Antiretroviral Research Articles

Metabolic Complications Associated with Use of Integrase Strand Transfer Inhibitors (InSTI) for the Treatment of HIV-1 Infection: Focus on Weight Changes, Lipids, Glucose and Bone Metabolism.

This review aims to summarize recently published peer reviewed papers on the influence of treatment with Integrase Strand Transfer Inhibitors (InSTI) in people with HIV (HIV) on metabolic health, including weight gain, lipid parameters, glucose homeostasis, and bone health. InSTI have a mild/moderate effect on weight gain in both antiretroviral (ART) naïve and ART experienced PWH, which is more pronounced in certain groups (i.e. women, people of Black African ethnicity, those with lower socioeconomic status, and older people). The effect on weight is also driven by other components of the ART regimen as well as previous exposure to certain ART. InSTI have a relatively safe profile in terms of lipid parameters and bone health, compared to other ART classes, although some studies suggest a greater risk of insulin resistance and diabetes in PWH using InSTI, especially 2nd generation InSTI. While there is some evidence suggesting a negative impact of InSTI on some aspects of metabolic health (weight gain and glucose homeostasis), they remain the preferred treatment option for most PWH, due to their high efficacy and tolerability. However, an individualised approach to ART choice in PWH should be used in order to avoid negative outcomes in populations at higher risks of metabolic complications.

Obesity is associated with higher levels of circulating cytokines involved in the development of cardiovascular disease in people living with HIV.

Obesity is increasingly described in people living with HIV (PLWH), but its impact on immune activation and inflammation in HIV is still poorly characterised. We aimed to analyse the difference in circulating cytokines involved in pathways associated with co-morbidities in PLWH according to the presence or absence of obesity. Age and sex matched PLWH with and without obesity (BMI ≥30 kg/m2) from a multicentre, prospective cohort were recruited with a 1:2 ratio. Twenty-three biomarkers covering pathways associated with systemic inflammation (hsCRP, IL-2, IL-6, TNFR1, TNFR2, TNF-α, IFN-γ, IL-18), coagulation (vWF, D-dimer, sCD40L), endothelial function (E-selectin, P-selectin, sICAM-1, sVCAM-1), atherosclerosis (MPO, Lp-PLA2), immune regulation (IL-1RA), innate immune activation (MIP-1, MCP-1, sCD163, sCD14) and microbial translocation (LBP) were measured in the two groups. Between-group difference in biomarkers were assessed using Mann-Whitney test. Associations between obesity and biomarkers were assessed using logistic regression adjusted for age, gender, ethnicity, smoking status, and antiretroviral therapy (ART). Ninety-nine ART-treated PLWH were included in the analysis (33 with obesity, 66 without obesity). PLWH with obesity had higher levels of hsCRP, IL-6, vWF, D-dimer, E-selectin, MPO, IL-1RA, and LBP. Six markers (hsCRP, IL-6, vWF, E-selectin, MPO, IL-1RA), reflecting systemic inflammation, coagulation and atherosclerosis pathways were associated with increased odds of obesity in the adjusted logistic regression model: hsCRP (aOR 2.7, 95% CI [1.7, 4.29]), IL-6 (3.77 [1.43, 9.93]), vWF (5.33 [1.51, 18.75]), E-selectin (6.28 [1.36, 29.04]), MPO (6.85 [1.87, 25.04]), IL-1RA (6.45 [2.28, 18.2]). No association was observed between obesity and markers of innate immune activation and gut microbial translocation. Obesity in PLWH was associated with activation of systemic inflammatory, endothelial, atherosclerosis and coagulation pathways, rather than those associated with innate immune activation and gut microbial translocation. These pathways point towards an unfavourable cardiovascular profile in PLWH with obesity, which will have to be further explored in future studies on long-term outcomes.

THE ASSOCIATION OF ANEMIA WITH SURVIVAL AMONG PEOPLE WITH HIV FOLLOWING ANTIRETROVIRAL INITIATION IN THE NA-ACCORD 2007-2016.

