Sociodemographic and Clinical Predictors of Weight Gain During the First Year of Antiretroviral Therapy among Adults Living With HIV in Urban Tanzania.

Antiretroviral therapy (ART) has improved the survival of people living with HIV (PLHIV) but this success has been accompanied by an increase in noncommunicable diseases. We conducted a prospective cohort study of 4000 adult PLHIV who were initiating ART in Dar es Salaam, Tanzania, to assess weight gain during the first year of treatment and associated sociodemographic and clinical factors. Anthropometric data were collected at ART initiation and monthly follow-up visits. The mean weight gain during the first year of treatment was 2.6 ± 0.3 kg, and the prevalence of overweight or obesity increased from 26.3% at baseline to 40.7%. Female sex, greater household wealth, lower CD4-T-cell counts, higher WHO HIV disease stage, and pulmonary tuberculosis were associated with a greater increase in body mass index (P < .05). Weight gain following ART initiation was common but was greater among females and PLHIV with advanced HIV or comorbidities.

Differential T-cell profiles determined by Hepatitis B surface antigen decrease among people with Human Immunodeficiency Virus /Hepatitis B Virus coinfection on treatment.

BACKGROUND: Several studies have reported that combination antiretroviral therapy (cART) enhances the hepatitis B surface antigen (HBsAg) clearance rate in Human Immunodeficiency Virus-1/Hepatitis B Virus (HIV/HBV) coinfected patients, yet the associated immunological characteristics remain unclear. METHODS: Global and specific immune phenotypic profiles were examined in 48 patients with HIV/HBV coinfection before cART and at 1-year, and 3-year after cART using flow cytometry. In addition, 61 patients with HBV monoinfection were included for comparison. RESULTS: HBsAg response (sAg-R) was defined as > 0.5 log decrease within six months of cART initiation, and 16 patients achieved it. Patients with sAg-R (the sAg-R group) exhibited distinct immune phenotypes compared to those of HBsAg-retained patients (the sAg-NR group). Notably, patients with sAg-R had lower CD4+ T cell counts and a higher number of HBcAg-specific T cells. Further, the sAg-R group exhibited upregulation of HLA-DR, Ki67, and PD-1 in CD4+ T cells and heightened HLA-DR and T-bet in CD8+ T cells. However, the sAg-R group had fewer TEMRA cells but more TEM and Th17 cells than those in the sAg-NR group. Expression of various markers, including HLA-DR+CD4+, Ki67+CD4+, PD-1+CD4+, CD38+CD8+, HLA-DR+CD8+, TIM-3+CD8+, HBV-specific CD4+ T cell secreting IFN-γ and IL-2, and specific CD8+ T cell secreting IFN-γ and IL-2, correlated with HBsAg decrease. CONCLUSION: The decline in HBsAg levels during cART in HIV/HBV coinfection involves significant alterations in CD4+ and CD8+ T cells phenotypes, offering a novel perspective on a functional HBV cure.

Viral load non-suppression among adolescents and youth living with HIV in South Africa.

Background: Despite the increased initiation and uptake of antiretroviral therapy (ART) in South Africa, some people living with HIV (PLHIV) who are on ART still have non-suppressed viral load (VL). Objectives: This study aimed to determine the prevalence of VL non-suppression among adolescents and youth (aged 12 years - 24 years) living with HIV and on ART in South Africa, as well as the factors associated with it. Method: Data from the 2017 South African national HIV prevalence, incidence, behaviour, and communication survey were analysed. The survey used a multistage-stratified cluster sampling design. A backward stepwise multivariable generalised linear model was used to identify factors associated with VL non-suppression. Results: The study included 340 participants aged 12 years - 24 years, with a median age of 21 (interquartile range [IQR]: 18-23). The proportion of adolescents and youth living with HIV and on ART with non-suppressed VL was 19.2% (95% confidence interval [CI]: 14.4-25.3). Approximately 60% of the participants were not on ART. The odds of VL non-suppression were significantly higher among youth aged 15 years - 19 years (adjusted odds ratio [AOR] = 1.63 [95% CI: 1.24-2.13], p = 0.001) and aged 20 years - 24 years (AOR = 1.22 [95% CI: 1.06-1.41], p = 0.005) compared to adolescents aged 12 years - 14 years. The odds were significantly lower among individuals of other races (AOR = 0.80 [95% CI: 0.69-0.92], p = 0.003) compared to black African people. Conclusion: Findings suggest a need for ART education and counselling as part of treatment support. In addition, the promotion of HIV awareness as part of strengthening the HIV treatment and prevention cascade. Contribution: The article showed the prevalence of VL non-suppression and associated factors among adolescents and youth.

