Antiretroviral Research Articles

Gonadal Hormonal Changes in HIV-Positive Individuals Following Anti –retroviral Theraphy at K.R. Hospital, Mysuru, Karnataka, India

Aims: HIV infection and AIDS remain global health challenges, with many individuals suffering from endocrine disorders such as gonadal dysfunction. This study assesses the levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol in HIV-positive individuals before and after six months of antiretroviral therapy (ART). Study Design: Clinical observational study. Place and Duration of Study: ART Center, K.R. Hospital, Mysuru. Methodology: The clinical–observational study involved seventy patients who were HIV positive, who were recruiting to ART clinic which is located at KR hospital Mysuru. The patients were split into two groups according to their CD4 count (≤200 cells/µL ND >200 cells/µ L). The baseline values were measured for LH, FSH, testosterone and estradiol just prior to ART and the levels of hormones were measured again six months after commencing ART. Results: Our study conducted among 70 patients, 38 were males and 32 were females, average age being around 40 years. These patients were divided into two groups based on CD4 counts (≤200 cells/µL and >200 cells/µL). Gonadal hormone level were checked pre-ART and six months post-ART therapy. After six months of ART therapy, there was significant improvement in testosterone (7.93 pg/mL to 8.94 pg/mL (p < 0.0001)) and LH level noted among male patients, estradiol and FSH levels were not improved significantly. Same degree of improvement in hormone level were not seen in female patients. Hypogonadism improved from 18.57% improved to 69.23% after six-month post-ART therapy. This signifies role of ART therapy in improvement in gonadal dysfunction. Conclusion: Gonadal deficiency or more specifically hypogonadism is common among patients infected with HIV. The improvement in male testosterone and LH levels after ART suggests that hypogonadism may reverse in some cases. However, these observations need long term and larger volume studies to support the hypothesis.

Mother-child dyads living with HIV in the Western Cape, South Africa: Undetectable = Undetectable?

Globally, children living with HIV continue to lag behind UNAIDS targets for viral suppression (VS). Because studies with linked mother-child data are limited, we describe VS and associated factors among young children in a setting with early infant HIV testing (at birth, age 10 weeks and 6 months) and early protease inhibitor-based first-line antiretroviral therapy (ART). We analysed routinely collected mother-child data for children living with HIV born 2018-2022 in Western Cape province, South Africa (followed through mid-2023). We assessed associations between child and maternal viral load (VL) results at 12 and 24 months after child ART start using logistic regression, adjusted for child sex, birthyear, severity of child immunodeficiency at ART start, maternal age and timing of maternal HIV diagnosis. Among 2219 children living with HIV; 30% were diagnosed at birth (≤7 days), 41% before age 1 year (8-365 days) and 29% at age >1 year. Overall, 5% (n = 112/2219) of children died, a third of whom had not started ART; 90% of children (n = 1990) started ART, at median age 5 months (IQR 1-16). Median follow-up from ART start was 26 months (IQR 14-40). Among children with available VL at 12 months (n = 853/1582), 24 months (n = 614/1129) and 36 months (n = 350/658) after ART start, 36%, 43% and 48% were virally suppressed, respectively (VL<100 copies/ml). VS among children at 12 and 24 months was more likely if maternal VL was <100 versus ≥100 copies/ml at 12 months (adjusted odds ratio [aOR] = 3.5; 95% CI 1.9-6.5) and 24 months (aOR = 6.1; 95% CI 2.8-13.1) after child ART start. Children with no/mild versus advanced/severe immunodeficiency at ART start were more likely to achieve VS at 12 months (aOR = 2.3; 95% CI 1.3-4.2) but not at 24 months. Eligible children with missing VL at 24 months (39%) were more likely to have gaps in care of >6 months than those with VL≥100 or VL<100 copies/ml (84% vs. 28% vs. 14%, respectively; p<0.001). Less than half of children on ART achieved VS, and children were more likely to achieve VS if their mothers were also virally suppressed. Significant efforts are needed to support mother-child dyads to achieve optimal VS.

