indinavir-sulfate and Skin-Diseases

Since 1998, many cases of antiretroviral therapy-related paronychia of the toes or fingers and ingrown toenails have been reported. Most of them were related to indinavir. Other indinavir-induced mucocutaneous disorders resembling the adverse effects of systemic retinoid therapy have also been reported. Although there is some uncertainty in the literature regarding a cause-effect relationship, results of several epidemiological and in vitro studies, together with cumulated clinical experience leave no doubt that indinavir causes a retinoid-like effect and nail alterations. Indeed, indinavir is the only antiretroviral drug that produces these disorders, although ritonavir may enhance indinavir-induced retinoid-like effects through pharmacokinetic interactions leading to increased plasma indinavir concentrations. Approximately 30% of patients receiving indinavir show two or more retinoid-like manifestations and 4-9% develop paronychia. These adverse effects are not related to other epidemiological variables such as the patient's sex, age or other risk factors or immune status. They seem to be exposure dependent and, therefore, largely dose-dependent. Chronic paronychia is considered generally to be caused by contact irritants and candidal infection. Nevertheless, indinavir is currently the most frequent cause of chronic or recurrent paronychia in HIV-infected patients. In addition, retinoid-like manifestations such as cutaneous xerosis and cheilitis are frequent mucocutaneous adverse effects related to indinavir. The exact mechanism of indinavir-induced retinoid-like effects is unclear. Hypotheses for pathogenesis include interference with retinoid metabolism by enhancing the retinoic acid signalling pathway, or by increasing retinoic acid synthesis, or by reducing cytochrome p450-mediated retinoic acid oxidative metabolism. Replacement of therapy by an antiretroviral regimen not containing indinavir, while retaining other protease inhibitors and lamivudine, resolves retinoid-like manifestations without recurrences.

Topics: Anti-HIV Agents; HIV Infections; Humans; Incidence; Indinavir; Retinoids; Skin Diseases

Treatment with indinavir/ritonavir (IDV/RTV) is very effective but hampered by frequent development of IDV-associated adverse events (mainly nephrotoxicity and skin changes). We tested whether dose reduction of IDV guided by therapeutic drug monitoring resulted in improved tolerability without compromising antiviral efficacy.. HIV-infected patients with any IDV/RTV regimen who suffer from IDV-related adverse events were included. Viral load had to be adequately controlled for at least 2 months prior to inclusion. Dose reduction from 800 mg to 600 or 400 mg IDV b.i.d. followed a specified protocol. IDV-related toxicity and IDV plasma concentrations were monitored for 24 weeks. IDV concentrations were quantified with a validated high performance liquid chromatography method.. Twenty patients were included. Reasons for inclusion were: skin abnormalities 11, nephrotoxicity five, metabolic disturbances three, and hypertension one. IDV dose could be lowered to 400 mg b.i.d. in 13, to 600 mg b.i.d. in two patients. Five patients discontinued the treatment. Overall tolerability improved with respect to incidence and severity of adverse events. Median trough concentrations decreased from 1.02 mg/l (range 0.08-7.1) at baseline to 0.48 mg/l (0.11-1.4) after 24 weeks (p = 0.03) and remained above the critical threshold of 0.1 mg/l at any time after dose reduction. There was no change of CD4 cell counts or viral suppression. There were no significant changes in other laboratory parameters (creatinine, bilirubin, triglycerides, cholesterol, blood count, and urinalysis).. Dose reduction of IDV improved tolerability of IDV-containing highly active antiretroviral treatment (HAART). Sufficient IDV trough concentrations were maintained in all patients as was virologic control.

Topics: Adult; Aged; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Monitoring; Female; Germany; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Hypertension; Indinavir; Kidney Diseases; Male; Metabolic Diseases; Middle Aged; Prospective Studies; Ritonavir; Severity of Illness Index; Skin Diseases; Time Factors; Treatment Outcome; Viral Load

