Hepatitis: Ribera Pascuet E

Ribera Pascuet E, Curran A. · Servicio de Enfermedades Infecciosas. Hospital Universitario Vall d'Hebron. Barcelona · Enferm Infecc Microbiol Clin. · Pubmed #19338072 links to  free full text

Abstract: Standard antiretroviral therapy (ART) consists of a combination of three active drugs. The selection of these drugs varies considerably according to the clinical scenario. The "gold standard" in patients initiating ART is tenofovir (TDF)/emtricitabine (FTC)/efavirenz. TDF/FTC is also considered a combination of choice when, for various reasons, ART is initiated with a boosted protease inhibitor. Abacavir and lamivudine (ABC/3TC) is also considered a combination of choice in most clinical practice guidelines. HLA-B*5701 determination minimizes the possibility of hypersensitivity of ABC and is a positive datum for the use of ABC/3TC. However, negative findings from the data collection on Adverse Events of Anti-HIV drugs (DAD) and ACTG5202 studies on this combination should be bourne in mind. TDF can also be a good choice for substituting another nucleoside analogue to avoid or reverse certain toxicities in patients with good virological control. Substituting thymidine analogues for TDF improves lipid profile and produces partial recuperation of subcutaneous fat. Because of the profile of resistance to TDF, this drug continues to be active in most patients with one, or even several, therapeutic failures. TDF plays and especially important role in patients coinfected with hepatotrophic viruses. In summary, TDF is a widely used drug in clinical practice due to its excellent combination of effectiveness, durability and tolerability, in addition to its ease of administration in a single daily dose, whether in its individual formation (Viread), or associated with FTC (Truvada), or with FTC and efavirenz (Atripla).

Curran A, Ribera Pascuet E. · Servicio de Enfermedades Infecciosas. Hospital Universitario Vall d'Hebron. Barcelona. España. · Enferm Infecc Microbiol Clin. · Pubmed #19195455 links to  free full text

Abstract: Lopinavir/ritonavir (LPV/r) has been the gold standard in first line rescue treatment for many years. No other boosted protease inhibitor (PI/r) has managed to demonstrate that it is superior to LPV/r. In this regard, the TITAN study compared the efficacy and safety of darunavir (DRV/r) in 595 patients, at a dose of 600/100 mg two times a day against the normal LPV/r dose, combined with at least 2 other optimised antiretroviral drugs. The efficacy of the treatment at 48 weeks (VL<400 copies/mL) was significantly higher in the DRV/r goup compared to the LPV/r group, both in the analysis by protocol (77% vs. 68%), the non-inferiority of DRV/r being demonstrated (estimated difference +9%, 95% CI 2-16), and by intention to treat (77% vs. 67%), the superiority of DRV/r being demonstrated (estimated difference 10%, 95% CI 2-17%). The incidence of diarrhoea and increase in triglycerides was higher in the LPV/r group. The differences in efficacy of both treatments in favour of DRV/r started to be seen from a basal primary mutation in the protease, with these differences increasing as the number of these mutations increased. In patients with virological failure, DRV/r protected the protease and reverse transcriptase against mutations, thus preserving future therapeutic options. We have some theoretical and clinical data available that enables us to consider the possibility of administering DRV/r once a day in some patients with a few mutations in the protease and in those where this dosing regime is considered important. With the results of the TITAN study, DRV/r must be considered the new gold standard in first line rescue, at least in those patients with a primary mutation in the protease.