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.

Staff perspectives on the feasibility of the person-centered care assessment tool (PCC-at) in HIV treatment settings in Ghana: a mixed-methods study.

Person-centered care (PCC) aims to improve client's experiences in HIV care while advancing outcomes. This study team developed the PCC assessment tool (PCC-AT) to assess PCC service performance in HIV treatment settings in Ghana. Study objectives aimed to describe the range of PCC-AT scores within and across study facilities and examine the feasibility of PCC-AT implementation in diverse HIV treatment settings. The PCC-AT was piloted at five health facilities providing HIV services among 37 staff. Immediately following each pilot, focus group discussions (FGDs) were conducted to gather feasibility data. Thematic qualitative analysis was conducted on translated FGD transcripts. Across facilities, providers scored highest in the staffing domain, followed by service provision, and direct client support. Time required to implement the PCC-AT averaged 62 minutes. Providers described the tool as well-structured, user-friendly, relevant, reflective of the core PCC delivery elements, and useful in elucidating actions to improve PCC service delivery across domains. The PCC-AT holds potential to strengthen activities that support clients' broader clinical, mental and psychosocial wellbeing by offering friendly services that attend to each client's holistic needs while contributing progress towards epidemic control.

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.

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.

In vitro anti-HIV, cytotoxicity and nutritional analysis of Trianthema portulacastrum L. (Aizoaceae).

The development of antiretroviral therapy has brought a tremendous relief to the world as it minimizes mortality, reduces HIV transmission, and suppresses progression in infected patients. However, the orthodox antiretroviral therapy is faced with limitations which have necessitated a continuous search for more novel plant-based antiviral compounds, which can bypass the existing barriers created by drug resistance and target more viral proteins. Despite the edibility and enormous pharmacological benefits of T. portulacastrum, little is known about its nutrient profiles and potential use as a natural source of antiviral drug. This study focuses on the full feed analysis and anti-HIV potential of two biotypes of T. portulacastrum. Ethanolic extracts of both biotypes of T. portulacastrum (T01 and T02) had significant inhibitory effects on the level of replication of the HIV-1. Both extracts induced the inhibition of at least 50% of the HIV-1 viral load at considerably low IC50 values of 1.757 mg/mL (T01) and 1.205 mg/mL (T02) which is comparable to the AZT standard. The protein composition ranged between 8.63-22.69%; fat (1.84-4.33%); moisture (7.89-9.04%); fibre (23.84-49.98%); and carbohydrate content (38.54-70.14%). Mineral contents of tested T. portulacastrum varied considerably in different parts of the plant. Nitrogen N mineral ranged between 13.8-36.3 mg/g; sodium Na (2.0-14.0 mg/g); potassium K (14.0-82.0 mg/g); magnesium Mg (2.8-7.1 mg/g); calcium Ca (9.1-24.7 mg/g); phosphorus P (1.3-3.6 mg/g); iron Fe (193.5-984.0 ppm); zinc Zn (42.5-96.0 ppm); manganese Mn (28.5-167.5 ppm); and copper Cu (2.0-8.5 ppm). These mineral values are comparable or higher than values quoted for common vegetables, suggesting that T. portulacastrum is a nutrient-dense vegetable that could provide alternative sources of antiviral nutrients to HIV-infected individuals. Further studies are recommended to unravel key metabolites responsible for high nutrient profiles and antiretroviral effects in T. portulacastrum.

A Comprehensive Review on Patents, Herbal Treatment and Clinical Trials on Acquired Immune Deficiency Syndrome.

This paper provides an outline of the Human immunodeficiency virus (HIV), its mechanism of action, and types of HIV/AIDS. Additionally, it offers recent advances and patent data on HIV medications and formulations for the last ten years. The HIV/AIDS patents describes how compounds can stop viruses from spreading and stop HIV from multiplying. It also gives information about monolithic tablets, fixed oral doses of triple HIV formulations, and drug delivery systems that use electrospun fibers. The patents also reveals the treatment for patients having liver disease by using herbal ingredients. The effects of various herbal ingredients and preparations on HIV replication, immunological function, and symptom management have been researched. Despite the encouraging randomized trial data available, it is crucial to proceed cautiously when using herbal treatments for HIV/AIDS treatment. Recent years clinical trials of HIV/AIDS were also reviewed. Herbal remedies are preferred more than other drugs because they have fewer side effects and have long-lasting effects for the treatment of HIV/AIDS. The regulation, quality assurance, and standardization of herbal products are the challenges for the industry.

