ABSTRACT
BACKGROUND: Human Immunodeficiency Virus (HIV) significantly affects adolescents globally, with the sub-Saharan Africa (SSA) reporting a high burden of the disease. HIV testing, treatment, and retention to care are low among adolescents. We conducted a mixed-method systematic review to assess anti-retroviral therapy (ART) adherence; barriers and facilitators to ART adherence and ART outcomes among adolescents living with HIV and on ART in sub-Saharan Africa. METHODS: We conducted searches in four scientific databases for studies conducted between 2010 and March 2022 to identify relevant primary studies. Studies were screened against inclusion criteria and assessed for quality, and data was extracted. Meta-analysis of rates and odd ratios was used to plot the quantitative studies and meta-synthesis summarized the evidence from qualitative studies. RESULTS: A total of 10 431 studies were identified and screened against the inclusion/ exclusion criteria. Sixty-six studies met the inclusion criteria (41 quantitative, 16 qualitative, and 9 mixed-methods study designs). Fifty-three thousand two hundred and seventeen (53 217) adolescents (52 319 in quantitative studies and 899 in qualitative studies) were included in the review. Thirteen support focused interventions for improved ART adherence were identified from quantitative studies. The plotted results from the meta-analysis found an ART adherence rate of 65% (95%CI 56-74), viral load suppression was 55% (95%CI 46-64), un-suppressed viral load rate of 41% (95%CI 32-50), and loss to follow up of 17% (95%CI 10-24) among adolescents. Meta-synthesis found six themes of barriers to ART (social, patient-based, economic, health system-based, therapy-based, and cultural barriers) in both the qualitative and quantitative studies, and three themes of facilitators to ART were also identified (social support, counselling, and ART education and secrecy or confidentiality) from qualitative studies. CONCLUSION: ART adherence remains low among adolescents in SSA despite multiple interventions implemented to improve ART adherence. The low adherence rate may hinder the attainment of the UNAIDS 2030 targets. Additionally, various barriers to ART adherence due to lack of support have been reported among this age group. However, interventions aimed at improving social support, educating, and counselling adolescents may improve and sustain ART adherence. TRIAL REGISTRATION: Systematic review registration: PROSPERO CRD42021284891.
Subject(s)
Anti-HIV Agents , HIV Infections , Humans , Adolescent , HIV , Medication Adherence , HIV Infections/drug therapy , HIV Infections/epidemiology , Anti-HIV Agents/therapeutic use , Africa South of the Sahara/epidemiology , Anti-Retroviral Agents/therapeutic useABSTRACT
A selection of drugs and vaccines newly available in Switzerland is reviewed. Shingrix: recombinant shingles vaccine recommended for all patients ≥65 years and some immunosuppressed patients. Nirmaltrevir/ritonavir: oral treatment of SARS-CoV-2 with a high potential of drug-drug interactions. Tixagevimab/cilgavimab: antibody combination for pre-exposure prophylaxis of SARS-CoV-2 in subjects without vaccine response or contraindication to vaccine. Cabotegravir/rilpivirine: 1st long-acting injectable treatment for HIV. Imvanex: monkeypox vaccine for subjects most at risk. Tezepelumab: first-in-class treatment for severe asthma. Eptinezumab: another anti-CGRP antibody for the prevention of migraine. Ponesimod: multiple sclerosis treatment with the advantage of a shorter half-life than fingolimod or ozanimod.
Une sélection de nouveaux médicaments et vaccins disponibles en Suisse est passée en revue. Shingrix : vaccin recombinant du zona recommandé chez les ≥ 65 ans et certains immunosupprimés. Nirmaltrevir/ritonavir : traitement oral du SARS-CoV-2 à haut potentiel d'interactions. Tixagévimab/cilgavimab : anticorps pour la prophylaxie préexposition du SARS-CoV-2 chez des sujets sans réponse vaccinale ou avec contre-indication au vaccin. Cabotégravir/rilpivirine : premier injectable à longue durée d'action contre le VIH. Imvanex : vaccin contre la variole du singe destiné aux sujets les plus à risque. Tézépélumab : premier traitement de sa classe pour l'asthme grave. Eptinézumab : un anticorps anti-CGRP de plus pour la prévention des migraines. Ponésimod : pour traiter la sclérose en plaques, avec l'avantage d'une plus courte demi-vie que le fingolimod ou l'ozanimod.
Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Vaccines , Humans , Rilpivirine/therapeutic use , Anti-HIV Agents/therapeutic use , HIV Infections/prevention & control , Pyridones/therapeutic use , COVID-19/prevention & control , SARS-CoV-2ABSTRACT
BACKGROUND: In the context of increasing injection-related HIV outbreaks across the United States, particularly among people who inject drugs (PWID) experiencing homelessness, there is an urgent need to expand access to pre-exposure prophylaxis (PrEP) for HIV prevention. Peer-based interventions for PrEP could be helpful for promoting PrEP uptake, yet the social experiences of using PrEP among PWID experiencing homelessness have not been thoroughly explored. METHODS: To better understand social experiences surrounding PrEP use among PWID experiencing homelessness, we conducted qualitative interviews from March-December 2020 with current and former PrEP patients of an innovative, low-threshold program implemented by Boston Health Care for the Homeless Program (BHCHP) in Boston, MA. Thematic analysis of coded interview data explored participants' perspectives and experiences with PrEP disclosure and discussions within their social networks. RESULTS: Among interviews with 21 participants, we identified the following four interrelated aspects of their social experiences using PrEP: (1) participants' were aware of increasing HIV transmission within their social networks, which motivated their PrEP use and disclosure; (2) participants generally avoided disclosing their PrEP use within public spaces or casual conversations; (3) participants expressed greater willingness to discuss PrEP with their close social contacts; and (4) some participants self-identified as leaders or expressed interest in leading the dissemination of PrEP information within their social networks. CONCLUSIONS: Findings highlight the significance of PrEP disclosure and discussions within the social networks of PWID experiencing homelessness, suggesting a need for continued social network and intervention research-particularly to establish the feasibility and acceptability of peer-based interventions for promoting PrEP-with this marginalized population.
Subject(s)
Anti-HIV Agents , Drug Users , HIV Infections , Ill-Housed Persons , Pre-Exposure Prophylaxis , Substance Abuse, Intravenous , Humans , United States , Substance Abuse, Intravenous/epidemiology , Anti-HIV Agents/therapeutic use , HIV Infections/epidemiology , Disclosure , Social NetworkingABSTRACT
This Medical News Q&A discusses research highlights from the recent Conference on Retroviruses and Opportunistic Infections.
Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , HIV Infections , Post-Exposure Prophylaxis , Protease Inhibitors , Humans , Anti-HIV Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19 , Goals , HIV Infections/prevention & control , HIV Infections/transmission , Opportunistic Infections , Protease Inhibitors/therapeutic use , Retroviridae , Sexually Transmitted Diseases/prevention & control , Post-Exposure Prophylaxis/methods , COVID-19 Drug Treatment/methods , Patient-Centered CareABSTRACT
BACKGROUND: Long-term engagement in HIV care is essential to achieving and maintaining viral suppression. Adolescents living with HIV (ALHIV) experience many barriers to remaining engaged in care and treatment programs. Higher attrition among adolescents compared to adults remains a huge concern due to unique psychosocial and health systems challenges adolescents face, and recently the COVID-19 pandemic effects. We report on determinants and rates of retention in care in adolescents aged 10-19 years enrolled on antiretroviral therapy (ART) in Windhoek, Namibia. METHODS: A retrospective cohort analysis of routine clinical data of 695 adolescents aged 10-19 years enrolled for ART at 13 Windhoek district public healthcare facilities, between January 2019 and December 2021 was conducted. Anonymized patient data were extracted from an electronic database and registers. Bivariate and Cox proportional hazards analysis were performed to determine factors associated with retention in care among ALHIV at 6, 12, 18, 24 and 36 months. Retention in care trends were also described using the Kaplan-Meier survival analysis. RESULTS: The retention in care rates at 6, 12, 18, 24 and 36 months were 97.7%, 94.1%, 92.4%, 90.2%, and 84.6%, respectively. Our study population had predominantly treatment-experienced adolescents, who initiated ART between birth and 9 years (73.5%), were on treatment for > 24 months (85.0%), and on first-line ART (93.1%). After controlling for confounders, the risk of dropping out of care was increased for older adolescents aged 15-19 years (aHR = 1.964, 95% CI 1.033-3.735); adolescents on switched ART regimens (Second line + Third line regimen) (aHR = 4.024, 95% CI 2.021-8.012); adolescents who initiated ART at 15-19 years (aHR = 2.179, 95%CI 1.100-4.316); and male adolescents receiving ART at a PHC clinic (aHR = 4.322, 1.332-14.024). Conversely, the risk of ALHIV dropping out of care decreased for adolescents whose TB screen results were negative (aHR = 0.215, 95% CI 0.095-0.489). CONCLUSION: Retention in care rates among ALHIV in Windhoek do not meet the UNAIDS revised target of 95%. Gender-specific interventions are needed to keep male and older adolescents motivated and engaged in long-term care, and to promote adherence amongst those adolescents who were initiated on ART in late adolescence (15-19 years).
Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Adult , Humans , Male , Adolescent , Retrospective Studies , Anti-HIV Agents/therapeutic use , Namibia/epidemiology , Pandemics , COVID-19/epidemiology , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/psychology , Cohort StudiesABSTRACT
In 2018, the pre-exposure prophylaxis (PrEP) program was initiated in British Columbia (BC), Canada, providing PrEP at no cost to qualifying residents. This observational study discussed the steps to develop key evidence-based monitoring indicators and their calculation using real-time data. The indicators were conceptualized, developed, assessed and approved by the Technical Monitoring Committee of representatives from five health authority regions in BC, the BC Ministry of Health, the BC Centre for Disease Control, and the BC Centre for Excellence in HIV/AIDS. Indicator development followed the steps adopted from the United States Centers for Disease Control and Prevention framework for program evaluation in public health. The assessment involved eight selection criteria: data quality, indicator validity, existing scientific evidence, indicator informativeness, indicator computing feasibility, clients' confidentiality maintenance capacity, indicator accuracy, and administrative considerations. Clients' data from the provincial-wide PrEP program (January 2018-December 2020) shows the indicators' calculation. The finalized 14 indicators included gender, age, health authority, new clients enrolled by provider type and by the health authority, new clients dispensed PrEP, clients per provider, key qualifying HIV risk factor(s), client status, PrEP usage type, PrEP quantity dispensed, syphilis and HIV testing and incident cases, and adverse drug reaction events. Cumulative clients' data (n = 6966; 99% cis-gender males) identified an increased new client enrollment and an unexpected drop during the COVID-19 pandemic. About 80% dispensed PrEP from the Vancouver Coastal health authority. The HIV incidence risk index for men who have sex with men score ≥10 was the most common qualifying risk factor. The framework we developed integrating indicators was applied to monitor our PrEP program, which could help reduce the public health impact of HIV.
Subject(s)
Acquired Immunodeficiency Syndrome , Anti-HIV Agents , COVID-19 , HIV Infections , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Male , Humans , British Columbia/epidemiology , Homosexuality, Male , Acquired Immunodeficiency Syndrome/epidemiology , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV Infections/drug therapy , Pandemics , COVID-19/epidemiology , Anti-HIV Agents/therapeutic useABSTRACT
INTRODUCTION: In 2016, South Africa (SA) initiated a national programme to scale-up pre-exposure prophylaxis (PrEP) among female sex workers (FSWs), with â¼20,000 PrEP initiations among FSWs (â¼14% of FSW) by 2020. We evaluated the impact and cost-effectiveness of this programme, including future scale-up scenarios and the potential detrimental impact of the COVID-19 pandemic. METHODS: A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self-reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down-adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0-70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2-87.6% efficacy). FSWs can transition between adherence levels, with lower loss-to-follow-up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40-0.85; TAPS data). The model was calibrated to monthly data on the national scale-up of PrEP among FSWs over 2016-2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016-2020) and the future impact (2021-2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost-effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016-2040) of the current PrEP provision. RESULTS: Calibrated to national data, model projections suggest that 2.1% of HIV-negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35-0.57%) of HIV infections among FSWs over 2016-2020 or 605 (444-840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99-23.29). PrEP is cost-saving, with $1.42 (1.03-1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572-9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7-11.6%) and impact increases 4.3 times with 24,114 (15,308-38,107) infections averted by 2040. CONCLUSIONS: Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services.
Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Pre-Exposure Prophylaxis , Sex Workers , Humans , Female , HIV Infections/drug therapy , South Africa , Cost-Benefit Analysis , Pandemics , Anti-HIV Agents/therapeutic useABSTRACT
Aim of this study is to assess the impact of doravirine (DOR)-based regimens on cardiovascular risk in treatment-experienced people living with HIV (PLWHIV). We retrospectively analyzed a cohort of 40 treatment-experienced PLWHIV switching to a DOR-based three-drug regimen, evaluating 10-year risk of manifesting clinical cardiovascular diseases (CD) through the Framingham Risk Score at baseline, 12, and 24 weeks of follow-up. At baseline, median predicted 10-year risk of cardiovascular disease (10Y-CD) was 8.0% (interquartile range 4.0-13.0). After 12 weeks, we observed a significant reduction in 10Y-CD (mean decrease -2.21, p = .012); similarly, we observed a nonsignificant reduction at week 24 (p = .336). Regarding metabolic parameters, after 24 weeks we observed a significant reduction in total cholesterol (median change -8.8 mg/dL, p = .018), low-density lipoprotein cholesterol (median -9.5 mg/dL, p = .007), and triglycerides (median -19.8 mg/dL, p < .001). Our results show a favorable metabolic impact of DOR-based regimens along with a promising reduction in 10-year risk of cardiovascular disease.
Subject(s)
Anti-HIV Agents , Cardiovascular Diseases , HIV Infections , HIV-1 , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/drug therapy , HIV Infections/complications , HIV Infections/drug therapy , Retrospective Studies , Preliminary Data , Cholesterol, LDL , Anti-HIV Agents/therapeutic useABSTRACT
The paper identifies common barriers and challenges to Pre-Exposure Prophylaxis (PrEP) uptake and offers considerations for state and local public health departments to address barriers and retool infrastructure to increase access to PrEP to new users. Authors identify synergistic opportunities with federal agencies and funders to advance PrEP-related HIV prevention efforts, that prioritize strategies and investments to provide PrEP to people who could benefit from the intervention but are unaware of PrEP or struggle to access it. Barriers discussed and examined include financing strategies to reduce financial burden of PrEP medication, expanding PrEP access and outreach beyond clinical settings, and increasing the network and reach of the provider community to serve people we oppress through policy choices and discourses of racial and socioeconomic inferiority.
Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Anti-HIV Agents/therapeutic use , HIV Infections/prevention & control , Humans , Public HealthSubject(s)
COVID-19/epidemiology , Epidemiology/organization & administration , Pandemics , SARS-CoV-2 , Anti-HIV Agents/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/therapy , Clinical Trials as Topic , Combined Modality Therapy , Epidemiologic Research Design , Epidemiology/trends , Humans , Hydroxychloroquine/therapeutic use , Italy/epidemiology , United States/epidemiology , COVID-19 Drug TreatmentABSTRACT
This article describes the processes of transforming an in-person group-based intervention to promote uptake of PrEP among young woman in South Africa to an online interactive "workshop" during the COVID-19 pandemic. Beginning in person and continuing virtually, we used a step-by-step participatory approach with multiple stakeholder groups to develop nine activities to increase knowledge about, as well as motivation and intention to take PrEP, and to address gender-based barriers to PrEP. Activities were informed by our theoretical framework and formative work with young women ages 18-25. We demonstrate how we developed a gender-enhanced online PrEP workshop that was interactive, group-based, and in accordance with elements of established successful intervention design; why WhatsApp emerged as the most accessible application for the young women in our workshop; and how an intervention with a hybrid approach-alternating between chat box and live sessions-combined with verbal, written, and emoji-based communication enabled interaction among participants.
Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Pre-Exposure Prophylaxis , Humans , Female , Adolescent , Young Adult , Adult , HIV Infections/prevention & control , South Africa , Motivation , Anti-HIV Agents/therapeutic use , Pandemics , COVID-19/prevention & controlABSTRACT
INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) is an essential prevention strategy being scaled up for priority populations in Kenya, including for HIV serodiscordant couples. The COVID-19 pandemic posed challenges to PrEP rollout. We conducted a qualitative study of PrEP providers to understand how clinics adjusted PrEP delivery during the COVID-19 pandemic. METHODS: Since 2017, the Partners Scale-Up Project has integrated PrEP into 25 HIV clinics in Central and Western Kenya. We conducted qualitative interviews with 40 purposively sampled clinic personnel. We interviewed personnel once during the first pandemic wave (May-Aug 2020) and again after some decline in COVID-19 rates (Nov-Jan 2021). We analysed data using inductive memo-writing and summarized data by themes along the PrEP delivery cascade, guided by the Framework for Reporting Adaptation and Modifications (FRAME). RESULTS: We interviewed 27 clinical officers, five nurses, four health records and information officers, and four counsellors from Central (n = 20) and Western (n = 20) Kenya. About half (n = 19) were female, with a median age of 32 (IQR: 29-34) and 2.3 years of experience delivering PrEP (IQR: 2-3). All participants reported clinic changes in PrEP demand creation and service delivery during the pandemic. Modifications occurred during PrEP implementation and sustainment phases, were partly reactive to the pandemic and also facilitated by interim Ministry of Health guidance on PrEP delivery during COVID, and were made by PrEP delivery teams, clients and clinic managers. Commonly reported modifications included dispensing multiple-month PrEP refills, intensifying phone-based client engagement and collaborating with other HIV clinics to ensure that clients with prolonged stays in other regions could continue to access PrEP. Some clinics also adopted practices to streamline visits, such as within clinical-room PrEP dispensing, pre-packing PrEP and task-shifting. Most providers liked these changes and hoped they would continue after the pandemic subsides. CONCLUSIONS: COVID-19 served as a catalyst for PrEP delivery innovations in Kenya. HIV clinics successfully and rapidly adapted their PrEP demand creation, refill and retention strategies to promote PrEP uptake and effective use. These modified implementation strategies highlight opportunities to streamline the delivery of PrEP, as well as other HIV and chronic care services, and strengthen engagement with populations post-pandemic.
Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Pre-Exposure Prophylaxis , Humans , Female , Adult , Male , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV Infections/drug therapy , Pre-Exposure Prophylaxis/methods , Pandemics/prevention & control , Kenya/epidemiology , COVID-19/prevention & control , Anti-HIV Agents/therapeutic useABSTRACT
BACKGROUND: Preventing HIV transmission among people who inject drugs (PWID) is a key element of the US Ending the HIV Epidemic strategy and includes both pre-exposure prophylaxis (PrEP) and medications for opioid use disorder (MOUD). While both lead to decreases in HIV transmission, MOUD has other social and health benefits; meanwhile, PrEP has additional HIV prevention advantages from sexual risk and the injection of stimulants. However, these medications are often prescribed in different settings and require multiple visits before initiation. Strategies to integrate these services (i.e., co-prescription) and offer same-day prescriptions may reduce demands on patients who could benefit from them. METHODS: Nominal group technique, a consensus method that rapidly generates and ranks responses, was used to ascertain barriers and solutions for same-day delivery of PrEP and MOUD as an integrated approach among PWID (n = 14) and clinical (n = 9) stakeholders. The qualitative portion of the discussion generated themes for analysis, and the ranks of the proposed barriers and solutions to the program are presented. RESULTS: The top three barriers among PWID to getting a same-day prescription for both PrEP and MOUD were (1) instability of insurance (e.g., insurance lapses); (2) access to a local prescriber; and (3) client-level implementation factors, such as lack of personal motivation.â¯Among clinical stakeholders, the three greatest challenges were (1) time constraints on providers; (2) logistics (e.g., coordination between providers and labs); and (3) availability of providers who can prescribe both medications.â¯Potential solutions identified by both stakeholders included pharmacy delivery of the medications, coordinated care between providers and health care systems (e.g., case management), and efficiencies in clinical care (e.g., clinical checklists), among others. CONCLUSIONS: Implementing and sustaining a combined PrEP and MOUD strategy will require co-training providers on both medications while creating efficiencies in systems of care and innovations that encourage and retain PWID in care. Pilot testing the co-prescribing of PrEP and MOUD with quality performance improvement is a step toward new practice models.