Anemia is an independent predictor of mortality, which may be utilized as a signal of deteriorating health. We estimated the association between anemia severity categories and mortality following the initiation of antiretroviral therapy (ART) among people with HIV (PWH) in North America. Within the NA-ACCORD, annual median hemoglobin measurements between 01/01/2007-12/31/2016 were categorized using World Health Organization criteria into mild (11.0-12.9g/dL men, 11.0-11.9g/dL women), moderate (8.0-10.9g/dL men/women) and severe (<8.0g/dL men/women) anemia. Discrete time-to-event analyses using complementary log-log link models estimated mortality hazards ratios adjusted for demographics, comorbidities, and HIV clinical markers with 95% confidence intervals for the association between anemia and mortality. Among 67,228 PWH contributing a total of 320,261 annual median hemoglobin measurements, 257,293 (80%) demonstrated no anemia, 44,041 (14%) mild, 18,259 (6%) moderate, and 668 (0.2%) severe anemia during follow-up. Mortality risk was 5.6-fold higher among PWH with (vs. without) anemia. The association was greater among males (aHR=5.8 [5.4, 6.2]) versus females (aHR=4.1 [3.2, 5.4]). Mortality risk was 3.8-fold higher among PWH with mild anemia, 13.7-fold higher with moderate anemia, and 34.5-fold higher with severe anemia (vs. no anemia). Median hemoglobin levels significantly declined within 4 years prior to death, with the maximum decrease the year prior to death. Macrocytic anemia was associated with an increased and microcytic anemia a decreased mortality risk (vs. normocytic anemia). Anemia among PWH who have initiated ART is an important predictive marker for mortality with macrocytic anemia having an increased and microcytic anemia a decreased association with mortality compared with normocytic anemia.

Prevalence and correlates of frailty among older people with and without HIV in rural Uganda.

The relationship between HIV and frailty, a predictor of poor outcomes in the face of stressors, remains unknown in older people in sub-Saharan Africa. We analysed data from the Quality of Life and Ageing with HIV in Rural Uganda cohort study to estimate the prevalence and correlates of frailty among older people with HIV (PWH) on long-term antiretroviral therapy and among age and sex-similar HIV-uninfected comparators. Frailty was defined as a self-report of 3 or 4 (and pre-frailty as 1 or 2) of the following phenotypic variables: weight loss, exhaustion, low activity, and slowness. We estimated the prevalence of frailty and pre-frailty and fitted logistic regression models to estimate the association between HIV and frailty, adjusting for sociodemographic factors, depression, and other comorbidities. We enrolled 599 participants (49% women) with a mean age of 58 years. PWH had a similar prevalence of frailty (8.1% vs. 10.9%, p=0.24) but a lower prevalence of pre-frailty (54.2% vs. 63.2%, p=0.03) compared with their HIV-uninfected comparators. In multivariable regression models, people with depression (AOR 7.52 [95% CI: 3.67-15.40], p<0.001) and those with ≥1 comorbidities (AOR 3.15 [95% CI: 1.71-3.82], p<0.001) were more likely to be frail. HIV serostatus was not significantly associated with frailty (AOR 0.71 [95% CI: 0.37-1.34], p=0.29). Older PWH had a similar prevalence of frailty as those without HIV. These findings call for additional study of the factors that contribute to the robustness of older PWH in sub-Saharan Africa.

Brief Report: Switching to Long-Acting CAB/RPV: Data From an Italian Monocentric Cohort

Background: Cabotegravir (CAB)/rilpivirine (RPV) is the first long-acting injectable (LAI) antiretroviral therapy approved for virologically suppressed adults with HIV-1. Setting: Italian single centre cohort. Methods: We conducted a retrospective observational study to assess the durability, adherence to the prescribed injection schedule, and reasons for discontinuation of CAB/RPV LAI administered every 8 weeks (Q8W). Results: One hundred thirty-eight patients were included with a median observation period of 43 weeks [interquartile range (IQR) 34–47 weeks]. Of these, 32 (23.2%) were female, and the median age was 51 years (IQR 40–58 years). Twelve patients (8.7%) discontinued CAB/RPV LAI treatment with a median time to discontinuation of 21 weeks (IQR 12–35 weeks), and 92.8% of the injections occurred within the CAB/RPV LAI schedule. The most common reason for discontinuation was injection-related pain (5/12). No confirmed virological failure occurred during the period of observation with 3 individuals who experienced virological blips. Conclusions: Our findings showed that CAB/RPV LAI Q8W is tolerated well in clinical practice, with high adherence to the injection schedule and few discontinuations mainly related to injection site–related pain.

