ABSTRACT
BACKGROUND & AIMS: We conducted an open-label phase 2 study to assess the efficacy and safety of the oral nucleotide polymerase inhibitor sofosbuvir in combination with ribavirin in patients of Egyptian ancestry, chronically infected with genotype 4 hepatitis C virus (HCV). METHODS: Treatment-naive and previously treated patients with genotype 4 HCV were randomly allocated in a 1:1 ratio to receive sofosbuvir 400mg and weight-based ribavirin, for 12 or 24 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response (HCV RNA <25IU/ml) 12 weeks after cessation of therapy (SVR12). RESULTS: Thirty treatment-naive and thirty previously treated patients were enrolled and treated for 12 weeks (n=31) or 24 weeks (n=29). Overall, 23% of patients had cirrhosis and 38% had diabetes. 14% of treatment-naive patients were interferon ineligible and 63% of treatment-experienced patients had prior non-response. SVR12 was achieved by 68% of patients (95% CI, 49-83%) in the 12-week group, and by 93% of patients (95% CI, 77-99%) in the 24-week group. The most common adverse events were headache, insomnia, and fatigue. No patient discontinued treatment due to an adverse event. CONCLUSIONS: The findings from the present study suggest that 24 weeks of sofosbuvir plus ribavirin is an efficacious and well tolerated treatment in patients with HCV genotype 4 infection.
Subject(s)
Hepacivirus , Hepatitis C, Chronic , Ribavirin , Sofosbuvir , Adult , Aged , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Drug Therapy, Combination/methods , Egypt , Female , Hepacivirus/drug effects , Hepacivirus/genetics , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/ethnology , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , RNA, Viral/analysis , RNA-Dependent RNA Polymerase/antagonists & inhibitors , Ribavirin/administration & dosage , Ribavirin/adverse effects , Sofosbuvir/administration & dosage , Sofosbuvir/adverse effects , Treatment Outcome , United States , Viral Load/drug effects , Viral Load/methods , Viral Nonstructural Proteins/antagonists & inhibitorsABSTRACT
OBJECTIVE: To compare the long-term efficacy and tolerability of two efavirenz-containing regimens with those of an indinavir-containing regimen in the initial use of HAART. METHOD: HIV-1-infected patients (N = 1266) were randomly assigned to receive one of three regimens: efavirenz, zidovudine plus lamivudine, n = 422; efavirenz plus indinavir, n = 429; or indinavir, zidovudine plus lamivudine, n = 415. Entrance criteria included baseline viral load greater than 10 000 copies/ml HIV-1 RNA, CD4 cell count 50 cells/mul or greater, and no previous use of lamivudine, any non-nucleoside reverse-transcriptase inhibitor or protease inhibitor. The primary endpoint was the proportion of patients (response rate) in each regimen with a viral load under 400 copies/ml at 168 weeks of treatment. RESULTS: Response rates at 168 weeks were 30% in the indinavir, zidovudine, lamivudine group, 48% in the efavirenz, zidovudine, lamivudine group (P < 0.0001, difference estimate; 97.5% confidence interval (CI) 18.5; 10.9, 26), and 40% in the efavirenz plus indinavir group (P = 0.0018, difference estimate; 97.5% CI 10.2; 2.9, 17.6). Median CD4 cell counts increased above respective baselines by 292 cells/mul (efavirenz, zidovudine, lamivudine and indinavir, zidovudine, lamivudine) and 300 cells/mul (efavirenz plus indinavir). Total discontinuations were 54% (efavirenz, zidovudine, lamivudine), 63% (efavirenz plus indinavir), and 69% (indinavir, zidovudine, lamivudine) of which 13, 12 and 26%, respectively, were caused by adverse events. No new or unexpected increases in the rates or severity of adverse events occurred from long-term treatment with efavirenz-containing regimens. CONCLUSION: Long-term HIV therapy with efavirenz-containing regimens, particularly efavirenz, zidovudine, lamivudine, provides significantly greater antiviral activity and tolerability than a regimen of indinavir, zidovudine plus lamivudine.
Subject(s)
Acquired Immunodeficiency Syndrome/drug therapy , Benzoxazines/therapeutic use , HIV-1 , Reverse Transcriptase Inhibitors/therapeutic use , Acquired Immunodeficiency Syndrome/virology , Adolescent , Adult , Aged , Aged, 80 and over , Alkynes , Antiretroviral Therapy, Highly Active , Benzoxazines/administration & dosage , Cyclopropanes , Drug Administration Schedule , Europe , Female , Humans , Male , Middle Aged , North America , Reverse Transcriptase Inhibitors/administration & dosage , Treatment Outcome , Viral LoadABSTRACT
The safety and antiviral activity of lopinavir (Lpv), a protease inhibitor (PI) coformulated with ritonavir (Rtv) to enhance its pharmacokinetic properties, were evaluated in 70 patients with plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 1000-100,000 copies/mL on a first PI-containing regimen. Patients were randomized to substitute only the PI with Lpv/Rtv, 400/100 mg or 400/200 mg twice daily. On day 15, nevirapine (200 mg 2x/day) was added, and nucleoside reverse-transcriptase inhibitors were changed. Despite a >4-fold reduction in phenotypic susceptibility to the preentry PI in 63% of patients, mean plasma HIV-1 RNA levels declined by 1.14 log(10) copies/mL after 2 weeks of Lpv/Rtv. At week 48, 86% of subjects receiving treatment had plasma HIV-1 RNA levels of <400 copies/mL; 76% had levels <50 HIV-1 RNA copies/mL (intent-to-treat: 70% and 60%, respectively). Mean CD4 cell counts increased by 125 cells/muL. Three patients discontinued therapy for drug-related adverse events.