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.

Plasma Concentrations of Rosmarinic Acid in Patients on Antiretroviral Therapy: In Silico Exploration Based on Clinical Data.

Rosmarinic acid (RA) is a phenolic compound with antiviral properties, often encountered in dietary supplements and herbal drugs. Data on the pharmacokinetics of RA are lacking in cases of the chronic use of supplements containing this compound, and only limited data on the metabolism and distribution of RA are available. The aim of the study was to investigate the plasma levels of RA after 12 weeks of use and determine potential interactions of RA and selected antiretroviral drugs. Patients infected with human immunodeficiency virus took a supplement containing RA for 12 weeks, after which the RA concentrations in the plasma samples were analyzed. A detailed in silico analysis was conducted in order to elucidate the potential interactions between RA and the drugs efavirenz, darunavir and raltegravir. It was found that RA can be detected in patients' plasma samples, mainly in the form of sulphoglucuronide. The potential interactions are suggested on the level of liver metabolizing enzymes and efflux P-glycoprotein, with RA competing with antiretroviral drugs as a substrate in metabolism and distribution systems. The present study suggests that the simultaneous use of RA and antiretroviral therapy (containing efavirenz, darunavir or raltegravir) may affect the plasma levels of RA after prolonged supplementation.

Cannabis Use Associates With Reduced Proviral Burden and Inflammatory Cytokine in Tissues From Men With Clade C HIV-1 on Suppressive Antiretroviral Therapy.

BACKGROUND: Human immunodeficiency virus 1 (HIV-1) tissue reservoirs remain the main obstacle against an HIV cure. Limited information exists regarding cannabis's effects on HIV-1 infections in vivo, and the impact of cannabis use on HIV-1 parenchymal tissue reservoirs is unexplored. METHODS: To investigate whether cannabis use alters HIV-1 tissue reservoirs, we systematically collected 21 postmortem brain and peripheral tissues from 20 men with subtype C HIV-1 and with suppressed viral load enrolled in Zambia, 10 of whom tested positive for cannabis use. The tissue distribution and copies of subtype C HIV-1 LTR, gag, env DNA and RNA, and the relative mRNA levels of cytokines IL-1ß, IL-6, IL-10, and TGF-ß1 were quantified using PCR-based approaches. Utilizing generalized linear mixed models we compared persons with HIV-1 and suppressed viral load, with and without cannabis use. RESULTS: The odds of tissues harboring HIV-1 DNA and the viral DNA copies in those tissues were significantly lower in persons using cannabis. Moreover, the transcription levels of proinflammatory cytokines IL-1ß and IL-6 in lymphoid tissues of persons using cannabis were also significantly lower. CONCLUSIONS: Our findings suggested that cannabis use is associated with reduced sizes and inflammatory cytokine expression of subtype C HIV-1 reservoirs in men with suppressed viral load.

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.

Impact of HIV treat-all and complementary policies on ART linkage in 13 PEPFAR-supported African countries.

BACKGROUND: In 2015, the World Health Organization recommended that all people living with HIV begin antiretroviral treatment (ART) regardless of immune status, a policy known as 'Treat-All to end AIDS', commonly referred to as Treat-All. Almost all low- and middle-income countries adopted this policy by 2019. This study describes how linkage to treatment of newly diagnosed persons changed between 2015 and 2018 and how complementary policies may have similarly increased linkage for 13 African countries. These countries adopted and implemented Treat-All policies between 2015 and 2018 and were supported by the U.S. Government's President's Emergency Plan for AIDS Relief (PEPFAR). The focuses of this research were to understand 1) linkage rates to ART initiation before and after the adoption of Treat-All in each country; 2) how Treat-All implementation differed across these countries; and 3) whether complementary policies (including same-day treatment initiation, task-shifting, reduced ART visits, and reduced ART pickups) implemented around the same time may have increased ART linkage. METHODS: HIV testing and treatment data were collected by PEPFAR country programs in 13 African countries from 2015 to 2018. These countries were chosen based on the completeness of policy data and availability of program data during the study period. Program data were used to calculate proxy linkage rates. These rates were compared relative to the Treat All adoption period and the adoption of complementary policies. RESULTS: The 13 countries experienced an average increase in ART linkage of 29.3% over the entire study period. In examining individual countries, all but two showed increases in linkage to treatment immediately after Treat All adoption. Across all countries, those that had adopted four or more complementary policies showed an average increased linkage of 39.8% compared to 13.9% in countries with fewer than four complementary policies. CONCLUSIONS: Eleven of 13 country programs examined in this study demonstrated an increase in ART linkage after Treat-All policy adoption. Increases in linkage were associated with complementary policies. When exploring new public health policies, policymakers may consider which complementary policies might also help achieve the desired outcome of the public health policy.