Brief Report: Aging With HIV: An Epidemiological Profile of Persons With Diagnosed HIV Aged 50 Years and Older in New York State, 2012–2021

Background: Advanced antiretroviral treatment has led to a growing population of older persons with HIV. To understand the characteristics of persons aging with HIV, this analysis examines epidemiological profiles of persons with diagnosed HIV through 2021 aged 50 years and older in New York State. Methods: Persons diagnosed with HIV and reported to the NYS HIV registry by December 31, 2021, were included in the analysis. Characteristics of persons aged 50 years and older were compared with persons younger than 50 years. Results: Persons diagnosed with HIV and aged 50 years and older more often reported heterosexual transmission risk and were more often females than individuals diagnosed with HIV younger than 50 years. Among new diagnoses in 2021, persons aged 50 years and older were more likely to have a stage 3 HIV diagnosis. By the end of 2021, 57% of persons living with diagnosed HIV were aged 50 years and older. There was an upward trend of deaths with cardiovascular disease as an underlying cause of death among persons aged 50 years and older. Conclusions: More females diagnosed with HIV and a higher percentage of persons who reported heterosexual transmission risk among persons aged 50 years and older suggest a need for enhanced clinician education and sexual health discussions with this adult population. A greater rate of stage 3 HIV diagnoses in persons aged 50 years and older emphasizes the need for specialized HIV testing and treatment, care for comorbidities, and social supports for this aging population.

Patterns of HIV treatment preferences among people with diverse demographic, social, and behavioral characteristics who are living with HIV in the United States.

New dosage form and frequency options may improve HIV treatment outcomes and reduce disparities in access and use. People with HIV (PWH) in the US completed a demographic and discrete choice experiment survey of preference for 13 hypothetical HIV treatment options: daily and weekly oral tablets; 1-, 3-, or 6-monthly injections by self or a health care provider; yearly implant; or combinations. Best-worst scaling and a latent class model were used to analyze overall preference choices and for groups of individuals with similar patterns of preferences; the model also predicted uptake of products. Among the diverse 829 respondents, weekly oral tablets and 6-monthly injections by an HCP were significantly more favored than daily oral tablets. Convenience of the treatment and being tired of taking pills were the top drivers of preference responses. Latent class analysis identified four groups of respondents with distinct preference patterns; approximately two-thirds belonged to groups strongly preferring products other than daily oral tablets. The modelled uptake of a monthly pill, yearly implant, 6-monthly Health Care Provider (HCP) injection, oral daily pill, and 3-monthly HCP injection were 24%, 24%, 24%, 18%, and 11%, respectively. Patterns of HIV medication preference can inform development of new forms of HIV therapy products as the majority of patients do not prefer the currently most available treatment option of daily oral tablets. Looking beyond population-level preferences and into similar groups of PWH increases the ability to develop patient-centered products to fill gaps in care and increase treatment effectiveness.

MPO interacts with hRSV particles, contributing to the virucidal effects of NETs against clinical and laboratory hRSV isolates

Human Respiratory syncytial virus (hRSV) mainly affects immunosuppressed patients requiring hospitalization. No specific treatment is financially accessible, and available vaccines do not cover all risk groups. During hRSV infection, there is a robust neutrophilic influx into the airways. hRSV-activated neutrophils release substantial neutrophil extracellular traps (NETs) in lung tissue, comprising DNA, histones, cytosolic, and granular proteins. NETs form mucus buildup in the lungs, compromising respiratory capacity and neutralizing viral particles. Understanding responsible NETs molecules requires improvement. We evaluated NETs interacting with hRSV particles and their contribution to anti-hRSV NET effects. Immunoblotting, immunoprecipitation, and peptide sequencing assays confirmed hRSV binding to a 50–75 kDa NET protein, Myeloperoxidase (MPO). MPO, a microbicide enzyme in NETs, interacts with hRSV, likely at F0 protein (site IV) on the viral surface. Additionally, MPO (32 μM) and NETs (0.4 μg/mL) reduced in vitro replication of clinical (hRSV A and B) and laboratory (Long) hRSV isolates by approximately 30 %, reversible by selective MPO inhibitor (PF-06281355; 48 μM). Thus, MPO contributes to virucidal NET effects on diverse hRSV strains, enhancing comprehension of NETs' role in infection and aiding treatment strategies for respiratory diseases.