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.

Evaluation of the probable synergistic toxicity of selected potentiated antiretroviral and antibiotics on some aquatic biomarker organisms.

Environmental effects of active pharmaceutical compounds (APCs) in the environment are not well characterized, hence the need for comprehensive evaluation. This study employed three bioassays using three organisms, namely, Allium cepa, Daphnia magna, and Salmonella typhimurium, in the ecotoxicity study of lone and a mixture of selected APCs, namely, lamivudine (L), an antiretroviral, and ciprofloxacin (C) and sulfamethoxazole (S), antibiotics, at a concentration range between 10 and 100 ppb, in order to evaluate the potential of the lone and ternary mixture to exert synergistic toxicity. Study results from exposure to lone APCs showed that the L, C, and S trio individually had fatal impacts on daphnids, with mortality rates of 100, 75, and 95%, respectively, after 48 h. Sulfamethoxazole showed a mutagenic tendency, with a mutation ratio (background/sample ratio) of 2.0. Lamivudine showed a lethal impact on the root length of A. cepa (p > 0.05, p = 3.60E-3). Further microscopic examination of the A. cepa root tip revealed chromosomal aberrations on exposure to each compound. The LCS-mix ecotoxicology bioassays indicated a synergistic effect on the daphnids, probably due to potentiation. Although the LCS mix had a cytotoxic effect (evidenced by the absence of bacteria colonies) on exposed TA 98 P450 Salmonella typhimurium strain, this effect was not observed in other bacterial strains. Microscopic examination of A. cepa exposed to the LCS-mix revealed an aberration in the mitotic stage of the cell. The impact of combination of the pharmaceuticals in aqueous ecosystems was greater than when exposed to the tested individual pharmaceutical compounds. Study result showed that these compounds have tendencies to pose a higher risk to exposed living entities when in combined/potentiated forms, and this could lead to distortion of the regular functioning of the ecosystem, particularly bacterial and other microbial populations that are listed among primary producers of the aquatic food web.

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.

Clinical Relevance of Drug Interactions in People Living with Human Immunodeficiency Virus on Antiretroviral Therapy-Update 2022: Systematic Review.

BACKGROUND: The clinical outcomes of antiretroviral drugs may be modified through drug interactions; thus, it is important to update the drug interactions in people living with HIV (PLHIV). AIM: To update clinically relevant drug interactions in PLHIV on antiretroviral therapy with novel drug interactions published from 2017 to 2022. METHODS: A systematic review in Medline/PubMed database from July 2017 to December 2022 using the Mesh terms antiretroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full-text access were retrieved. The clinical relevance of drug interactions was grouped into five levels according to the gravity and probability of occurrence. RESULTS: A total of 366 articles were identified, with 219 (including 87 citation lists) were included, which allowed for the identification of 471 drug interaction pairs; among them, 291 were systematically reported for the first time. In total 42 (14.4%) and 137 (47.1%) were level one and two, respectively, and 233 (80.1%) pairs were explained with the pharmacokinetic mechanism. Among these 291 pairs, protease inhibitors (PIs) and ritonavir/cobicistat-boosted PIs, as well as integrase strand transfer inhibitors (InSTIs), with 70 (24.1%) and 65 (22.3%) drug interaction pairs of levels one and two, respectively, were more frequent. CONCLUSIONS: In PLHIV on antiretroviral therapy, we identify 291 drug interaction pairs systematically reported for the first time, with 179 (61.5%) being assessed as clinically relevant (levels one and two). The pharmacokinetic mechanism was the most frequently identified. PIs, ritonavir/cobicistat-boosted PIs, and InSTIs were the antiretroviral groups with the highest number of clinically relevant drug interaction pairs (levels one and two).

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.

