High quality of life, treatment tolerability, safety and efficacy in HIV patients switching from triple therapy to lopinavir/ritonavir monotherapy: A randomized clinical trial.

TRIAL DESIGN: The QoLKAMON study evaluated quality of life, efficacy and treatment safety in HIV patients receiving lopinavir/ritonavir in monotherapy (MT) versus continuing combined antiretroviral triple treatment with a boosted protease inhibitor (TT). METHODS: This was a 24-week, open-label, multicentre study in virologically-suppressed HIV-infected participants (N = 225) with a 2:1 randomization: 146 patients who switched to MT were compared with 79 patients who remained on a TT regimen. The primary endpoint was change in patient-reported outcomes in quality of life as measured by the MOS-HIV and EQ-5D questionnaires. Secondary endpoints included treatment adherence, patient satisfaction, incidence of adverse events and differences in plasma HIV-1 RNA viral load (VL) and CD4 cell counts. RESULTS: Baseline quality of life, measured with the MOS-HIV score, was very good (overall score of 83 ± 10.5 in the MT arm and 82.3 ± 11.3 in the TT arm) and suffered no change during the study in any of the arms (at week 24, 83.5 ± 12.2 in MT arm and 81.9 ± 12.7 in TT arm), without statistically significant differences when compared. In regards to adherence to therapy and patient satisfaction, some aspects (number of doses forgotten in the last week and satisfaction of treatment measured with the CESTA score, dimension 1) improved significantly with MT. There were also no differences in the incidence and severity of adverse events, even though 22.8% of those in the MT arm switched their treatment when they were included in the study. Moreover, there was also no significant difference between the immunological and virological evolution of MT and TT. In the MT arm, the VL was always undetectable in 83% of patients (vs 90.7% in the TT arm) and there were only 6.7% of virological failures with VL > 50 copies/mL (vs 2.3% in the TT arm), without resistance mutations and with resuppression of VL after switching back to TT. CONCLUSIONS: In a new clinical trial, monotherapy as a treatment simplification strategy in HIV-1 infected patients with sustained viral suppression has demonstrated quality of life, safety and efficacy profiles comparable to those of conventional triple therapy regimens.

[LDL-cholesterol levels in a series of HIV-infected patients]. / Colesterol ligado a lipoproteínas de baja densidad en una serie de pacientes con infección por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: To analyse the prevalence of HIV-infected patients who do not reach their target LDL-cholesterol (LDL-C) levels. PATIENTS AND METHODS: Multicenter, cross-sectional study of all HIV-infected patients on regular follow-up in 5 hospitals in the province of Malaga (March-August/07). They were classified depending on their target LDL-C levels (NCEP): group A:<160mg/dl, if /=2 CVRF; group C: <100mg/dl, if cardiovascular disease or equivalents or CVR at 10 years >20%). A comparison between patients reaching their target LDL-C levels and those not reaching them was done. Statistic program: SPSS. RESULTS: Of 1019 included patients, 232 (22.8%) did not reach their target LDL-C levels. There were 693 patients in Group A, 163 in Group B, and 153 in Group C (6.6%, 53.3 % and 65.0% respectively (p<0.05)) who did not reach their target LDL-C. Factors associated with LDL-C levels higher than target were: obesity (OR=1.98; 95%CI: 1.14-3.46; p=0.01), time on antiretroviral therapy (for each 2 years OR=1.92; 95%CI: 1.85-1.99; p=0.02), and being included in Groups B and C (OR=16.9; 95%CI: 10.8-26.6; p=0.00001). CONCLUSIONS: More than 20% of the patients in this cohort did not reach their target LDL-C levels. Factors associated with high LDL-C levels were central obesity, time on antiretroviral therapy and being included in Groups B and C.

Hepatic safety of tipranavir plus ritonavir (TPV/r)-based antiretroviral combinations: effect of hepatitis virus co-infection and pre-existing fibrosis.

OBJECTIVES: The aim of this study was to evaluate the incidence and risk factors of severe liver events among HIV-infected patients treated with drug combinations including tipranavir boosted with ritonavir (TPV/r). METHODS: One hundred and fifty patients were selected because they started a regimen that included TPV/r (500/200 mg twice a day) and had clinical visits at least every 3 months. Patients who discontinued TPV/r before their first visit were included. RESULTS: Twelve (8%) individuals developed grade>or=3 transaminase elevation (G>or=3TE). Nine (6%) patients discontinued TPV/r due to liver events. Six (8.6%) of 70 hepatitis C virus (HCV) co-infected patients and 6 (7.5%) of 80 subjects without HCV co-infection developed G>or=3TE (P=1). Liver fibrosis was evaluable in 48 (63%) of 76 individuals with hepatitis B virus and/or HCV infection. Four (13%) of 30 subjects with moderate-to-severe fibrosis and none of 18 with mild fibrosis showed G>or=3TE (P=0.3). None of nine patients with cirrhosis showed G>or=3TE. CONCLUSIONS: Liver tolerability of TPV/r was generally good in a cohort of patients with a high proportion of HCV co-infection, including subjects with advanced fibrosis. The presence of HCV co-infection was not associated with an increased risk of severe transaminase elevations.

High prevalence of hepatitis C virus subtypes 4c and 4d in Malaga (Spain): phylogenetic and epidemiological analyses.

Hepatitis C virus (HCV) is a major aetiological agent of chronic hepatitis and it may lead to the development of liver cirrhosis and hepatocellular carcinoma. HCV has been classified into six clades as a result of high genetic variability. A commercial procedure to genotype HCV in 678 patients from Carlos Haya Regional University Hospital, Malaga was used to study the distribution of HCV genotypes in Malaga, southern Spain. A high prevalence of HCV-4 (10.2%) was found. This genotype is found more commonly in Egypt, Central Africa and the Middle East. The distribution of the different subtypes in the 69 patients with HCV-4 was as follows: 4.3% subtype 4e, 7.2% subtype 4a, 11.5% not subtypable, and 76.8% subtype 4c/4d. Of the 53 4c/4d patients, 69% were intravenous drug users and 31% non-intravenous drug users. In order to characterise further the HCV-4c/4d patients, sequences of the non-structural 5B gene (393 bp) were obtained from 36 HCV-4c/4d-infected untreated patients. Phylogenetic tree topologies distinguished clearly the two subtypes: 11 patients were infected by subtype 4c and 25 by 4d. This phylogenetic analysis, reinforced by the epidemiological characteristics, suggests the extension of the HCV-4c and -4d subtypes in the area of Malaga among both intravenous drug users and non-intravenous drug users.