Pre-exposure prophylaxis (PrEP) involves the use of antiretroviral medication in concert with safer sex practices to significantly reduce the risk of type 1 human immunodeficiency virus infection. In October 2019, daily use of emtricitabine/tenofovir alafenamide (FTC/TAF) 200 mg/25 mg was approved as a newer agent for PrEP to prevent HIV-1 infection in at-risk adults and adolescents. The purpose of this article is to: 1) provide an overview of the FTC/TAF regimen and its safety and efficacy profiles, 2) discuss indications and contraindications of FTC/TAF as PrEP, 3) provide a focused comparison of FTC/TDF with FTC/TAF, and 4) examine issues surrounding cost and accessibility in the United States. 相似文献
Daily oral antiretroviral therapy regimens produce limited drug exposure in tissues where residual HIV persists and suffer from poor patient adherence and disparate drug kinetics, which all negatively impact outcomes. To address this, we developed a tissue- and cell-targeted long-acting 4-in-1 nanosuspension composed of lopinavir (LPV), ritonavir, tenofovir (TFV), and lamivudine (3TC). In 4 macaques dosed subcutaneously, drug levels over 5 weeks in plasma, lymph node mononuclear cells (LNMCs), and peripheral blood mononuclear cells (PBMCs) were analyzed by liquid chromatography–tandem mass spectrometry. Plasma and PBMC levels of the active drugs (LPV, TFV, and 3TC) were sustained for 5 weeks; PBMC exposures to LPV, ritonavir, and 3TC were 12-, 16-, 42-fold higher than those in plasma. Apparent T1/2z of LPV, TFV, and 3TC were 219.1, 63.1, and 136.3 h in plasma; 1045.7, 105.9, and 127.7 h in PBMCs. At day 8, LPV, TFV, and 3TC levels in LNMCs were 4.1-, 5.0-, and 1.9-fold higher than in those in PBMCs and much higher than in plasma. Therefore, 1 dose of a 4-drug nanosuspension exhibited persistent drug levels in LNMCs, PBMCs, and plasma for 5 weeks. With interspecies scaling and dose adjustment, this 4-in-1 HIV drug-combination could be a long-acting treatment with the potential to target residual virus in tissues and improve patient adherence. 相似文献
Fast‐dissolving vaginal film formulations release antiretroviral drugs directly into vaginal fluid and may be as efficient at drug delivery yet more acceptable to women than gels. In this Phase 1 vaginal film study, the safety, acceptability, pharmacokinetics and pharmacodynamics of two doses of tenofovir (TFV) film and TFV 1% gel were compared to corresponding placebo formulations.
Methods
Seventy‐eight healthy HIV negative women were randomized to self‐insert daily vaginal film (10 mg TFV, 40 mg TFV or placebo) or 4 mL of vaginal gel (TFV 1% [40 mg] or placebo) for seven days. Grade 2 and higher adverse events (AEs) related to study product were compared across study arms using Fisher's exact test. Plasma TFV concentrations were measured before and 2 hours after last product use. Paired cervical and vaginal tissue biopsies obtained 2 hours after the last dose were measured to determine tenofovir diphosphate (TFV‐DP) concentrations and exposed to HIV in an ex vivo challenge assay. Acceptability was assessed through questionnaire.
Results
There was only one grade 2 or higher related AE, the primary endpoint; it occurred in the placebo gel arm. AEs occurred in 90% of participants; the majority (91%) were grade 1. AEs were similar across study arms. TFV concentrations in plasma and TFV‐DP concentrations in cervical and vaginal tissues were comparable between 40 mg TFV film and the TFV gel groups. There was a significant relationship between reduced viral replication and TFV‐DP concentrations in cervical tissues. Film users were less likely to report product leakage than gel users (66% vs. 100%, p < 0.001).
Conclusions
Films were safe and well tolerated. Furthermore, films delivered TFV to mucosal tissues at concentrations similar to gel and were sufficient to block HIV infection of genital tissue ex vivo. 相似文献
The nucleotide analogues, tenofovir disoproxil fumarate and adefovir dipivoxil, inhibit viral replication and are both effective against the hepatitis B virus (HBV). In our department, tenofovir was prescribed in addition to lamivudine for the treatment of lamivudine resistant chronic hepatitis B. After registration of adefovir, 10 patients were switched to adefovir monotherapy. We studied changes in HBV-DNA and alanine aminotransferase (ALT) in these patients. The median treatment duration with tenofovir was 78 weeks resulting in a median viral load reduction of 5.4 (range 6.8-2.3) log(10) copies/mL compared to baseline (P = 0.005). Two patients had an increase >1 log(10) copies/mL during tenofovir treatment. After the switch to adefovir, six out of 10 patients had an HBV-DNA >4 log(10) copies/mL and the median HBV-DNA increased from 2.8 to 4.5 log(10) copies/mL (P = 0.017). The factors associated with relapse were HBV-DNA PCR positivity at the time of switch and genotype B or D. ALT levels at the beginning of tenofovir treatment also might be a factor. Retreatment with tenofovir (n = 3) resulted in a rapid decline in HBV-DNA. Tenofovir is a potent antiviral drug. Switching to adefovir resulted in viral relapse in 60% of patients and retreatment with tenofovir resulted again in viral decline, which suggests that tenofovir is a more potent antiviral agent. 相似文献
Introduction: Treatment of HIV infection with nucleos(t)ide analogs active against hepatitis B virus (HBV) highly improves hepatic outcomes in HIV-HBV coinfected patients, especially when tenofovir (TDF) is part of the antiviral regimen. Drug resistance has been the major drawback and must remain as the most important caveat when planning to treat dually or HIV and HBV independently in coinfected patients.
Areas covered: The use of lamivudine (LAM) as the only active anti-HBV agent should strongly be discouraged in HIV-HBV coinfected patients, although it might be considered for individuals with low serum HBV-DNA and in the absence of liver cirrhosis as an exception. In any other case drug resistance may cause any clinical benefit of this antiviral HBV therapy to disappear, and lead to cross-resistance with other antivirals and even occasionally select for HBV vaccine escape mutants. In cirrhotics, liver enzyme flares may be accompanied by life-threatening decompensation. Entecavir is generally not recommended as an anti-HBV agent in HIV-HBV coinfected patients given its low residual antiretroviral activity and potential for selection of resistance mutations in HIV. Adefovir is not active against HIV using HBV dosing and is no longer recommended as HBV therapy given its limited antiviral effect. Finally, telbivudine is not active against HIV, it is less potent than TDF against HBV and depicts low barrier to resistance and cross-resistance to LAM or emtricitabine.
Expert Opinion: The introduction of TDF has drastically reduced the clinical relevance of hepatitis B drug resistance in HIV-HBV coinfected individuals. The use of LAM as the only active anti-HBV agent should strongly be discouraged in this population. 相似文献