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1.
AIDS Patient Care STDS ; 38(3): 115-122, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38471090

RESUMO

Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first complete injectable antiretroviral for patients living with HIV. To facilitate patient access to long-acting injectable treatment, a system-wide, pharmacist-led, LA-CAB/RPV transition program was developed at four health system-based New York clinics. Provider referrals were received across four clinics between January 22nd, 2021, and December 31st, 2022. All referrals were evaluated by a pharmacist for clinical eligibility and medication access. The primary outcome was the treatment retention rate defined as the percentage of patients who remained on LA-CAB/RPV at 3 months post-transition. A total of 171 referrals were received, with 73 patients (43%) initiating LA-CAB/RPV. Baseline demographics included a median age of 38 years, 81% patients were male, 41% were African American, and 49% had commercial insurance coverage. The treatment retention rate was 90% at 3 months post-transition. By the end of the study period, 84% of patients who transitioned remained on LA-CAB/RPV. Treatment was discontinued due to reasons such as viral breakthrough (4%), emergence of mutations (4%), and intolerable side effects (4%). Injection site reactions were commonly reported (51%), but only resulting in treatment discontinuation for one patient. A pharmacist-led program can transition a diverse population of patients living with HIV to LA-CAB/RPV. Results from this study further add to clinical experiences with LA-CAB/RPV, demonstrating real-world treatment retention despite more frequent clinic visits for patients.


Assuntos
Fármacos Anti-HIV , Dicetopiperazinas , Infecções por HIV , Soropositividade para HIV , HIV-1 , Piridonas , Humanos , Masculino , Adulto , Feminino , Rilpivirina/efeitos adversos , HIV-1/genética , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , New York , Farmacêuticos , Antirretrovirais/uso terapêutico , Soropositividade para HIV/tratamento farmacológico
2.
Lancet HIV ; 11(3): e156-e166, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38417976

RESUMO

BACKGROUND: The combination of dolutegravir plus rilpivirine has been studied in people with virologically suppressed HIV with no previous history of treatment failure or resistance. We investigated the potential to maintain viral suppression with dolutegravir plus rilpivirine in people with Lys103Asn mutations whose HIV was previously managed with other treatment regimens. METHODS: In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38. FINDINGS: Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference -0·5, -11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups. INTERPRETATION: Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine. FUNDING: ViiV Healthcare.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Oxazinas , Piperazinas , Piridonas , Adulto , Humanos , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Projetos Piloto , Resultado do Tratamento , Rilpivirina/efeitos adversos , Antirretrovirais/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Soropositividade para HIV/tratamento farmacológico , RNA/uso terapêutico , Mutação , Carga Viral , Fármacos Anti-HIV/efeitos adversos
4.
AIDS ; 38(3): 430-434, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300162

RESUMO

Injectable cabotegravir and rilpivirine long-acting therapy is a revolutionary new antiretroviral treatment (ART) option for HIV infection in virologically suppressed adults on a stable ART. The aim of this study from SCOLTA multicenter observational prospective database is to describe the first people living with HIV (PWH) who started this regimen in Italy, assessing adherence to eligibility criteria, describing clinical-epidemiological characteristics compared to registration trials-population and describe early treatment-discontinuations.


Assuntos
Dicetopiperazinas , Infecções por HIV , Piridonas , Rilpivirina , Adulto , Humanos , Infecções por HIV/tratamento farmacológico , Antirretrovirais , Itália
5.
Br J Clin Pharmacol ; 90(3): 895-899, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38163749

