Alcohol Impairs Bioenergetics and Differentiation Capacity of Myoblasts from Simian Immunodeficiency Virus-Infected Female Macaques.

Alcohol misuse and HIV independently induce myopathy. We previously showed that chronic binge alcohol (CBA) administration, with or without simian immunodeficiency virus (SIV), decreases differentiation capacity of male rhesus macaque myoblasts. We hypothesized that short-term alcohol and CBA/SIV would synergistically decrease differentiation capacity and impair bioenergetic parameters in female macaque myoblasts. Myoblasts from naïve (CBA-/SIV-), vehicle [VEH]/SIV, and CBA/SIV (N = 4-6/group) groups were proliferated (3 days) and differentiated (5 days) with 0 or 50 mM ethanol (short-term). CBA/SIV decreased differentiation and increased non-mitochondrial oxygen consumption rate (OCR) versus naïve and/or VEH/SIV. Short-term alcohol decreased differentiation; increased maximal and non-mitochondrial OCR, mitochondrial reactive oxygen species (ROS) production, and aldolase activity; and decreased glycolytic measures, ATP production, mitochondrial membrane potential (ΔΨm), and pyruvate kinase activity. Mitochondrial ROS production was closely associated with mitochondrial network volume, and differentiation indices were closely associated with key bioenergetic health and function parameters. Results indicate that short-term alcohol and CBA non-synergistically decrease myoblast differentiation capacity. Short-term alcohol impaired myoblast glycolytic function, driving the bioenergetic deficit. Results suggest potentially differing mechanisms underlying decreased differentiation capacity with short-term alcohol and CBA, highlighting the need to elucidate the impact of different alcohol use patterns on myopathy.

HIV/AIDS in Indonesia: current treatment landscape, future therapeutic horizons, and herbal approaches.

HIV/AIDS is still a major worldwide health concern, and Indonesia is making efforts to mitigate its effects. Antiretroviral therapy (ARV), which aims to decrease viral replication, boost immunological function, and lengthen the lifespans of persons living with HIV/AIDS, is the cornerstone of Indonesia's strategy. The availability of ARV has significantly increased, yet problems including stigma and the requirement for regular medication adherence still exist. To address the broader needs of those affected by HIV/AIDS, Indonesia lays a major focus on comprehensive care, which includes mental health and social support, in addition to ARV. Data show that, despite progress, there is still a stigma surrounding HIV/AIDS, which affects patient outcomes and access to care. With vigorous research into cutting-edge antiretroviral medications and treatment techniques, Indonesia has a thriving future therapeutic landscape. The goals of these programs are to increase treatment effectiveness, decrease side effects, and increase access to cutting-edge treatments. Preventive methods, such as PrEP (pre-exposure prophylaxis), are making progress, and efforts to find a cure are gaining prominence. Notably, HIV/AIDS management plan of Indonesia heavily relies on natural remedies. Patient care incorporates traditional Indonesian medicine, such as jamu and several herbal medicines. Although there is little scientific proof to support the effectiveness of these herbal remedies, complementary and alternative therapies frequently employ them to manage symptoms and promote general wellness. In terms of the 95-95-95 targets, Indonesia is making an effort to comply with these international goals by seeking to diagnose 95% of HIV-positive individuals, provide sustained ARV to 95% of those diagnosed, and achieve viral suppression in 95% of ARV recipients. Although there are gaps in reaching these aims, progress is being made, in part because of the aforementioned challenges. In summary, Indonesia employs a multimodal approach to HIV/AIDS management, including traditional herbal cures, continuous research into cutting-edge treatments, and conventional ARV. In order to enhance overall health outcomes and create a healthier society, the future of HIV/AIDS treatment in Indonesia is concentrated on expanding therapeutic alternatives, reaching the 95-95-95 targets, decreasing stigma, and improving access to care.

Barriers and enabling structural forces affecting access to antiretroviral therapy in Nigeria.

