HIV therapy has evolved rapidly since the 1990s; the arrival of more potent and safer antiretroviral drugs has transformed HIV infection into a chronic condition, which is rarely fatal. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are frequently used as a third agent - as part of a triple-combination therapy. Side effects and low barriers to resistance have been the major drawbacks of NNRTIs. Rilpivirine (RPV) is a next-generation non-nucleoside analogue, the unique features of which might favor choosing this drug over other NNRTIs. RPV is the latest NNRTI approved for the treatment of HIV infection. Along with its high efficacy and good safety profile, data on pharmacokinetics and drug interactions make RPV particularly attractive.
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African and Asian cohort studies have demonstrated the feasibility and efficacy of HAART in resource-poor settings. The long-term virological outcome and clinico-immunological criteria of success remain important questions. We report the outcomes at 24 months of antiretroviral therapy (ART) in patients treated in a Médecins Sans Frontières/Ministry of Health programme in Cambodia.
The presence of K103N mutant virus in plasma above 2000 copies/ml prior to therapy in treatment-naive individuals correlated with increased risk of virologic failure of these efavirenz-containing triple-drug regimens.
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From the results it is proved that this method is less time consuming, inexpensive, and reproducible. Drug-release studies indicate, PEGylated 5.0 G PAMAM-EFV dendrimers have shown prolonged drug-release property.
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The antiretroviral drug efavirenz (EFV) and the antimalarial artemisinin-based combination therapy artemether-lumefantrine (AL) are commonly co-administered to treat HIV and malaria. EFV is a known inducer of cytochrome P450 3A4, which converts artemether to dihydroartemisinin (DHA) that is also active and metabolizes longer acting lumefantrine (LR). A study in healthy volunteers was completed to address the concern that EFV impacts AL pharmacokinetics (PKs).
Twenty years following the description of the broad-spectrum antiviral activity of S-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA] [De Clercq E, Holý A, Rosenberg I, Sakuma T, Balzarini J, Maudgal PC. A novel selective broad-spectrum anti-DNA virus agent. Nature 1986;323:464-7], the acyclic nucleoside phosphonates have acquired a prominent therapeutic position: (i) cidofovir in the treatment of papilloma-, herpes-, adeno- and poxvirus infections, (ii) adefovir in the treatment of chronic hepatitis B virus (HBV) infections, and (iii) tenofovir in the treatment of human immunodeficiency virus (HIV) infections (AIDS). Although formally approved only for the treatment of human cytomegalovirus (HCMV) retinitis in AIDS patients, cidofovir has been used successfully in the treatment of various other DNA virus infections, particularly human papilloma virus (HPV)-associated lesions. Adefovir dipivoxil has become a standard therapy for HBV infections, especially when resistant to lamivudine. Tenofovir disoproxil fumarate (TDF) is the corner stone of the triple-drug (TDF, emtricitabine, and efavirenz) combination therapy for AIDS, and TDF, alone or combined with emtricitabine may in the future evolve to the standard therapy of hepatitis B. Guided by the results obtained with tenofovir in the prevention of parenteral, intravaginal and perinatal infections with simian immunodeficiency virus in monkeys, and the safety profile gathered with TDF in humans with AIDS over the past 5 years since TDF was licensed for clinical use, it should be further pursued for the pre- and post-exposure prophylaxis of HIV infections in humans. Meanwhile, new classes of both acyclic (i.e. PMPO-DAPy, PMEO-DAPy, HPMPO-DAPy) and cyclic nucleoside phosphonates (i.e. PMDTA, PMDTT, GS9148) have been accredited with an antiviral potency and selectivity similar to those of cidofovir, adefovir and/or tenofovir.
Rash was more frequent with FD nevirapine, but 88% had no clinical toxicity; elevated AST or ALT levels were transient and resolved spontaneously, suggesting that routine laboratory monitoring has limited value. Dual pediatric stavudine-lamivudine minitablets are preferred for safe and simple DE; if unavailable, initiating FD Triomune requires timely review for rash, which could be managed by temporary reduction to half-dose Triomune or efavirenz substitution.
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Safety and tolerance of efavirenz is good in most patients, even in a population with a high rate of IVDU. The most common AEs are CNS disturbances; they are not severe and rarely lead to TI.
The median reduction of the viral load for the total study population was 1.9 log10 (0.8 - 4.7), 2.3 log(10) (0.5 - 4.7) and 2.6 log(10) (0-4.7) after 12, 24 and 52 weeks, respectively. After 24 weeks 7/15 children and after 52 weeks 9/15 patients had reductions of the VL below the detection limit. The median increase of CD4-cells in the study population during the treatment period were 104 cells/microl (189-969), 220 cells/microl (170-831) and 321 cells/ml (162-574) after 12, 24 and 52 weeks, respectively.
Despite the high costs, use of MD-ARVs, such as HAART, for PMTCT offer societal savings because fewer perinatally acquired infections are anticipated to require treatment.
To encapsulate efavirenz (EFV) within poly(epsilon-caprolactone) (PCL) nanoparticles (NPs) and compare the oral pharmacokinetics with that of EFV-loaded micelles and pure EFV NPs.
The Cox proportional hazards model or its discrete time analogue, the logistic failure time model, posit highly restrictive parametric models and attempt to estimate parameters which are specific to the model proposed. These methods are typically implemented when assessing effect modification in survival analyses despite their flaws. The targeted maximum likelihood estimation (TMLE) methodology is more robust than the methods typically implemented and allows practitioners to estimate parameters that directly answer the question of interest. TMLE will be used in this paper to estimate two newly proposed parameters of interest that quantify effect modification in the time to event setting. These methods are then applied to the Tshepo study to assess if either gender or baseline CD4 level modify the effect of two cART therapies of interest, efavirenz (EFV) and nevirapine (NVP), on the progression of HIV. The results show that women tend to have more favorable outcomes using EFV while males tend to have more favorable outcomes with NVP. Furthermore, EFV tends to be favorable compared to NVP for individuals at high CD4 levels.