Subject(s)
Anti-HIV Agents , HIV Infections , Opioid-Related Disorders , Pre-Exposure Prophylaxis , Substance Abuse, Intravenous , Humans , Anti-HIV Agents/therapeutic use , Substance Abuse, Intravenous/epidemiology , HIV Infections/epidemiology , Opioid-Related Disorders/complications , Opioid-Related Disorders/drug therapyABSTRACT
The presence of neutralizing antibodies (NAbs) is a major correlate of protection for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thus, different in vitro pseudoviruses-based assays have been described to detect NAbs against SARS-CoV-2. However, the determination of NAbs against SARS-CoV-2 in people living with HIV (PLWH) through HIV-based pseudoparticles could be influenced by cross-neutralization activity or treatment, impeding accurate titration of NAbs. Two assays were compared using replication-defective HIV or VSV-based particles pseudotyped with SARS-CoV-2 spike to measure NAbs in COVID-19-recovered and COVID-19-naïve PLWH. The assay based on HIV-pseudoparticles displayed neutralization activity in all COVID-19-recovered PLWH with a median neutralizing titer 50 (NT50) of 1417.0 (interquartile range [IQR]: 450.3-3284.0), but also in 67% of COVID-19-naïve PLWH (NT50: 631.5, IQR: 16.0-1535.0). Regarding VSV-pseudoparticles system, no neutralization was observed in COVID-19-naïve PLWH as expected, whereas in comparison with HIV-pseudoparticles assay lower neutralization titers were measured in 75% COVID-19-recovered PLWH (NT50: 100.5; IQR: 20.5-1353.0). Treatment with integrase inhibitors was associated with inaccurate increase in neutralization titers when HIV-based pseudoparticles were used. IgG purification and consequent elimination of drugs from samples avoided the interference with retroviral cycle and corrected the lack of specificity observed in HIV-pseudotyped assay. This study shows methodological alternatives based on pseudoviruses systems to determine specific SARS-CoV-2 neutralization titers in PLWH.
Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Humans , SARS-CoV-2 , COVID-19/diagnosis , Antibodies, Viral , Integrase Inhibitors , Spike Glycoprotein, Coronavirus , Antibodies, NeutralizingABSTRACT
This study presents proof of concept for designing a novel HIV-1 covalent inhibitor targeting the highly conserved Tyr318 in the HIV-1 non-nucleoside reverse transcriptase inhibitors binding pocket to improve the drug resistance profiles. The target inhibitor ZA-2 with a fluorosulfate warhead in the structure was found to be a potent inhibitor (EC50 = 11-246 nM) against HIV-1 IIIB and a panel of NNRTIs-resistant strains, being far superior to those of NVP and EFV. Moreover, ZA-2 was demonstrated with lower cytotoxicity (CC50 = 125 µM). In the reverse transcriptase inhibitory assay, ZA-2 exhibited an IC50 value of 0.057 µM with the ELISA method, and the MALDI-TOF MS data demonstrated the covalent binding mode of ZA-2 with the enzyme. Additionally, the molecular simulations have also demonstrated that compounds can form covalent binding to the Tyr318.
Subject(s)
Anti-HIV Agents , HIV-1 , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/chemistry , HIV-1/metabolism , Anti-HIV Agents/pharmacology , Anti-HIV Agents/chemistry , HIV Reverse Transcriptase/metabolism , Drug Design , Structure-Activity RelationshipABSTRACT
Menopause is a high-risk period for osteoporosis, which may be exacerbated by HIV and/or antiretroviral therapy (ART). Our goal was to study the impact of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) on bone mineral density (BMD) in peri- and early postmenopausal women living with HIV. This is a randomized international multicenter study of an early versus delayed (48-week) switch. BMD was measured by dual energy X-ray absorptiometry scan. Thirty-four women were enrolled: 19 in the immediate and 15 in the delayed switch arm from September 2017 to April 2019; 30 completed the 96-week protocol. The study closed for futility during the COVID-19 pandemic. The median (intraquartile range [IQR]) age was 51 years (47, 53), with a median (IQR) of 16.5 years (14, 23) since HIV diagnosis, median (IQR) 14 years (11, 20) of ART, and mean 8.6 years TDF. At enrollment, TDF was used in combination with a boosted protease inhibitor (n = 7), a non-nucleoside reverse transcriptase inhibitor (n = 13), an integrase inhibitor (n = 11), or more than one ART class (n = 3). The median (95% confidence interval [CI]) percentage change in BMD at the lumbar spine from 0 to 48 weeks in the immediate switch group was 1.97% (-1.15 to 5.49) compared with a median (95% CI) decrease of 2.32% (-5.11 to 0.19) in the delayed arm. The median (95% CI) percentage change in BMD from 0 to 96 weeks was 2.33% (0-4.51) in the immediate arm compared with 0.70% (-3.19 to 2.47) in the delayed arm. We demonstrated a trend to increased BMD at the lumbar spine after a switch from TDF to TAF in peri- and early postmenopausal women living with HIV. Clinical Trials.gov: NCT02815566.
