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1.
Expert Rev Anti Infect Ther ; : 1-15, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38517686

RESUMO

INTRODUCTION: The HIV/AIDS epidemic has been one of the greatest challenges in global health, significantly affecting women of reproductive potential. Considerable advances in antiretroviral therapy for women living with HIV have contributed to improvements in quality of life, better reproductive and birth outcomes, and a reduced risk of perinatal transmission. AREAS COVERED: Despite the progress made, persistent challenges in access and adherence to antiretroviral drugs may limit their benefits for some women. More pharmacokinetic and safety studies in pregnant and lactating women are urgently needed, as are prospective surveillance systems to evaluate associations between fetal and infant antiretroviral exposures, drug-drug interactions, and pregnancy outcomes. EXPERT OPINION: Multipurpose technologies, such as combined HIV and other STI or unintended pregnancy prevention, and innovative delivery methods, such as the development of long-acting antiretrovirals, have the potential to reduce adherence challenges and enhance quality of life for women with HIV. Parallel advances in drug safety testing and surveillance are needed to ensure the health and safety of women with or at risk for HIV and children at risk for perinatal transmission.

2.
Antimicrob Agents Chemother ; : e0134423, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456707

RESUMO

Lenacapavir is a novel, first-in-class, multistage inhibitor of HIV-1 capsid function approved for the treatment of multidrug-resistant HIV-1 infection in combination with other antiretrovirals for heavily treatment-experienced people with HIV. Two Phase 1, open-label, parallel-group, single-dose studies assessed the pharmacokinetics (PK) of lenacapavir in participants with moderate hepatic impairment [Child-Pugh-Turcotte (CPT) Class B: score 7-9] or severe renal impairment [15 ≤ creatinine clearance (CLcr) ≤29 mL/min] to inform lenacapavir dosing in HIV-1-infected individuals with organ impairment. In both studies, a single oral dose of 300 mg lenacapavir was administered to participants with normal (n = 10) or impaired (n = 10) hepatic/renal function who were matched for age (±10 years), sex, and body mass index (±20%). Lenacapavir exposures [area under the plasma concentration-time curve from time 0 to infinity (AUCinf) and maximum concentration (Cmax)] were approximately 1.47- and 2.61-fold higher, respectively, in participants with moderate hepatic impairment compared to those with normal hepatic function, whereas lenacapavir AUCinf and Cmax were approximately 1.84- and 2.62-fold higher, respectively, in participants with severe renal impairment compared to those with normal renal function. Increased lenacapavir exposures with moderate hepatic or severe renal impairment were not considered clinically meaningful. Lenacapavir was considered generally safe and well tolerated in both studies. These results support the use of approved lenacapavir dosing regimen in patients with mild (CPT Class A: score 5-6) or moderate hepatic impairment as well as in patients with mild (60 ≤ CLcr ≤ 89 mL/min), moderate (30 ≤ CLcr ≤ 59 mL/min), and severe renal impairment.

3.
PLoS One ; 19(3): e0290810, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38446777

RESUMO

BACKGROUND: The human immunodeficiency virus (HIV) has caused a lot of havoc since the early 1970s, affecting 37.6 million people worldwide. The 90-90-90 treatment policy was adopted in Ghana in 2015 with the overall aim to end new infections by 2030, and to improve the life expectancy of HIV seropositive individuals. With the scale-up of Highly Active Antiretroviral Therapy, the lifespan of People Living with HIV (PLWH) on antiretrovirals (ARVs) is expected to improve. In rural districts in Ghana, little is known about the survival probabilities of PLWH on ARVs. Hence, this study was conducted to estimate the survival trends of PLWH on ARVs. METHODS: A retrospective evaluation of data gathered across ARV centres within Tatale and Zabzugu districts in Ghana from 2016 to 2020 among PLWH on ARVs. A total of 261 participants were recruited for the study. The data was analyzed using STATA software version 16.0. Lifetable analysis and Kaplan-Meier graph were used to assess the survival probabilities. "Stptime" per 1000 person-years and the competing risk regression were used to evaluate mortality rates and risk. RESULTS: The cumulative survival probability was 0.8847 (95% CI: 0.8334-0.9209). The overall mortality rate was 51.89 (95% CI: 36.89-72.97) per 1000 person-years. WHO stage III and IV [AHR: 4.25 (95%CI: 1.6-9.71) p = 0.001] as well as age group (50+ years) [AHR: 5.02 (95% CI: 1.78-14.13) p = 0.002] were associated with mortality. CONCLUSION: Survival probabilities were high among the population of PLWH in Tatale and Zabzugu with declining mortality rates. Clinicians should provide critical attention and care to patients at HIV WHO stages III and IV and intensify HIV screening at all entry points since early diagnosis is associated with high survival probabilities.


