[Interruption of antiretroviral therapy in chronically HIV-infected patients]. / Interrupción del tratamiento antirretroviral en pacientes con infección crónica por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: To describe the immunological, virological and clinical outcomes of HIV-infected patients who stop antiretroviral therapy (ART) and to identify the factors related to durability. PATIENTS AND METHOD: Retrospective study of patients who interrupt therapy after six months without clinical events, level of CD4+ > or = 500 cells/microl and HIV RNA > or = 5,000 copies/ml (3.7 log10). RESULTS: In October 2004, 44 patients were included, 32 (72%) of them were stables after one year of ART cessation (group A) and 12 (28%) patients had to restart therapy due to a decreased CD4+ count < 300 cells/microl (group B). Both groups were compared. CD4 cell count nadir (414 cells/microl [199] versus 171 cells/microl [107]; p = 0.000) and CD4+ count level at time of ART stop (920 [302] cells/microl versus 633 cells/microl [177] p = 0.004) showed differences with statistical significance. The most important CD4+ count fall was observed at third month after stopping ART; 588 cells/microl (288) on group A and 382 cells/microl (167) on group B. The mean time without ART was 27 months on group A and 7 months on group B. Two patients had acute retroviral syndrome, and one had Pneumocystis jiroveci pneumonia. Cholesterol levels were 199 mg/dl (42) and triglycerides 257 mg/dl (271) on ART and during interruption decreased to 155 (38) and 165 (122) mg/dl respectively. After multivariate analysis, a CD4+ count nadir > 200 cells/microl (p = 0,0005; OR = 0,12; 95% CI, 0.036-0,398) and a CD4+ count at time of ART stop > 800 cells/microl (p = 0,04; OR: 0,11; CI 95%: 0,015-0,936) were independently related to durability of therapy interruption. CONCLUSIONS: Prolonged discontinuation of ART guided by CD4+ response causes a low morbi-mortality. The cell count CD4+ nadir and the CD4+ count at time of ART cessation are protective factors of durability. An improvement of metabolic parameters is observed during the discontinuation of ART.

Experimental diabetes induces hyperreactivity of rabbit renal artery to 5-hydroxytryptamine.

The influence of diabetes on the response of isolated rabbit renal arteries to 5-hydroxytryptamine (5-HT) was examined. 5-HT induced a concentration-related contraction that was higher in arteries from diabetic rabbits than in arteries from control rabbits. Endothelium removal did not significantly modify 5-HT contractions in arteries from control rabbits but enhanced the response to 5-HT in arteries from diabetic rabbits. Incubation with N(G)-nitro-L-arginine (L-NA) enhanced contractions to 5-HT in arteries from control and diabetic rabbits. In arteries with endothelium, this L-NA enhancement was lower in diabetic rabbits than in control rabbits. In arteries without endothelium, incubation with L-NA enhanced the maximal contractions to 5-HT in control rabbits but did not in diabetic rabbits. Indomethacin inhibited 5-HT-induced contraction of arteries from control rabbits and enhanced the maximal contraction to 5-HT of arteries from diabetic rabbits. In summary, diabetes enhances contractile response of rabbit renal artery to 5-HT. In control animals, this response is regulated by both endothelial and non-endothelial (neuronal) nitric oxide (NO) and by a vasoconstrictor prostanoid. Diabetes impairs the release of non-endothelial NO and the vasoconstrictor prostanoid.

Cross-sectional epidemiology of hepatitis C virus detection and treatment in HIV-infected patients.

BACKGROUND: Sustained virologic response to peginterferon plus ribavirin reduces liver-related complications and mortality in patients co-infected with HIV and hepatitis C virus. Therefore, the presence of any barriers to start hepatitis C virus therapy should be identified and eliminated in order to recruit all eligible patients. METHODS: Cross-sectional study. In a HIV referral clinic we assessed the proportion of patients eligible for hepatitis C virus evaluation and treatment according to consensus guidelines. RESULTS: We identified 134 patients with hepatitis C virus and HIV co-infection. Twenty-one patients were excluded from the analysis due to never attending the HIV clinic (n=12) or having hepatitis C virus RNA not detectable (n=9). In the remaining 113 patients, only 61% had identification of hepatitis C virus genotype and quantification of hepatitis C viral load. Thirty-six patients started peginterferon plus ribavirin, and 16 (44%) achieved sustained virologic response. Seventy-seven patients did not receive treatment for hepatitis C virus due to the presence of medical contraindications (n=22), provider barriers (n=15), or patient barriers (n=40). Multivariate analysis identified lower education degree (odds ratio: 4.53; 95% confidence intervals: 1.36-15.16, p=0.014) and patient civil status single, separated or widower (odds ratio: 4.81; 95% confidence intervals: 1.54-14.99, p=0.007) as the independent determinants associated to not initiating therapy for hepatitis C virus infection in patients with barriers. CONCLUSION: A minor proportion of HIV-infected patients received appropriate assessment and treatment for hepatitis C virus infection. Social disadvantages require multidisciplinary models of health care to improve hepatitis C virus treatment initiation and success.

Net benefits of resistance testing directed therapy compared with standard of care in HIV-infected patients with virological failure: A meta-analysis.

BACKGROUND: We incorporated the latest available information to evaluate the net benefit of using resistance testing in HIV-infected patients with virological failure. METHODS: Meta-analysis of randomized controlled trials comparing the clinical impact of selecting antiretroviral therapy according to results of resistance testing (phenotype or genotype) or according to the standard of care. The population studied included HIV-infected patients with virological failure. The outcome measures were the proportion of patients with HIV-RNA below the detection limit, and the decline in HIV-RNA and increase in CD4 lymphocyte count at the end of follow-up (< or = 24 weeks). Clinical trials were identified through searches in MEDLINE, EMBASE and proceedings from major infectious diseases meetings. RESULTS: Eight trials including a total of 1810 patients were eligible. Therapy guided by resistance testing resulted in a higher percentage of patients with HIV-1 RNA below the detection limit at the end of follow-up (< or = 24 weeks) as compared with the standard of care (40.2% vs. 32.9%). The pooled risk ratio was 1.23; 95% CI 1.09-1.40, p = 0.0009; test for heterogeneity I(2)=0%; p = 0.46). The number needed to treat [NNT] was 13 (95% CI: 9-25). Subgroup analysis showed greater benefits in therapy guided by genotype testing with expert interpretation, when compared with standard of care (NNT: 5; 95% CI: 3-9; p = 0.06). The heterogeneity among trials for evaluating HIV-1 RNA decline and CD4 lymphocyte cell count increase made unfeasible pooling the results across studies. CONCLUSION: Genotype testing with expert interpretation showed the greatest benefit for guiding therapy in patients with HIV infection and virological failure.