Sofosbuvir plus ribavirin for treatment of hepatitis C virus in patients co-infected with HIV (PHOTON-2): a multicentre, open-label, non-randomised, phase 3 study.

BACKGROUND: Although interferon-free regimens are approved for patients co-infected with HIV and genotype-2 or genotype-3 hepatitis C virus (HCV), interferon-based regimens are still an option for those co-infected with HIV and HCV genotypes 1 or 4. These regimens are limited by clinically significant toxic effects and drug interactions with antiretroviral therapy. We aimed to assess the efficacy and safety of an interferon-free, all-oral regimen of sofosbuvir plus ribavirin in patients with HIV and HCV co-infection. METHODS: We did this open-label, non-randomised, uncontrolled, phase 3 study at 45 sites in seven European countries and Australia. We enrolled patients (aged ≥18 years) co-infected with stable HIV and chronic HCV genotypes 1-4, including those with compensated cirrhosis. Once-daily sofosbuvir (400 mg) plus twice-daily ribavirin (1000 mg in patients with bodyweights <75 kg and 1200 mg in those with weights ≥75 kg) was given for 24 weeks to all patients except treatment-naive patients with genotype-2 HCV, who received a 12-week regimen. The primary efficacy endpoint was sustained virological response 12 weeks after treatment. We did analysis by modified intention to treat. This study is registered with ClinicalTrials.gov, number NCT01783678. FINDINGS: Between Feb 7, 2013, and July 29, 2013, we enrolled 275 eligible patients, of whom 262 (95%) completed treatment; 274 patients were included in the final analysis. Overall rates of sustained virological response 12 weeks after treatment were 85% (95% CI 77-91) in patients with genotype-1 HCV, 88% (69-98) in patients with genotype-2 HCV, 89% (81-94) in patients with genotype-3 HCV, and 84% (66-95) in patients with genotype-4 HCV. Response rates in treatment-naive patients with HCV genotypes 2 or 3 (89% [95% CI 67-99] and 91% [81-97], respectively) were similar to those in treatment-experienced patients infected with those genotypes (83% [36-100] and 86% [73-94], respectively). There was no emergence of sofosbuvir-resistance mutations in patients with HCV viral relapse. Six (2%) patients discontinued treatment because of adverse events. The most common adverse events were fatigue, insomnia, asthenia, and headache. Four (1%) patients had serious adverse events regarded as related to study treatment. Additionally, four (1%) patients receiving antiretroviral treatment had a transient HIV viral breakthrough; however, none required changes in antiretroviral regimen. INTERPRETATION: Sofosbuvir and ribavirin provided high rates of sustained virological response after 12 weeks of treatment in treatment-naive and treatment-experienced patients co-infected with HIV and HCV genotypes 1-4. The characteristics of this interferon-free combination regimen make sofosbuvir plus ribavirin a useful treatment option for this patient population. FUNDING: Gilead Sciences.

Inflammatory, procoagulant markers and HIV residual viremia in patients receiving protease inhibitor monotherapy or triple drug therapy: a cross-sectional study.

BACKGROUND: Protease inhibitor monotherapy is associated with more frequent episodes of viral rebounds above 50 copies/mL than triple therapy. OBJECTIVE: To evaluate if, compared to triple-drug therapy, protease inhibitor monotherapy is associated with increased levels of inflammatory/procoagulant markers and more frequent plasma residual viremia detection. METHODS: In this cross-sectional study, we included patients treated for ≥ 1 year with darunavir/ritonavir or lopinavir/ritonavir as monotherapy (n=72) or with two nucleos(t)ides (n=74). All samples were tested for CRP, IL-6, fibrinogen and D-dimer. Residual viremia was determined using an ultrasensitive qualitative nested-PCR of the HIV pol gene with a limit of detection of 1 copy of HIV-RNA. RESULTS: We found no differences in levels of inflammatory/procoagulant markers or in the proportion of patients with plasma residual viremia detection by treatment group. CONCLUSION: The long-term treatment with protease inhibitor monotherapy in the setting of routine clinical practice is not associated with a higher prevalence of plasma residual viremia or more elevated inflammatory/procoagulant markers levels than triple drug therapy.

[Hypertension, HIV infection, and highly active antiretroviral therapy]. / Hipertensión arterial, infección por el virus de la inmunodeficiencia humana y tratamiento antirretrovírico de gran actividad.

The decline in mortality resulting from the use of highly active antiretroviral therapy (HAART) has been accompanied by an increase in metabolic complications that produce accelerated atherosclerosis. Hypertension is one of the most important cardiovascular risk factors. Little is known about the impact of HAART on blood pressure, and it is uncertain whether chronic HIV infection or HAART have a role in the development of hypertension. In this study, the research on the relationships between hypertension and HIV infection published to date is reviewed. Antiretroviral therapy appears to have a modest impact on blood pressure and to be partially mediated by the metabolic changes occurring with this treatment.

Infectious and non-infectious diseases burden among Haitian immigrants in Chile: a cross-sectional study.