RESUMO

Antiretroviral therapy administration is challenging in patients with HIV requiring enteral nutrition. There are limited pharmacokinetic data available regarding the absorption of crushed rilpivirine (RPV) and its impact on drug bioavailability, plasma concentrations and, consequently, the efficacy of treatment. We present the case of a 60-year-old woman with HIV diagnosed with squamous cell carcinoma who needed enteral administration of antiretroviral therapy following the insertion of a gastrotomy tube in September 2018. Initially, the patient was treated with a daily dose of RPV 25 mg, dolutegravir 50 mg and emtricitabine 200 mg. The treatment was later intensified with darunavir boosted with ritonavir. RPV and dolutegravir were crushed, dissolved in water and administered via a percutaneous endoscopic gastrostomy tube. Therapeutic drug and viral load monitoring determined the adequacy of enteral antiretroviral dosing. RPV plasma concentrations remained within the expected therapeutic range of 43-117 ng/mL, with only 1 below the currently used 50 ng/mL efficacy threshold. After the treatment intensification with darunavir boosted with ritonavir, the patient achieved an undetectable viral load. While we observed satisfactory RPV plasma concentrations, it is essential to maintain strict monitoring of administration method, plasma concentrations and virological responses when initiating treatment with crushed RPV. Hence, additional pharmacokinetic data are necessary to ensure the effective enteral administration of RPV and to establish the best antiretroviral dosing regimens.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Feminino , Humanos , Pessoa de Meia-Idade , Rilpivirina/uso terapêutico , Ritonavir , Darunavir/farmacologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Antirretrovirais/uso terapêutico , Carga Viral
6.
AIDS Res Ther ; 21(1): 1, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38173008

RESUMO

We assessed whether the impact of cabotegravir plus rilpivirine on inflammation reduction differs from that of oral antiretrovirals, using real-world data. Inflammatory biomarkers and lipid profiles were followed from baseline to 8 months after switching. Seventy-eight participants were analyzed. The CD4/CD8 ratio and C-reactive protein did not change. There were transient decreases in CD8 and CD4 counts in the group that switched from the dolutegravir-based regimen, but not in the tenofovir alafenamide-based regimen group. High-density lipoprotein (HDL) cholesterol increased, resulting in a decrease in the total-cholesterol to HDL cholesterol ratio, whereas there was no significant change in low-density lipoprotein cholesterol.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Rilpivirina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Antirretrovirais/uso terapêutico , Biomarcadores , Colesterol/uso terapêutico , Lipídeos , Fármacos Anti-HIV/uso terapêutico
7.
J Control Release ; 366: 548-566, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38211640

RESUMO

The lymphatic system possesses the main viral replication sites in the body following viral infection. Unfortunately, current antiretroviral agents penetrate the lymph nodes insufficiently when administered orally and, therefore, cannot access the lymphatic system sufficiently to interrupt this viral replication. For this reason, novel drug delivery systems aimed at enhancing the lymphatic uptake of antiretroviral drugs are highly desirable. Dissolving polymeric microarray patches (MAPs) may help to target the lymph intradermally. MAPs are intradermal drug delivery systems used to deliver many types of compounds. The present work describes a novel work investigating the lymphatic uptake of two anti-HIV drugs: cabotegravir (CAB) and rilpivirine (RPV) when delivered intradermally using dissolving MAPs containing nanocrystals of both drugs. Maps were formulated using NCs obtained by solvent-free milling technique. The polymers used to prepare the NCs of both drugs were PVA 10 Kda and PVP 58 Kda. Both NCs were submitted to the lyophilization process and reconstituted with deionized water to form the first layer of drug casting. Backing layers were developed for short application times and effective skin deposition. In vivo biodistribution profiles of RPV and CAB after MAP skin application were investigated and compared with the commercial intramuscular injection using rats. After a single application of RPV MAPs, a higher concentration of RPV was delivered to the axillary lymph nodes (AL) (Cmax 2466 ng/g - Tmax 3 days) when compared with RPV IM injection (18 ng/g - Tmax 1 day), while CAB MAPs delivered slightly lower amounts of drug to the AL (5808 ng/g in 3 days) when compared with CAB IM injection (9225 ng/g in 10 days). However, CAB MAPs delivered 7726 ng/g (Tmax 7 days) to the external lumbar lymph nodes, which was statistically equivalent to IM delivery (Cmax 8282 ng/g - Tmax 7 days). This work provides strong evidence that MAPs were able to enhance the delivery of CAB and RPV to the lymphatic system compared to the IM delivery route.