Beliefs affecting ART adherence in newly diagnosed HIV-positive participants in Manzini, Eswatini.

Background: Achieving optimal adherence to antiretroviral therapy (ART) is challenging. Consistency in HIV care and treatment is crucial for achieving viral load suppression and preventing HIV-related illnesses, disease progression to AIDS, mortality, drug resistance, and onward transmission. Objectives: The purpose of this research was to gain a comprehensive understanding of the beliefs that play a role in determining the level of ART adherence among individuals newly diagnosed with HIV. By examining these beliefs, the researchers aimed to identify potential barriers and facilitators to adherence, ultimately contributing to the development of effective interventions and strategies to improve ART adherence. Method: An exploratory qualitative approach was employed in this study, utilising the Theory of Planned Behaviour (TPB) as its theoretical framework. To gather insights, in-depth interviews were conducted with 19 participants recruited post diagnosis, who shared their beliefs regarding ART adherence. Thematic analysis identified beliefs, categorised under TPB precursors, namely behavioural outcomes, subjective norms, and perceived behavioural control. Results: Participants emphasised health improvement, treatment effectiveness, and disease prevention as advantages to ART adherence, while disadvantages included fear of lifelong commitment, side effects, and stigma. ART adherence was enhanced by family support but impeded by a number of social factors. Participants expressed confidence in creating personal reminders or seeking external help, but anticipated various challenges. Conclusion: The research has shown that the beliefs affecting ART adherence in individuals recently diagnosed with HIV but not yet on treatment are like those that have been reported to influence adherence in HIV-positive participants currently receiving treatment.

Effect of high-dose multivitamin supplements on alanine aminotransferase elevations among adults living with HIV on antiretroviral therapy in Tanzania.

BACKGROUND: HIV infection can cause malabsorption and rapid utilization of nutrients. A randomized trial of multivitamin supplementation among people living with HIV/AIDS (PLWHA) initiating antiretroviral therapy (ART) in Tanzania was stopped early due to increased alanine aminotransferase (ALT) concentrations in the multiple recommended dietary allowances (RDA) multivitamin group. We conducted detailed analysis to assess the effect of multivitamins on ALT elevations and evaluate whether subgroups of PLWHA have greater hepatotoxicity risks associated with the use of high-dose multivitamins. METHODS: We utilized data from a randomized, double-blind trial conducted in 2006-2009 that assessed the effect of high-dose multivitamins that contained vitamin B complex, vitamin C, and vitamin E at multiple RDA as compared to standard-dose multivitamins containing single RDAs among adults initiating ART in Tanzania. We evaluated the effect of high-dose multivitamins on incident mild/moderate ALT elevations > 40 IU/L, persistent ALT elevations > 40 IU/L (2 + clinic visits), and severe ALT elevations > 200IU/L using Cox proportional hazard models. We then evaluated effect modification by patient characteristics to determine if subgroups of PLWHA experienced different magnitudes of risk for ALT elevations associated with high-dose multivitamins. RESULTS: High-dose multivitamins increased the risk of incident mild/moderate ALT elevations > 40 IU/mL as compared to standard-dose multivitamins (hazard ratio (HR): 1.41; 95%CI: 1.26,1.58) as well as incident sustained mild/moderate ALT elevations (HR: 1.19; 95%CI: 1.04,1.36), but there was no overall effect on severe ALT elevations (HR: 1.44; 95% CI: 0.91,2.28). There was no evidence that the effect of high-dose multivitamins on any or sustained mild/moderate ALT elevations was modified by any patient characteristic. However, CD4 T-cell count was found to modify the effect of high-dose multivitamins on severe ALT elevations (p-value for interaction:0.01). Among participants with a baseline CD4 T-cell count ≤ 100 cells/µL, individuals receiving high-dose multivitamins had 3.74 times (95%CI: 1.52-9.17) the risk of incident severe ALT elevations compared to standard-dose multivitamins, while participants with CD4 T-cell counts > 100 cells/µL, appeared to have no effect of high-dose multivitamins on severe ALT elevations (HR:0.92; 95% CI: 0.50,1.67). CONCLUSIONS: High-dose RDA multivitamin supplementation increased the incidence of any mild to moderate ALT elevations among adults starting ART in Tanzania and the magnitude of the risk does not appear to differ by patient characteristics. However, immunocompromised PLWHA with CD4 T-cell counts < 100 cells/µL may experience greater risk of severe ALT elevations associated with the use of high-dose multivitamins. Although the study findings offer significant insights, it is essential to take into account limitations imposed by newer cART regimes.

