The 2012 revised Dutch national guidelines for the treatment of chronic hepatitis B virus infection.

In 2008, the Netherlands Association of Gastroenterologists and Hepatologists (Nederlands Vereniging van Maag-Darm-Leverartsen) published the Dutch national guidelines for the treatment of chronic hepatitis B virus infection. New insights into the treatment of chronic hepatitis B with relevance for clinical practice have been adopted in these concise, revised guidelines. The most important changes include the choice of initial antiviral therapy, licensing of tenofovir for the treatment of chronic hepatitis B and the management of antiviral resistance.

Unboosted atazanavir plus co-formulated lamivudine/abacavir as a ritonavir-sparing simplification strategy in routine clinical practice.

OBJECTIVE: To assess the effectiveness and safety of antiretroviral therapy with unboosted atazanavir (400 mg once daily) plus co-formulated abacavir/lamivudine as a treatment simplification strategy in HIV-infected patients with sustained viral suppression in routine clinical practice. METHODS: We performed a retrospective study including patients who were switched to unboosted atazanavir plus abacavir/lamivudine and whose HIV-1 RNA was <50 copies/mL. The primary endpoint was the percentage of subjects who maintained viral suppression after 48 weeks of follow-up. Secondary endpoints included the percentage of subjects who maintained viral suppression after 96 weeks of follow-up, the incidence of adverse events, changes in CD4+ T-cell count and in lipid profile, and the percentage of patients with subtherapeutic atazanavir trough concentrations during follow-up. RESULTS: Forty-six patients were included. None had a prior history of resistance to protease inhibitors or to lamivudine or abacavir. The percentage of patients with viral suppression at Week 48 was 73.9% when all the included patients were considered (full dataset analysis) and 85.0% when only subjects on treatment were considered. There was a continuous immune recovery and an improvement in lipid profile during follow-up. Two thirds of the patients had subtherapeutic atazanavir trough concentrations in plasma in at least one determination during follow-up. CONCLUSION: Antiretroviral therapy with unboosted atazanavir plus abacavir/lamivudine is safe and effective in the long term as a treatment simplification strategy in HIV-infected patients with sustained virological suppression in routine clinical practice.

Virologic response and safety of the abacavir/lamivudine fixed-dose formulation as part of highly active antiretroviral therapy: analyses of six clinical studies.

OBJECTIVE: We analyzed virologic response and safety data from six recent clinical studies conducted in antiretroviral-naïve subjects treated with ABC/3TC or its components to assess the impact of baseline viral load on efficacy and safety endpoints used in the ACTG5202 protocol. METHODS: Primary endpoints were time to virologic failure (confirmed HIV-1 RNA > or = 1,000 copies/mL at 16-24 weeks or > or = 200 copies/mL at > or = 24 weeks) and time to first grade 3 or 4 adverse event or laboratory abnormality that was at least one grade higher than at baseline. The survival distributions of both endpoints were estimated using the Kaplan-Meier method overall and by baseline viral load (<100,000 vs. 100,000 copies/mL). A weighted mean of the virologic response and 95% confidence intervals (CI) were calculated by inverse-variance weighting for baseline viral load 100,000 copies/mL across studies. RESULTS: For subjects with baseline HIV-1 RNA 100,000 copies/mL, the rate of virologic survival ranged from 87% to 95% by 48 weeks. Few subjects treated with ABC/3TC developed grade 3 or 4 adverse events, laboratory toxicities, or changes in lipid levels. The weighted mean (CI) for the pooled virologic response was 91% (87%-96%). CONCLUSION: Based on the A5202 endpoints, ABC/3TC-containing regimens in this analysis had a high rate of virologic survival and were generally well tolerated in antiretroviral-naïve subjects regardless of baseline viral load. The pooled virologic response for ABC/3TC in our analysis is higher than the A5202 estimate.

Long-term efficacy and safety of fosamprenavir plus ritonavir versus lopinavir/ritonavir in combination with abacavir/lamivudine over 144 weeks.

PURPOSE: The KLEAN study extension assessed the long-term efficacy and safety of fosamprenavir-ritonavir (FPV/r) and lopinavir-ritonavir (LPV/r), both administered with abacavir/lamivudine (ABC/3TC) fixed dose combination, over 144 weeks. METHODS: KLEAN was an open-label, noninferiority study that randomised antiretroviral-naïve patients to FPV/r twice daily (bid) or LPV/r bid with ABC/3TC once daily (qd). Patients with a viral load of <400 copies/mL at Week 48 were eligible to participate in the KLEAN study extension (up to 144 weeks) and continued with their previously randomised therapy. RESULTS: The KLEAN study extension (48 to 144 weeks) randomized 199 patients. The proportion of TLOVR responders (HIV-1 RNA <50 copies/mL) at Week 144 was 73% and 60% in the FPV/r and LPV/r arms, respectively. The proportion of TLOVR responders (<50 copies/mL) was the same irrespective of baseline HIV-1 RNA (>100,000 or 100,000 copies/mL). The Week 144 median (interquartile range) change from baseline CD4+ cell count was 300 (236-433) cells/mm3 and 335 (225-444) cells/mm3 in the FPV/r and LPV/r arms, respectively. Diarrhea was the most frequently reported adverse event. A small proportion of patients (FPV/r, 13%; LPV/r, 9%) discontinued study medication due to adverse events. Three patients (FPV/r, 1; LPV/r, 2) experienced virological failure between Week 48 and Week 144. CONCLUSION: The findings of the KLEAN study extension (48 to 144 weeks) support durable viral suppression with both FPV/r and LPV/r treatment regimens when used in combination with ABC/3TC irrespective of viral load at baseline. Both regimens were well tolerated and had similar safety profiles.