Complaints of dry skin in HIV-infected individuals were reported after the advent of HAART. The objective of the study was to evaluate the prevalence of dry skin and associated factors in HIV-infected and control subjects.. Cross-sectional.. A total of 1026 HIV-infected subjects and 274 controls [from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based study of cardiovascular risk assessment] in the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) had skin assessed by self-report and examination. Multivariable logistic regression identified factors associated with dry skin.. Self-reported dry skin was more prevalent in HIV-infected subjects than controls. In multivariable analysis, HIV infection was associated with self-reported dry skin. In HIV-infected men, current indinavir use, CD4 cell count less than 200 cells/microl and recent opportunistic infections were associated with dry skin. Indinavir use had an elevated risk in men with CD4 cell counts of 200 cells/microl or greater but not with CD4 cell counts less than 200 cells/microl. In HIV-infected women, a CD4 cell count less than 200 cells/microl was associated with dry skin; indinavir use did not reach statistical significance but, as in men, indinavir use had an elevated risk in those with higher CD4 cell counts than in those with CD4 cell counts less than cells/microl.. Dry skin is more common in HIV-infected individuals than controls. In HIV-infected individuals, low CD4 cell counts and indinavir use in those with higher CD4 cell counts are associated with dry skin.

Topics: Adult; Antiretroviral Therapy, Highly Active; Case-Control Studies; CD4 Lymphocyte Count; Cross-Sectional Studies; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Middle Aged; Prevalence; Risk Factors; Skin Diseases; United States

Highly active antiretroviral therapy (HAART) is a combination of an HIV protease inhibitor (PI), one or two reverse transcriptase inhibitors (RTIs) and/or non-nuclease reverse transcriptase inhibitors (NNRTIs). This combination therapy is able to reduce peripheral HIV viral load, elevate CD4+ cell counts and improve the clinical outcome.. To evaluate the impact of HAART therapy, including one PI, on the prevalence of skin diseases in patients with HIV/AIDS.. The study was performed by collecting data about HIV populations followed at the 'M. Bufalini' Infectious Diseases Unit and San Patrignano Medical Centre, Italy. The medical records regarding the dermatological diseases of such people were retrospectively examined in 12-month periods before (1996) and after (1999) the introduction of HAART.. The two groups of patients were matched for age, gender and stage of HIV disease. During the first part of the study, 328 of the 456 patients (72%) sought medical advice 689 times for dermatoses. In the second period, 196 of the 502 patients (39%) made a total of 255 visits. There was a considerable decrease in the number of dermatological visits (-63%) and patients with dermatological problems (-40%). In the group that did not receive HAART, 66% of the patients had cutaneous infections, 25% had inflammatory cutaneous disorders, 8% adverse cutaneous drug reactions and 1% cutaneous neoplasms. In the group of patients treated with HAART, cutaneous infections were observed in 53% of patients, while 21% of patients had inflammatory dermatoses, 20% of patients showed adverse cutaneous drug reactions, and 1% had skin cancers. The remaining 5% asked to see a dermatologist for cosmetic reasons.. The group of patients who received combination regimens including PIs had significantly lower cutaneous morbidity than those treated with nucleoside analogs alone. This tendency included both opportunistic infections and inflammatory cutaneous diseases. Adverse cutaneous drug reactions related to multidrug combination therapy were significantly higher in the group receiving HAART.

Topics: Adult; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Italy; Male; Morbidity; Prevalence; Reverse Transcriptase Inhibitors; Skin Diseases; Treatment Outcome; Viral Load; Zidovudine

The introduction of HIV-1 protease inhibitors into the treatment of patients infected with HIV-1 has had a major influence on clinical practice. However, the use of protease inhibitors is frequently associated with the development of resistance and several side effects and interactions with other drugs have been reported.. We present the first pediatric patient with paronychia with pyogenic granuloma associated with the administration of the protease inhibitor indinavir. Clinical findings are discussed in view of a possible interference of indinavir with endogenous retinoid metabolism.. Considerable evidence advocates the mediation of indinavir side effects by impaired oxidative metabolism of retinoic acid through the inhibition of cytochromes P450 3A by indinavir rather than by impaired formation of 9-cis-retinoic acid.

Topics: Adolescent; Child; Granuloma, Pyogenic; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Male; Paronychia; Retinoids; Skin Diseases; Toes

Topics: Adolescent; Adult; Cheilitis; Female; HIV Infections; Humans; Indinavir; Male; Middle Aged; Nails, Ingrown; Paronychia; Protease Inhibitors; Skin Diseases; Time Factors