Case series of two persons living with HIV with detectable viral loads initiated then suppressed on cabotegravir/rilpivirine with lenacapavir.

Long-acting (LA) cabotegravir/rilpivirine (CAB/RPV) is primarily prescribed for virologically suppressed persons living with HIV (PLWH). Patients experiencing pill dysphagia or profound adherence challenges were excluded from the phase 3 studies, but recent reports demonstrate successful treatment in PWLH with baseline viremia. We describe two PLWH with detectable viral loads (VL) with multidrug resistance mutations. They were unable to sustain virologic suppression on oral therapy with historical poor adherence and dysphagia. Initiation of intramuscular CAB/RPV with subcutaneous lenacapavir (LEN) injections was necessary with baseline resistance. Due to anorexia and a low muscle mass, one patient received CAB/RPV injections in the vastus lateralis rather than the gluteal muscle with a 67-day delay between injections three and four due to health challenges. Both achieved viral suppression on monthly CAB/RPV with LEN. A return to health with a BMI increase from <14 kg/m2 to almost 17 kg/m2 resulted in the second patient. Injectable LA ART (CAB/RPV + LEN) in PLWH with detectable viremia results in sustained virologic suppression and a return to health and should now be considered a novel option for MDR patients with an inability to adhere to oral regimens.

Coinfections and In-Hospital Mortality in a Group of Patients With HIV/AIDS: A Longitudinal Study.

Human immunodeficiency virus (HIV) is a global public health problem. Coinfections in HIV patients are frequent complications that increase their mortality. The aim of this study was to assess coinfections and in-hospital mortality in a group of patients infected with HIV in Colombia. A retrospective longitudinal study was carried out. Patients treated in 4 highly complex clinics in Colombia between 2015 and 2023 were included. The cases were identified from International Classification of Diseases codes related to HIV. Sociodemographic, clinical, laboratory and pharmacological variables were collected. Descriptive, bivariate, and multivariable analyses were performed. Of the 249 patients identified, 79.1% were men, and the median age was 38.0 years. Approximately 81.1% had a diagnosis of acquired immune deficiency syndrome (AIDS). Coinfections caused by Mycobacterium tuberculosis (24.1%) and Treponema pallidum (20.5%) were the most frequent. A total of 20.5% of the patients had sepsis, 12.4% had septic shock, and the fatality rate was 15.7%. Antibiotics and antifungals were used in 88.8% and 53.8%, respectively, of the patients. Patients with a diagnosis of HIV before admission, those infected with M. tuberculosis, and those who presented with sepsis were more likely to die, whereas patients who received antiretroviral agent treatment before admission presented a lower risk. In this study, most HIV patients were in an advanced stage of the disease. Coinfection with M. tuberculosis was common and was associated with an increased risk of death. Previous HIV diagnosis and sepsis also increased the risk. Approximately half of the patients with a previous HIV diagnosis were receiving antiretroviral therapy and had a better prognosis.

48-week viral suppression rates in people with HIV starting long-acting CAB/RPV with initial viremia.

BACKGROUND: We previously demonstrated at the Ward 86 HIV clinic in San Francisco that long-acting cabotegravir/rilpivirine (LA-CAB/RPV) can rapidly lead to viral suppression (VS) in people with HIV (PWH) with viremia due to adherence challenges. We now evaluate VS durability in this population. METHODS: We conducted a retrospective cohort study of PWH who started LA-CAB/RPV with viremia (HIV RNA viral load [VL]≥50 copies/mL) before December 2022. Our primary outcome was VS (VL<50 copies/mL) with LA-CAB/RPV persistence (not discontinued or late by >14 days) at 48 weeks, using the closest VL to 48+/-8 weeks. We also describe viral failure (VF), defined as <2-log VL decline at 4 weeks or VL≥200 copies/mL after initial VS with emergent CAB- or RPV-associated resistance mutations; and overall 48-week VS including those switched to alternative ART. RESULTS: Fifty nine PWH initiated LA-CAB/RPV with viremia and were included in analysis; 49% had CD4<200 cells/µL and median baseline VL was 42,900 copies/mL (Q1-Q3 5,272-139,038). At 48 weeks, 47 met the primary outcome of VS with LA-CAB/RPV persistence (80%; 95%CI 67-89%). Five had VF with resistance (three with RPV-associated mutations, two with CAB and RPV-associated mutations) and one was lost-to-follow-up. At week 48, two of those with VF were suppressed on alternative regimens (lenacapavir+BIC/TAF/FTC and CAB+lenacapavir). Overall week 48 VS on either LA-CAB/RPV or alternative ART was 92% (54/59). CONCLUSIONS: In PWH initiating LA-CAB/RPV with initial viremia, 48-week VS (<50 copies/mL) was 92%. Long-acting ART can be an important tool for improving VS among patients who face adherence challenges to oral ART.