Assuntos
Dicetopiperazinas , Infecções por HIV , Piridonas , Rilpivirina , Animais , Ratos , Preparações Farmacêuticas , Distribuição Tecidual , Antirretrovirais , Polímeros
8.
Artigo em Inglês | MEDLINE | ID: mdl-36737372

RESUMO

BACKGROUND: Rilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography. METHODS: Retrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV. RESULTS: We selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29-68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of -0.8kPa in non-RPV-exposed patients (p=0.254) and -1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, -2.8kPa [p<0.001]; non-RPV-exposed, -1.1kPa [p=0.22]). CONCLUSION: RPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C.


Assuntos
Fármacos Anti-HIV , Coinfecção , Infecções por HIV , Hepatite C , Animais , Humanos , Rilpivirina/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Estudos Retrospectivos , Coinfecção/tratamento farmacológico , Antirretrovirais/efeitos adversos , Hepatite C/tratamento farmacológico , Hepacivirus , Cirrose Hepática/tratamento farmacológico
9.
Pediatr Infect Dis J ; 43(1): 40-48, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37922511

RESUMO

BACKGROUND: Virologic characterization of newly HIV-diagnosed adolescents could help to improve their specific needs. The objective was to describe the transmitted drug resistance mutations (TDR) and its transmission by clusters in this population in Spain. METHODS: TDR to retrotranscriptase and protease inhibitors included in the WHO TDR list 2009 implemented in the Calibrated Population Resistance tool v8.0 (Stanford) were studied in HIV pol sequences from all HIV-diagnosed adolescents (12-19-year-old) enrolled during 2004-2019 period in the Spanish pediatric and adult (CoRISpe-CoRIS) cohorts. The found TDR were compared with the provided by the Stanford algorithm v9.0 2021. HIV-1 variants and transmission clusters were also studied. RESULTS: Among 410 HIV-1 adolescents diagnosed, 141 (34.4%) had available ART-naive sequences. They were mostly male (81.6%), Spanish (55.3%) and with behavioral risk (92.2%), mainly male-to-male sexual contact (63.1%). TDR prevalence was significantly higher by Stanford versus WHO list (18.4% vs. 7.1%; P = 0.004). The most prevalent TDR by the WHO list was K103N (3.6%) and by Stanford E138A (6.6%), both at retrotranscriptase. E138A, related to rilpivirine/etravirine resistance, was absent in the WHO list. One in 4 adolescents carried HIV-1 non-B variants. We described 5 transmission clusters, and 2 carried TDR mutations. CONCLUSIONS: Our data suggest a high TDR prevalence in adolescents with a new HIV diagnosis in Spain, similar to adults, 2 active TDR transmission clusters, and the need for the WHO TDR list update. These findings could have implications for the options of the recently available rilpivirine-related long-acting treatment and in first-line regimen election.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Soropositividade para HIV , HIV-1 , Adulto , Humanos , Masculino , Adolescente , Criança , Adulto Jovem , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Espanha/epidemiologia , Farmacorresistência Viral/genética , Mutação , HIV-1/genética , Rilpivirina/uso terapêutico , Prevalência , Genótipo , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico
10.
AIDS ; 38(4): 521-529, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38061030