Impact of Cannabis Use on Immune Cell Populations and the Viral Reservoir in People With HIV on Suppressive Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus (HIV) infection remains incurable due to the persistence of a viral reservoir despite antiretroviral therapy (ART). Cannabis (CB) use is prevalent amongst people with HIV (PWH), but the impact of CB on the latent HIV reservoir has not been investigated. METHODS: Peripheral blood cells from a cohort of PWH who use CB and a matched cohort of PWH who do not use CB on ART were evaluated for expression of maturation/activation markers, HIV-specific T-cell responses, and intact proviral DNA. RESULTS: CB use was associated with increased abundance of naive T cells, reduced effector T cells, and reduced expression of activation markers. CB use was also associated with reduced levels of exhausted and senescent T cells compared to nonusing controls. HIV-specific T-cell responses were unaffected by CB use. CB use was not associated with intact or total HIV DNA frequency in CD4 T cells. CONCLUSIONS: This analysis is consistent with the hypothesis that CB use reduces activation, exhaustion, and senescence in the T cells of PWH, and does not impair HIV-specific CD8 T-cell responses. Longitudinal and interventional studies with evaluation of CB exposure are needed to fully evaluate the impact of CB use on the HIV reservoir.

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.

Comparative Assessment of Serum Selenium Status in HIV-Infected and Non-infected Children: A Pilot Study in a Tertiary Hospital in Nigeria.

Background Selenium is an essential micronutrient that plays a crucial role in a wide range of physiological processes, including immune responses. Selenium deficiency has been recognized as an associated factor in the progression of HIV to advanced HIV disease and/or mortality. Although selenium supplementation has been shown to reduce hospitalizations and improve cellular immunity, the evidence remains mixed. This study aimed to determine the prevalence of selenium deficiency and its relationship with HIV disease markers in HIV-infected children at the Lagos University Teaching Hospital. Methodology This is a cross-sectional, comparative, pilot study of plasma concentrations of selenium in HIV-infected (n = 30) and non-infected (n = 20) children enrolled in the pediatric HIV clinic of the Lagos University Teaching Hospital, Lagos, Nigeria, from May 2019 to May 2021. HIV-infected children were on stable antiretroviral therapy (ART) with an undetectable viral load. The serum concentration of selenium was measured using the automated atomic absorption spectrophotometer (hydride generation method). Logistic regression was used to study the effect of selenium status on the levels of HIV disease markers (CD4 count, viral load, weight, opportunistic infections) in the study participants. Results The median age of all participants was nine (4-12) years, with 74% being boys. The mean selenium concentrations were lower in HIV-infected children (91.1 ± 12.0 µg/L) compared to the comparison group without HIV (147.8 ± 4.9 µg/L) (p = 0.001). After controlling for age, ART duration, markers of HIV infection, and other potentially confounding variables, participants with selenium deficiency had approximately 11-fold odds of increased hospital admissions (adjusted odds ratio = 10.57, 95% confidence interval = 1.58 to 70.99; p = 0.015). Conclusions In this study, selenium concentrations were significantly lower in HIV-infected children than in the HIV-negative comparison group. Lower serum selenium concentrations were associated with increased hospitalizations. Although our findings suggest the potential need for selenium supplementation for children living with HIV in Nigeria, further studies are warranted to determine the safety and efficacy of selenium supplementation in this key population.

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.

Moringa oleifera Lam Leaf Extract Stimulates NRF2 and Attenuates ARV-Induced Toxicity in Human Liver Cells (HepG2).

The World Health Organization (WHO) reported that there are 37 million individuals living with the human immunodeficiency virus (HIV) worldwide, with the majority in South Africa. This chronic disease is managed by the effective use of antiretroviral (ARV) drugs. However, with prolonged use, ARV drug-induced toxicity remains a clinically complex problem. This study investigated the toxicity of ARV drugs on mitochondria and the NRF2 antioxidant pathway and its possible amelioration using Moringa oleifera Lam (MO) leaf extracts. This medicinal plant has a range of functional bioactive compounds. Liver (HepG2) cells were treated with individual ARV drugs: Tenofovir disoproxil fumarate (TDF), Emtricitabine (FTC), and Lamivudine (3TC) for 96 h, followed by MO leaf extracts for 24 h. Intracellular ROS, cytotoxicity, lipid peroxidation, total and reduced glutathione (GSH), ATP, and mitochondrial polarisation were determined. Finally, protein (pNRF2, NRF2, SOD2, CAT, and Sirt3) and mRNA (NRF2, CAT, NQO1 SOD2, Sirt3, and PGC1α) expression were measured using Western blot and qPCR, respectively. TDF, FTC, and 3TC significantly increased intracellular ROS and extracellular levels of both MDA and LDH. ARVs also reduced the GSH and ATP levels and altered the mitochondrial polarization. Further, ARVs reduced the expression of NRF2 SOD2, Sirt3, CAT, NQO1, UCP2 and PGC1α mRNA and consequently pNRF2, NRF2, SOD2, Sirt3 and CAT protein. In contrast, there was a significant reduction in the extracellular MDA and LDH levels post-MO treatment. MO significantly reduced intracellular ROS while significantly increasing GSH, ATP, and mitochondrial membrane polarization. The addition of MO to ARV-treated cells significantly upregulated the expression of NRF2, SOD2, Sirt3, CAT, UCP2, PGC1α, and NQO1 mRNA and pNRF2, NRF2, SOD2, Sirt3 proteins. Thus, MO ameliorates ARV-induced hepatotoxicity by scavenging oxidants by inducing the NRF2 antioxidant pathway. MO shows great therapeutic potential and may be considered a potential supplement to ameliorate ARV drug toxicity.