BACKGROUND: Access to antiretroviral therapy (ART) helps to improve quality of life and reduces the spread of HIV. However, while a lot of studies focus on supply factors, such as resources for the purchase of antiretroviral drugs, demand and structural forces are not given much emphasis. In this paper it is argued that structural forces shape the way people access antiretroviral therapy in Nigeria. METHODS: A Grounded Theory methodology was undertaken in the research. Semi structured qualitative interviews were administered to select people living with HIV/AIDS in Nigeria. This was facilitated by the Network of People Living with HIV/AIDS in Nigeria (NEPWHAN) to understand their perspectives with regard to barriers and enablers to ART access in Nigeria. Thirty persons living with HIV/AIDS were interviewed and recorded. The interview recordings were transcribed and coded using a constructionist epistemological approach. This was triangulated with results of preliminary and secondary literature review analysis. RESULTS: In this research, the participants discussed structural forces (barriers and enablers) that influenced how they accessed ART. These included economic factors such as poverty that enabled transactional sex. Unequal gender relations and perceptions influenced how they accessed ART. The participants' belief in 'God' and religious activities such as 'prayer' and the use of 'traditional medicine' had an impact on how and when they accessed ART. Political activity at the international, national, and local levels influenced access to ART as well as resources. The individual's familial, social, and organisational connections also influenced their ease of accessing ART. CONCLUSIONS: This study identifies structural forces that affect access to antiretroviral therapy and provides recommendations on how they can be harnessed to enable improved access to ART and consequently improved health.

Alcohol and drug use severity are independently associated with antiretroviral adherence in the current treatment era.

Substance use in people with HIV (PWH) negatively impacts antiretroviral therapy (ART) adherence. However, less is known about this in the current treatment era and the impact of specific substances or severity of substance use. We examined the associations of alcohol, marijuana, and illicit drug use (methamphetamine/crystal, cocaine/crack, illicit opioids/heroin) and their severity of use with adherence using multivariable linear regression in adult PWH in care between 2016 and 2020 at 8 sites across the US. PWH completed assessments of alcohol use severity (AUDIT-C), drug use severity (modified ASSIST), and ART adherence (visual analogue scale). Among 9400 PWH, 16% reported current hazardous alcohol use, 31% current marijuana use, and 15% current use of ≥1 illicit drugs. In multivariable analysis, current methamphetamine/crystal use, particularly common among men who had sex with men, was associated with 10.1% lower mean ART adherence (p < 0.001) and 2.6% lower adherence per 5-point higher severity of use (ASSIST score) (p < 0.001). Current and more severe use of alcohol, marijuana, and other illicit drugs were also associated with lower adherence in a dose-dependent manner. In the current HIV treatment era, individualized substance use treatment, especially for methamphetamine/crystal, and ART adherence should be prioritized.

Reasons for using traditional and complementary care by people living with HIV on antiretroviral therapy and association with interrupted care: a mixed methods study in Eswatini.

The use of traditional, complementary, and alternative medicine (TCAM) can lead to delays and interruptions in the HIV continuum of care. This study explores reasons for TCAM use in people living with HIV on antiretroviral therapy (ART) in Eswatini and compares interrupted care between different types of TCAM users. Data were collected using surveys in the MaxART study (a test-and-treat trial) between 2014 and 2017 to assess the exposure, namely visiting a TCAM provider. Additionally, visit dates were retrieved from clinic records to assess the outcome, interrupted care. Open-ended questions were analysed with qualitative content analysis (n = 602) and closed questions with bivariable and multivariable analysis (n = 202). Out of 202 participants, 145 (72%) never used TCAM, 40 (20%) ever used, and 17 (8%) is currently using TCAM (diviners, herbalists, and religious healers). No differences in interrupted care were found comparing never (reference category), past (Odds Ratio: 1.31, 95% confidence interval: 0.63-2.72), and current users (1.34, 0.47-3.77), while adjusting for gender, time since HIV diagnosis, and time on ART. Contextual factors affecting the choice for TCAM were the influence of family, advice from the health facility, and religious beliefs. Individual factors include trust in biomedical care, type of illness, no need for additional care, and practical reasons such as financial means. In conclusion, individual and contextual factors influence the choice for TCAM. Interrupted care does not differ between never, past, and current users.

Exploring the Relation Between Diabetes and HIV: A Narrative Review.