Effect of dolutegravir on weight changes and lipid profile compared with efavirenz in people living with HIV: A retrospective cohort study.

There are limited data on DTG-associated weight gain among treatment-naïve Asian people living with HIV (PLHIV). Eighty-one and 100 PLHIV initiating DTG-based and efavirenz (EFV)-based antiretroviral therapy (ART), respectively, were retrospectively investigated for weight changes and lipid profiles at 6 and 12 months after ART initiation. At baseline, the DTG group had a lower mean body weight (BW) (60.7 kg vs. 64.3 kg, p = 0.071) and lower mean cholesterol level (172 mg/dL vs. 185 mg/dL, p = 0.029) than the EFV group. Mean BW remained lower in the DTG group than in the EFV group at 6 [58.2 kg vs. 66.0 kg, mean difference (MD) -7.8, p = 0.005] and 12 (59.6 kg vs. 67.0 kg, MD -7.3, p = 0.008) months. BW did not significantly change between baseline and 12 months in the DTG group (60.7 kg vs. 59.6 kg, p = 0.495), whereas it significantly increased between baseline and 12 months in the EFV group (64.3 kg vs. 66.9 kg, p = 0.019). Cholesterol levels did not significantly increase between baseline and 12 months in either group. After adjustment, DTG use [MD -5.85, 95 % confidence interval (CI) -10.45, -1.24, p = 0.013] and baseline BW (MD 0.97, 95 % CI 0.79, 1.15, p < 0.001) were significantly associated with BW changes over time. DTG-based ART was not significantly associated with increased BW and cholesterol levels compared with EFV-based ART in treatment-naïve Thai PLHIV.

Experiences and Preferences in Zambia and South Africa for Delivery of HIV Treatment During a Client's First Six Months: Results of the PREFER Study's Cross-Sectional Baseline Survey.

Disengagement from antiretroviral therapy (ART) is highest in the early treatment period (≤ 6 months after initiation/re-initiation), but low intensity models designed to increase retention generally exclude these clients. We describe client preferences for HIV service delivery in the early treatment period. From 9/2022 to 6/2023, we surveyed adult clients who were initiating or on ART for ≤ 6 months at primary health facilities in South Africa and Zambia. We collected data on experiences with and preferences for HIV treatment. We enrolled 1,098 participants in South Africa (72% female, median age 33) and 771 in Zambia (67% female, median age 32), 38% and 34% of whom were initiating/re-initiating ART in each country, respectively. While clients expressed varied preferences, most participants (94% in South Africa, 87% in Zambia) were not offered choices regarding service delivery. 82% of participants in South Africa and 36% in Zambia reported receiving a 1-month supply of medication at their most recent visit; however, South African participants preferred 2- or 3-month dispensing (69%), while Zambian participants preferred 3-or 6-month dispensing (85%). Many South African participants (65%) would prefer to collect medication in community settings, while Zambian participants (70%) preferred clinic-based collection. Half of participants desired more one-on-one counselling and health information. Most participants reported positive experiences with providers, but long waiting queues were reported by South African participants.During the first six months on ART, many clients would prefer less frequent clinic visits, longer dispensing intervals, and frequent, high-quality counselling. Care models for the early treatment period should reflect these preferences.Registration: Clinicaltrials.gov NCT05454839, Clinicaltrials.gov NCT05454852.

Health disparities in HIV care and strategies for improving equitable access to care.