Assuntos
Antirretrovirais , Infecções por HIV , Humanos , Pessoa de Meia-Idade , Gana/epidemiologia , Estudos Retrospectivos , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia
4.
Front Public Health ; 12: 1336845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38500732

RESUMO

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Adulto , Homossexualidade Masculina , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Portugal/epidemiologia , Europa (Continente)
5.
BMC Infect Dis ; 24(1): 316, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486188

RESUMO

INTRODUCTION: In 2022, the WHO reported that 29.8 million people around the world were living with HIV (PLHIV) and receiving antiretroviral treatment (ART), including 25| 375 people in Gabon (54% of all those living with HIV in the country). The literature reports a frequency of therapeutic failure with first-line antiretrovirals (ARVs) of between 20% and 82%. Unfortunately, data relating to the failure of second-line ARVs are scarce in Gabon. This study aims to determine the profiles of HIV drug resistance mutations related to protease inhibitors in Gabon. METHODOLOGY: Plasma from 84 PLHIV receiving ARVs was collected from 2019 to 2021, followed by RNA extraction, amplification, and sequencing of the protease gene. ARV resistance profiles were generated using the Stanford interpretation algorithm version 8.9-1 ( https://hivdb.stanford.edu ) and statistical analyses were performed using EpiInfo software version 7.2.1.0 (CDC, USA). RESULTS: Of 84 HIV plasma samples collected from 45 men and 39 women, 342 mutations were detected. Of these, 43.3% (148/342) were associated with nucleoside reverse transcriptase inhibitors (NRTIs), 30.4% (104/342) with non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 26.3% (90/342) with protease inhibitors (PIs). Most NRTI mutations were associated with thymidine analogues (TAMs) (50.7%; 75/148), including T215F/V (14.9%; 22/148), D67DN/E/G/N/T (10.1%; 15/148), M41L (9.5%; 14/148), and K70E/KN/S/R (9.5%; 14/148). Resistance mutations related to non-TAM NRTIs (33.1%; 49/148) were M184V (29.1%; 43/148), and L74I/V (8.1%; 12/148). NNRTI mutations were predominantly K103N/S (32.7%; 34/104), V108I (10.6%; 11/104), A98G (10.6%; 11/104), and P225H (9.6%; 10/104). Minor mutations associated with PIs (60.0%; 54/90) were predominantly K20I (15.6%; 14/90) and L10F/I/V (14.5%; 13/90). The major mutations associated with PIs (40.0%; 36/90) were M41L (12.2%; 11/90), I84V (6.7%; 06/90), and V82A (6.7%; 06/90). The four most prescribed therapeutic regimens were TDF + 3TC + LPV/r (20.3%; 17/84), ABC + DDI + LPV/r (17.9%; 15/84), TDF + FTC + LPV/r (11.9%; 10/84), and ABC + 3TC + LPV/r (11.9%; 10/84). CONCLUSION: This study revealed that HIV drug resistance mutations are common in Gabon. The major mutations associated with PIs were M41L, I84V, and V82A. There is a need for access to new NRTIs, NNRTIs, and PIs for a better therapeutic management of PLHIV in Gabon.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Masculino , Humanos , Feminino , Inibidores da Transcriptase Reversa/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , Protease de HIV/genética , Gabão , HIV-1/genética , Antirretrovirais/uso terapêutico , Inibidores de Proteases/uso terapêutico , Mutação , Farmacorresistência Viral/genética
6.
Lancet HIV ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38513674

RESUMO

Collective antiretroviral protection is an evolving sexual health strategy in HIV prevention, used in particular by gay, bisexual, and other men who have sex with men. The strategy involves HIV-negative individuals who engage in condomless sexual activities but, instead of using pre-exposure prophylaxis (PrEP) themselves, choose partners who either have undetectable viral loads or are on PrEP. This biomedical-sorting practice, rooted in the scientific principles of undetectable equals untransmittable (U=U) and PrEP, relies on an indirect protection strategy. Collective antiretroviral protection allows for HIV-negative individuals not on PrEP to benefit from their partner's antiretroviral use, without directly consuming antiretrovirals themselves for HIV prevention, during condomless sex. Empirical research is needed to evaluate the public health implications of this emerging sexual health approach. Research and public health initiatives should adopt a non-stigmatising approach to individuals engaging in collective antiretroviral protection and look beyond individual behaviour to understand the broader community-level effects of this innovative HIV prevention strategy.