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.

Organisation and integrated healthcare approaches for people living with HIV, multimorbidity, or both: a systematic review.

BACKGROUND: Universal recommendation for antiretroviral drugs and their effectiveness has put forward the challenge of assuring a chronic and continued care approach to PLHIV (People Living with HIV), pressured by aging and multimorbidity. Integrated approaches are emerging which are more responsive to that reality. Studying those approaches, and their relation to the what of delivery arrangements and the how of implementation processes, may support future strategies to attain more effective organizational responses. METHODS: We reviewed empirical studies on either HIV, multimorbidity, or both. The studies were published between 2011 and 2020, describing integrated approaches, their design, implementation, and evaluation strategy. Quantitative, qualitative, or mixed methods were included. Electronic databases reviewed cover PubMed, SCOPUS, and Web of Science. A narrative analysis was conducted on each study, and data extraction was accomplished according to the Effective Practice and Organisation of Care taxonomy of health systems interventions. RESULTS: A total of 30 studies, reporting 22 different interventions, were analysed. In general, interventions were grounded and guided by models and frameworks, and focused on specific subpopulations, or priority groups at increased risk of poorer outcomes. Interventions mixed multiple integrated components. Delivery arrangements targeted more frequently clinical integration (n = 13), and care in proximity, community or online-telephone based (n = 15). Interventions reported investments in the role of users, through self-management support (n = 16), and in coordination, through multidisciplinary teams (n = 9) and continuity of care (n = 8). Implementation strategies targeted educational and training activities (n = 12), and less often, mechanisms of iterative improvement (n = 3). At the level of organizational design and governance, interventions mobilised users and communities through representation, at boards and committees, and through consultancy, along different phases of the design process (n = 11). CONCLUSION: The data advance important lessons and considerations to take steps forward from disease-focused care to integrated care at two critical levels: design and implementation. Multidisciplinary work, continuity of care, and meaningful engagement of users seem crucial to attain care that is comprehensive and more proximal, within or cross organizations, or sectors. Promising practices are advanced at the level of design, implementation, and evaluation, that set integration as a continued process of improvement and value professionals and users' knowledge as assets along those phases. TRIAL REGISTRATION: PROSPERO number CRD42020194117.

[Stigmatization of people living with HIV in health care services in Togo]. / Stigmatisation des personnes vivant avec le VIH dans les services de soins au Togo.

Introduction: The elimination of AIDS as a threat to public health implies comprehensive care for those tested in all health facilities and without discrimination/stigmatization. The aim of this study is to evaluate the problems of stigmatization and discrimination of people living with HIV (PLHIV) in health care facilities and their implications for access to care for PLHIV. Methodology: This is a descriptive cross-sectional study in the 6 health regions of Togo targeting people aged 18 years and over, living with HIV. A hybrid sampling method combining a limited chain referral and a sampling based on the mapping of meeting places/activities was used. Data were collected using the digitized version 2.0 of the PLHIV Stigma Index questionnaire. Results: A total of 1 119 PLHIV with a mean age of 39 years were included. The sex-ratio was 0.5, and 43.4% had known their HIV status for 1 to 4 years. In the last 12 months, the experiences of stigmatization reported by the PLHIV from health personnel were: gossip (13%), disclosure of status without consent (10%) or avoidance of physical contact (2.6%). In terms of reproductive health, 2.1% of respondents had been advised not to become fathers/mothers and 1.4% had their access to antiretroviral drugs (ARV) conditioned by the use of a contraceptive method. 28.4% of those on ARV had missed one dose of treatment in the last 12 months for fear that someone would find out they were HIV positive. Also, 39.5% of the respondents who were not on ARV justified this by the fear that health workers would treat them badly or reveal their HIV status without their consent. Conclusion: In health care settings, this phenomenon of HIV-related stigma is multifaceted and deserves to be documented so that it can be taken into account in order to improve the quality of services offered to beneficiary populations.

Withania somnifera extracts induced attenuation of HIV-1: a mechanistic approach to restrict viral infection.