Highly active antiretroviral therapy adherence among HIV-POSITIVE women in Southern Ethiopia.

Background: Adherence to Highly Active Antiretroviral Therapy (HAART) medication is the major predictor of HIV/AIDS treatment success. Poor adherence to HAART creates the risk of transmitting HIV, deteriorating health conditions, treatment failure, increased occurrences of drug-resistant HIV, morbidity and mortality. The objective of the study was to explore and describe factors influencing HAART adherence among HIV-positive women in Southern Ethiopia. Methods: A hospital-based descriptive cross-sectional survey was used among 220 randomly selected respondents. Data was collected with a structured interview guide after each respondent had given consent to take part in the study. The collected data was entered into and analyzed by using the Statistical Package for Social Sciences (SPSS) software program version 27. Results: The level of self-reported adherence (measured by dose) to HAART in the past 30 days was found to be 82.7%. In multivariate analysis, the divorced/separated HIV-positive women had poor adherence to their HAART medication as compared to those who were married [AOR: 2.94, 95% CI: (1.02-8.44)]. Respondents who used reminders in their medication were 75% less likely to be poorly adherent to their HAART medication than those who did not use reminders [AOR: 0.25, 95% CI: (0.06-0.97)]. Those who self-reported depression, perceived stigma, and low perceived susceptibility had poor adherence to their HAART than those who did not report depression, perceived stigma, and low perceived susceptibility [AOR:2.34, 95% CI: (1.01-5.42)], [AOR:2.37, 95% CI: (1.06-5.34)], and [AOR: 4.1, 95% CI: (1.53-11.1)] respectively. HIV-positive women who self-reported low perceived severity were poorly adherent to HAART than those who self-reported high perceived severity [AOR: 2.92, 95% CI: (1.14-7.47)]. Conclusion: Factors including being divorced/separated, not using reminders, depression, perceived stigma, perceived susceptibility, and perceived severity negatively impact HIV-positive women's adherence to HAART.

Zinc and selenium supplementation on treated HIV-infected individuals induces changes in body composition and on the expression of genes responsible of naïve CD8+ T cells function.

Background and aim: Deficiency of zinc and selenium is common in persons living with human immunodeficiency virus (PLWHIV) and has been associated with the development of non-AIDS related comorbidities, impaired immune system function and mortality. Micronutrient supplementation on long-term-treated PLWHIV could bring potential clinical and immunological benefits improving their health status and quality of life. The aim of the present study is to analyze the effect of zinc and selenium supplementation on body composition, bone mineral density, CD4+ T-cell counts, metabolic profile and immune system status on clinical stable PLWHIV on long-term antiretroviral therapy (ART). Methods: This is a randomized pilot clinical trial in which we recruited 60 PLWHIV on ART who were assigned to the intervention groups: zinc (30 mg of zinc gluconate), selenium (200 µg of selenium yeast), zinc + selenium (same doses and presentations) or to a control group (without nutritional supplementation) who received supplementation during 6 months. Primary outcome was defined as changes in body composition (weight, muscle and fat mass and bone mineral density) and secondary outcomes as changes in biochemical and immunological parameters (CD4+ T-cell count, cholesterol, glucose, triglycerides and seric zinc and selenium seric concentrations) before and after supplementation. Peripheral blood mononuclear cells (PBMCs) of one individual of each intervention group were analyzed for single cell transcriptomics before and after supplementation. Results: BMI (p = 0.03), fat mass (p = 0.03), and trunk fat (p = 0.01) decreased after 6 months of selenium supplementation. No changes were observed for cholesterol, glucose or triglycerides after supplementation (p > 0.05 in all cases). CD4+ T cells percentage increased after 6 months of selenium supplementation (p = 0.03). On the transcriptome analysis, zinc and selenium supplementation induced changes on de expression of genes associated with the function of naive and memory CD8+ T-cells (p < 0.05 in all cases). Conclusion: Zinc and selenium supplementation could represent a complementary intervention that may improve the health status and immune response of treated PLWHIV.