The US HIV/AIDS Strategy and Ending the HIV Epidemic (EHE) initiatives aim to reduce HIV transmission by 90% by 2030 through targeted care and prevention initiatives such as the Undetectable = Untransmittable strategy. Effective HIV management involves implementation of widely available testing to ensure early diagnosis, immediate or early initiation of antiretroviral therapy (ART), patient adherence to medication, and retention in care to achieve viral suppression and improve clinical outcomes. A disproportionate burden of HIV incidence is experienced by certain populations that include Black/African American and Hispanic/Latinx people, transgender individuals, those who inject drugs, older adults, and people living in the southeastern US. People with HIV (PWH) in vulnerable and underserved populations are more likely to be affected by the negative impacts of structural and social determinants of health-such as experiencing HIV-related stigma, poverty, and homelessness-resulting in barriers to accessing HIV care and achieving favorable treatment outcomes. Suboptimal HIV care negatively impacts outcomes for both individuals and society. Overall and comorbidity-free life expectancies are lower for individuals who start ART late than for the overall PWH population, and a lack of viral suppression increases community transmission rates. These poor outcomes increase costs for both patients and health care systems. Maintaining access to high-quality care by optimizing ART regimens, decreasing delays in ART initiation, and engaging patients in care by building trust and empowering patient choice will improve individual and population-level outcomes and support the EHE initiative. This manuscript examines strategies to improve HIV care access and outcomes for underserved populations, focusing on social determinants of health, stigma, geographic disparities, and treatment adherence, while highlighting the role of national initiatives and managed care programs in advancing health equity.

SHMT2 regulates CD8+ T cell senescence via the reactive oxygen species axis in HIV-1 infected patients on antiretroviral therapy.

Although antiretroviral therapy (ART) effectively inhibits viral replication, it does not fully mitigate the immunosenescence instigated by HIV infection. Cellular metabolism regulates cellular differentiation, survival, and senescence. Serine hydroxymethyltransferase 2 (SHMT2) is the first key enzyme for the entry of serine into the mitochondria from the de novo synthesis pathway that orchestrates its conversion glutathione (GSH), a key molecule in neutralising ROS and ensuring the stability of the immune system. It remains incompletely understood whether SHMT2 is involved in the senescence of CD8+ T cells, crucial for immune vigilance against HIV. HIV-infected individuals receiving antiretroviral therapy were enrolled in our study. SHMT2-siRNA was electroporated into T cells to disrupt the gene expression of SHMT2, followed by the quantification of mRNA levels of crucial serine metabolism enzymes using real-time PCR. Immunophenotyping, proliferation, cellular and mitochondrial function, and senescence-associated signalling pathways were examined using flow cytometry in CD8+ T cell subsets. Our findings revealed that CD8+ T cells in HIV-infected subjects are inclined towards senescence, and we identified that SHMT2, a key enzyme in serine metabolism, plays a role in CD8+ T cell senescence. SHMT2 can regulate glutathione (GSH) synthesis and protect mitochondrial function, thus effectively controlling intracellular reactive oxygen species (ROS) levels. Moreover, SHMT2 significantly contributes to averting immunosenescence and sustaining CD8+ T cell competence by modulating downstream DNA damage and phosphorylation cascades in pathways intricately linked to cellular senescence. Additionally, our study identified glycine can ameliorate CD8+ T cell senescence in HIV-infected individuals. Decreased SHMT2 levels in HIV-infected CD8+ T cells affect ROS levels by altering mitochondrial function and GSH content. Increased ROS levels activate senescence-related signalling pathways in the nucleus. However, glycine supplementation counteracts these effects and moderates senescence. This study was supported by grants from the National Key R&D Program of China (2021YFC2301900-2021YFC2301901), National Natural Science Foundation of China (82372240), and Department of Science and Technology of Liaoning Province Project for the High-Quality Scientific and Technological Development of China Medical University (2022JH2/20200074).

Evidence of zero-risk transmission of HIV in the era of antiretroviral therapy: A systematic review and meta-analyses.

This systematic review aimed to assess the evidence on sexual transmission of HIV in high-income settings between serodiscordant couples where the index partner infected with HIV is on antiretroviral therapy. Systematic review and meta-analyses. We performed a systematic search in four databases: Embase, MEDLINE, The Cochrane Library, and Web of Science on September 24, 2022. We assessed the risk of bias with ROBINS-I and pooled estimates in meta-analyses using a Poisson regression model with a random effect of the study and population size. The study protocol was pre-registered at PROSPERO. The study involved high-income countries. The search identified 6886 studies, of which six were included for review. Altogether, studies reported zero linked transmissions among 2383 couples, more than 160,000 acts of intercourse, and 3578 couple years. The risk estimate from overall meta-analyses was 0.000 95%CI (0.000-0.103) per 100 couple-years. This systematic review and meta-analyses provide epidemiological evidence for a low risk of HIV transmission under antiretroviral therapy in high-income countries and thus cannot reject the theoretical "treatment as prevention" paradigm.