RESUMO

OBJECTIVE: Bone loss in people with HIV (PWH) is poorly understood. Switching tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) has yielded bone mineral density (BMD) increases. PETRAM (NCT#:03405012) investigated whether BMD and bone turnover changes correlate. DESIGN: Open-label, randomized controlled trial. SETTING: Single-site, outpatient, secondary care. PARTICIPANTS: Nonosteoporotic, virologically suppressed, cis-male PWH taking TDF/emtricitabine (FTC)/rilpivirine (RPV) for more than 24 weeks. INTERVENTION: Continuing TDF/FTC/RPV versus switching to TAF/FTC/RPV (1 : 1 randomization). MAIN OUTCOME MEASURES: :[ 18 F]NaF-PET/CT for bone turnover (standardized uptake values, SUV mean ) and dual-energy x-ray absorptiometry for lumbar spine and total hip BMD. RESULTS: Thirty-two men, median age 51 years, 76% white, median duration TDF/FTC/RPV 49 months, were randomized between 31 August 2018 and 09 March 2020. Sixteen TAF:11 TDF were analyzed. Baseline-final scan range was 23-103 (median 55) weeks. LS-SUV mean decreased for both groups (TAF -7.9% [95% confidence interval -14.4, -1.5], TDF -5.3% [-12.1,1.5], P  = 0.57). TH-SUV mean showed minimal changes (TAF +0.3% [-12.2,12.8], TDF +2.9% [-11.1,16.9], P  = 0.77). LS-BMD changes were slightly more favorable with TAF but failed to reach significance (TAF +1.7% [0.3,3.1], TDF -0.3 [-1.8,1.2], P  = 0.06). Bone turnover markers decreased more with TAF ([CTX -35.3% [-45.7, -24.9], P1NP -17.6% [-26.2, -8.5]) than TDF (-11.6% [-28.8, +5.6] and -6.9% [-19.2, +5.4] respectively); statistical significance was only observed for CTX ( P  = 0.02, P1NP, P  = 0.17). CONCLUSION: Contrary to our hypothesis, lumbar spine and total hip regional bone formation (SUV mean ) and BMD did not differ postswitch to TAF. However, improved LS-BMD and CTX echo other TAF-switch studies. The lack of difference in SUV mean may be due to inadequate power.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Masculino , Humanos , Pessoa de Meia-Idade , Tenofovir/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adenina/efeitos adversos , Emtricitabina/uso terapêutico , Rilpivirina/uso terapêutico
11.
Antimicrob Agents Chemother ; 68(1): e0078123, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38038460

RESUMO

Cabotegravir + rilpivirine administered via intramuscular gluteal injections is the first complete long-acting (LA) regimen approved for maintaining HIV-1 virologic suppression. The vastus lateralis (lateral) thigh muscle could be a potential alternative site of administration in circumstances such as injection site fatigue, intolerability, or contraindication for gluteal administration. Cabotegravir and rilpivirine pharmacokinetics and participant tolerability were evaluated following single intramuscular injections to the lateral thigh. Healthy adult participants received 4 weeks of daily oral cabotegravir (30 mg) and rilpivirine (25 mg), followed by a 10- to 14-day washout and single 3 mL intramuscular injections of cabotegravir LA 600 mg and rilpivirine LA 900 mg to the lateral thigh. Safety, tolerability, and pharmacokinetics were evaluated through 52 weeks post injection. Pharmacokinetic parameters were estimated using non-compartmental analysis. Fifteen participants (female at birth, n = 6) enrolled. Median age was 33 years. Median weight was 93.6 kg. Median body mass index was 31.4 kg/m2. One participant withdrew due to pregnancy after oral dosing before receiving an injection. Plasma concentrations at Weeks 4 and 8 were 15.4- and 5.3-fold above the protein-adjusted 90% inhibitory concentration for cabotegravir and 4.7- and 2.4-fold for rilpivirine, respectively. The most common injection site reactions were pain [28/28 (100%)], induration [15/28 (54%)], and swelling [12/28 (42%)]; 94% were Grade 1 or 2. Cabotegravir and rilpivirine plasma pharmacokinetic profiles observed in this study support further evaluation of thigh administration in target populations of people living with HIV-1. Tolerability of cabotegravir + rilpivirine LA intramuscular lateral thigh injections was similar to gluteal administration.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Adulto , Recém-Nascido , Humanos , Feminino , Rilpivirina/farmacocinética , Injeções Intramusculares , Fármacos Anti-HIV/farmacocinética , Músculo Quadríceps , Coxa da Perna , Infecções por HIV/tratamento farmacológico , Piridonas/farmacocinética , Antirretrovirais/uso terapêutico
12.
Int J STD AIDS ; 35(4): 311-313, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37997937