BACKGROUND: Several anti-retroviral drugs are available against Human immunodeficiency virus type-1, but have multiple adverse side effects. Hence, there is an incessant compulsion for effectual anti-retroviral agents with minimal or no intricacy. Traditionally, natural products have been the most successful source for the development of new medications. Withania somnifera, also known as Ashwagandha, is the utmost treasured medicinal plant used in Ayurveda, which holds the potential to give adaptogenic, immunomodulatory, and antiviral effects. However, its effect on HIV-1 replication at the cellular level has never been explored. Herein, we focused on the anti-HIV-1 activity and the probable mechanism of action of hydroalcoholic and aqueous extracts of Withania somnifera roots and its phytomolecules. METHODS: The cytotoxicity of the extracts was determined through MTT assay, while the in vitro anti-HIV-1 activity was assessed in TZM-bl cells against the HIV-1 strains of X4 and R5 subtypes. Results were confirmed in peripheral blood mononuclear cells, using the HIV-1 p24 antigen assay. Additionally, the mechanism of action was determined through the Time of Addition assay, which was further validated through the series of enzymatic assays, i.e. HIV-1 Integrase, Reverse transcriptase, and Protease assays. To explore the role of the identified active metabolites of Withania somnifera in antiretroviral activity, molecular docking analyses were performed against these key HIV-1 replication enzymes. RESULTS: The hydroalcoholic and aqueous extracts of Withania somnifera roots were found to be safer at the sub-cytotoxic concentrations and exhibited their ability to inhibit replication of two primary isolates of HIV-1 through cell-associated and cell-free assays, in dose-dependent kinetics. Several active phytomolecules found in Withania somnifera successfully established hydrogens bonds in the active binding pocket site residues responsible for the catalytic activity of HIV replication and therefore, signifying their role in the attenuation of HIV-1 infection as implied through the in silico molecular docking studies. CONCLUSIONS: Our research identified both the hydroalcoholic and aqueous extracts of Withania somnifera roots as potent inhibitors of HIV-1 infection. The in silico analyses also indicated the key components of Withania somnifera with the highest binding affinity against the HIV-1 Integrase by 12-Deoxywithastramonolide and 27-Hydroxywithanone, HIV-1 Protease by Ashwagandhanolide and Withacoagin, and HIV-1 Reverse transcriptase by Ashwagandhanolide and Withanolide B, thereby showing possible mechanisms of HIV-1 extenuation. Overall, this study classified the role of Withania somnifera extracts and their active compounds as potential agents against HIV-1 infection.

Genetic characterization of HIV-1 viruses among cases with antiretroviral therapy failure in Suzhou City, China.

BACKGROUND: This retrospective study aimed to characterize the distribution of HIV-1 genotypes and the prevalence of drug resistance mutations in people with antiretroviral treatment (ART) failure in Suzhou City, China. METHODS: Pol gene of HIV-1 viruses in blood samples of EDTA anticoagulants from 398 patients with failed antiviral treatment was successfully amplified by using an in-house assay. Drug resistance mutations were analyzed by using the Stanford HIV Drug Resistance Database system ( https://hivdb.stanford.edu/hivdb/by-mutations/ ). HIV-1 genotypes were determined by the REGA HIV subtyping tool (version 3.46, https://www.genomedetective.com/app/typingtool/hiv ). Near full-length genomes (NFLG) of HIV-1 viruses were obtained by next generation sequencing method. RESULTS: Sequences analysis of the pol gene revealed that CRF 01_AE (57.29%, 228/398) was the dominant subtype circulating in Suzhou City, followed by CRF 07_BC (17.34%, 69/398), subtype B (7.54%, 30/398), CRF 08_BC (6.53%, 26/398), CRF 67_01B (3.02%, 12/398) and CRF55_01B (2.51%, 10/398). The overall prevalence of drug-resistant mutations in cases with ART failure was 64.57% (257/398), including 45.48% (181/398) for nucleotide reverse transcriptase inhibitors (NRTIs) mutations, 63.32% (252/398) for non-nucleoside reverse transcriptase inhibitors (NNRTIs) mutations, and 3.02% (12/398) for protease inhibitors (PIs) mutations. Ten near full-length genomes (NFLG) of HIV-1 viruses were identified, including six recombinants of CRF 01_AE and subtype B, two recombinants of CRF 01_AE, subtype B and subtype C sequences, one recombinant of CRF 01_AE and subtype C and one recombinant of CRF 01_AE, subtype A1 and subtype C. CONCLUSIONS: The high prevalence of drug-resistant HIV-1 viruses was a serious challenge for HIV prevention and treatment of people with HIV infection. Treatment regimens for ART failure patients should be adjusted over time based on the outcome of drug resistance tests. NFLG sequencing facilitates the identification of new recombinants of HIV-1.