7.
BMC Infect Dis ; 24(1): 343, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515041

RESUMO

BACKGROUND: Dolutegravir is an integrase strand transfer inhibitor that has been recommended for use in first-line antiretroviral regimens by the World Health Organisation and is currently being rolled out globally. There has been safety concerns with dolutegravir which has caused concern about its use in the general population. Dolutegravir first-line regimens have been used in South Africa since early 2020. Therefore, the aim of the present study was to assess the efficacy, safety, and tolerability of first-line dolutegravir-based antiretrovirals amongst adults living with HIV in Durban, South Africa. METHODS: This was a mixed-methods study, which comprised a cross-sectional survey and longitudinal retrospective follow-up of medical records. The study was conducted between October 2020 and January 2022. Data were described using descriptive and summary statistics. Bivariate logistic regression was applied to socio-demographic and clinical variables and crude odds ratios with a 95% confidence interval was calculated. Pearson chi-square tests, paired sample T-tests, and cross-tabulations were performed on selected variables. RESULTS: A total of 461 participants were enrolled in the study. There was a significant change in immunological outcomes (p < 0.001) after dolutegravir initiation. Furthermore, an assessment of laboratory parameters showed that there was a significant decrease in cholesterol (p < 0.001) and increase in creatinine (p < 0.001) levels. Increased weight was shown by 60.7% of the participants but was not associated with age, gender, CD4 counts, and previous antiretroviral usage. The study found that 43.6% of the participants experienced at least one side-effect. A total of 21.6% and 23.2% of the participants experienced neuropsychiatric and central nervous system side-effects, respectively. In the bivariate analyses, only gender was shown to be associated with side-effects, and only 1.7% of the participants discontinued the study due to side-effects. CONCLUSION: Our results suggest that dolutegravir is effective, safe, and well tolerated in the study population.


Assuntos
Infecções por HIV , Inibidores de Integrase de HIV , Oxazinas , Piperazinas , Piridonas , Adulto , Humanos , Infecções por HIV/tratamento farmacológico , Estudos de Coortes , Estudos Retrospectivos , África do Sul , Estudos Transversais , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Antirretrovirais/uso terapêutico , Inibidores de Integrase de HIV/efeitos adversos
8.
Sci Adv ; 10(9): eadn0042, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38427738

RESUMO

People living with human immunodeficiency virus (HIV) receiving integrase strand transfer inhibitors (INSTIs) have been reported to experience virological failure in the absence of resistance mutations in integrase. To elucidate INSTI resistance mechanisms, we propagated HIV-1 in the presence of escalating concentrations of the INSTI dolutegravir. HIV-1 became resistant to dolutegravir by sequentially acquiring mutations in the envelope glycoprotein (Env) and the nucleocapsid protein. The selected Env mutations enhance the ability of the virus to spread via cell-cell transfer, thereby increasing the multiplicity of infection (MOI). While the selected Env mutations confer broad resistance to multiple classes of antiretrovirals, the fold resistance is ~2 logs higher for INSTIs than for other classes of drugs. We demonstrate that INSTIs are more readily overwhelmed by high MOI than other classes of antiretrovirals. Our findings advance the understanding of how HIV-1 can evolve resistance to antiretrovirals, including the potent INSTIs, in the absence of drug-target gene mutations.