RESUMO

Switching from oral antiretroviral treatment to intramuscular (IM) cabotegravir (CAB) + rilpivirine (RPV) has an optional oral lead-in to ensure tolerability. The British HIV Association guidelines advise against directly switching from oral antiretroviral (ART) combinations containing strong/moderate cytochrome inducers like efavirenz (EFV) to IM CAB + RPV. EFV has a prolonged elimination half-life, leading to a residual induction of UGT1A1 and CYP3A4 after discontinuation. These enzymes are responsible for CAB and RPV metabolism and their induction might lead to sub-optimal concentrations of CAB and RPV, risking drug resistance. When switching from EFV to oral CAB + RPV, the ATLAS and ATLAS 2M studies showed reduced RPV concentrations but with maintained viral suppression during the oral lead-in and subsequent long-acting injectable (LAI) phases. Also, a recent pharmacokinetic modelling study indicated reduced RPV concentrations, without viral implication, when switching from EFV to IM CAB + RPV. However, there are limited real-world data on direct switching from EFV-based therapy to long-acting IM CAB + RPV. We describe a case where oral intake was impossible in a critical care scenario, switching from emitricitabine/tenofovir-DF (FTC/TDF) 200/245 mg + 600 mg EFV to IM CAB + RPV for treatment optimisation.


Assuntos
Antirretrovirais , Benzoxazinas , Ciclopropanos , Dicetopiperazinas , Piridonas , Rilpivirina , Humanos , Rilpivirina/uso terapêutico , Alcinos , Tenofovir
13.
Br J Clin Pharmacol ; 90(1): 350-353, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37917870

RESUMO

A middle-aged Caucasian man living with HIV, clinically stable (viral load <20 copies/mL) on injectable antiretroviral cabotegravir plus rilpivirine every 2 months presented with a 6-month history of bilateral enlargement of the breasts associated with pain. His hormonal profile was normal, and no other underlying cause was identified. He was diagnosed with idiopathic gynecomastia. Tamoxifen is an anti-oestrogen recommended for gynecomastia and has been described in people living with HIV but can potentially induce the activity of cytochrome P450 3A4 (CYP3A4), reducing rilpivirine concentrations, which consequently may cause virological failure and resistance. This is the same for other antiretroviral agents majorly induced by CYP3A4. To date, there have been no reported cases of using anastrozole as a treatment for gynecomastia in people living with HIV or of its co-administration with antiretroviral. We describe the use of an aromatase inhibitor instead of tamoxifen in a person living with HIV, diagnosed with gynecomastia.


Assuntos
Fármacos Anti-HIV , Ginecomastia , Infecções por HIV , Masculino , Pessoa de Meia-Idade , Humanos , Anastrozol/uso terapêutico , Ginecomastia/induzido quimicamente , Ginecomastia/tratamento farmacológico , Citocromo P-450 CYP3A , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Rilpivirina/uso terapêutico , Antirretrovirais/uso terapêutico , Tamoxifeno/efeitos adversos , Fármacos Anti-HIV/efeitos adversos
14.
Br J Clin Pharmacol ; 90(1): 264-273, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37602480