Norwegian scabies in HIV and tuberculosis infected patient: A case report

Norwegian scabies is a rare scabies with the manifestation of thick crusts of the extremities of the skin that contain eggs and mites. Several conditions in which scabies infection is easily transmitted include immunocompromised, home nursing, and severe neurological disorder. The aim of this case report was to present a thorough analysis of a comprehensive resource for the management of Norwegian scabies patients, with a specific focus on individuals who also have HIV or other immunocompromising diseases. A 56 – year – old female presented with dermatitis lesions and itching with sever hyperkeratosis, several maculae and papules on neck and armpits for four months duration.Sarcoptes scabiei was found from microscopy examination of skin scraping. The patient received antiretroviral drugs, antituberculosis medication and scabicidal treatment.

Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease

AbstractDespite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging &gt;500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~ 2.83 weeks; week 5-24: t1/2 ~ 15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PLWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PLWH with earlier timing of ART initiation, higher initial CD4 + T cell count, and lower pre-ART viral load. In this study, we advanced our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.

Defining Appropriate Comparator Populations for Placental Pathology for Pregnant People With HIV

Background. Widespread adoption of antiretroviral therapy has reduced perinatal transmission of HIV; however, people living with HIV (PWH) have higher rates of preterm birth and hypertensive disorders of pregnancy. The placenta is the critical fetal support organ in pregnancy, and multiple investigations have sought associations in PWH between HIV and placental pathology. However, results have been inconclusive. We posit that selection of control group populations influences the apparent anomalies in placentas from PWH and examined the differences seen between these placentas and those of four comparator populations. Methods. Placentas from PWH were compared with those from all patients without HIV, controls from a recent study of severe acute respiratory syndrome coronavirus 2 in pregnancy, patients with a history of melanoma—an indication for examination relatively orthogonal to other problems in pregnancy, and patients paired with PWH using propensity score matching. Results. People living with HIV differ in demographics and comorbidities from comparator groups other than propensity score–matched patients. Placentas from PWH had higher rates of acute placental inflammation, including maternal inflammatory response and fetal inflammatory response, than multiple comparator groups. Placentas from PHW had lower rates of chronic placental inflammation than three of four comparator groups, including the largest comparator group and the group matched to PWH using propensity scores. Conclusion. Differences in placental pathology in PWH depend on the comparator group. Commonly used comparator groups have significantly different demographic and comorbidity profiles, suggesting they are inappropriate comparators for PWH. Propensity score matching may be useful in identifying comparator populations.

Efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus dolutegravir-based three-drug regimens in people with HIV with varying adherence to antiretroviral therapy

Abstract Objective Five Phase 3 bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) clinical studies demonstrated that the efficacy of B/F/TAF was non-inferior to dolutegravir (DTG) + 2 NRTIs. We retrospectively assessed drug adherence and effect on virologic outcomes. Methods Studies (NCT02607930, NCT02607956, NCT03547908, NCT02603120 and NCT03110380) were double-blind, placebo-controlled and enrolled treatment-naïve or virologically suppressed adults. Adherence was calculated by pill count from returned pill bottles; virologic outcome was assessed by last on-treatment HIV-1 RNA. Results Altogether, 2622 participants (B/F/TAF: n = 1306; DTG + 2 NRTIs: n = 1316) were categorized as having high (≥95%), intermediate (≥85% to &amp;lt;95%) or low (&amp;lt;85%) adherence. Through Week 48, low adherence was observed in 46 (3.5%) participants in the B/F/TAF group (78% median adherence) and 69 (5.2%) in the DTG + 2 NRTI group (80% median adherence). Overall, 1287 (98.5%) participants in the B/F/TAF group and 1292 (98.2%) in the DTG + 2 NRTI group had virologic suppression (VS; HIV-1 RNA &amp;lt; 50 copies/mL) through Week 48. VS in participants with low adherence versus high or intermediate adherence was similar in the B/F/TAF group, but lower in the DTG + 2 NRTI group (P ≤ 0.002). Similar results were observed at Weeks 96 and 144. Two participants (&amp;lt;95% adherence) in the DTG + 2 NRTI group receiving DTG and abacavir/lamivudine developed M184V; there was no treatment-emergent resistance to B/F/TAF. Conclusions Participants with suboptimal (&amp;lt;85%) adherence to B/F/TAF maintained high levels of VS, whereas suboptimal DTG + 2 NRTI adherence was associated with lower VS.