Assuntos
Inibidores de Integrase de HIV , Integrase de HIV , HIV-1 , Humanos , Raltegravir Potássico/farmacologia , Inibidores de Integrase de HIV/farmacologia , HIV-1/genética , HIV-1/metabolismo , Integrase de HIV/genética , Integrase de HIV/metabolismo , Mutação
9.
Int J Antimicrob Agents ; : 107137, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38508536

RESUMO

BACKGROUND: Blood brain barrier impairment is frequent in people living with HIV (PLWH), affecting the penetration of target cells and antiretrovirals into the central nervous system, through transporters (e.g. ABCB1), leading to neuroinflammation. OBJECTIVES: The aim of this study was to identify variants of genes encoding transporters able to predict neuroinflammation biomarker levels. MATERIALS AND METHODS: Cerebrospinal fluid (CSF) and plasma samples were obtained from PLWH. CSF biomarkers were quantified by commercial assays. Genetic variants were evaluated through real-time polymerase chain reaction (PCR). RESULTS: 107 PLWH (163 samples) were included in the study: 79% were male, median age was 48.5 years, CD4% was 25%, HIV-associated neurolocognitive disorder (HAND) was observed in 17.8% of patients. ABCB1 2677G>T genetic variant showed a different allelic distribution according to the clinical group (p=0.026). In linear regression analyses, HIV-related central nervous system disorders, ABCG2 1194+928CC genotype, log viral load, CSAR, ß-1,42 levels and CSF proteins were retained in the final model as factors independently associated with CSF neopterin levels; CSF proteins and integrase inhibitors use were associated with CSF tau level in the multivariate model. Phospho-tau regression analysis reported ABCB1 2677GT/TT genotype and CSF proteins as predictors in the final model; gender and protease inhibitors, neopterin, ABCB1 2677 GT/ TT genotype resulted predictors in the multivariate regression for ß-1,42. CONCLUSIONS: For the first time, pharmacogenetic and clinical features were predictors of neuro-inflammation biomarkers.

10.
Open Forum Infect Dis ; 11(3): ofae110, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38486814

RESUMO

To gauge the safety and utility of extended tecovirimat/cidofovir for severe mpox, here we report our experience caring for 4 patients with mpox and advanced human immunodeficiency virus (HIV) at the Hospitals of the University of Pennsylvania during the 2022 global outbreak. Three patients had recurrent courses complicated by superinfections, coinfections and insufficient nutrition/housing, requiring extended tecovirimat (5-16 weeks) and cidofovir (1-12 doses) with probenecid and fluids. At follow-up, patients had undetectable HIV RNA on antiretrovirals, improved ulcers and stable renal function on antivirals. Serology guided cessation for one 7-month cidofovir course. Overall findings support a comprehensive approach of prolonged tecovirimat/cidofovir with antiretrovirals for severe mpox, while addressing social factors.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38530862

RESUMO

OBJECTIVE: Large inter-individual variability in the pharmacokinetics of rilpivirine and cabotegravir has been reported in the first weeks after starting long-acting injectable (LAI) therapy. Here, we assessed the distribution of rilpivirine and cabotegravir trough concentrations in people with HIV (PWH) on long-term LAI treatment. METHODS: Adult PWH treated with LAI for at least 32 weeks with an assessment of drug plasma trough concentrations were considered. The proportion of rilpivirine and cabotegravir plasma trough concentrations below four-times the protein-adjusted concentrations required for 90% inhibition of viral replication (4×PA-IC90) was estimated. RESULTS: Sixty-seven PWH were identified. LAI treatment duration was 216 ±â€Š80 weeks (range 32-320 weeks). Cabotegravir concentrations were associated with lower inter-individual variability compared with rilpivirine (45% versus 84%; P < 0.05). No differences were found in rilpivirine (160 ±â€Š118 versus 189 ±â€Š81 ng/mL; P = 0.430) and cabotegravir (1758 ±â€Š807 versus 1969 ±â€Š802 ng/mL; P = 0.416) trough concentrations in males (n = 55) versus females (n = 12). A non-significant trend for lower cabotegravir concentrations was found in PWH with a body mass index >30 kg/m2 (n = 9) versus non-obese participants (1916 ±â€Š905 versus 1606 ±â€Š576 ng/mL; P = 0.131). Three out of the 67 PWH had at least one drug concentration <4×PA-IC90: 100% of PWH had undetectable HIV viral load. CONCLUSIONS: At steady state, optimal systemic exposure of cabotegravir and rilpivirine was found in most PWH; cabotegravir trough concentrations were associated with lower inter-individual variability compared with rilpivirine. The study was not powered to assess the contribution of sex and/or body weight on LAI exposure due to the small number of females and obese PWH included.