The effect of supervision on community health workers' effectiveness with households in rural South Africa: A cluster randomized controlled trial.

BACKGROUND: Community health workers (CHWs) can supplement professional medical providers, especially in rural settings where resources are particularly scarce. Yet, outcomes of studies evaluating CHWs effectiveness have been highly variable and lack impact when scaled nationally. This study examines if child and maternal outcomes are better when existing government CHWs, who are perinatal home visitors, receive ongoing enhanced supervision and monitoring, compared to standard care. METHODS AND FINDINGS: A cluster randomized controlled effectiveness trial was conducted comparing outcomes over 2 years when different supervision and support are provided. Primary health clinics were randomized by clinic to receive monitoring and supervision from either (1) existing supervisors (Standard Care (SC); n = 4 clinics, 23 CHWs, 392 mothers); or (2) supervisors from a nongovernmental organization that provided enhanced monitoring and supervision (Accountable Care [AC]; n = 4 clinic areas, 20 CHWs, 423 mothers). Assessments were conducted during pregnancy and at 3, 6, 15, and 24 months post-birth with high retention rates (76% to 86%). The primary outcome was the number of statistically significant intervention effects among 13 outcomes of interest; this approach allowed us to evaluate the intervention holistically while accounting for correlation among the 13 outcomes and considering multiple comparisons. The observed benefits were not statistically significant and did not show the AC's efficacy over the SC. Only the antiretroviral (ARV) adherence effect met the significance threshold established a priori (SC mean 2.3, AC mean 2.9, p < 0.025; 95% CI = [0.157, 1.576]). However, for 11 of the 13 outcomes, we observed an improvement in the AC compared to the SC. While the observed outcomes were not statistically significant, benefits were observed for 4 outcomes: increasing breastfeeding for 6 months, reducing malnutrition, increasing ARV adherence, and improving developmental milestones. The major study limitation was utilizing existing CHWs and being limited to a sample of 8 clinics. There were no major study-related adverse events. CONCLUSIONS: Supervision and monitoring were insufficient to improve CHWs' impact on maternal and child outcomes. Alternative strategies for staff recruitment and narrowing the intervention outcomes to the specific local community problems are needed for consistently high impact. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02957799.

Factors influencing adherence to anti-retroviral therapy in amazonian indigenous people living with HIV/AIDS.

BACKGROUND: Indigenous communities in Peru has been historically affected by high mortality rates attributable to HIV-AIDS infection, associated with a low access to health services, and socio-cultural barriers. In this context, the study aimed to describe factors associated with antiretroviral treatment adherence in people from Awajun and Wampis indigenous communities, living with HIV-AIDS in a Peruvian Amazonian region. METHODS: A cross-sectional study was completed with a consecutive sample of people from indigenous communities (Awajun or Wampis) living with HIV, who were receiving antiretroviral treatment for at least the last three months. Participants were recruited between October 1 and December 30, 2021, from four districts of Bagua and Condorcanqui provinces in the Amazonian region. An ad-hoc questionnaire was used to collect information about demographic, economic, and socio-cultural factors and access to health services. The Simplified Medication Adherence Questionnaire (SMAQ) was used to evaluate adherence to antiretroviral therapy. Multivariate logistic regression analysis with backward stepwise was performed to explore factors that might influence adherence. RESULTS: Of the 208 participants, 28.8% reported complete adherence to antiretroviral treatment. The multivariate logistic regression showed that occupation (aPR: 1.86; 95%CI 1.15-3.02), economic income (aPR: 0.64; 95%CI 0.41-0.99), and adverse reactions to antiretroviral therapy (aPR: 0.36; 95%CI 0.18-0.70) were related to complete adherence to medication. CONCLUSION: Only a third of participants reported complete adherence to antiretroviral therapy. Factors associated with adherence to antiretroviral medication were related to socioeconomic conditions and adverse reactions to the therapeutic scheme. Interventions to improve adherence in indigenous people living with HIV should consider these factors in order to develop effective implementation strategies.