Diabetes mellitus, more usually abbreviated as DM or just diabetes, is a devastating metabolic disorder that claims many lives every year. Due to various variables, including the aging of the HIV (human immunodeficiency virus)-infected population and the high prevalence of chronic medical conditions among persons living with HIV, the crossroads of DM and HIV infection has become a significant research topic. Although the connection between HIV and diabetes is not simple, many aspects of the virus and its treatment have been connected to the onset of diabetes. The presence of inconclusive evidence that HIV is a risk factor for diabetes makes this area more challenging and debatable. This article examines the prevalence of DM in the HIV-positive community, along with its assessment, management, and treatment objectives. The most recent diabetes treatment recommendations from authoritative groups are considered in this article to give readers thorough and current advice. These guidelines emphasize the importance of tailoring pharmacological therapy and treatment goals to suit the specific needs of individuals with diabetes, including those who are also living with HIV. Individualizing treatment plans ensures that healthcare professionals consider comorbidities, medication interactions, and potential side effects when managing diabetes concerning HIV. In the later part of the article, a holistic approach is discussed to address the increased risk of cardiovascular disease and associated complications in HIV-positive individuals with diabetes. This approach aims to mitigate cardiovascular risks and improve overall health outcomes through comprehensive strategies such as lifestyle modifications, regular monitoring, medication management, and integration of multidisciplinary healthcare teams. By considering the unique challenges and considerations of individuals living with both HIV and diabetes, healthcare providers can develop targeted interventions and provide optimal care. In order to improve the life and health of persons living with HIV and diabetes, the article stresses the significance of cooperation amongst professionals in these fields.

Perceptions of Long-Acting Injectable Antiretroviral Therapy Among People Living with HIV Who Use Drugs and Service Providers: a Qualitative Analysis in Rhode Island.

Long-acting injectable antiretroviral therapy (LAI-ART) is a novel method to deliver HIV treatment, and the first regimen was approved in the USA in 2021. LAI-ART may mitigate barriers to oral treatment adherence, but little is known about LAI-ART perceptions among people living with HIV (PLWH) who use drugs, despite these populations facing greater barriers to treatment retention and ART adherence. We assessed LAI-ART perceptions and implementation considerations among PLWH who use drugs and health and ancillary service providers in Rhode Island. Data was collected from November 2021 to September 2022, and include in-depth interviews with 15 PLWH who use drugs and two focus groups with HIV clinical providers (n = 8) and ancillary service providers (n = 5) working with PLWH who use drugs. Data were analyzed thematically, with attention paid to how levels of structural vulnerability and social-structural environments shaped participants' LAI-ART perceptions and the HIV care continuum. Willingness to consider LAI-ART was impacted by HIV outcomes (e.g., viral suppression) and previous experiences with oral regimens, with those on stable regimens reluctant to consider alternative therapies. However, LAI-ART was seen as potentially improving HIV outcomes for PLWH who use drugs and enhancing people's quality of life by reducing stress related to daily pill-taking. Recommendations for optimal implementation of LAI-ART varied across participants and included decentralized approaches to delivery. HIV care delivery must consider the needs of PLWH who use drugs. Developing patient-centered and community-based delivery approaches to LAI-ART may address adherence challenges specific to PLWH who use drugs.

Hypertension and traditional risk factors for cardiovascular diseases among treatment naïve HIV- infected adults initiating antiretroviral therapy in Urban Tanzania.

BACKGROUND: Cardiovascular diseases (CVDs) have become an important cause of ill health and death among people living with HIV and/or AIDS (PLHIV) in the antiretroviral therapy (ART) era. There is scarce data on the burden of hypertension (HTN) and risk factors for CVDs among PLHIV in developing countries, including Tanzania during the ART era. OBJECTIVE(S): To determine the prevalence of HTN and risk factors for CVDs among ART naïve PLHIV initiating ART. METHODS: We analysed baseline data of 430 clinical trial participants on the effect of low-dose aspirin on HIV disease progression among HIV-infected individuals initiating ART. HTN was the outcome CVD. Traditional risk factors for CVDs studied were age, alcohol consumption, cigarette smoking, individual and family history of CVDs, diabetes mellitus (DM), obesity/overweight, and dyslipidaemia. A generalized linear model (robust Poisson regression) was used to determine the predictors for HTN. RESULTS: The median (IQR) age was 37 (28, 45) years. Females were the majority contributing 64.9% of all participants. The prevalence of HTN was 24.8%. The most prevalent risk factors for CVDs were dyslipidaemia (88.3%), alcohol consumption (49.3%), and overweight or obesity (29.1%). Being overweight or obese predicted the occurrence of HTN, aPR 1.60 (95% CI 1.16-2.21) while WHO HIV clinical stage 3 was protective against HTN, aPR 0.42(95% CI 0.18-0.97). CONCLUSION: The prevalence of HTN and traditional risk factors for CVDs in the treatment naïve PLHIV initiating ART are significant. Identifying these risk factors and managing them at the time of ART initiation may lower future CVDs among PLHIV.