HIV/AIDS treatment and physicochemical quality control of medicines: evaluation of non-generic lamivudine + zidovudine tablets manufactured in Brazil

In this work it was evaluated the physicochemical quality of lamivudine + zidovudine tablets, whose association belongs to the list of drugs distributed by the Brazil's National Program on Sexually Transmitted Diseases and AIDS. Four non-generic products (lamivudine + zidovudine tablets) were analyzed. They were obtained from different Brazilian manufacturers, besides a reference product. The quality was evaluated by physicochemical tests described in the official codes. A validated reversed-phase high performance liquid chromatography (HPLC) method was used for the assay of the active substances. All samples were in accordance to the requisites in relation to their physicochemical characteristics. Dissolution studies showed similar drug percentual dissolved among all samples. The results reflect the interest of the national pharmaceutical industry to ensure the delivery of safer and cheaper drugs to the Brazilian people, with particular importance in the National Program on Sexually Transmitted Diseases and AIDS.

HIV/AIDS treatment and physicochemical quality control of medicines: evaluation of non-generic lamivudine + zidovudine tablets manufactured in Brazil.

In this work it was evaluated the physicochemical quality of lamivudine + zidovudine tablets, whose association belongs to the list of drugs distributed by the Brazil's National Program on Sexually Transmitted Diseases and AIDS. Four non-generic products (lamivudine + zidovudine tablets) were analyzed. They were obtained from different Brazilian manufacturers, besides a reference product. The quality was evaluated by physicochemical tests described in the official codes. A validated reversed-phase high performance liquid chromatography (HPLC) method was used for the assay of the active substances. All samples were in accordance to the requisites in relation to their physicochemical characteristics. Dissolution studies showed similar drug percentual dissolved among all samples. The results reflect the interest of the national pharmaceutical industry to ensure the delivery of safer and cheaper drugs to the Brazilian people, with particular importance in the National Program on Sexually Transmitted Diseases and AIDS.

Didanosine, lamivudine-emtricitabine and efavirenz as initial therapy in naive patients.

There are currently several suitable and different antiretroviral regimens to start highly active antiretroviral therapy (HAART), and many clinicians and patients prefer once-daily therapy. The efficacy and potency of efavirenz (EFV) has been established in many clinical trials and cohort studies; its pharmacokinetics, allowing for a convenient once-daily administration, make EFV one of the first agents to be included in once-daily regimens in naive patients. The two nucleoside reverse transcriptase inhibitors (NRTIs) accompanying the third drug have become the central skeleton, or the 'backbone' of the therapeutic scheme. Among the different NRTI pairs, a didanosine-lamivudine (3TC) or emtricitabine backbone for combination antiretroviral therapy may be a good option compared with any current NRTI-combinations due to its security, tolerance and once-daily dose. In this article, we review the advantages and drawbacks of didanosine-XTC-EFV as the initial regimen of HAART in HIV-infected patients.

Dissolution test for lamivudine tablets: optimization and statistical analysis.

A comparison of different methods for dissolution test used by five different manufacturer laboratories of lamivudine tablets is made, evaluated, and discussed. Dissolution medium (water and hydrochloric acid pH 1.2), apparatus (paddles and baskets) and time (30 and 60 min) were analyzed. The determination was accomplished by spectrophotometry at 270 nm. Analysis of variance (ANOVA) factorial design 5 x 2 x 2 x 2 with six repetitions, with post hoc multiple comparisons between means conducted by Duncan test at 0.05 significance level was used. After the comparative analysis of the results, optimal dissolution conditions were determined as follows: water as dissolution medium, paddles at the stirring speed of 50 rpm as apparatus and time of 30 min. The method was applied to the dissolution test of samples from eleven batches of tablets, produced by five different laboratories.

Adherence, side effects and efficacy of stavudine plus lamivudine plus nelfinavir in treatment-experienced HIV-infected patients.

OBJECTIVES: To evaluate adherence, side effects and efficacy of a modality of highly active antiretroviral therapy (HAART) in HIV-infected patients. METHODS: In a cohort, prospective study, 65 previously treated patients received stavudine plus lamivudine plus nelfinavir. Fifty-three participants (81%) had a history of intravenous drug use. Patients were evaluated at 3-month intervals. The association of adherence with demographic variables, hepatitis C virus infection, number of stopped antiretroviral regimens, HIV RNA level, CD4 cell count, and adverse effects to drugs was assessed. RESULTS: After a median follow-up of 12 months, 30 participants (46%) showed adequate adherence in all visits. An association was observed between adherence and female sex: 18 of 47 men (38%) vs. 12 of 18 women (67%) presented adequate adherence in all visits (P=0. 0416). An association was also observed between adherence and low baseline HIV RNA level (P=0.0229). Discontinuation of treatment took place because of refusal to take medication in 11 participants (17%) and because of side effects in seven participants (11%). Undetectable HIV RNA level was achieved in 26 patients (40%) at 3 months and in lower percentages at months 6, 9 and 12. CONCLUSIONS: Overall adherence to the employed HAART regimen was poor. Female sex and low baseline HIV RNA were associated with better adherence. Refusal to take medications and side effects were the main reasons to stop therapy. At 3 months' follow-up, virological efficacy was achieved in 40% of patients.