrequent working-class testers. The paper also examines the spillover effect of HIVST on antiretroviral (ART) treatment initiation. To identify these effects, the author focused on South Africa and exploited the HIVST distribution data of 6259 beneficiaries of HIVST. Methods: The author used a two-stage least-squared model to quantify the impact of the HIVST on these vulnerable working populations. Results: The results show that HIVST fosters a 27.6% higher testing uptake in infrequently testing workers compared to frequently testing workers, and that the uptake of HIVST is 11.5% higher in rural regions than in urban settings, as well as 14.5% more prominent in infrequent male testers than infrequent female testers. Notably, the positive effects of HIVST are also confirmed by the presence of positive spillover effects in workers screening positive for HIV. The paper documents a 7.6% increase in ART initiation in infrequent testers. Conclusions: There is a case for adopting this technology to improve the uptake of HIV testing and ART initiation as the country seeks to attain the UNAIDS 95–95–95 targets by 2030. [ABSTRACT FROM AUTHOR]

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