A new class of capsid-targeting inhibitors that specifically block HIV-1 nuclear import.

HIV-1 capsids cross nuclear pore complexes (NPCs) by engaging with the nuclear import machinery. To identify compounds that inhibit HIV-1 nuclear import, we screened drugs in silico on a three-dimensional model of a CA hexamer bound by Transportin-1 (TRN-1). Among hits, compound H27 inhibited HIV-1 with a low micromolar IC50. Unlike other CA-targeting compounds, H27 did not alter CA assembly or disassembly, inhibited nuclear import specifically, and retained antiviral activity against PF74- and Lenacapavir-resistant mutants. The differential sensitivity of divergent primate lentiviral capsids, capsid stability and H27 escape mutants, together with structural analyses, suggest that H27 makes multiple low affinity contacts with assembled capsid. Interaction experiments indicate that H27 may act by preventing CA from engaging with components of the NPC machinery such as TRN-1. H27 exhibited good metabolic stability in vivo and was efficient against different subtypes and circulating recombinant forms from treatment-naïve patients as well as strains resistant to the four main classes of antiretroviral drugs. This work identifies compounds that demonstrate a novel mechanism of action by specifically blocking HIV-1 nuclear import.

Opportunistic Infections in HIV-Infected Children on Treatment in Southern Morocco: A 12-Years Retrospective Follow-up Study.

BACKGROUND: Human immunodeficiency virus (HIV) infection in children is a significant public health concern, increasing the risk of infant mortality. Immunodeficiency caused by HIV favors the development of opportunistic infections (OIs), which are responsible for over 90% of HIV-related deaths. This study seeks to determine the primary OIs in children with HIV followed at the Hassan II Regional Hospital Center in Sous Massa, during the period from 2012 to 2023. MATERIALS AND METHODS: This retrospective study is the first in Morocco to investigate OIs among HIV-infected children. It analyzed 76 complete medical records, using a data collection form designed based on existing literature. RESULTS: This study revealed that 37% of participants were suffering from OIs, mainly diarrhea (11%), tuberculosis (9%) and pneumonia (7%).There was a significant correlation between OIs and HIV clinical stage (P=0.001), age (P=0.007), and anemia (P=0.001). Despite progress in management, the presence of OIs remains a risk factor for infant morbidity and mortality. CONCLUSION: The study highlights the importance of early detection, prevention, and adherence to treatment in reducing this burden. Management of anemia is essential.

Epidemiological determinants and quality of life in PLHIV patients with tuberculosis in Bihar State, India.

BACKGROUND: This study aimed to determine the prevalence of TB among patients living with HIV in Patna district, India. It also assessed the factors contributing to co-infection and evaluated patients' quality of life. METHODS: This cross-sectional study was conducted at the Antiretroviral Therapy (ART) Centre in Patna, India, for a period of eight months. The socio-demographic information was collected through a pre-defined semi-structured questionnaire administered by the interviewer during face-to-face interviews at the time of enrolment. Clinical details were obtained from the hospital records. The statistical analysis was performed using SPSS software. RESULTS: The study showed that out of 289 people living with HIV, 31% had TB as a co-infection. Male patients had a higher probability of contracting HIV-TB co-infection compared to female patients. The study indicated that advanced WHO staging, male gender, past history of TB, and opportunistic infections were strong predictors. Conversely, the odds of HIV-TB co-infection reduced with a CD4 count of over 300 cells/mm3. However, an increase in age, lower socio-economic status, BMI below the normal range, and presence of comorbidities might increase the odds of HIV-TB co-infection but were not statistically significant. The QoL of HIV-TB patients was significantly lower than that of HIV-only patients. CONCLUSIONS: People with low CD4+ T cell count are at a higher risk of developing TB due to HIV/TB co-infection. The baseline clinical staging of HIV is significantly correlated with TB co-infection. Those in WHO Clinical Stage III and IV have a four times higher risk of developing TB.