A comprehensive overview on the role of phytocompounds in human immunodeficiency virus treatment.

Acquired immune deficiency syndrome (AIDS) is a worldwide epidemic caused by human immunodeficiency virus (HIV) infection. Newer medicines for eliminating the viral reservoir and eradicating the virus are urgently needed. Attempts to locate relatively safe and non-toxic medications from natural resources are ongoing now. Natural-product-based antiviral candidates have been exploited to a limited extent. However, antiviral research is inadequate to counteract for the resistant patterns. Plant-derived bioactive compounds hold promise as powerful pharmacophore scaffolds, which have shown anti-HIV potential. This review focuses on a consideration of the virus, various possible HIV-controlling methods and the recent progress in alternative natural compounds with anti-HIV activity, with a particular emphasis on recent results from natural sources of anti-HIV agents. Please cite this article as: Mandhata CP, Sahoo CR, Padhy RN. A comprehensive overview on the role of phytocompounds in human immunodeficiency virus treatment. J Integr Med. 2023; 21(4):332-353.

Cannabis Use Is Associated With Decreased Antiretroviral Therapy Adherence Among Older Adults With HIV.

Background: Conflicting evidence exists on the impact of cannabis use on antiretroviral therapy (ART) adherence among people with human immunodeficiency virus (PWH). We leveraged data collected among older PWH to characterize longitudinal associations between cannabis use and ART adherence. Methods: AIDS Clinical Trials Group (ACTG) A5322 study participants were categorized as <100% (≥1 missed dose in past 7 days) or 100% (no missed doses) ART adherent. Participants self-reported current (past month), intermittent (past year but not past month), and no cannabis (in past year) use at each study visit. Generalized linear models using generalized estimating equations were fit and inverse probability weighting was used to adjust for time-varying confounders and loss to follow-up. Results: Among 1011 participants (median age, 51 years), 18% reported current, 6% intermittent, and 76% no cannabis use at baseline; 88% reported 100% ART adherence. Current cannabis users were more likely to be <100% adherent than nonusers (adjusted risk ratio [aRR], 1.53 [95% CI, 1.11-2.10]). There was no association between ART adherence and current versus intermittent (aRR, 1.39 [95% CI, .85-2.28]) or intermittent versus no cannabis use (aRR, 1.04 [95% CI, .62-1.73]). Conclusions: Among a cohort of older PWH, current cannabis users had a higher risk of <100% ART adherence compared to nonusers. These findings have important clinical implications as suboptimal ART adherence is associated with ART drug resistance, virologic failure, and elevated risk for mortality. Further research is needed to elucidate the mechanisms by which cannabis use decreases ART adherence in older PWH and to advance the development of more efficacious methods to mitigate nonadherence in this vulnerable population.

Prevalence of Polypharmacy and Potential Drug-Drug Interactions Associated with Risk Factors in the Era of HIV Integrase Inhibitors: A Prospective Clinical Study.