Pretreatment and acquired HIV drug resistance in Belize—results of nationally representative surveys, 2021–22

Abstract Background The rising prevalence of pretreatment drug resistance (PDR) to non-nucleoside reverse-transcriptase inhibitors threatens the effectiveness of ART. In response, the WHO recommends dolutegravir-based ART regimens due to their high genetic barrier to resistance and better treatment outcomes. This is expected to contribute to achieving the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of 95% viral suppression in people on ART. Objectives To estimate the prevalence of PDR among adults initiating ART and assess viral suppression and acquired HIV drug resistance (ADR) among individuals receiving ART in Belize. Patients and methods Nationally representative cross-sectional PDR and ADR surveys were conducted between 2021 and 2022. Sixty-seven adults were included in the PDR survey, and 43 children and adolescents and 331 adults were included in the ADR survey. Demographic and clinic data and blood specimens were collected. HIV drug resistance (HIVDR) was predicted using the Stanford HIVdb tool. Results The prevalence of PDR to efavirenz or nevirapine in adults was 49.3% (95% CI 42.2%–56.4%) and was significantly higher in those with previous antiretroviral exposure (OR: 7.16; 95% CI 2.71–18.95; P = 0.002). Among children and adolescents receiving ART, 50.0% had viral suppression, with better rates for those receiving dolutegravir-based ART (OR: 5.31; 95% CI 3.02–9.34; P &amp;lt; 0.001). In adults, 79.6% achieved viral suppression. No resistance to integrase inhibitors was observed in those on dolutegravir-based ART. Conclusions Prioritizing dolutegravir-based ART is critical for achieving HIV epidemic control in Belize. Efforts should focus on retention in care and adherence support to prevent HIVDR.

Dissecting the Role of Donors in Capacity Building for HIV/AIDS Treatment, Care and Support: A Case Study of an Antiretroviral Therapy Programme in Zimbabwe

Donor involvement in development activities in the Global South has been questioned for failing to capacitate communities in the recipient country. Therefore, the need to establish whether the Médecins Sans Frontières (MSF) antiretroviral treatment (ART) programme in Zimbabwe contributed to capacity building for HIV and AIDS support, care and treatment triggered this study. A qualitative methodology involving semi-structured interviews with purposively selected participants was adopted. As a result of the MSF programme, community-based clinics created ART support groups which facilitated easy access to medication and health-related information. Dispensing of medication and testing could also be done in these clinics, which were previously the district hospitals. These interventions reduced waiting periods and long-distance travel to access HIV and AIDS care, support and treatment, thus improving the healthcare quality. Community-influenced strategies are recommended to sustain these improvements.

IMPLANTES DENTÁRIOS INSTALADOS EM PACIENTES PORTADORES DO VIRUS DA IMUNODEFICIENCIA HUMANA (HIV)