Intersecting Structural and Psychosocial Conditions: Investigating Injection Drug Use and HIV Among Transgender Women.

Transgender women continue to face a significant burden of health disparities with HIV infection as a critical public health concern. Substance use is higher among transgender women than among cisgender women. However, little is known about transgender women who inject drugs and risk for HIV in the United States. The objectives were to explore HIV prevalence, injection-related behaviors, and HIV prevention and care outcomes among transgender women who inject drugs and to compare transgender women with a general sample of persons who inject drugs. Participants from the National HIV Behavioral Surveillance were recruited through respondent-driven sampling, interviewed, and tested for HIV infection in 2019-2020. Log-linked Poisson regression models were used to test for associations between injection drug use and selected characteristics. Among 1561 transgender women, 7% injected drugs in the past 12 months. HIV prevalence was higher among transgender women who inject (adjusted prevalence ratio = 1.5, 95% confidence interval: 1.2 to 1.8) than among those who do not. Multiple psychosocial conditions were associated with injection drug use. Among transgender women with HIV, those who inject were less likely to take antiretroviral therapy (adjusted prevalence ratio = 0.8, 95% confidence interval: 0.7 to 1.0) than those who do not. Methamphetamine was the most commonly injected drug (67%); most accessed a syringe services program (66%). Transgender women who inject have substantial challenges related to health outcomes including high HIV prevalence and exposure to psychosocial conditions, such as homelessness, incarceration, and exchange sex, that may exacerbate risks associated with injection drug use. This population may benefit from increased access to nonjudgmental and culturally competent harm reduction services.

Longitudinal associations between intersectional stigmas, antiretroviral therapy adherence, and viral load among women living with HIV using multidimensional latent transition item response analysis.

In the US, Women, especially Black and Latina women living in disadvantaged environments, are disproportionally affected by HIV. Women living with HIV (WLHIV) have higher rates of suboptimal antiretroviral therapy (ART) adherence, and detectable viral load (VL). Experiences of intersectional poverty, HIV, gender, and racial stigmas may increase the rates of detectable VL through suboptimal ART adherence. To explore longitudinal associations between intersectional stigmas, ART adherence, and detectable VL using multidimensional latent transition item response analysis. WLHIV (N=459) in the [masked] sub-study of the [masked], from sites in Birmingham, AL, Jackson, MS, Atlanta, GA, and San Francisco, CA. Experienced poverty, HIV, gender, and racial stigma, self-report ART adherence, and VL were assessed at four yearly follow-ups between 2016 and 2020. We identified five classes of WLHIV with different combinations of experienced intersectional stigmas. Longitudinally, WLHIV with higher levels of poverty, gender, and racial stigma had higher odds of suboptimal ART adherence (<90%) (OR=3.59, p<0.001) and detectable VL (OR=2.08, p=0.028) compared to WLHIV with lower/moderately low stigmas levels. WLHIV in the highest stigma classes had higher odds of detectable VL, independently of ART adherence (Class 3: OR=1.38, p=0.016; Class 5: OR=1.31, p=0.046). These findings underscore the compounded effects of intersectional stigmas on HIV treatment outcomes. Intersecting experiences of HIV, racial, gender, and poverty stigmas can increase detectable VL risk through suboptimal ART adherence, although other mechanisms may also be involved. Recognizing the complexity of intersectional stigmas is essential for developing approaches to improve WLHIV's HIV treatment outcomes.

A case of newly onset rheumatoid arthritis successfully treated with methotrexate under the anti-retrovirus therapy against HIV infection.