12.
Infect Dis Ther ; 13(3): 609-617, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38372897

RESUMO

INTRODUCTION: The objective was to characterize real-world outcomes of drug-drug interactions (DDIs) between antiretrovirals (ARVs) and other drugs, including over-the-counter medications (OTC), and treatment outcomes in clinical practice. METHODS: www.clinicalcasesDDIs.com is an open-access website for healthcare providers to consult and briefly describe real-world clinical cases on DDI with ARVs. We reviewed all the clinical cases reported to the website between March 2019 and May 2023. RESULTS: A total of 139 cases were reported, mostly involving ritonavir or cobicistat (boosters; 74 cases), unboosted integrase inhibitors (InSTI; 29 cases), and non-nucleoside reverse transcriptase inhibitors (NNRTI; 23 cases). Central nervous system drugs (29 cases) and cardiovascular drugs (19 cases) were the most frequently described co-medications. Notably, OTC medications were implicated in 27 cases, including mineral supplements (11 cases), herbals (8 cases), weight loss drugs (4 cases), anabolic steroids (3 cases), and recreational drugs (1 case). OTC acted as the perpetrator drug in 21 cases, leading to loss of ARV efficacy in 17 instances (mineral supplements in 10 cases, weight loss drugs in 4 cases, herbals in 3 cases). Additionally, toxicity was reported in 4 out of 6 cases where OTC was considered the victim drug of the DDI (anabolic steroids in 3 cases, MDMA in 1 case). CONCLUSIONS: Frequent unwanted outcomes resulting from DDIs between ARVs and OTC medications underscore the importance of integrating non-prescription drugs into medication reconciliation. The real-world data available through www.clinicalcasesDDIs.com serves as a valuable resource for assessing the clinical relevance of DDIs.

13.
AIDS Patient Care STDS ; 38(2): 61-69, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38381949

RESUMO

Long-acting injectable antiretroviral therapy (LAI ART) has the potential to address adherence obstacles associated with daily oral ART, leading to enhanced treatment uptake, adherence, and viral suppression among people living with HIV (PLWH). Yet, its potential may be limited due to ongoing disparities in availability and accessibility. We need a better understanding of the organizational context surrounding the implementation of LAI ART, and to inform its widespread rollout, we conducted 38 in-depth interviews with medical and social service providers who offer HIV care at private and hospital-based clinics across six US cities. Our findings highlight real-world implementation barriers outside of clinical trial settings. Providers described ongoing and anticipated barriers across three stages of LAI ART implementation: (1) Patient enrollment (challenges registering patients and limited insurance coverage), (2) medication delivery (insufficient personnel and resources), and (3) leadership and management (lack of interprofessional coordination and a lack of programming guidelines). Providers described how these barriers would have a disproportionate impact on under-resourced clinics, potentially exacerbating existing disparities in LAI ART access and adherence. Our findings suggest strategies that clinic leadership, policymakers, and other stakeholders can pursue to promote rapid and equitable LAI ART implementation in clinics across the United States. Resource and staffing investments could support clinics to begin, sustain, and scale up LAI ART delivery; additionally, the establishment of guidelines and tools could facilitate wider adoption of LAI ART across clinical settings. These efforts are crucial to promote resourced, standardized, and equitable implementation of LAI ART and maximize its potential to help end the HIV epidemic.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Pesquisa Qualitativa , Inquéritos e Questionários , Estados Unidos/epidemiologia
14.
Br J Clin Pharmacol ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340019

RESUMO

AIMS: Long-acting cabotegravir and rilpivirine have been approved to manage HIV in adults, but data regarding safe use in pregnancy are limited. Physiologically-based pharmacokinetic (PBPK) modelling was used to simulate the approved dosing regimens in pregnancy and explore if Ctrough was maintained above cabotegravir and rilpivirine target concentrations (664 and 50 ng/mL, respectively). METHODS: An adult PBPK model was validated using clinical data of cabotegravir and rilpivirine in nonpregnant adults. This was modified by incorporating pregnancy-induced metabolic and physiological changes. The pregnancy PBPK model was validated with data on oral rilpivirine and raltegravir (UGT1A1 probe substrate) in pregnancy. Twelve weeks' disposition of monthly and bimonthly dosing of long-acting cabotegravir and rilpivirine was simulated at different trimesters and foetal exposure was also estimated. RESULTS: Predicted Ctrough at week 12 for monthly long-acting cabotegravir was above 664 ng/mL throughout pregnancy, but below the target in 0.5% of the pregnant population in the third trimester with bimonthly long-acting cabotegravir. Predicted Ctrough at week 12 for monthly and bimonthly long-acting rilpivirine was below 50 ng/mL in at least 40% and over 90% of the pregnant population, respectively, throughout pregnancy. Predicted medians (range) of cord-to-maternal blood ratios were 1.71 (range, 1.55-1.79) for cabotegravir and 0.88 (0.78-0.93) for rilpivirine between weeks 38 and 40. CONCLUSIONS: Model predictions suggest that monthly long-acting cabotegravir could maintain antiviral efficacy throughout pregnancy, but that bimonthly administration may require careful clinical evaluation. Both monthly and bimonthly long-acting rilpivirine may not adequately maintain antiviral efficacy in pregnancy.