The Human Immunodeficiency Virus (HIV) compromises the immune system and, as it progresses, causes acquired immunodeficiency syndrome (AIDS), characterized by the emergence of opportunistic infections. Transmission occurs mainly through sexual contact or via blood and, in Brazil, between 1980 and 2022, more than 1 million cases of AIDS were recorded. Regarding implantology, patients with HIV face oral complications such as gingivitis and candidiasis, and although the impact of osseointegrated implants in these patients is not yet entirely clear, prior evaluation of bone health and conditions is essential. This research aims to describe the care in the osseointegration process in HIV-positive patients, investigating the possible complications and the importance of biosafety, in addition to highlighting the relevance of treatment to improve the quality of life of these patients. The methodology used was the bibliographic review, using articles published between 2012 and 2022 in Portuguese. Oral rehabilitation with dental implants in HIV-positive patients has gained importance due to the increase in life expectancy provided by antiretroviral therapy. These patients, with an improved quality of life, are looking for viable options to replace missing teeth, with dental implants being an attractive alternative. Although the literature on the topic is limited, the results indicate that the success rates of implants in patients with HIV are similar to those of healthy patients, as long as the treatment considers the immune status. However, specific care is needed, such as monitoring for possible complications resulting from the continuous use of antiretrovirals, which can cause liver and kidney problems. Additionally, strict biosafety protocols are essential to ensure the safety of patients and healthcare providers. Further research is recommended to clarify outstanding issues and improve pre- and postoperative care, providing more predictable outcomes and greater safety in treatment with osseointegrated implants.

Feasibility and Impact of Community Pharmacy and Novel Pick-up Points for Antiretroviral Therapy Pre-exposure Prophylaxis Initiation and Continuation in Low and Middle-income Countries.

This review assesses recent developments in community access to pre-exposure prophylaxis (PrEP) for HIV prevention in low-and middle-income countries (LMICs). It examines literature on differentiated service delivery (DSD) and alternative delivery modes for PrEP, focusing on the role of community pharmacies and novel pick-up points. Key considerations include barriers to access, potential benefits, and strategies for implementation. Challenges to optimal HIV healthcare delivery persist globally, with LMICs facing greater barriers due to resource constraints and structural obstacles. Community pharmacies and novel pick-up points offer promising avenues to expand access to HIV medication, especially in hard-to-reach populations. However, operational complexities and regulatory frameworks present significant challenges. Recent initiatives, such as collaborative practice agreements and programmes by global health agencies, highlight efforts to integrate community pharmacies into HIV prevention and care delivery. Mobile health clinics and home delivery services have also shown promise in improving treatment coverage. Community pharmacies and novel pick-up points play a crucial role in enhancing access to HIV PrEP in LMICs. Despite challenges related to infrastructure, funding, and regulatory oversight, innovative strategies like DSD and mobile outreach offer opportunities to reach marginalized populations. Real-life examples from LMICs demonstrate the feasibility and effectiveness of leveraging community pharmacies for HIV treatment. However, addressing policy gaps, strengthening pharmacist training, and promoting patient-centred approaches are essential for scaling up access to PrEP. Collaboration between governments, health agencies, and local communities is key to realizing the full potential of community pharmacies in HIV prevention and care.

Impact of Expanded HIV Testing and Rapid Antiretroviral Therapy Initiation in Southwest China: An Interrupted Time-Series Analysis.

This study evaluates the impact of an expanded HIV testing initiative, launched in June 2018 in Luzhou, Sichuan, China, on antiretroviral therapy (ART) initiation rates among people living with HIV (PLWH). Using an uncontrolled interrupted time-series design, we analyzed data from 11,040 PLWH between June 2016 and December 2022, extracted from 108 health facilities via the Center for Disease Control and Prevention's ART database. The primary outcome measures were ART initiation rates within 7 and 30 days of HIV diagnosis. Results showed a significant improvement in the 30-day ART initiation rate following expanded testing, increasing from 46.1% to 90.9% by the study's end. The 7-day initiation rate also improved but remained below 30%. The study found that expanded testing enhanced the role of primary health care institutions in ART initiation. However, the COVID-19 pandemic, beginning January 2020, negatively impacted ART initiation rates, with a slight effect on 30-day rates but a persistent negative impact on 7-day rates. Despite these challenges and an increased HIV burden, Luzhou's ART initiation rates surpassed the national average. This study emphasizes the effectiveness of expanded HIV testing in ensuring timely ART access, crucial for HIV epidemic control, and improved patient outcomes. It also reveals challenges in maintaining HIV services during public health crises, offering insights into health care system resilience. Future research should focus on evaluating long-term treatment outcomes and strategies to support ending the AIDS epidemic.

