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In this preliminary study, a combination of a protease inhibitor, a nonnucleoside polymerase inhibitor, and ribavirin was effective for the treatment of HCV genotype 1 infection. Hepatitis C virus (HCV) infection is a leading cause of cirrhosis, liver cancer, and liver transplantation. Peginterferon-free regimens of direct-acting antiviral agents have the potential to improve both the safety and efficacy of HCV therapy, as compared with the current standard treatment of peginterferon and ribavirin with telaprevir or boceprevir. 1 , 2 Interferon is associated with substantial toxicity, and many patients with HCV infection are not eligible for interferon therapy owing to coexisting medical or psychiatric conditions or adverse events related to interferon, or they decline such therapy. 3 , 4 There is also a large population of HCV-infected patients in whom interferon . . .

In this phase 2 study, peginterferon-free regimens were effective in patients with hepatitis C virus genotype 1 infection. Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis, liver cancer, and end-stage liver disease. 1 The current standard of care for chronic HCV genotype 1 infection is pegylated interferon (peginterferon) and ribavirin, with a protease inhibitor (boceprevir or telaprevir). 2 Although the addition of a protease inhibitor has been associated with a significant increase in response rates, only approximately one third of patients who had not had a response to prior therapy with peginterferon and ribavirin had a sustained virologic response when re-treated with the addition of a protease inhibitor. 3 , 4 Furthermore, these therapies are associated with adverse . . .

Residual viremia can be detected in most HIV-1-infected patients on antiretroviral therapy despite suppression of plasma RNA to <50 copies per ml, but the source and duration of this viremia is currently unknown. Therefore, we analyzed longitudinal plasma samples from 40 patients enrolled in the Abbott M97-720 trial at baseline (pretherapy) and weeks 60 to 384 by using an HIV-1 RNA assay with single-copy sensitivity. All patients were on therapy (lopinavir/ritonavir, stavudine, and lamivudine) with plasma HIV RNA <50 copies per ml by week 96 of the study and thereafter. Single-copy assay results revealed that 77% of the patient samples had detectable low-level viremia (≥1 copy per ml), and all patients had at least one sample with detectable viremia. A nonlinear mixed effects model revealed a biphasic decline in plasma RNA levels occurring over weeks 60 to 384: an initial phase of decay with a half-life of 39 weeks and a subsequent phase with no perceptible decay. The level of pretherapy viremia extrapolated for each phase of decay was significantly correlated with total baseline viremia for each patient (R² = 0.27, P = 0.001 and R² = 0.19, P < 0.005, respectively), supporting a biological link between the extent of overall baseline viral infection and the infection of long-lived reservoirs. These data suggest that low-level persistent viremia appears to arise from at least two cell compartments, one in which viral production decays over time and a second in which viral production remains stable for at least 7 years.

Antiretroviral-naive HIV-1-infected volunteers received zidovudine/lamivudine plus either lopinavir/ritonavir (n = 104) or efavirenz (n = 51). Lopinavir/ritonavir-treated subjects demonstrating 3 consecutive monthly HIV-1 RNA levels <50 copies/mL started lopinavir/ritonavir monotherapy. In previous-failure=failure analysis, 48% (lopinavir/ritonavir) and 61% (efavirenz) maintained HIV-1 RNA at <50 copies/mL through week 96, (P = .17; 95% confidence interval [CI] for the difference, −29% to 4%); in noncompletion=failure analysis, 60% (lopinavir/ritonavir) and 63% (efavirenz) maintained HIV-1 RNA at <50 copies/mL at week 96 (P = .73; 95% CI for the difference, −19% to 13%). Significant sparing of peripheral lipoatrophy was noted in the lopinavir/ritonavir simplification strategy. This study has provided important information for future studies using treatment simplified to lopinavir/ritonavir monotherapy. Trial registration. ClinicalTrials.gov identifier: NCT00075231.

