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Introduction: A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. Methods: PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA [less than or equal to]100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion ofpatients with HIV-1 RNA Results: Median HIV-1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686-36,794). Albeit as per protocol, all patients had pVL [less than or equal to]100,000 copies/mL at screening as required by inclusion criteria, four patients had [greater than or equal to]100,000 copies/mL at baseline. Median baseline CD4+ T-cell count was 507 per cubic millimetre (IQR: 296-517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL Conclusions: This novel dual regimen of dolutegravir and lamivudine warrants further clinical research and consideration as a potential therapeutic option for ARV-therapy-naive patients. ClinicalTrials.gov Identifier: NCT02211482. Keywords: dual therapy; dolutegravir; lamivudine; naive patients, Introduction Zidovudine (ZDV) monotherapy was the first attempt to control HIV replication. Soon after, two-drug combination became the preferred strategy, as ZDV effects lasted only for the short term, due [...]

Maintenance with a triple nucleoside reverse transcriptase Inhibitor (NRTI) regimen after successful induction with a dual NRTI/protease inhibitor (PI) combination may be advantageous, because of low pill burden, favorable lipids, and less drug interactions. This strategy to become free of PI-related problems without losing viral efficacy has not been formally tested. We performed a randomized, open-label, multicenter, 96-week comparative study in antiretroviral therapy (ART)-naive patients with CD4 50 copies per milliliter). Two hundred seven patients had similar baseline (BL) char- acteristics: median CD4 180 cells/[mm.sup.3], median VL 5.19 log10 copies per milliliter. One hundred twenty subjects (58%) met randomization criteria. Baseline VL differed significantly between dropouts and randomized subjects (median 5.41 versus 5.06 log10 copies per milliliter, p = 0.017), as did CD4 cells (median 160 and 200 cells/ram3, p = 0.044). Sixty-one subjects received TZV and 59 subjects continued NRTIs/PI. At week 48, 2 patients in the TZV group and 5 in the PI group did not have a sustained virologic suppression (log rank test; p = 0.379). CD4 counts increased significantly in both arms. In ART-naive patients, TZV maintenance had similar antiviral efficacy compared to continued standard ART at 48 weeks after baseline. Patients on successful standard ART can be safely switched to a NRTI-only regimen, at least for the tested time period. DOI: 10.1089/apc.2009.0236

A cross-sectional study was conducted in HIV-1-infected patients receiving lamivudine-containing antiretroviral therapy (ART) to determine the prevalence and risk factors of hepatitis B virus drug resistance (HBV-DR). HBV DNA and HBV genotypic resistance test were performed. Patients were categorized into two groups: with and without HBV-DR. There were 84 patients with a mean age (standard deviation [SD]) of 42.2 (10.2) years and 77% were males. Median (range) duration of ART and lamivudine use was 46 (3-177) and 40 (3-140) months, respectively. Median (range) CD4 cell count was 352 (49-790) cells/[mm.sup.3]. Of all, 19 (23%) had HBV-DR with a median (range) HBV DNA of 2.56 x [10.sup.7] (2.54 x [10.sup.3]-11 x [10.sup.7]) IU/mL. In univariate analysis, there were no differences in age, gender, ART regimen, liver function test, anti-HBc antibody, anti-HCV antibody between the two groups. Patients with HBV-DR had a higher proportion of positive HBeAg (68.4% versus 3.8%, p < 0.001). In multivariate analysis, positive HBeAg (odds ratio [OR) 16.64; 95% confidence interval [CI], 3.31-83.60] and duration of lamivudine use [per 6-month increment, OR 1.24; 95% CI, 1.06-1.36] were significant risk factors for HBV-DR. All 19 patients with HBV-DR had lamivudine resistance with the mutations as follows: M204V/I (95%), L180M/A181T (95%), L80V/I (47%), V173L (32%), and N236T (21%). Of these, 95%, 84%, 84%, and 0% of patients had HBV-DR to telbivudine, entecavir, adefovir, and tenofovir, respectively. HBV-DR is common in HBV/HIV-1 coinfected patients receiving lamivudine-containing ART without tenofovir. Positive HBeAg and longer duration of lamivudine use are risk factors for HBV-DR. In addition to lamivudine resistance, cross-resistance to other anti-HBV drugs is also frequently observed. DOI: 10.1089/apc.2009.0322

Patients with chronic hepatitis B are randomly assigned to receive some amount of telbivudine or lamivudine once daily and the primary efficacy end point is noninferiority of telbivudine to lamivudine for therapeutic response. Telbivudine demonstrated greater HBV DNA suppression with less resistance than did lamivudine in both the HBeAg-negative and the HBeAg-positive groups of patients.