15.
HIV AIDS (Auckl) ; 16: 9-16, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348377

RESUMO

Background: Oral mucosal lesions in human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) patients, posing a concern for healthcare professionals, impact their oral health-related quality of life (OHRQoL). This study aimed to evaluate the association between oral mucosal lesions and OHRQoL as measured by the validated Indonesian version of the oral health impact profile-14 questionnaire (OHIP-14) among people living with HIV/AIDS (PLWHA). Methods: A cross-sectional study was conducted at the Central Referral Hospital in West Java, Indonesia. The validity of OHIP-14 was evaluated in 30 PLWHA using inter-item corrected correlation, while reliability was assessed through Cronbach's alpha and kappa coefficient agreement. Subsequently, a consecutive sample of 110 PLWHA self-completed the validated Indonesian version of OHIP-14 and underwent an oral examination. The association between oral mucosal lesions and OHRQoL was analyzed using the chi-squared test. Results: The validity test of the OHIP-14 questionnaire produced a rcount > 0.189, meaning that all question items were valid and could be used to describe OHRQoL. The reliability test of the OHIP-14 questionnaire produced a Cronbach's alpha value of 0.960 (> 0.7), which means that overall, the OHIP-14 questionnaire is reliable and feasible to be used to assess OHRQoL. Among the 110 enrolled participants, 61.8% were female and 38.2% were male, with the mean age 23.5 years old, the majority of them (59.1%) had been taking antiretrovirals (ARV), and (81.5%) had good QoL. There was a statistically significant relationship between oral lesions and quality of life (p<0.05), particularly acute pseudomembranous candidiasis, angular cheilitis, recurrent intraoral herpes, and Stevens-Johnson syndrome. Conclusion: This study indicated a significant association between oral mucosal lesions and OHRQoL in PLWHA. The successfully validated Indonesian version of the OHIP-14 questionnaire serves as a reliable and effective tool for assessing OHRQoL among PLWHA.

16.
BMJ Open ; 14(2): e080606, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341206

RESUMO

PURPOSE: The PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance (4DR). Key research purposes include the evaluation of residual susceptibility to specific antiretrovirals and the validation of treatment and monitoring strategies in this population. PARTICIPANTS: The PRESTIGIO Registry collects annual plasma and peripheral blood mononuclear cell samples and demographic, clinical, virological, treatment and laboratory data from PLWH followed at 39 Italian clinical centres and characterised by intermediate-to-high genotypic resistance to ≥1 nucleoside reverse transcriptase inhibitors, ≥1 non-nucleoside reverse transcriptase inhibitors, ≥1 protease inhibitors, plus either intermediate-to-high genotypic resistance to ≥1 integrase strand transfer inhibitors (INSTIs) or history of virological failure to an INSTI-containing regimen. To date, 229 people have been recorded in the cohort. Most of the data are collected from the date of the first evidence of 4DR (baseline), with some prebaseline information obtained retrospectively. Samples are collected from the date of enrollment in the registry. FINDINGS TO DATE: The open-ended cohort has been used to assess (1) prognosis in terms of survival or development of AIDS-related or non-AIDS-related clinical events; (2) long-term efficacy and safety of different antiretroviral regimens and (3) virological and immunological factors predictive of clinical outcome and treatment efficacy, especially through analysis of plasma and cell samples. FUTURE PLANS: The registry can provide new knowledge on how to implement an integrated approach to study PLWH with documented resistance to the four main antiretroviral classes, a population with a limited number of individuals characterised by a high degree of frailty and complexity in therapeutic management. Given the scheduled annual updates of PLWH data, the researchers who collaborate in the registry can send study proposals at any time to the steering committee of the registry, which evaluates every 3 months whether the research studies can be conducted on data and biosamples from the registry and whether they are aimed at a better understanding of a specific health condition, the emergence of comorbidities or the effect of potential treatments or experimental drugs that may have an impact on disease progression and quality of life. Finally, the research studies should aim to be inclusive, innovative and in touch with the communities and society as a whole. TRIAL REGISTRATION NUMBER: NCT04098315.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Inibidores da Transcriptase Reversa/uso terapêutico , Inibidores da Transcriptase Reversa/farmacologia , HIV-1/genética , Inibidores de Integrase/farmacologia , Inibidores de Integrase/uso terapêutico , Peptídeo Hidrolases/farmacologia , Peptídeo Hidrolases/uso terapêutico , Leucócitos Mononucleares , Qualidade de Vida , Estudos Retrospectivos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Sistema de Registros , Itália , DNA Polimerase Dirigida por RNA/farmacologia , DNA Polimerase Dirigida por RNA/uso terapêutico
17.
Pharmaceutics ; 16(2)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38399255