People living with human immunodeficiency virus (PLWH), with the availability of modern antiretroviral drugs, have multiple comorbidities, which increase the risk of polypharmacy and potential drug-drug interactions (PDDIs). This is a particularly important issue for the aging population of PLWH. This study aims to review the prevalence and risk factors for PDDIs and polypharmacy in the era of HIV integrase inhibitors. A cross-sectional, two-center, prospective observational study was conducted on Turkish outpatients between October 2021 and April 2022. Polypharmacy was defined as the use of ≥5 non-HIV medications, excluding over-the-counter (OTC) drugs, and PDDIs were classified using the University of Liverpool HIV Drug Interaction Database (harmful/red flagged and potentially clinically relevant/amber flagged). The median age of the 502 PLWH included in the study was 42 ± 12.4 years and 86.1% were males. Most individuals (96.4%) were given integrase-based regimens (unboosted 68.7% and boosted 27.7%). In total, 30.7% of individuals were taking at least one OTC drug. The prevalence of polypharmacy was 6.8% (9.2% when OTC drugs were included). During the study period, the prevalence of PDDIs was 1.2% for red flag PDDIs and 16% for amber flag PDDIs. CD4+ T cell count >500 cells/mm3, number of comorbidities ≥3, comedication with drugs affecting blood and blood-forming organs, cardiovascular drugs, and vitamin/mineral supplements were associated with red flag or amber flag PDDIs. Drug interaction prevention is still important in HIV care. Individuals with multiple comorbidities should be closely monitored for non-HIV medications to prevent PDDIs.

Milk Calcium and Phosphorus in Ugandan Women with HIV on Tenofovir-Based Antiretroviral Therapy.

BACKGROUND: Breastfed infants depend on human milk calcium and phosphorus for bone mineral accretion and growth. We reported greater mobilization of bone mineral and delayed skeletal recovery in lactating Ugandan women with HIV initiated on tenofovir-based antiretroviral therapy during pregnancy compared to HIV-uninfected counterparts in the Gumba Study. However, it is unknown if these disruptions in maternal bone metabolism affect milk mineral concentrations. RESEARCH AIM: To compare concentrations and patterns of change in milk calcium and phosphorus between lactating women with and without HIV. METHODS: A longitudinal observational study was conducted to compare milk mineral concentrations between women with HIV receiving tenofovir-based ART and uninfected women in the Gumba Study. Milk collected at 2, 14, 26, and 52 weeks lactation was analyzed for calcium and phosphorus. Sodium and potassium were measured at 2 and 14 weeks to detect sub-clinical mastitis. Differences in milk composition between 84 women with HIV and 81 uninfected women were investigated. RESULTS: Women with HIV had higher milk calcium than uninfected women at 14 weeks. The percent difference was +10.2% (SE = 3.0, p = .008) and there was a tendency to greater values at 2 and 26 weeks. Milk calcium decreased in both groups during lactation (p ≤ .001) but was more pronounced in women with HIV. The magnitude of change within individuals in the 1st year of lactation from 2 to 52 weeks was -28.3% (SE 3.9) versus -16.5% (SE 3.5), p for interaction = .05. Differences in milk phosphorus and calcium-to-phosphorus ratio were smaller and mostly not significant. CONCLUSIONS: Participants with HIV on tenofovir-based antiretroviral therapy had altered milk mineral composition. Studies are needed to investigate mechanisms and health implications for the woman and infant.

Use of Apixaban in Atrial Fibrillation With Ritonavir-Boosted Antiretroviral Therapy: A Case Report.

Purpose: Direct oral anticoagulants (DOACs) pose a challenge when given with potent CYP3A4 and P-gp inhibitors, such as the commonly prescribed pharmacokinetic booster ritonavir. As per the manufacturer, apixaban offers a dose reduction when administered concurrently with ritonavir; thus, we explore the clinical indication and safety of apixaban when given with ritonavir-boosted highly active antiretroviral therapy (HAART) in an HIV patient. Summary: We describe a 73-year-old male with extensive cardiac history, including a past medical history of resolved left ventricular thrombus, newly diagnosed non-valvular atrial fibrillation treated with warfarin, and HIV infection treated with ritonavir-boosted HAART. The patient presented to the emergency department with bleeding from multiple sites, necessitating the use of vitamin K. Consequently, his hospital course was complicated by episodes of minor bleeding and labile INR. Due to the complicated nature of his condition and the potential for drug-drug interactions (DDIs), he was transitioned from warfarin to apixaban. Since there is little readily available data to support the use of rivaroxaban and dabigatran with ritonavir, our patient was safely started on dose-reduced apixaban for stroke prophylaxis in atrial fibrillation due to the predictable nature of apixaban pharmacokinetics and proven superiority regarding adverse effects, as compared to other DOACs. Conclusion: Dose-reduced apixaban is a safe and viable choice in patients with atrial fibrillation warranting stroke prophylaxis while concurrently receiving ritonavir-boosted HAART.