The patient was a 70-year-old woman. In July 2018, she developed pneumocystis pneumonia and was diagnosed with human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). Antiretroviral therapy (ART) was continued, the HIV-RNA load was suppressed, and the CD4+cells count was maintained. In 2024, the polyarticular pain and swelling persisted. HIV-associated arthropathy, reactive arthritis, and other diseases were excluded. The patient was diagnosed with rheumatoid arthritis (RA) according to the ACR/EULAR 2010 Rheumatoid Arthritis Classification Criteria. Joint radiography revealed narrowing of the wrist joint, and joint ultrasonography showed synovial thickening and power doppler signals, supporting the diagnosis of RA. Methotrexate was initiated, and remission was achieved and maintained. After starting MTX, HIV-RNA load increased transiently but rapidly decreased after that. CD4+cells count was maintained. Patients with HIV have underlying immune dysfunction, and RA requires treatment with immunosuppressants (DMARDs), which makes treatment challenging. Recently, HIV infection has been considered a factor that makes the diagnosis of RA difficult. When symptoms suggestive of RA are observed in HIV-infected patients, it is important to make a thorough differential diagnosis and determine a treatment plan based on the characteristics of RA complicated by HIV infection.

An updated overview on long-acting therapeutics for the prevention and treatment of human immunodeficiency virus (HIV) from a perspective of pharmaceutics.

Conventional drug formulations release active pharmaceutical ingredients (APIs) immediately after administration, while long-acting (LA) drug products are designed for prolonged therapeutic effects, thereby reducing administration frequency and improving patient compliance. The development of LA therapeutics for chronic disease treatment has significantly helped patients adhere to their regimens, reducing the need for daily doses and easing the burden on healthcare systems. Advances in treatment have transformed Human Immunodeficiency Virus (HIV) into a manageable chronic disease, and efforts are underway to eliminate HIV in the future. Nowadays, antiretroviral therapies (ARTs) are widely available and accessible, daily oral pre-exposure prophylaxis (PrEP) has been highly effective and the new LA ARTs and LA PrEP are being actively pursued. The development of LA antiretrovirals for HIV has revolutionized the landscape of global implementation of HIV prevention and treatment. This article provides an overview of LA medicines (pills, injections, solid implants, and in situ forming depots) for the prevention and treatment of HIV from a pharmaceutics perspective, describing approved medicines, recognizing promising technologies, and discussing the pros and cons of poly (lactic-co-glycolic acid) (PLGA) particles, liposomes, hydrogels, and organogel formulations.

Examining the Prevalence and Associated Factors of Sexually Transmitted Infections in People Living With HIV/AIDS at a Community Health Center in Bandung City, Indonesia.

This study aims to investigate the prevalence of sexually transmitted infections (STIs) and associated factors among people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (PLWHA) registered in a community health center (CHC) with HIV/AIDS support and treatment services in Indonesia. A cross-sectional study that included all PLWHA data from medical records registered in a CHC with HIV/AIDS support and treatment services was conducted in Bandung City, Indonesia, between March 2019 and March 2024. This CHC provides comprehensive and continuous HIV/AIDS services, including HIV testing, antiretroviral therapy (ART), and opportunistic infection management. The factors associated with the prevalence of STIs in PLWHA, including sociodemographic factors such as gender, age, education level, marital status, occupation, population group, referral origin, and clinical factors such as length of illness, duration of ART, clinical stage, and comorbidities, were analyzed by using chi-square analysis. Total 156 PLWHA data with STIs from medical records were collected (male, n = 152, 97.4%; female, n = 4, 2.6%). The prevalence of STIs among PLWHA was 32.1%, consisting of syphilis (n = 36; 72%), gonorrhea (n = 11; 22%), genital herpes (n = 2; 4%), and condyloma (n = 1; 2%). The following significant factors associated with the prevalence of STIs were population group men who have sex with men (MSM) (p = 0.046), referral origin from non-government organizations (NGOs) (p = 0.030), duration of disease (p = 0.023) and duration of ART ranging from 12 to 36 months (p = 0.023), and early clinical stage (p = 0.010). STIs affected over one-third of CHC-registered PLWHA, with syphilis being the most common. MSMs and patients referred by NGOs, with illness and treatment durations ranging from 12 to 36 months, as well as the early clinical stage of HIV, are associated with STIs among PLWHA. Intervention strategies to improve STI prevention and control in these populations are urgently needed.