A Comprehensive Review of HIV-Associated Tuberculosis: Clinical Challenges and Advances in Management.

Human immunodeficiency virus (HIV) and tuberculosis (TB) are two of the most pressing global health issues, each contributing significantly to morbidity and mortality worldwide. This review provides a comprehensive analysis of HIV-associated TB (HIV-TB), focusing on the clinical challenges and advancements in its management. HIV-positive individuals are at a heightened risk of developing active TB due to the immunosuppressive effects of the virus, which complicates both diagnosis and treatment. The interplay between these two diseases exacerbates health outcomes, presenting unique challenges related to drug interactions, adherence to treatment regimens, and management of adverse effects. This review explores the current diagnostic approaches, including advances in testing technologies and screening strategies, and examines treatment protocols, highlighting the integration of antiretroviral therapy with TB treatment. Special considerations for managing HIV-TB in various populations, such as children, pregnant women, and the elderly, are discussed. Additionally, the review addresses public health strategies for prevention and the impact of socio-economic and healthcare system factors on disease management. Finally, it highlights recent research innovations and future directions aimed at improving outcomes for individuals with HIV-TB. By synthesizing the latest evidence and clinical practices, this review aims to enhance understanding and guide effective management of this critical co-infection, ultimately contributing to reduced global burden and improved patient care.

Transgender-Specific Differentiated HIV Service Delivery Models in the South African Public Primary Health Care System (Jabula Uzibone): Protocol for an Implementation Study.

BACKGROUND: Almost 60% of transgender people in South Africa are living with HIV. Ending the HIV epidemic will require that transgender people successfully access HIV prevention and treatment. However, transgender people often avoid health services due to facility-based stigma and lack of availability of gender-affirming care. Transgender-specific differentiated service delivery (TG-DSD) may improve engagement and facilitate progress toward HIV elimination. Wits RHI, a renowned South African research institute, established 4 TG-DSD demonstration sites in 2019, with funding from the US Agency for International Development. These sites offer unique opportunities to evaluate the implementation of TG-DSD and test their effectiveness. OBJECTIVE: The Jabula Uzibone study seeks to assess the implementation, effectiveness, and cost of TG-DSD for viral suppression and prevention-effective adherence. METHODS: The Jabula Uzibone study collects baseline and 12-month observation checklists at 8 sites and 6 (12.5%) key informant interviews per site at 4 TG-DSD and 4 standard sites (n=48). We seek to enroll ≥600 transgender clients, 50% at TG-DSD and 50% at standard sites: 67% clients with HIV and 33% clients without HIV per site type. Participants complete interviewer-administered surveys quarterly, and blood is drawn at baseline and 12 months for HIV RNA levels among participants with HIV and tenofovir levels among participants on pre-exposure prophylaxis. A subset of 30 participants per site type will complete in-depth interviews at baseline and 12 months: 15 participants will be living with HIV and 15 participants will be HIV negative. Qualitative analyses will explore aspects of implementation; regression models will compare viral suppression and prevention-effective adherence by site type. Structural equation modeling will test for mediation by stigma and gender affirmation. Microcosting approaches will estimate the cost per service user served and per service user successfully treated at TG-DSD sites relative to standard sites, as well as the budget needed for a broader implementation of TG-DSD. RESULTS: Funded by the US National Institutes of Mental Health in April 2022, the study was approved by the Human Research Ethics Committee at University of Witwatersrand in June 2022 and the Duke University Health System Institutional Review Board in June 2023. Enrollment began in January 2024. As of July 31, 2024, a total of 593 transgender participants have been enrolled: 348 are living with HIV and 245 are HIV negative. We anticipate baseline enrollment will be complete by August 31, 2024, and the final study visit will take place no later than August 2025. CONCLUSIONS: Jabula Uzibone will provide data to inform HIV policies and practices in South Africa and generate the first evidence for implementation of TG-DSD in sub-Saharan Africa. Study findings may inform the use of TG-DSD strategies to increase care engagement and advance global progress toward HIV elimination goals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/64373.

Retention in Care Among People Living with HIV in Nigeria: A Systematic Review and Meta-analysis.