RESUMO

Long-acting injectable cabotegravir is more effective than daily oral PrEP at preventing HIV transmission due to improved adherence, but requires bi-monthly large-volume intramuscular injections. Subcutaneous (SC) contraceptive implants can be formulated with antiretrovirals for extended-duration HIV PrEP. Islatravir (ISL) is a first-in-class, investigational antiretroviral with pharmacologic properties well-suited for implant delivery. We performed preclinical studies for the development of a reservoir-style, poly(ε-caprolactone) ISL-eluting implant by conducting a single-dose SC ISL dose-ranging pharmacokinetic (PK) study of 0.1, 0.3, and 1 mg/kg in adult Wistar rats. Non-compartmental analysis was conducted, and dose proportionality assessed for ISL plasma and intracellular islatravir-triphosphate (ISL-tp). Population PK models estimated ISL's unit impulse response to deconvolve ISL-implant in vivo absorption rate (mg/day) and cumulative mass (mg) from published rat plasma PK (n = 10). Drug release was interpreted using four kinetic models. Dose proportionality was affirmed for ISL and ISL-tp. A first-order, two-compartment model fitted the SC ISL bolus data. Mean (SD) absorption rate from 0 to 154 days was 0.072 ± 0.024 mg/day, and cumulative mass at 154 days was 8.67 ± 3.22 mg. ISL absorption was well-described by zero-order (r2 = 0.95) and Ritger-Peppas (r2 = 0.98). Our zero-order ISL-release poly(ε-caprolactone) implant is projected to achieve clinical PK above ISL-tp's PrEP efficacy threshold. Continued development for HIV PrEP applications is warranted.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38346426

RESUMO

BACKGROUND: Long-acting (LA) antiretrovirals may provide meaningful benefit to people who use drugs and people experiencing homelessness (PEH) who face disproportionate structural and psychosocial barriers in adhering to daily oral HIV antiretroviral therapy (ART) or pre-exposure prophylaxis (PrEP), but their use in these populations has not been studied. SETTING: The Maria X. Martinez Health Resource Center is a low-barrier (e.g., no appointment) community-based clinic serving San Francisco PEH. METHODS: A multidisciplinary care model with robust monitoring and outreach support was developed to provide LA-ART and LA-PrEP to eligible patients experiencing difficulties adhering to oral antiretrovirals. Feasibility was assessed by evaluating rates of HIV viremia and on-time injections among patients receiving LA antiretrovirals over the first 24 months of program implementation. RESULTS: Between November 2021 and November 2023, 33 patients initiated LA-ART or LA-PrEP (median age, 37 years; 27% transgender/non-binary; 73% non-White; 27% street homeless; 52% sheltered homeless; 30% with opioid use disorder; 82% with methamphetamine use disorder). Among 18 patients with HIV, 14 initiated LA-ART injections with detectable viremia (median CD4 count, 340 cells/mm3; mean log10 viral load, 3.53; standard deviation [SD], 1.62), eight had never previously been virally suppressed, and all but one achieved or maintained virologic suppression (mean, 9.67 months; SD, 8.30). Among 15 LA-PrEP patients, all remained HIV-negative (mean, 4.73 months; SD, 2.89). Of 224 injections administered total, 8% were delayed >7 days. DISCUSSION: The implementation of LA antiretrovirals is feasible in low-barrier, highly supportive clinical settings serving vulnerable PEH. Expansion of such programs will be critical to Ending the HIV Epidemic.