Utility of Therapeutic Drug Monitoring in Identifying Clinically Significant Interactions Between St. John's Wort and Prescription Drugs.

BACKGROUND: The general population widely uses herbal medicines, as they are regarded as effective and safe. St. John's wort, which is an effective herbal antidepressant, exhibits both pharmacokinetic and pharmacodynamic interactions with several drugs. The aim of this review was to highlight the clinically significant interactions of St. John's wort with drugs that require to be monitored to assess their therapeutic effect. METHODS: Published literature was searched using electronic databases, such as MEDLINE, PubMed, and Elsevier ScienceDirect using terms such as "herbal medicine," "herbal toxicity," "legislation herbal medicine," "drug-herb interactions," "St. John's wort," and "St. John's wort-drug interactions." Searches were limited to the English language, and there was no restriction on the date of publication. RESULTS: St. John's wort exhibits a number of pharmacokinetic and pharmacodynamic interactions with drugs. The most dangerous interactions occurred when used concurrently with the immunosuppressants, cyclosporine, and tacrolimus (treatment failure or organ rejection) or warfarin (treatment failure resulting in thromboembolic events) or antiretroviral agents (treatment failure and the emergence of new viral variants that are resistant to conventional drugs). CONCLUSIONS: Patients should consult their health care providers before consuming herbal supplements, especially St. John's wort, to avoid potentially dangerous drug-herb interactions.

Potential drug-drug interactions between antiretroviral drugs and comedications, including dietary supplements, among people living with HIV: A clinical survey.

OBJECTIVE: Age-related comorbidities, polypharmacy and thereby the risk of potential drug-drug interactions (PDDIs) among people living with HIV (PLWH) have increased over the years. We estimated the prevalence of comedications, including dietary supplements, and evaluated PDDIs among PLWH receiving antiretroviral therapy (ART) in Denmark in an outpatient setting. METHODS: Information on prescription medication, over-the-counter medication and dietary supplements was obtained from adult PLWH receiving ART attending two outpatient clinics in Denmark. The PDDIs were identified using the University of Liverpool's drug interaction database. Associations between PDDIs and relevant variables were compared using logistic regression models. RESULTS: A total of 337 PLWH receiving ART with a median age of 53 years (interquartile range: 45-61) were included; 77% were male and 96% had a HIV-RNA viral load < 50 copies/mL. Twenty-six per cent of participants received five or more comedications and 56% consumed dietary supplements. Co-administration of drugs requiring dose adjustment or monitoring was identified in the medication lists of 52% of participants, and 4.5% were on drugs that should not be co-administered. Male sex [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.0-3.4], being on a protease inhibitor (OR = 4.3, 95% CI: 1.9-9.7), receiving five or more comedications (OR = 3.3, 95% CI: 1.5-7.2), taking over-the-counter medications (OR = 1.9, 95% CI: 1.1-3.3) and dietary supplements (OR = 2.0, 95% CI: 1.2-3.3) were independent predictors of PDDIs. CONCLUSION: Potential drug-drug interactions were common among our study population Our study confirms that polypharmacy and being on a protease inhibitor-based regimen increase the risk of PDDIs considerably and highlights the importance of questioning PLWH about dietary supplement intake.

Achievement of virologic suppression with HIV antiretroviral therapy in a patient also taking multiple daily cation supplement doses: A case report and review of the literature.

PURPOSE: To describe a case report of antiretroviral regimen selection, with considerations for drug-supplement interactions, for a patient living with HIV with complicated nutrition needs. SUMMARY: A 56-year-old white female with a history of sleeve gastrectomy was initiated on coformulated bictegravir/emtricitabine/tenofovir alafenamide for treatment of HIV infection. Her baseline HIV viral load was 139,790 RNA copies/mL, and the baseline CD4 cell count was 544 cells/mm3. The patient additionally had a nutritional supplement regimen of twice-daily calcium and twice-daily multivitamins with minerals following sleeve gastrectomy. Due to binding interactions between polyvalent cations and bictegravir and the potential impact on antiretroviral efficacy, construction of a daily medication schedule to avoid interactions between the antiretroviral regimen and the supplements while promoting optimal dosing of each supplement was necessary; however there is currently no guidance on twice-daily cation dosing with coadministered bictegravir and limited guidance on multivitamin coadministration in this context. A review of the available literature on bictegravir interactions and pharmacokinetic parameters was performed. A dose separation strategy was utilized to design a regimen that maximized separation of doses of supplements from doses of bictegravir/emtricitabine/tenofovir alafenamide while minimizing interaction potential. At follow-up 8 weeks after regimen initiation, the HIV viral load was undetectable (<40 copies/mL) and the CD4 cell count had increased to 821 cells/mm3. CONCLUSION: Integrase strand transferase inhibitor interactions with polyvalent cations in nutritional supplements can be avoided or mitigated with attention to timing of each dose and optimizing separation strategies. This case report shows the potential for alleviating such interactions through optimal dose scheduling.