In this trial in previously untreated patients with HCV genotype 1 infection and no cirrhosis, high rates of sustained response were achieved with three new direct-acting antiviral agents and ribavirin. Serious adverse events and treatment discontinuation were infrequent. Approximately 184 million people worldwide have chronic hepatitis C virus (HCV) infection, and more than 350,000 people die of HCV-related liver disease each year. 1 , 2 Until recently, the standard of care for chronic HCV genotype 1 infection was a first-generation protease inhibitor, telaprevir or boceprevir, with peginterferon and ribavirin; this therapy resulted in rates of sustained virologic response of 67 to 75% among previously untreated patients. 3 , 4 The new standard of care is peginterferon and ribavirin combined with either the nucleotide nonstructural (NS) 5B polymerase inhibitor sofosbuvir or the protease inhibitor simeprevir. 5 Peginterferon-based treatment is associated with clinically significant systemic . . .

In patients with HCV genotype 1 infection and cirrhosis, the rate of sustained virologic response was 92% with three new antiviral agents plus ribavirin for 12 weeks and 96% with the same regimen for 24 weeks. Two percent of patients discontinued treatment because of adverse events. An estimated 184 million people worldwide have hepatitis C virus (HCV) infection, 1 a leading cause of chronic liver disease and the leading indication for liver transplantation globally. 2 , 3 Approximately 25% of persons with HCV infection in the United States have cirrhosis, and this number is expected to rise to 37% by 2020. 4 , 5 Eradication of HCV with antiviral therapy reduces the risk of hepatic decompensation, hepatocellular carcinoma, and death from a liver-related cause or any cause. 6 – 10 Among patients with HCV infection and cirrhosis in whom peginterferon–ribavirin treatment has failed, rates of sustained virologic response to retreatment with interferon-containing regimens . . .

In this trial in patients with HCV genotype 1 infection and no cirrhosis who had previously been treated with peginterferon and ribavirin, retreatment with three new oral antiviral agents and ribavirin resulted in a sustained virologic response in 96% of patients. Patients with chronic hepatitis C virus (HCV) infection are at risk for progressive liver fibrosis, cirrhosis, portal hypertension, hepatocellular carcinoma, and decompensated liver disease. HCV infection can be cured with antiviral therapy, reducing the risk of illness and death associated with end-stage liver disease. 1 – 3 For more than a decade, patients with HCV genotype 1 infection have been treated with peginterferon–ribavirin dual therapy, resulting in rates of sustained virologic response of approximately 40 to 50%. 4 – 6 Response rates among previously untreated patients have been shown to increase to 68 to 75% with peginterferon–ribavirin plus a protease inhibitor (telaprevir or boceprevir, . . .

Baseline CD4 cell counts and human immunodeficiency virus (HIV)-1 RNA levels have been shown to predict immunologic and virologic responses in HIV-infected patients receiving antiretroviral therapy. In our randomized, double-blind, comparative trial, 653 antiretroviral therapy-naive patients received lopinavir/ritonavir or nelfinavir, plus stavudine and lamivudine, for up to 96 weeks. The risk of loss of virologic response was significantly higher for nelfinavir-treated patients than for lopinavir/ritonavir-treated patients (Cox model hazard ratio, 2.2; 95% confidence interval, 1.7–3.0; P <.001). For nelfinavir-treated patients, but not for lopinavir/ritonavirtreated patients, higher baseline HIV-1 RNA levels and lower baseline CD4 cell counts were associated with a higher risk of loss of virologic response.

In this study of the initial treatment of human immunodeficiency virus (HIV) infection, 653 patients were randomly assigned to treatment with either lopinavir–ritonavir or nelfinavir. All patients also received stavudine and lamivudine. After 48 weeks, there was suppression of HIV RNA to fewer than 50 copies per milliliter in 67 percent of the patients in the lopinavir–ritonavir group, as compared with 52 percent of those in the nelfinavir group (P<0.001). Protease inhibitor–based combination antiretroviral therapy has led to dramatic improvements in morbidity and mortality associated with human immunodeficiency virus (HIV) infection. 1 – 4 However, virologic failure occurs within 12 months in up to 50 percent of patients in whom combination antiretroviral therapy is initiated. 5 – 7 Major factors contributing to failure are poor tolerability and toxicity of the drugs, incomplete adherence to the regimen on the part of patients, and pharmacokinetic properties that result in trough concentrations close to or below the levels required to inhibit HIV replication effectively. 8 , 9 Lopinavir is a novel peptidomimetic protease inhibitor with potent in vitro activity . . .