19.
Antivir Ther ; 29(1): 13596535241233128, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38375582

RESUMO

BACKGROUND: In British Columbia, antiretrovirals (ARVs) for HIV treatment (HIV-Tx) and pre-exposure prophylaxis (PrEP) are free-of-charge through publicly-funded Drug Treatment Programs (DTPs). When available, less costly generics are substituted for brand-name ARVs. We describe the incidence and type of product substitution issue (PSI) adverse drug reactions (ADRs) attributed to generic ARVs. METHODS: Cohorts included DTP clients ≥19 years who received generic ARVs for HIV-Tx (abacavir-lamivudine, emtricitabine-tenofovir DF, efavirenz-emtricitabine-tenofovir DF, atazanavir or darunavir between 01 Jun 2017 and 30 Jun 2022) or PrEP (emtricitabine-tenofovir DF, 01 Apr 2018 to 30 Jun 2022). Demographic, ARV and ADR data were extracted from DTP databases and summarized by descriptive statistics. PSI incidence was calculated for each product during the year following brand-to-generic and generic-to-generic transitions (first-year-post-rollout), and compared between generic versions using generalized estimating equations. For context, incidence of any ARV product-related ADR was calculated in the same 1-year periods. RESULTS: During first-year-post-rollout periods, 5339 HIV-Tx (83% male, median age 52 years) and 8095 PrEP (99% male, median 33 years) clients received generic ARVs, and reported 78 and 23 generic PSIs, respectively. PSI incidence was <1% for most generic ARVs, with mild-moderate symptoms including gastrointestinal upset, headache, dizziness, fatigue/malaise and skin rash. In HIV-Tx clients, the efavirenz-containing product had higher PSI incidence than other ARVs (2.2%, p = .004), due to more neuropsychiatric adverse reactions. Any ADR incidence was stable across measurement periods, and generic PSIs represented less than one third of all product-related ADRs. CONCLUSIONS: Generic substitution of antiretrovirals for HIV-Tx and PrEP was well tolerated, with ≤2% incidence of mild-moderate PSI ADRs.


Assuntos
Alcinos , Fármacos Anti-HIV , Benzoxazinas , Ciclopropanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Profilaxia Pré-Exposição , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , HIV , Colúmbia Britânica/epidemiologia , Substituição de Medicamentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Infecções por HIV/diagnóstico , Antirretrovirais/uso terapêutico , Tenofovir/efeitos adversos , Emtricitabina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos
20.
Clin Transl Sci ; 17(3): e13721, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38421210

RESUMO

Transgender women may have concerns of drug interactions between feminizing hormone therapy (FHT) and antiretrovirals, leading to nonadherence. This randomized, three-period crossover, open-label, phase I trial assessed the effects of doravirine (DOR) and tenofovir disoproxil fumarate (TDF) on the pharmacokinetics (PKs) of estradiol, spironolactone, and total testosterone and vice versa in healthy transgender women. Volunteers were randomized 1:1 into two sequences containing three treatment groups (DOR, lamivudine [3TC], and TDF alone; estradiol, spironolactone, and placebo; and DOR/3TC/TDF, estradiol, and spironolactone). Eight subjects enrolled in the study and six had completed all study periods. The geometric mean ratios for DOR area under the concentration-time curve from zero to last measured concentration (AUC0-last ), maximum concentration (Cmax ), and concentration at 24 h (C24 ) were similar. However, tenofovir (TFV) AUC0-last , Cmax , and C24 moderately increased by 14%-38%. Last, estradiol AUC0-last , Cmax , and C24 were increased by 10%-13%. Whereas most 90% confidence intervals did not meet the bioequivalence bounds of 80%-125%, the point estimates fell within the intervals. Log-transformed DOR, TFV, and estradiol PK parameters computed with and without co-administration were not statistically different (p > 0.05). There were no serious adverse events. There is not a clinically significant impact of FHT on DOR/TFV PKs. Similarly, there is no observed impact on estradiol PKs and total testosterone following use of DOR/3TC/TDF.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Piridonas , Pessoas Transgênero , Triazóis , Humanos , Feminino , Tenofovir/efeitos adversos , Estudos Cross-Over , Espironolactona , Lamivudina , Estradiol , Testosterona , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico
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