A comprehensive overview on the role of phytocompounds in human immunodeficiency virus treatment / 中西医结合学报

Acquired immune deficiency syndrome (AIDS) is a worldwide epidemic caused by human immunodeficiency virus (HIV) infection. Newer medicines for eliminating the viral reservoir and eradicating the virus are urgently needed. Attempts to locate relatively safe and non-toxic medications from natural resources are ongoing now. Natural-product-based antiviral candidates have been exploited to a limited extent. However, antiviral research is inadequate to counteract for the resistant patterns. Plant-derived bioactive compounds hold promise as powerful pharmacophore scaffolds, which have shown anti-HIV potential. This review focuses on a consideration of the virus, various possible HIV-controlling methods and the recent progress in alternative natural compounds with anti-HIV activity, with a particular emphasis on recent results from natural sources of anti-HIV agents. Please cite this article as: Mandhata CP, Sahoo CR, Padhy RN. A comprehensive overview on the role of phytocompounds in human immunodeficiency virus treatment. J Integr Med. 2023; 21(4):332-353.

Impact of an intensive facility-community case management intervention on 6-month HIV outcomes among select key and priority populations in Uganda.

INTRODUCTION: Key and priority populations (with risk behaviours and health inequities) are disproportionately affected by HIV in Uganda. We evaluated the impact of an intensive case management intervention on HIV treatment outcomes in Kalangala District, predominantly inhabited by fisher folk and female sex workers. METHODS: This quasi-experimental pre-post intervention evaluation included antiretroviral therapy naïve adults aged ≥ 18 years from six health facilities in the pre-intervention (Jan 1, 2017-December 31, 2017) and intervention phase (June 13, 2018-June 30, 2019). The primary outcomes were 6-month retention and viral suppression (VS) before and after implementation of the intervention involving facility and community case managers who supported participants through at least the first three months of ART. We used descriptive statistics to compared the characteristics, overall outcomes (i.e., retention, lost to follow up, died), and VS of participants by phase, and used mixed-effects logistic regression models to determine factors associated with 6-month retention in care. Marginal (averaging over facilities) probabilities of retention were computed from the final multivariable model. RESULTS: We enrolled 606 and 405 participants in the pre-intervention and intervention phases respectively. Approximately 75% of participants were aged 25-44 years, with similar age and gender distributions among phases. Approximately 46% of participants in the intervention were fisher folk and 9% were female sex workers. The adjusted probability of 6-month retention was higher in the intervention phase, 0.83 (95% CI: 0.77-0.90) versus pre-intervention phase, 0.73 (95% CI: 0.69-0.77, p = 0.03). The retention probability increased from 0.59 (0.49-0.68) to 0.73 (0.59-0.86), p = 0.03 among participants aged 18-24 years, and from 0.75 (0.71-0.78) to 0.85 (0.78-0.91), p = 0.03 among participants aged ≥ 25 years. VS (< 1,000 copies/mL) was approximately 87% in both phases. CONCLUSIONS: After implementation of the case management intervention, we observed significant improvement in 6-month retention in all age groups of a highly mobile population of predominantly fisher folk.

Factors influencing adherence to antiretroviral therapy from the experience of people living with HIV and their healthcare providers in Sierra Leone: a qualitative study.

BACKGROUND: Antiretroviral therapy (ART) is the primary mode of treatment for Human Immunodeficiency Virus (HIV). It slows disease progression and reduces the spread of infection. HIV treatment is also known to require a high level of adherence of over 90% to achieve good treatment outcomes and viral load suppression. In Sierra Leone, about 70% of People Living with HIV (PLHIV) are non-adherent in their first year of treatment. Understanding the reasons behind this high rate of non-adherence from the perspectives of both PLHIV and health workers is critical for developing strategies to improve adherence. This qualitative study is rooted in the field of public health services. It identifies the barriers and facilitators influencing adherence to antiretroviral treatment in Sierra Leone.  METHODS: A qualitative study design using in-depth interviews of four healthcare workers and 16 PLHIV in two districts in Sierra Leone- Freetown and Bo. The interviews were analyzed using a grounded theory approach to identify emerging themes from the data. RESULTS: The study identified several facilitators and barriers to ART adherence at the personal, community, and health system levels. The facilitators included perceived benefits of ART, family support, having an informal caregiver, receiving free ART medicines, and belonging to peer support groups. The identified barriers were stigma and discrimination, frequency of medication, use of traditional medicine, lack of money for food and transport, work barriers, inadequate medicines and test kits, limited health workers, and long distances to clinics. CONCLUSIONS: Our study emphasized the need for implementing behavioural change communication programmes and activities to reduce stigma and discrimination in the community. Knowledge of the facilitators and barriers to antiretroviral therapy could provide relevant information for more responsive and equitable programmes supporting adherence implementation in low- and middle-income countries. This study also identifies the vital need for community integration of HIV treatment services.