Interactions of Antiretroviral Drugs with Food, Beverages, Dietary Supplements, and Alcohol: A Systematic Review and Meta-analyses.

Multiple factors may affect combined antiretroviral therapy (cART). We investigated the impact of food, beverages, dietary supplements, and alcohol on the pharmacokinetic and pharmacodynamic parameters of 33 antiretroviral drugs. Systematic review in adherence to PRISMA guidelines was performed, with 109 reports of 120 studies included. For each drug, meta-analyses or qualitative analyses were conducted. We have found clinically significant interactions with food for more than half of antiretroviral agents. The following drugs should be taken with or immediately after the meal: tenofovir disoproxil, etravirine, rilpivirine, dolutegravir, elvitegravir, atazanavir, darunavir, lopinavir, nelfinavir, ritonavir, saquinavir. Didanosine, zalcitabine, zidovudine, efavirenz, amprenavir, fosamprenavir, and indinavir should be taken on an empty stomach for maximum patient benefit. Antiretroviral agents not mentioned above can be administered regardless of food. There is insufficient evidence available to make recommendations about consuming juice or alcohol with antiretroviral drugs. Resolving drug-food interactions may contribute to maximized cART effectiveness and safety.

RESUMEN: Múltiples factores pueden afectar la terapia antirretroviral combinada (cART). Investigamos el impacto de los alimentos, las bebidas, los suplementos dietéticos y el alcohol en los parámetros farmacocinéticos y farmacodinámicos de 33 medicamentos antirretrovirales. Se realizó la revisión sistemática en apego a las guías PRISMA, con 109 reportes de 120 estudios incluidos. Para cada fármaco se realizaron metanálisis o análisis cualitativos. Hemos encontrado interacciones clínicamente significativas con alimentos para más de la mitad de los fármacos antirretrovirales. Los siguientes medicamentos deben tomarse durante o inmediatamente después de comer: tenofovir, disoproxil, etravirina, rilpivirine, dolutegravir, elvitegravir, atazanavir, darunavir, lopinavir, nelfinavir, ritonavir, saquinavir. Didanosina, zalcitabina, zidovudina, efavirenz, amprenavir, fosamprenavir e indinavir deben tomarse con el estómago vacío para obtener el máximo beneficio para el paciente. Los fármacos antirretrovirales no mencionados anteriormente se pueden administrar independientemente de los alimentos. No hay suficiente evidencia disponible para hacer recomendaciones sobre el consumo de jugo o alcohol con medicamentos antirretrovirales. Resolver las interacciones entre medicamentos y alimentos puede contribuir a maximizar la eficacia y la seguridad de cART.

Preliminary Effects of an Urban Gardens and Peer Nutritional Counseling Intervention on HIV Treatment Adherence and Detectable Viral Load Among People with HIV and Food Insecurity: Evidence from a Pilot Cluster Randomized Controlled Trial in the Dominican Republic.

A pilot cluster randomized controlled trial involving two HIV clinics in the Dominican Republic assessed preliminary efficacy of an urban garden and peer nutritional counseling intervention. A total of 115 participants (52 intervention, 63 control) with moderate or severe food insecurity and sub-optimal antiretroviral therapy (ART) adherence and/or detectable viral load were assessed at baseline, 6- and 12-months. Longitudinal multivariate regression analysis controlling for socio-demographics and accounting for serial cluster correlation found that the intervention: reduced the prevalence of detectable viral load by 20 percentage points at 12 months; reduced any missed clinic appointments by 34 and 16 percentage points at 6 and 12 months; increased the probability of "perfect" ART adherence by 24 and 20 percentage points at 6 and 12 months; and decreased food insecurity at 6 and 12 months. Results are promising and warrant a larger controlled trial to establish intervention efficacy for improving HIV clinical outcomes.Trial registry Clinical Trials Identifier: NCT03568682.