The changes in viral populations in HIV-1-infected patients treated with zidovudine/lamivudine and subsequent failing therapy are analyzed. The analysis has shown that lamivudine-sensitive and lamivudine-resistant HIV-1 variants are able to persist despite highly unfavorable conditions in vivo and in vitro and that selective advantages of viral variants can change depending on the complexity of other simultaneously replicating viral variants.

A study was conducted to determine if the variation in genes of pharmacological interest were associated with the pharmacokinetic and pharmacodynanic profile of indinavir (IDV), zidovudine (ZDV), and lamivudine. Results revealed that the novel relationships were identified among genetic variants in drug transporters and indinavir, lamivudine-triphosphate, and zidovudine-triphosphate concentrations.

A study to compare the efficacy and safety of the fixed-dose combination group to the separate entities group, in combination with tenofovir and a new protease inhibitor or nonnucleoside reverse transcription inhibitor in antiretroviral-experienced adults experiencing virologic failure is illustrated. Combination antiretroviral therapy has dramatically reduced the morbidity and mortality associated with HIV infection and a one-tablet, once-daily abacavir/lamivudine (FDC) has been recently approved to treat HIV-1 infection.

The study is conducted to analyze the safety and effectiveness of abacavir, lamivudine, and zidovudine (ABC/3TC/ZDV) in antiretroviral therapy (ART)-naive HIV-infected patients. The triple-nucleoside regimen of (ABC/3TC/ZDV) is a reasonable option for ART-naive patients with a plasma HIV-1 viral load (pVL)

A randomized crossover bioequivalence study of generic and brand name formulation of navirapine, zidovudine, and lamivudine in HIV-negative Indian women using US Food and Drug Administration criteria. Subjects took single doses of all formulations separated by a 14-day washout period.

A prospective, randomized, multicenter noninferiority study comparing the regiments of tenofovir DF, emtricitabine and efavirenz and a fixed dose of zidovudine and lamivudine plus efavirenz were conducted. Results revealed that the combination of tenofovir DF and emtricitabine plus efavirenz fulfilled the criteria for noninferiority to a fixed dose of zidovudine and lamivudine plus efavirenz and proved superior in terms of virologic suppression, CD4 response, and adverse events resulting in discontinuation of the study drugs.

Abacavir (ABC) and lamivudine (3TC) administered twice daily, were compared with an ABC + 3TC fixed-dose combination administered once daily, both in combination with a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI). It was shown that a dual-nucleoside backbone of ABC and 3TC administered once or twice daily is effective, durable and well tolerated.

The efficacy and safety of pegylated interferon alpha plus lamivudine, pegylated alfa without lamivudine, and lamivudine alone for the treatment of hepatitis B e antigen (HBeAg)-positive hepatitis B are compared. It is concluded that in patients with HBeAg-positive chronic hepatitis B, peginterferon alfa-2a offers superior efficacy over lamivudine, on the basis of HBeAg seroconversion, HBV DNA suppression and HBsAg seroconversion.

The safety and pharmacokinetics of nelfinavir coadministered with zidovudine and lamivudine in 26 infants during the first six weeks of life is described. It is found that nelfinavir is well tolerated by the infants, with few adverse events attributed to the drug.

Pharmacokinetic (PK) profile and single-dose tolerability of 2 marketed brands of lamivudine (3TC) 150-mg tablets, Lamivir (Cipla, Mumbai, India) and Epivir (GSK, Basingstoke, UK) are compared. However, it is concluded that 2-tablet formulations of 3TC are bioequivalent and hence interchangeable.

A randomized double-blind clinical trial compared the efficacy and safety of 600mg of abacavir (ABC) administered once daily versus 300mg of ABC administered twice daily n combination with 300 mg of lamivudine (3TC) and 600 mg of efavirenz (EFV) administered once daily in antiretroviral-naive patients over 48 weeks. The ABC once-daily and twice-daily regimens were similar with respect to infrequency of virologic failure, and emergence of resistarnce mutations.

Patients with chronic hepatitis B who had histologically confirmed cirrhosis or advanced fibrosis were observed to study the effectiveness of antiviral therapy in preventing disease progression in such patients. Continuous treatment with lamivudine delays clinical progression in patients with chronic hepatitis B and advanced fibrosis or cirrhosis by significantly reducing the incidence of hepatic decompensation and the risk of hepatocellular carcinoma.

Simultaneous treatment with three antiviral medications appears to be substantially more effective at reducing viral loads than sequential use of the drugs in HIV infection. Researchers treated 97 HIV patients with indinavir, zidovudine, and lamivudine together or sequentially. Seventy-eight percent of patients who received the simultaneous three-drug regimen achieved clinically significant viral load reductions, which persisted at 100 weeks. Only 30-45% of those who took the drugs in sequence achieved the same level of viral suppression.