Substance Use and Adherence to Antiretroviral Therapy among People Living with HIV in the United States.

People with HIV (PWH) report substance use at higher rates than HIV-uninfected individuals. The potential negative impact of single and polysubstance use on HIV treatment among diverse samples of PWH is underexplored. PWH were recruited from the Center for Positive Living at the Montefiore Medical Center (Bronx, NY, USA) from May 2017-April 2018 and completed a cross-sectional survey with measures of substance use, antiretroviral therapy (ART) use, and ART adherence. The overall sample included 237 PWH (54.1% Black, 42.2% female, median age 53 years). Approximately half of the sample reported any current substance use with 23.1% reporting single substance use and 21.4% reporting polysubstance use. Polysubstance use was more prevalent among those with current cigarette smoking relative to those with no current smoking and among females relative to males. Alcohol and cannabis were the most commonly reported polysubstance combination; however, a sizeable proportion of PWH reported other two, three, and four-substance groupings. Single and polysubstance use were associated with lower ART adherence. A thorough understanding of substance use patterns and related adherence challenges may aid with targeted public health interventions to improve HIV care cascade goals, including the integration of substance use prevention into HIV treatment and care settings.

Why people die of active tuberculosis in the era of effective chemotherapy in Southern Ethiopia: A qualitative study.

Background: High TB mortality is increasingly understood as an indicator of different problems in the health system and community. Limited awareness of TB in the community, restricted accessibility and/or quality of health services can hamper survival. Exploration and analysis of death among TB patients can lead to a clearer and specific understanding of why the deaths happened and where interventions are likely to make a difference in a specific context. Objective: The study aimed to assess why people die of active tuberculosis in the era of effective chemotherapy. Methods: The study was conducted from October to December 2020 in Arba Minch Health and Demographic Surveillance System (AM-HDSS) by applying phenomenological study design. A total of 27 family members of people who had died of TB, 9 health extension workers (HEW) and 8 health care professionals working in TB clinics were participated in open in-depth interview. A total of 130 individuals participated in 16 focus group discussion which composed of patient survived from TB, religious leader, health development army (HAD) and HEWs. Adequacy of information (saturation) was considered as an adequate sample size to create the intended qualitative product. All the interviews and FGD were tape recorded and recordings were transcribed immediately. ATLAS TI 9 software was used to analyse and process qualitative data. From data set codes were created then by identifying pattern among them themes were created. Then, generated themes were compared and some of them were split, combined, discarded and new ones created after returning to data set. Finally, themes were defined and a concise and easily understandable name was given for each theme. Result: Luck of sufficient knowledge about TB was considered to be a reason for cause of death. Most of the time, TB patients underestimate and ignore when the symptoms first emerge and will not relate it with any diseases. The low level of community awareness about the cause, transmission, treatment and prevention highly contributed to increased transmission rate and death due to TB. The study identified misconceptions in the community; they prefer traditional medicine to the scientific way. First, they try different herbal medicine to get relief from their illness. At the end, if the disease is getting worse, they visit health facilities. Participants mentioned high transportation cost, poor health seeking behaviours, inadequate food consumption and lack of TB awareness as reasons for low treatment adherence. The health facilities were inaccessible for the community. Most of them indicated that health facilities were too far to reach. In some health institution, right amount and combination of medication were not delivery on time and Diagnostic facilities for TB were reported to be inadequate. Conclusion: Poor treatment adherence, lack of TB awareness, stigma, inadequate food consumption, poor health care seeking behaviour and inaccessibility of health facility were identified as major reasons for death. To prevent death of TB patients all sectors such as education, health, and agriculture should work to address health education, infrastructures, nutritional supplementation needs of TB patients, caregivers and the community as a whole.