Assessing HIV/AIDS patients’ access to antiretroviral drugs using the healthcare accessibility framework: a cross-sectional study from Shandong, China

BackgroundAntiretroviral drugs are important for HIV/AIDS patients, but we know little about the real-life barriers patients face in accessing them. Following the Levesque framework, this study described the five abilities of HIV/AIDS patients in Shandong Province to perceive, to seek, to reach, to pay and to engage in accessing antiretroviral drugs and the factors associated with them.MethodsA cross-sectional questionnaire survey, using convenience sampling, was conducted among HIV/AIDS patients in three AIDS-designated hospitals in Shandong Province. We used catastrophic cost methods and the HIV Treatment Adherence Self-efficacy Scale to assess patients' ability to pay and engage, respectively.ResultsA total of 301 participants completed the questionnaire, with 20.9% having a CD4 cell count of less than 200 cells/µL. For the ability to perceive, only 16.6% of respondents self-reported low knowledge of HIV progression and medication. For the ability to seek, 24.3% self-reported having experienced social discrimination, and 21.9% reported 'choosing not to seek health insurance reimbursement due to fear of privacy disclosure. For the ability to reach, the average time spent on purchasing drugs was 2.1 ± 1.3 h, with respondents living in rural areas and having low levels of education most likely to spend more hours. For the ability to pay, the overall incidence of catastrophic health expenditures for drugs was 28.9%. For the ability to engage, the overall median score on the HIV-ASES scale was 118.0 (IQR: 107–120), and 69.4% had high treatment compliance. Respondents who experienced drug toxicities were more likely to have poorer treatment compliance (OR = 2.12, P = 0.011).ConclusionsIn general, access to antiretroviral drugs for HIV/AIDS patients was relatively good, while their ability to reach and pay was unsatisfactory. There should be a great concern for health education intervention and geographical accessibility of antiretroviral drugs in healthcare institutions. Policy should focus on the impact of social discrimination and drug toxicity on access to antiretroviral drugs.

Ptosis in human immunodeficiency virus-infected patients under long-term antiretroviral treatment.

To present cases of ptosis in HIV-1 patients on long-term antiretroviral therapy (ART) and review the existing literature. Five HIV-1-positive patients with slowly progressive bilateral ptosis underwent a comprehensive diagnostic evaluation, including imaging studies, neurophysiological testing, muscle biopsy, and genetic analysis. A literature review was conducted. On clinical examination, all patients presented with bilateral symmetrical non-fatigable ptosis, three exhibited facial lipoatrophy and two also had mild multidirectional ophthalmoparesis and all had ocular abnormalities in Hess screen test. Additionally, one patient displayed proptosis, three had floppy lower eyelids, and four presented with exotropia. Anti-acetylcholine receptor antibodies were negative in all patients. Brain magnetic resonance imaging (MRI), motor unit potential analysis, and single-fiber electromyography were unremarkable. Orbital MRI revealed introrbital fat expansion in one patient, and limb muscle biopsies were inconclusive in two cases. Blood genetic testing for chronic progressive external ophthalmoplegia was negative in all patients. A total of 30 similar cases have been documented in the literature, with some studies reporting key findings such as muscle histology indicative of mitochondrial myopathy, MRI revealing patchy extraocular muscle hyperintensity, and muscle genetic testing identifying mitochondrial deoxyribonucleic acid (DNA) deletions. Ptosis surgical repair appears to be the most effective treatment. HIV patients on long-term ART may develop ocular muscle involvement due to mitochondrial dysfunction, with bilateral ptosis being the primary manifestation. Diagnosis is challenging and requires the exclusion of other conditions. Ptosis surgery can significantly improve quality of life.

A blueprint for large language model-augmented telehealth for HIV mitigation in Indonesia: A scoping review of a novel therapeutic modality.

