didanosine and Lipodystrophy

The impact of antiretroviral drug exposure and associated lipodystrophy and/or insulin resistance (IR) on advanced liver fibrosis in HIV/HCV-coinfected patients is not fully documented. We determined the prevalence of advanced liver fibrosis (defined by hepatic stiffness ≥9.5 kPa) and associated factors, focusing on the impact of highly active antiretroviral therapy and its major adverse effects (lipodystrophy and IR), in 671 HIV/HCV-coinfected patients included in the ANRS CO13 HEPAVIH cohort. One hundred ninety patients (28.3%) had advanced liver fibrosis. In univariate analysis, advanced liver fibrosis was significantly associated with male sex, higher body mass index, HCV infection through intravenous drug use, a lower absolute CD4 cell count, a longer history of antiretroviral treatment, longer durations of protease inhibitors, non-nucleoside reverse transcriptase inhibitors and NRTI exposure, lipodystrophy, diabetes, and a high homeostasis model assessment method (HOMA) value. The only antiretroviral drugs associated with advanced liver fibrosis were efavirenz, stavudine and didanosine. In multivariate analysis, male sex (OR 2.0, 95% CI 1.1-3.5; P = 0.018), HCV infection through intravenous drug use (OR 2.0, 95% CI 1.1-3.6; P = 0.018), lipodystrophy (OR 2.0, 95% CI 1.2-3.3; P = 0.01), median didanosine exposure longer than 5 months (OR 1.7, 95% CI 1.0-2.8; P = 0.04) and a high HOMA value (OR 1.1, 95% CI 1.0-1.2; P = 0.005) remained significantly associated with advanced liver fibrosis. Mitochondrial toxicity and IR thus appear to play a key role in liver damage associated with HIV/HCV-coinfection, and this should be taken into account when selecting and optimizing antiretroviral therapy. Antiretroviral drugs with strong mitochondrial toxicity (e.g. didanosine) or a major effect on glucose metabolism should be avoided.

Topics: Adult; Alkynes; Antiretroviral Therapy, Highly Active; Antiviral Agents; Benzoxazines; CD4 Lymphocyte Count; Coinfection; Cyclopropanes; Didanosine; Female; Hepatitis C; HIV Infections; Humans; Insulin Resistance; Lipodystrophy; Liver Cirrhosis; Male; Middle Aged; Mitochondria; Sex Factors; Stavudine

Topics: Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Blepharoptosis; Didanosine; DNA, Mitochondrial; Genetic Predisposition to Disease; HIV Infections; Humans; Lipodystrophy; Male; Middle Aged; Mitochondria; Mitochondrial Diseases; Muscle, Skeletal; Mutation; Oculomotor Muscles; Ophthalmoplegia; Ophthalmoplegia, Chronic Progressive External; Recovery of Function; Risk Factors; Time

We report a case of gynaecomastia developed in a HIV-seropositive man, associated with a severe lipodystrophy. We hypothesize the responsibility of stavudine and didanosine in the development of these 2 complications. If many reports suggest that the protease inhibitors may promote gynaecomastia, long-term nucleoside analogue therapy may also cause this side effect.

Topics: Adult; Anti-HIV Agents; Didanosine; Gynecomastia; HIV Infections; HIV Seropositivity; Humans; Lipodystrophy; Male; Stavudine

HIV-protease inhibitors demonstrated such high efficacy in short-term studies that they have been approved by the FDA, even though possible toxicity still needs further investigation. In the period between January 1997 and August 1998, 101 patients, staying at San Patrignano Medical Centre (Italy), received an HIV protease inhibitor (indinavir) plus two nucleoside reverse transcriptase inhibitors (NRTI's) selected from the following: AZT, didanosine, zalcitabine, lamivudine or stavudine. Seventy-three patients were male, 28 female and their ages ranged from 25 to 60 years, with an average of 34. At the end of the study, 84 patients were suitable for evaluation, as the other 17 dropped out for various reasons. Forty-eight patients (57.1%) developed cheilitis, 34 (40.5%) experienced diffuse cutaneous dryness and pruritus, 10 (11.9%) developed asteatotic dermatitis on the trunk, arms and thighs and another 10 (11.9%) complained of scalp defluvium. A severe alopecia was observed in only 1 patient (1.2%), while 6 reported that their body hair had become fairer, thinner and shed considerably. Multiple pyogenic granulomas were observed in the toenails of 5 patients (5. 9%). Softening of the nail plate was noted in 5 subjects as well. A peripheral lipodystrophy syndrome was noted in 12 patients (14.3%). Among these, one patient only developed a "buffalo hump" and another had diffused lipomatosis. The temporal relationship between the taking of indinavir and the onset of such cutaneous effects was striking. This was confirmed by the regression of symptoms in those patients who later discontinued indinavir. The emerging side effects of protease inhibitors require a multidisciplinary team for adequate diagnosis and treatment. Cutaneous toxicity involving the patient's own body image has a peculiar influence on compliance to the treatment and the patient's quality of life.

Topics: Adult; Alopecia; Didanosine; Drug Eruptions; Drug Therapy, Combination; Female; HIV; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Lamivudine; Lipodystrophy; Male; Middle Aged; Pruritus; Pyoderma Gangrenosum; Retrospective Studies; Reverse Transcriptase Inhibitors; RNA, Viral; Scalp Dermatoses; Skin; Stavudine; Zalcitabine; Zidovudine

Topics: Adipose Tissue; Anti-HIV Agents; Didanosine; HIV Infections; HIV-1; Humans; Lipodystrophy; Male; Middle Aged; Stavudine