Chile has become a popular destination for migrants from South America and the Caribbean (low- and middle-income countries migration). Close to 200.000 Haitian migrants have arrived in Chile. Infectious and non-infectious disease burden among the Haitian adult population living in Chile is unknown. This study aimed to acquire the basic health information (selected transmissible and non-transmissible conditions) of the Haitian adult population living in Chile. A cross-sectional survey was performed, inviting Haitian-born residents in Chile older than 18 years old. Common conditions and risk factors for disease were assessed, as well as selected transmissible conditions (HIV, HBV, and HCV). 498 participants (60.4% female) from 10 communities in two regions of Chile were surveyed. Most subjects had never smoked (91.5%), and 80% drank less than one alcohol unit per month. The mean BMI was 25.6, with 45% of participants having a normal BMI (20-25). Hypertension was present in 31.5% (33% in the 25-44 age group). Prevalence of HIV was 2.4% (95 CI 1.3-4.2%), hepatitis B (HBsAg positive) was 3.4% (95 CI 2.1-5.5%), and hepatitis C was 0% (95 CI 0.0-0.9%). Quality of life showed a significant prevalence of depression and anxiety markers, particularly in those arriving in Chile less than 1 year ago. Low prevalence of obesity, diabetes, smoking, and drinking and estimated cardiovascular risk were found. Nonetheless, hypertension at a younger age, disproportionately higher prevalence of HIV and HBV infection and frequent markers of anxiety and depression were also found. Public policies for detecting and treating hypertension, HIV, and HBV screening, offering HBV vaccination, and organizing mental health programs for Haitian immigrants, are urgently needed.

Efficacy of a dual therapy based on darunavir/ritonavir and etravirine in ART-experienced patients.

INTRODUCTION: Nucleoside reverse transcriptase inhibitors (NRTI)-sparing regimens have been studied in antiretroviral therapy (ART)-naïve patients but data with ART-experienced are scarce. NRTI-sparing regimens may be an option in patients with toxicities and for simplification reasons. METHODS: Retrospective multicentre analysis including ART-experienced patients starting treatment with darunavir/ritonavir and etravirine (DRV/r 800 mg/100 mg QD or 600 mg/100 mg BID and ETV 400 mg QD or 200 mg BID) with at least six months of follow-up. Primary endpoint was proportion of patients with VL<50 copies/mL at 48 weeks with an ITT analysis (missing or switch equals failure). Secondary endpoints were safety, CD4 count and lipid changes over 48 weeks. RESULTS: Seventy-five patients were included of whom 44 (58.6%) had HIV RNA<50 copies/mL. Baseline characteristics: median age 50 years (IQR 34-65), 72% males, 93% Caucasians, 38.6% hepatitis C, and 45.4% with CDC C stage. Median HIV duration and time on ART were 20 (IQR 7-28) and 14 years (IQR 5-21) respectively. Reasons for switching were virologic failure in 27 (36%), simplification in 25 (33.3%), toxicity in 20 (26.6%) and other 3 (4.1%). Most of them received DRV/r and ETV QD. Thirty-nine patients had NNRTI resistance mutations [28 K103N (37.3%), 6 Y181I/C (8%), 3 G190A (4%)] and 29 patients had ≥1 primary PI mutations. Main analysis (ITT) showed that 67 (89.3%) had a VL undetectable at 24 weeks (95% CI 83.1-95.5) and 57 (76%) at 48 weeks (95% CI 68.4-83.6). On treatment analysis showed that 94.3% and 89% had a viral load<50 copies at 24 and 48 weeks, respectively. 11 (14.6%) patients discontinued the regimen (three virologic failures, three switching to darunavir/ritonavir monotherapy, two to salvage regimen and three due to toxicity). No significant changes in CD4+ count and lipid changes were observed at 48 weeks. CONCLUSIONS: Dual therapy with Darunavir/ritonavir and etravirine is an efficacious and safety option in ART-experienced HIV patients even in patients on virologic failure.

Is etravirine and two nucleosides an option for HIV with an isolated K103N mutation?

We report long-term virologic response to etravirine and tenofovir/emtricitabine in four HIV-1-infected patients who had prior standard genotypic resistance testing showing an isolated K103N mutation (three acquired, one transmitted). In three patients tested, the K103N mutation was detected in cellular HIV-1 DNA whereas remaining suppressed on etravirine plus tenofovir/emtricitabine.

Hypertension and isolated office hypertension in HIV-infected patients determined by ambulatory blood pressure monitoring: prevalence and risk factors.

OBJECTIVE: To determine prevalence and risk factors for hypertension and isolated office hypertension diagnosed by ambulatory blood pressure monitoring in HIV-infected patients. METHODS: Cross-sectional study of 310 patients. A 24-hour ambulatory blood pressure monitoring procedure was performed on the nondominant arm in those patients showing office systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg. RESULTS: Twenty patients (6.5%) had a prior diagnosis of hypertension. Hypertension was confirmed by ambulatory blood pressure monitoring in 26 patients and isolated office hypertension in 17 patients. Isolated office hypertension and hypertension prevalence were 5.5% (95% confidence interval: 3 to 8) and 14.8% (95% confidence interval; 10.8 to 18.8), respectively. Isolated office hypertension was present in 39% of patients with office hypertension. In the univariate analysis, variables significantly associated with hypertension were age, waist circumference, established cardiovascular disease, family history of hypertension, lipoatrophy, metabolic syndrome, duration of infection, CD4 nadir, HIV RNA <50 copies/mL, and antiretroviral treatment. In the multivariate analysis, family history of hypertension [odds ratio (OR): 2.24; P = 0.027], increasing age (OR: 1.08; P < 0.001), and number of different antiretroviral regimens (OR: 1.2; P = 0.001) were associated with hypertension and female gender (OR: 0.27; P = 0.02) had a protective effect. CONCLUSIONS: The prevalence of hypertension using ambulatory blood pressure monitoring in HIV-infected patients was 15%. Because isolated office hypertension occurs in 39% of HIV-infected patients with office hypertension, ambulatory blood pressure monitoring could be useful to confirm the diagnosis of hypertension. Hypertension is strongly associated with family history of hypertension, male gender, age, and number of antiretroviral regimens.

Respuesta de los autores: Monitorizacion ambulatoria de la presion arterial en el paciente VIH / Author’s reply: Outpatient blood pressure monitoring of the HIV patient

No disponible

No disponible

Mujer de 50 años con infiltrados pulmonares / 50-year-old woman with pulmonary infiltrates

No disponible

No disponible