Nutritional status and its determinants among adolescents with HIV on anti-retroviral treatment in low- and middle-income countries: a systematic review and meta-analysis.

PURPOSE: This review aimed to determine what methods are used to assess nutritional status, the levels of nutritional status, determinants of undernutrition, and nutritional interventions employed for adolescents with HIV on Anti-Retroviral Therapy follow-up in Low- and Middle-Income countries. METHODS: Established methods were used to systematically identify and retrieve studies published in five databases between January 2000 to May 2021, and citation searching. Quality was appraised and findings were synthesized using narrative analysis and meta-analysis. RESULT: Body Mass Index is the major indicator of nutritional status. The pooled prevalence of stunting, wasting, and overweight were 28.0%, 17.0%, and 5.0%, respectively. Adolescent males are 1.85 and 2.55 times more likely than adolescent females to suffer from both stunting and wasting at AOR = 1.85 (95%:1.47, 2.31) and AOR = 2.55 (95%: 1.88, 3.48), respectively. Similarly, adolescents with a history of opportunistic infections were 2.97 times more likely to be stunted than uninfected adolescents, AOR = 2.97 (95%:1.73, 5.12). One single intervention study found significant improvements in anthropometric status after nutritional supplementation. CONCLUSION AND RECOMMENDATION: The few studies that have been conducted on nutritional status in adolescents living with HIV in low- and middle-income countries indicate that stunting and wasting are common in this population. Avoiding opportunistic infections is an important protective factor but the review highlighted the generally inadequate and fragmented nature of nutritional screening and support programs. Development of comprehensive and integrated systems for nutritional assessment and intervention services during ART follow-up should be prioritized to improve adolescent clinical outcomes and survival.

Antiviral Potential of the Genus Panax: An updated review on their effects and underlying mechanism of action.

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

Antiviral and ROS scavenging potential of Carica papaya Linn and Psidium guajava leaves extract against HIV-1 infection.

Antiretroviral therapy is the only treatment option for HIV-infected patients; however, it has certain drawbacks in terms of developing multiple toxic side effects. Thus, there is a continuous need to explore safe and efficacious anti-retroviral agents. Carica papaya Linn and Psidium guajava are known for their various biological activities. In this study, we characterized the bioactive fractions of methanolic leaves extract from both plants using the High-resolution electrospray ionization mass spectrometry (HR-ESI-MS) technique, followed by the investigation of their potential as anti-HIV-1 and antioxidant agents through in vitro mechanistic assays. The anti-HIV-1 activity was examined in TZM-bl cells through luciferase gene assay against two different clades of HIV-1 strains, whereas the intracellular ROS generation was analyzed by Fluorescence-Activated Cell Sorting. Additionally, the mechanisms of action of these phyto-extracts were determined through the Time-of-addition assay. The characterization of Carica papaya Linn and Psidium guajava leaves extract through HR-ESI-MS fragmentation showed high enrichment of various alkaloids, glycosides, lipids, phenolic compounds, terpenes, and fatty acids like bioactive constituents. Both the phyto-extracts were found to be less toxic and exhibited potent antiviral activity against HIV-1 strains. Furthermore, the phyto-extracts also showed a decreased intracellular ROS in HIV-1 infected cells due to their high antioxidant potential. Overall, our study suggests the anti-HIV-1 potential of Carica papaya Linn and Psidium guajava leaves extract due to the synergistic action of multiple bioactive constituents.