RESUMO

AIMS: Dolutegravir (DTG) and rilpivirine (RPV) dual therapy is now recommended as a switch option in virologically suppressed HIV patients. Literature suggests that virological failure with dual therapy could possibly relate to subtherapeutic drug concentrations. In this study, we aimed at describing the DTG and RPV trough plasma concentrations (Cmin) and plasma HIV-1 RNA viral load (VL) during maintenance dual therapy. METHODS: We performed a retrospective analysis of DTG and RPV therapeutic drug monitoring in people living with HIV/AIDS (PLWHA) with dual therapy in 9 French centres. DTG and RPV trough plasma concentrations were estimated using a Bayesian approach to predict Cmin. The relationship between the pharmacokinetics of DTG and RPV and VL > 50 copies (cp)/mL was explored using joint nonlinear mixed models. The frequency of subtherapeutic threshold (DTG Cmin below 640 ng/mL and RPV Cmin below 50 ng/mL) were compared between PLWHA presenting VL > 50 cp/mL or not during the study. RESULTS: At baseline, 209 PLWHA were enrolled in the study. At week 48, 19 people living with HIV/AIDS (9.1%) discontinued their treatment and 15 PLWHA (7.1%) exhibited VL > 50 cp/mL. Six PLWHA out of 15 (40.0%) with VL > 50 cp/mL during the follow-up had at least 1 Cmin below the respective thresholds while only 26/194 patients (13.4%) without virological replication had at least 1 concentration below the threshold (P = .015). CONCLUSION: A majority of PLWHA receiving DTG/RPV maintenance dual therapy demonstrated VL < 50 cp/mL but virological replication was more frequent in people living with HIV/AIDS with subtherapeutic Cmin.


Assuntos
Síndrome de Imunodeficiência Adquirida , Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Fármacos Anti-HIV/uso terapêutico , Estudos Retrospectivos , Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Teorema de Bayes , Monitoramento de Medicamentos , Rilpivirina/uso terapêutico , Oxazinas , Piridonas/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Carga Viral
15.
Clin Infect Dis ; 78(1): 122-124, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-37740255

RESUMO

We report 12 patients with persistent viremia on oral antiretroviral therapy who were initiated on injectable cabotegravir/rilpivirine (iCAB/RPV) without oral lead-in. All patients achieved viral suppression without any virologic rebound. iCAB/RPV may be considered as an option for patients unable to maintain suppression on oral antiretroviral therapy.


Assuntos
Fármacos Anti-HIV , Dicetopiperazinas , Infecções por HIV , Piridonas , Humanos , Rilpivirina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico
16.
HIV Med ; 25(3): 381-390, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38147871

RESUMO

OBJECTIVES: Cabotegravir + rilpivirine (CAB + RPV) dosed monthly or every 2 months is the first complete long-acting (LA) regimen recommended by treatment guidelines for the maintenance of HIV-1 virological suppression. This post hoc analysis summarizes outcomes for Asian participants through week 96. METHODS: Data from Asian participants naive to CAB + RPV randomized to receive dosing every 4 weeks (Q4W) or every 8 weeks (Q8W) in the FLAIR (NCT02938520) and ATLAS-2M (NCT03299049) phase 3/3b studies were pooled. The proportion of participants with plasma HIV-1 RNA ≥50 and <50 copies/mL (per FDA Snapshot algorithm), incidence of confirmed virological failure (CVF; two consecutive HIV-1 RNA ≥200 copies/mL), pharmacokinetics, safety, and tolerability through week 96 were assessed. RESULTS: Overall, 41 Asian participants received CAB + RPV (Q8W, n = 17; Q4W, n = 24). At week 96, 83% (n = 34/41) of participants maintained HIV-1 RNA <50 copies/mL, none had HIV-1 RNA ≥50 copies/mL, and 17% (n = 7/41) had no virological data. No Asian participant met the CVF criterion. Drug-related adverse events occurred in 44% (n = 18/41) of participants; none were Grade ≥3. All injection site reactions were Grade 1 or 2; median duration was 2 days and most resolved within 7 days (90%, n = 390/435). CAB and RPV trough concentrations remained well above their respective protein-adjusted 90% inhibitory concentrations (CAB, 0.166 µg/mL; RPV, 12 ng/mL) through week 96. CONCLUSIONS: CAB + RPV LA demonstrated high efficacy, with no participants having CVF, and an acceptable safety profile in Asian participants through week 96. These data support CAB + RPV LA as a complete regimen for the maintenance of HIV-1 virological suppression in Asian individuals.