Factors associated with High Viral Loads among HIV Patients Under ARV at Gitwe District Hospital

Background: High viral load is a condition of rapid multiplication in blood stream. The high viral load among HIV patients under ARV may also occur due to the rapid multiplication of virus leading to compromise immune system of living organism up to death. The vast majority of people living with HIV virus face with persistent of high viral load while were under treatments (ARV). Aim: The aim of the study was to evaluate and assess the factors associated with high viral load among HIV patients under ARV at Gitwe District Hospital. Methodology: The retrospective study was conducted to assess high viral load of HIV patients under ARV. The only significance factor for viral load were adherence with (p=0.000173) and ages with (p=0.00023). Results and conclusion: A large of number of PLWH were highly VL tested, and 95 subjects were recorded for study. Among 95 subjects, 54.73% were female and 45.26% male. All data were analyzed using statistical package for social science (SPSS) version 20. The results have showed provider’s advices and ART use, adherence counselling. Keywords: High viral load, HIV, Antiretroviral therapy, Gitwe District Hospital.

In vitro and patient studies with platelets to explore off-target cardiovascular effects of integrase inhibitors.

People with HIV currently face a tenfold higher risk of developing cardiovascular disease (CVD) than those without HIV. Studies have shown various off-target effects of antiretroviral treatment (ART) on the cardiovascular system, but little is known about the effects of currently used integrase strand transfer inhibitors (INSTIs) on platelets. Platelet activation is associated with increased CVD, thrombus formation, and release of proinflammatory mediators, so exploring platelet effects from currently prescribed ART may contribute to the understanding of CVD etiopathogenesis in people with HIV. We aimed to identify potential effects of INSTIs on platelet aggregation and activation markers from individuals without HIV after in vitro treatment with clinically relevant drug concentrations. We used bictegravir (BIC) and dolutegravir (DTG) individually or in the therapeutic drug combinations BIC/emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) or DTG/lamivudine (3TC). Additionally, we conducted a pilot study to compare platelet activity profiles from people with HIV on BIC/FTC/TAF and DTG/3TC. Changes to in vitro platelet aggregation responses upon exposure to different INSTIs were observed both upon individual drug application and when using therapeutic combinations. However, these effects were not reflected in flow-cytometric evaluation of platelet degranulation. A pilot study in eight people with HIV and eight without HIV revealed no significant effects but established protocols for future patient studies. There is currently no consistent evidence of an effect of INSTIs on platelet activation. Further study is warranted, focusing on models with more pathophysiological relevance, including extensive studies in people with HIV.

Life Course Stressors, Latent Coping Strategies, Alcohol Use, and Latent Coping Strategies Among People with HIV.

People with HIV (PWH) have often experienced chronic stressors across their lifespan, including adverse childhood experiences (ACES), lifetime economic hardship (LEH), and concurrent stressors associated with living in urban areas (urban stress). Prolonged exposure to stressors might result in differential coping patterns among PWH that can impact care trajectories. We utilized a life course-informed approach to examine chronic stressors as antecedents of latent coping strategies among PWH in care. High-risk alcohol use and non-adherence to anti-retroviral therapy (ART) were examined as consequences of latent coping strategies. Data were utilized from the baseline and interim follow-up visit of the New Orleans Alcohol Use in HIV (NOAH) study. Three latent classes of coping strategies were identified: avoidance coping (31%), low-frequency coping (43%), and problem-solving coping (25%). Exposure to ACES was associated with greater use of avoidance versus low-frequency coping class at wave II. Urban stress was associated with greater use of avoidance coping compared to problem-solving or low-frequency coping classes at wave II. LEH was associated with greater use of low-frequency coping at wave II. Those utilizing low-frequency coping had a two-fold increase in ART non-adherence compared to problem-solving coping. PWH utilizing avoidance and low-frequency coping had a nearly two-fold increase in high-risk alcohol use versus problem-solving coping. These findings reveal important coping classifications that are linked to stressors across the life course of PWH. An understanding of coping styles and stressors may aid in improving the continuum of care among PWH by reducing alcohol use and improving medication adherence.