Background: The HIV epidemic in Indonesia is one of the fastest growing in Southeast Asia and is characterised by a number of geographic and sociocultural challenges. Can large language models (LLMs) be integrated with telehealth (TH) to address cost and quality of care? Methods: A literature review was performed using the PRISMA-ScR (2018) guidelines between Jan 2017 and June 2024 using the PubMed, ArXiv and semantic scholar databases. Results: Of the 694 records identified, 12 studies met the inclusion criteria. Although the role of eHealth interventions as well as telehealth in HIV management appears well established, there is a significant literature gap on the integration of telehealth and LLM technology. To address this, we provide a blueprint for the safe and ethical integration of LLM-TH into triage, history taking, patient education highlighting opportunities for reduced consultation time and improved quality of care. Conclusions: Variable access to mobile technology and the need for empirical validation stand out as limitations for LLM-TH. However, we argue that the current evidence base suggests the benefits far outweigh the challenges in applying LLM-TH for HIV care in Indonesia. We also argue this novel therapeutic modality is broadly applicable to the subacute general practice setting.

Pharmacokinetics, safety and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in children with HIV aged from 2 years and weighing at least 14 kg.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was efficacious and well tolerated in children/adolescents with HIV (aged ≥6years, weighing ≥25kg) in a Phase 2/3 study. Here, we report data from children aged ≥2years and weighing ≥14-<25kg. This is an analysis of data from the youngest cohort in an open-label, multicentre, multi-cohort, single-group, international study of children/adolescents with HIV. Participants in this cohort were children aged ≥2years, weighing ≥14-<25kg at screening and able to swallow tablets, on stable antiretroviral therapy with virologic suppression (HIV-1 RNA <50 copies/ml for ≥6 consecutive months) and a CD4 count ≥400 cells/µl. Eligible participants received low-dose E/C/F/TAF (90/90/120/6 mg) once daily through Week 48. The study included pharmacokinetic evaluation of the low-dose E/C/F/TAF tablet at Week 2. Safety, efficacy, palatability and acceptability were also evaluated. Between 16 January and 25 November 2019, 27 participants were enrolled with a median (quartile [Q]1, Q3) age of 6 (4, 8)years, body weight of 19.3 (17.0, 20.5)kg, CD4 count of 1061 (895, 1315) cells/µl and CD4 cell percentage of 37.4 (30.6, 40.3). Most (92.6%) participants acquired HIV through vertical transmission. On 6 October 2020 (data-cut), median (Q1, Q3) exposure to E/C/F/TAF was 48.3 (48.0, 60.1) weeks. Pharmacokinetic parameters were within the safe and efficacious range of previous data in adult and paediatric populations. Drug-related treatment-emergent adverse events occurred in 4/27 (15%) participants. There were no Grade 3/4 adverse events, or adverse events leading to E/C/F/TAF discontinuation. One participant experienced a serious treatment-emergent adverse event (Grade 2 pneumonia not considered E/C/F/TAF related). Virologic suppression (US FDA Snapshot algorithm) was maintained by 26/27 (96%) participants at Weeks 24 and 48. At Week 48, most children reported positive palatability (84.6%) and acceptability (96.2%). These data support the use of single-tablet E/C/F/TAF (90/90/120/6 mg) regimen for the treatment of HIV in children aged ≥2years and weighing ≥14-<25kg. NCT01854775.

The sex differences in diseases progression and prognosis among persons with HIV and HBV coinfection