Assuntos
Fármacos Anti-HIV , Dicetopiperazinas , Infecções por HIV , Soropositividade para HIV , Piridonas , Humanos , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Soropositividade para HIV/tratamento farmacológico , Rilpivirina , RNA Viral , Ensaios Clínicos Fase III como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
AIDS ; 38(1): 21-29, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37289582

RESUMO

OBJECTIVES: Data are lacking on the virologic efficacy and durability of modern antiretroviral treatment (ART) regimens during pregnancy. We compared virologic outcomes at delivery among women receiving dolutegravir versus other ART and the rate of change of the initial pregnancy regimen. DESIGN: Single-site retrospective cohort between 2009 and 2019. METHODS: We used univariable and multivariable generalized estimating equations to model the relationship between the maternal ART anchor and the proportion of women with a detectable viral load (greater than or equal to 20 HIV RNA copies/mL of plasma) closest to delivery (suboptimal virologic control) and with a detectable viral load at any time in the third trimester. We also compared changes in ART during pregnancy. RESULTS: We evaluated 230 pregnancies in 173 mothers. Rates of optimal virologic control at delivery did not significantly differ in mothers who received dolutegravir (93.1%), rilpivirine (92.1%), boosted darunavir (82.6%), or efavirenz (76.9%) but were significantly lower among mothers receiving atazanavir (49.0%) or lopinavir (40.9%). The odds of having a detectable viral load at any time in the third trimester was also higher for atazanavir and lopinavir. Raltegravir, elvitegravir, or bictegravir were used in less than 10 mothers at delivery, which precluded statistical analyses. The frequency of change in ART was significantly higher in mothers who initially received elvitegravir (68%) or efavirenz (47%) than dolutegravir (18%). CONCLUSION: Dolutegravir-containing, rilpivirine-containing, and boosted darunavir-containing regimens conferred excellent virologic control in pregnancy. Atazanavir and lopinavir, elvitegravir, and efavirenz were associated with either high rates of virologic failure or regimen change during pregnancy.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Feminino , Humanos , Gravidez , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Gestantes , Lopinavir/uso terapêutico , Sulfato de Atazanavir/uso terapêutico , Darunavir/uso terapêutico , Estudos Retrospectivos , Benzoxazinas/uso terapêutico , Rilpivirina/uso terapêutico , Antirretrovirais/uso terapêutico , Carga Viral
19.
J Acquir Immune Defic Syndr ; 95(1): 90-96, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37831614

RESUMO

BACKGROUND: Predictors of virologic failure in those receiving long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) have been evaluated; however, factors associated with low-level viremia, including blips and persistent low-level viremia (pLLV), are not well-described. METHODS: A retrospective cohort study was performed using data from April 2021 through December 2022. Inclusion criteria included treatment with CAB/RPV for at least 3 months, availability of pre- and postswitch HIV RNA values, HIV RNA value of <200 copies/mL (cpm) at the time of switch to CAB/RPV, and at least 1 postswitch HIV RNA collected >21 days after the start of CAB/RPV. Outcomes included incidence of HIV RNA ≥20, ≥50, and ≥200 cpm after switch and factors associated with detectable HIV RNA after switch. RESULTS: The median duration of follow-up among 144 participants was 287 days. After switching to CAB/RPV, occurrences of at least 1 HIV RNA ≥20, ≥50, and ≥200 cpm after switch were 34.7%, 15.3%, and 2.8%, respectively. Those with pLLV before switch were significantly more likely to have detectable HIV RNA after switch [hazard ratio 24.39 (8.71-68.34)], and 44.4% of those with pLLV before switch continued with pLLV after switch to LAI CAB/RPV. Body mass index, late injection, and monthly versus every two-month dosing were not associated with detectable viremia after switch. CONCLUSIONS: Despite virologic suppression at the time of switch and the perceived adherence benefits, participants still experienced blips or pLLV after switch to LAI CAB/RPV. Having detectable HIV RNA on oral therapy before switch was associated with detectable HIV RNA after switching.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Fármacos Anti-HIV/uso terapêutico , Rilpivirina/uso terapêutico , Infecções por HIV/epidemiologia , Estudos Retrospectivos , Viremia/tratamento farmacológico , Antirretrovirais/uso terapêutico , RNA Viral
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