BACKGROUND: In 2021, Nigeria had an estimated 1.9 million people living with the human immunodeficiency virus (PLHIV) and 1.7 million (90%) on antiretroviral therapy (ART). Study Design: A systematic review and meta-analysis. METHODS: This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. We searched PubMed, Embase, PsychINFO, CINAHL, Global Index Medicus, and Cochrane Library. Studies were included if they reported on ART retention in care among PLHIV in Nigeria. The random-effects meta-analyses were used to combine the studies that had complete retention data. The I2 statistic was used to assess the heterogeneity of the studies. A sensitivity analysis was then done by conducting a leave-one-out analysis. Afterward, data were analyzed using STATA version 18. RESULTS: The search yielded 966 unique articles, of which 52 studies met the inclusion criteria for the meta-analysis, and four experimental studies were split into their component arms. The total number of study participants was 563,410, and the pooled retention rate was 72% (95% CI: 67%, 76%; I2=99.9%; n=57). Sub-analysis showed that the Southeast region of Nigeria had the highest retention of 86% (95% CI: 78%, 92%), and the South-South had the lowest retention (58%; 95% CI: 38%, 79%). CONCLUSION: In Nigeria, the pooled ART retention rate is less than optimal to achieve the UNAIDS goal of 95%, thus developing new models for ART retention is needed.

Characteristics and real-world medication persistence of people living with HIV treated with DTG/3TC or BIC/FTC/TAF: a hospital claims database study in Japan.

Background: As the life expectancy of people living with human immunodeficiency virus (HIV) (PLWH) has improved, chronic disease burden and polypharmacy have increased in PLWH. Simplification of the antiretroviral therapy (ART) regimen for PLWH has become crucial. The real-world treatment patterns and medication persistence of the 2-drug single-tablet regimen (STR), dolutegravir/lamivudine (DTG/3TC), compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) prescribed were investigated. Methods: This retrospective, database study extracted data from a hospital-based medical claims database in Japan. The changes in ART distributions by year during the identification period between January 1, 2018 and December 31, 2021 were observed. Patients with disease record of HIV-1 infection and prescribed DTG/3TC or BIC/FTC/TAF as the first prescription of STR during the identification period were divided into two cohorts; DTG/3TC cohort and BIC/FTC/TAF cohort, respectively. Patient without medication records more than 3 months and no future data more than 6 months were excluded. Patients' characteristics were compared between the DTG/3TC cohort and the BIC/FTC/TAF cohort by Mantel-Haenszel test to adjust for age. Medication persistence was compared between the two cohorts by evaluating the continuation rates using Kaplan-Meier methods, using the log-rank test to assess the difference between the Kaplan-Meier curves. The median time-to-first prescription was compared between the two cohorts by Kaplan-Meier methods. Results: Prescriptions of DTG/3TC and BIC/FTC/TAF increased steadily from 2019 to 2021 after the release year of each STR. There was no significant difference in the time-to-first prescription (p = 0.3). A total of 959 patients were included, with 120 patients and 839 patients on DTG/3TC and BIC/FTC/TAF, respectively. The proportion of dyslipidemia at baseline was significantly higher in the DTG/3TC cohort than in the BIC/FTC/TAF cohort after adjusting for mean age (p = 0.002). There was no significant difference in medication persistence between the two cohorts (p = 0.91). Conclusion: This study showed that DTG/3TC was likely to be selected for elderly patients and those with chronic disease in real-world clinical practice, which seems in accordance with the treatment strategy recommended by guidelines. Comparable medication persistence was observed with both regimens, aligning with findings from other countries. The 2-drug single-tablet regimen DTG/3TC may be an important ART regimen for PLWH with multiple morbidities and polypharmacy in an aging society. Due to the limitations of the database, further research to assess viral loads, emergence of resistance and adverse events will be encouraged.

Correlation of APOE polymorphism, expression, and plasma levels with cardiac comorbidities among lipodystrophy in HIV-infected patients.