Subject(s)
Anti-HIV Agents , COVID-19 , HIV Infections , Humans , Female , Middle Aged , HIV Infections/complications , HIV Infections/drug therapy , Bone Density , Anti-HIV Agents/adverse effects , Tenofovir/adverse effects , Pandemics , Perimenopause , Adenine/pharmacology , AgingABSTRACT
ß-Nucleosides and their analogs are dominant clinically-used antiviral and antitumor drugs. α-Nucleosides, the anomers of ß-nucleosides, exist in nature and have significant potential as drugs or drug carriers. Currently, the most widely used methods for synthesizing ß- and α-nucleosides are via N-glycosylation and pentose aminooxazoline, respectively. However, the stereoselectivities of both methods highly depend on the assisting group at the C2' position. Herein, we report an additive-controlled stereodivergent iodocyclization method for the selective synthesis of α- or ß-nucleosides. The stereoselectivity at the anomeric carbon is controlled by the additive (NaI for ß-nucleosides; PPh3S for α-nucleosides). A series of ß- and α-nucleosides are prepared in high yields (up to 95%) and stereoselectivities (ß:α up to 66:1, α:ß up to 70:1). Notably, the introduced iodine at the C2' position of the nucleoside is readily functionalized, leading to multiple structurally diverse nucleoside analogs, including stavudine, an FDA-approved anti-HIV agent, and molnupiravir, an FDA-approved anti-SARS-CoV-2 agent.
Subject(s)
Anti-HIV Agents , COVID-19 , Humans , Nucleosides , Stereoisomerism , Antiviral Agents/pharmacologySubject(s)
Anti-Retroviral Agents , HIV Infections , Prisoners , Humans , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , Anti-Retroviral Agents/administration & dosage , Anti-Retroviral Agents/therapeutic use , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/therapeutic use , HIV Infections/drug therapy , InjectionsABSTRACT
OBJECTIVES: In January 2021, 56 Dean Street, a London sexual health clinic, changed clinic policy so that all those attending for post-exposure prophylaxis (PEP) were offered quick-start opt-out pre-exposure prophylaxis (PrEP) following completion of the 28-day PEP course. We assessed the uptake of this quick-start PrEP in service users attending for PEP. METHODS: We undertook a case note review of those who received PEP during the 2-week period from 17 February to 1 March 2021, assessing the data and comparing them to those from the same period in 2020 (15 February-28 February 2020) before quick-start opt-out PrEP was introduced. RESULTS: The number of service users receiving PEP was 82 in 2020 and 42 in 2021, of which an unmet PrEP need was demonstrated in 81.7% (67/82) in 2020 and 78.6% (33/42) in 2021 (p = 0.8106). Of those with an unmet need, a higher proportion (97.0% [32/33]) were offered PrEP in 2021 following the introduction of opt-out PrEP compared with the 85.1% (57/67) in 2020 (p = 0.0953). Of those eligible for PrEP who were offered it during their PEP consultation, 53.1% (17/32) in 2021 were dispensed PrEP compared with 17.5% (10/57) in 2020 (p = 0.0007). CONCLUSION: Since the introduction of quick-start opt-out PrEP, uptake in eligible candidates increased from 17.5% to 53.1%. This suggests that this strategy was acceptable to service users.