RESUMEN: Un estudio piloto de un ensayo controlado aleatorio por conglomerados que involucró a dos clínicas del VIH en la República Dominicana evaluó de forma preliminar la eficacia de una intervención de huertos urbanos y consejería nutricional entre pares. Un total de 115 participantes (52 de intervención, 63 de control) con inseguridad alimentaria moderada o grave y con adherencia subóptima a la terapia antirretroviral (TARV) y/o carga viral detectable fueron evaluados al inicio del estudio, y a los 6 y 12 meses. El análisis de regresión longitudinal multivariada controlando por variables sociodemográficas y tomando en cuenta la correlación serial de clúster encontró que la intervención: redujo la prevalencia de carga viral detectable en 20 puntos porcentuales a los 12 meses; redujo las citas clínicas perdidas en 34 y 16 puntos porcentuales a los 6 y 12 meses; aumentó la probabilidad de adherencia "perfecta" al TARV en 24 y 20 puntos porcentuales a los 6 y 12 meses; y disminuyó la inseguridad alimentaria a los 6 y 12 meses. Los resultados son prometedores y justifican un ensayo controlado más grande para establecer la eficacia de la intervención en mejorar los resultados clínicos del VIH.

A new era of HIV care for age-associated multimorbidity.

PURPOSE OF REVIEW: The management of people with HIV has shifted focus from acute AIDS-defining illness towards improving detection of chronic disease and reducing impact of multimorbidity. In this review, we explore this shifting paradigm of HIV care and the evidence for alternative models proposed to provide integrated holistic services for people with HIV (PWH) with multimorbidity. RECENT FINDINGS: Despite 25 years of the antiretroviral treatment (ART) era an increased incidence of noncommunicable disease (NCD) and multimorbidity in PWH persists. As the world moves closer to universal ART coverage this phenomenon is now reported in low- and middle-income settings. Multimorbidity affects PWH disproportionately compared to the general population and results in reduced health related quality of life (HRQoL), greater hospitalization and higher mortality. There is evidence that NCD care provision and outcomes may be inferior for PWH than their HIV negative counterparts. Various models of integrated multimorbidity care have developed and are grouped into four categories; HIV specialist clinics incorporating NCD care, primary care services incorporating HIV care, community NCD clinics offering integrated HIV care, and multidisciplinary care integrated with HIV in secondary care. Evidence is limited as to the best way to provide multimorbidity care for PWH. SUMMARY: A new era of HIV care for an ageing population with multimorbidity brings challenges for health providers who need to develop holistic patient focused services which span a range of coexisting conditions.

Impact of a standardized order set and medication-use process on medication error rates in sexual assault patients presenting to the emergency department for HIV nonoccupational postexposure prophylaxis.

PURPOSE: To evaluate the impact of a standardized order set and medication-use process on antiretroviral medication errors in sexual assault (SA) patients presenting to the emergency department (ED) for nonoccupational postexposure prophylaxis (nPEP). METHODS: In November 2019, a multidisciplinary group collaborated on an initiative to improve the nPEP medication-use process for SA patients presenting to the EDs within a large integrated health system. Electronic medical records of patients 13 years of age or older who presented for SA examination and were prescribed nPEP during the pre- (February 2018-August 2019) and poststandardization (February 2020-August 2021) periods were included. The primary objective was to compare the proportion of patients experiencing a medication error before and after SA/nPEP process standardization. Data regarding the following medication errors were evaluated: incomplete regimen; inappropriate/duplicative regimen; dosing, frequency, or quantity prescribed error; and initiation of nPEP without an HIV test. RESULTS: Two hundred six patients met criteria for inclusion. A higher proportion of patients experienced medication errors in the prestandardization group relative to the poststandardization group (46.5% vs 11.9%, P < 0.001). Fifty-five errors were observed in the prestandardization group, compared to 16 errors in the poststandardization group. The majority of errors in the prestandardization group were directly related to antiretroviral regimens, while the majority of errors in the poststandardization group involved initiation of nPEP without an HIV test. CONCLUSION: The standardization of the SA/nPEP process was associated with significantly lower medication error rates. Optimization of medication-use technology is an effective strategy in reducing medication errors.