Wenshen Jianpi recipe induced immune reconstruction and redistribution of natural killer cell subsets in immunological non-responders of human immunodeficiency virus/acquired immune deficiency syndrome: a randomized controlled trial.

OBJECTIVE: To evaluate the effects of the Wenshen Jianpi recipe (, WJR) on immune reconstruction and natural killer (NK) cells in immunological non-responders (INRs) of people living with human immunodeficiency virus (HIV) (PLWH) and propose new therapeutic strategies for HIV. METHODS: Based on Traditional Chinese Medicine treatment principle "invigorating and warming in the spleen and kidneys", WJR combined with antire-troviral therapy (ART) therapy was performed in a randomized, double-blind, placebo-controlled study of 60 patients with non-responders. The randomized process was executed by the Clinical Evaluation Center of China Academy of Chinese Medical Sciences. Sixty patients who met the inclusion criteria obtained random numbers (that is the drug number) was randomly divided into a treatment group and a placebo control group according to a 1∶1 ratio. CD4+T cell counts and natural killer (NK) cells counts were evaluated at baseline and 12-week, 24-week follow-ups. RESULTS: Four participants received random numbers and did not enter the group due to the patient's own reasons. A total of 56 patients were enrolled, including 28 in the treatment group and 28 in the control group. CD4+T cell counts in the treatment group were significantly increased at week 24 ( = 0.01 < 0.05), which were significantly higher than those in the control group (= 0.01 < 0.05). Although no significant differences were observed between two groups, the CD56briCD16- NK cell counts in the treatment group were significantly increased after duration. and CD56dimCD16+ NK cell counts in the treatment group were significantly higher than those in the control group after 24 weeks of treatment (= 0.025 < 0.05). As compared with the control group, the treatment group had significantly lower CD56negCD16+ NK cell counts after 24 weeks of treatment (= 0.023 < 0.05). CONCLUSIONS: WJR promotes the immune reconstruction of INRs and redistribution of NK cell subsets, notably decreasing CD56negCD16+ NK cell counts in INRs. However, the redistribution of NK cell subsets is not beneficial for immune reconstruction in INRs. Further large-scale RCTs are required to evaluate the effect of WJR on immune recovery in INRs and decipher the underlying mechanism.

HPLC-Based Purification and Isolation of Potent Anti-HIV and Latency Reversing Daphnane Diterpenes from the Medicinal Plant Gnidia sericocephala (Thymelaeaceae).

Despite the success of combination antiretroviral therapy (cART), HIV persists in low- and middle-income countries (LMIC) due to emerging drug resistance and insufficient drug accessibility. Furthermore, cART does not target latently-infected CD4+ T cells, which represent a major barrier to HIV eradication. The "shock and kill" therapeutic approach aims to reactivate provirus expression in latently-infected cells in the presence of cART and target virus-expressing cells for elimination. An attractive therapeutic prototype in LMICs would therefore be capable of simultaneously inhibiting viral replication and inducing latency reversal. Here we report that Gnidia sericocephala, which is used by traditional health practitioners in South Africa for HIV/AIDS management to supplement cART, contains at least four daphnane-type compounds (yuanhuacine A (1), yuanhuacine as part of a mixture (2), yuanhuajine (3), and gniditrin (4)) that inhibit viral replication and/or reverse HIV latency. For example, 1 and 2 inhibit HIV replication in peripheral blood mononuclear cells (PBMC) by >80% at 0.08 µg/mL, while 1 further inhibits a subtype C virus in PBMC with a half-maximal effective concentration (EC50) of 0.03 µM without cytotoxicity. Both 1 and 2 also reverse HIV latency in vitro consistent with protein kinase C activation but at 16.7-fold lower concentrations than the control prostratin. Both 1 and 2 also reverse latency in primary CD4+ T cells from cART-suppressed donors with HIV similar to prostratin but at 6.7-fold lower concentrations. These results highlight G. sericocephala and components 1 and 2 as anti-HIV agents for improving cART efficacy and supporting HIV cure efforts in resource-limited regions.