Lipodystrophy in HIV-infected patients (LDHIV) includes morphological and metabolic abnormalities, including lipid and glucose metabolism. ApoE plays a role in the transport and clearance of lipoprotein. In the general population, ApoE 112 (rs429358) and 158 (rs7412) polymorphisms were linked to severe dyslipidemia. Therefore, we investigated ApoE polymorphism using PCR-RFLP in 200 HIV patients (100 with HIV-associated lipodystrophy (HIVLD), 100 without HIVLD), as well as 100 healthy controls. We also assessed ApoE expression using qRT-PCR and measured its level using ELISA. The APOE 4/4, 3/4, and 2/4 genotypes have been associated with a decreased risk of HIV-1 infection. (P = 0.0001, OR = 0.18; P = 0.006, OR = 0.87; P = 0.006, OR = 0.09) when compared between HIV-positive individuals and healthy controls. Conversely, APOE allele 2 was linked to a higher risk of acquiring HIV-1 (P = 0.03, OR = 3.02). APOE allele 2 was linked to a higher likelihood of HIVLD severity when compared between patients with and without HIVLD (P = 0.05, OR = 2.82). When comparing patients with HIVLD to healthy controls, the APOE 4/4 and 2/4 genotypes as well as allele 4 were linked with the reduced risk of LDHIV (P = 0.0006, OR = 0.21; P = 0.01, OR = 0.18; P = 0.0002, OR = 0.40). When compared to patients without HIVLD from healthy controls, the ApoE 4/4 genotype, 2 and 4 alleles, were linked to a reduced risk of developing HIVLD (P = 0.0009, OR = 0.14; P = 0.0001, OR = 0.17; P = 0.00001, OR = 0.39). When comparing impaired to normal cholesterol levels in patients without HIVLD, the ApoE 3/4 genotype was linked with the increased risk of impaired cholesterol levels (P = 0.02, OR = 3.37). When comparing impaired and normal glucose levels in patients without HIVLD, the ApoE 4/4 genotype was associated to an elevated risk of impaired glucose levels (P = 0.03, OR = 8.27). In multivariate analysis, independent impaired cholesterol, LDL, and glucose levels were associated with a higher risk of lipodystrophy severity (P = 0.04, OR = 2.33; P = 0.001, OR = 4.05; P = 0.05, OR = 2.63). ApoE expression was up-regulated in LDHIV with a fold change value of 4.02 compared to those without HIVLD. ApoE protein level was found to be higher in patients of the HIVLD group (3.01 mg/dL) compared to those without HIVLD group (2.83 mg/dL). In conclusion, individuals with ApoE allele 2 were at higher risk for HIV-1 acquisition and severity of HIVLD, whereas those with ApoE allele 4 were at reduced HIVLD severity and development risk. It's possible that ApoE's increased level and its overexpression are related to the ApoE allele 2 in HIVLD patients. The development of LDHIV may be facilitated by the APOE 3/4 and 4/4 genotypes as well as abnormal glucose and cholesterol levels.

Antiretroviral Therapy during Long-term Surgical Care: 'Exploring Difficult Cases in HIV Clinics' of the Korean Society for AIDS Conference in 2023.

With advancements in antiretroviral therapy (ART), the average lifespan of people with human immunodeficiency virus (HIV) is increasing, as is the number of older adults with HIV. Accordingly, the number of patients with HIV who undergo surgery or require critical care for various reasons is increasing. Since the prognosis of people with HIV depends on the continuous and effective maintenance of ART, there is a need to consider effectively maintaining ART in people with HIV in these conditions. This case involved a 55-year-old patient with well-controlled HIV who received ART and presented to the emergency room with acute abdominal pain. He was diagnosed with extensive bowel infarction and panperitonitis and received critical care in the intensive care unit, including mechanical ventilation and continuous renal replacement therapy. The patient was administered enteral nutrition via a nasogastric tube. The patient subsequently underwent extensive small bowel resection and developed short bowel syndrome. The patient maintained ART during that period. A literature review related to the use of ART under these conditions is included in this study. This case was discussed at the [Exploring Difficult Cases in HIV Clinics] of the Korean Society for AIDS Conference held in 2023.

A Case Report of Lenacapavir Use in a Patient with Multidrug-Resistant HIV: The First Experience in Asia.

Lenacapavir is a novel, first-in-class, capsid inhibitor, which has been approved as an adjunctive therapy for multidrug-resistant human immunodeficiency virus (HIV)-1 virus in combination with optimized background regimen (OBR). Lenacapavir has demonstrated a significant decrease in viral load and high rate of virologic suppression in patients with multidrug-resistant HIV-1 infection with limited treatment options. Here, we report a case of 43-year-old male who was diagnosed with HIV-1 infection in 2005 but failed to achieve viral suppression due to multiclass resistance. After lenacapavir use with OBR, viral suppression was achieved, and recovery of CD4+ T-cell count was observed for 8 months. This case report shows the first lenacapavir experience in Asia in a heavily treatment-experienced HIV patient with limited treatment options.