To investigate sex differences in liver disease development and prognosis in individuals with HIV and HBV co-infection. This study comprised 752 HIV/HBV co-infected people who were diagnosed with HIV and started on combination antiretroviral therapy (cART) between January 31st, 2015 and January 31st, 2023. Their clinical data, including CD4+ T lymphocyte counts, HBV-DNA, and FIB-4 scores, were tracked once a year. The prognosis was determined during the long-term surveillance period. Risk factors related with the progression of liver diseases were included in both univariable and multivariable logistic regression. Then, sex differences in CD4+ T lymphocyte counts, HBV-DNA, FIB-4 scores, changes in liver fibrosis levels, and prognosis were investigated. Multivariable logistic regression analysis identified male as an independent risk factor for liver disease progression. Compared to the male group, the female group had a significantly greater decline of HBV DNA levels at years 1, 2, 3, 3–5, and > 5 post-cART. At each assessment point, the female group showed a significantly greater rise in CD4+ T lymphocyte counts than the male group based on their respective baseline values. Furthermore, females had greater CD4+ T lymphocyte counts and a lower prevalence of liver cirrhosis than males throughout the study period. Compared to female, higher incidence of end-stage-liver disease (1.190/100 person-years vs 0.714/100 person-years), higher all-cause mortality (0.440/100 person-years vs 0.148/100 person-years) and higher mortality associated with end-stage-liver diseases (0.273/100 person-years vs 0.074/100 person-years) were found in male. Among individuals with HIV and HBV coinfection, males had a worse therapeutic effect of HBV-active therapy and poorer prognosis than females.

Couple-Based Intervention to Improve HIV Care Engagement for Women and their Partners in KwaZulu-Natal, South Africa: Outcomes of a Pilot Randomized Controlled Trial.

We evaluated a couple-based intervention targeting human immunodeficiency virus (HIV) care needs of women, with the option to support HIV-related needs of male partners. Adult women with HIV adherence difficulties in a monogamous relationship with a male partner for ≥6 months were recruited in KwaZulu-Natal, South Africa. Twenty couples were randomized (1:1) to either START Together, a five-session manualized behavioral intervention, or treatment as usual, adherence counseling referral. Assessments were completed at baseline, post-treatment, and follow-up. Of the ten couples randomized to START Together, 70% attended at least one intervention session (feasibility); of those, 71% attended all five sessions (acceptability). Independently rated interventionist fidelity was very high (M ≥ 2.94 out of 3). Women's self-reported antiretroviral therapy adherence increased similarly in both interventions. For men, self-reported antiretroviral therapy adherence increased up to 25 percentage points in START Together, but not treatment as usual. Findings suggest that START Together may be potentially beneficial for improving HIV outcomes for men.

Receipt of long-acting injectable antiretroviral therapy among people with HIV in Southern US states: an assessment using electronic health records and claims data

BackgroundIn January 2021, the United States (US) Food and Drug Administration (FDA) approved the first long-acting injectable antiretroviral therapy (LAI ART) regimen for the treatment of HIV providing an alternative to daily oral regimens. We analyzed electronic health records (EHRs) to provide real-world evidence of demographic and clinical characteristics associated with the receipt of LAI ART among people with HIV (PWH).MethodsLeveraging EHRs from a large clinical research network in the Southern US - OneFlorida + linked with Medicaid (updated to 08/2022) - we identified a cohort of PWH who have been prescribed at least one dose of LAI ART since January 2021 and characterized their demographics, clinical characteristics, and HIV care outcomes.ResultsA total of 233 LAI ART recipients were identified: 56.7% female, 45.1% aged 30 to 44, 51.3% non-Hispanic Black, 78.1% on Medicaid and 4.7% on private insurance. Approximately three-quarters of injections (71.2%) were received within 37 days of the previous dose, and 84.4% were received within 67 days. About 8% of LAI ART recipients did not have optimal care engagement the year before LAI ART initiation; one in five recipients had a diagnosis of alcohol or substance use disorder in lifetime. All achieved viral suppression (< 50 copies/mL) before starting LAI ART. Of a subset of patients with HIV viral load test records, only 1 record of virologic failure (viral load > 200 copies/ml) was observed after the initiation of LAI ART.DiscussionThere has been an increasing trend of LAI ART initiation since approval. People with suboptimal care engagement and with substance use disorder in lifetime were not excluded from LAI ART treatment.

Enhancing drug delivery efficacy of antiretroviral drug Zalcitabine through silver/gold/platinum loaded silica nanocomposites: Surface modifications, molecular interactions, and computational insights.

Enhancing drug delivery efficacy of antiretroviral drug Zalcitabine through silver/gold/platinum loaded silica nanocomposites: Surface modifications, molecular interactions, and computational insights.