Treatment of hyperlipidemia in HIV-infected patients.

The treatment of hyperlipidemia in patients infected with HIV is discussed. Hyperlipidemia is common in HIV-infected patients receiving antiretroviral therapy, especially protease inhibitors and stavudine. The recommendations of the National Cholesterol Education Program (NCEP) may not entirely apply to HIV-infected patients. The pathogenesis of hyperlipidemia in these patients may make them refractory to traditional pharmacotherapy, and NCEP's emphasis on diet and exercise may be unrealistic. Other factors that may complicate treatment of hyperlipidemia include metabolism of many antiretroviral drugs by the cytochrome P-450 isoenzyme system, polypharmacy, and drug-food interactions. A patient's cardiac risk should first be assessed. Nonpharmacologic measures, such as a low-fat diet, weight reduction, and exercise, should be considered. Drug therapy is indicated for patients with familial combined hyperlipidemia that is associated with atherogenesis and for patients with triglyceride concentrations exceeding 1000 mg/dL. Drug therapy for hyperlipidemia involves niacin and statins, in addition to fibric acid derivatives and probucol. Switching among antiretroviral agents when one is found to cause hyperlipidemia should be done cautiously because of the risk for viral rebound and disease progression. NCEP guidelines recommend monitoring low-density-lipoprotein cholesterol levels four to six weeks after the start of lipid-lowering therapy and then at three months; more frequent monitoring may be necessary in HIV-infected patients. The treatment of hyperlipidemia in HIV-infected patients is complicated by their need for antiretroviral drugs, which can themselves contribute to lipid disorders.

Diabetes mellitus associated with recombinant human growth hormone for HIV wasting syndrome.

Recombinant human growth hormone (rhGH) is an important treatment option for patients with human immunodeficiency virus (HIV) wasting syndrome. Side effects of rhGH are minimal when administered at physiologic and moderately high dosages, as seen in growth hormone deficiency and Turner's syndrome, respectively. The dosage of rhGH is significantly higher to treat wasting syndrome and still is being studied to determine its long-term efficacy and safety. Individuals with HIV infection are at increased risk for adverse effects due to polypharmacy, immune system alterations, and treatment with newer agents that lack long-term safety data. In addition, rhGH's potential for side effects becomes greater when given at high dosages for wasting syndrome. Clinically significant hyperglycemia developed in an HIV-positive man who started rhGH for wasting syndrome 38 days before the diagnosis of diabetes mellitus.

Decreased methadone effect after ritonavir initiation.

Combination antiretroviral therapy including protease inhibitors such as ritonavir has added significant potency to therapy for human immunodeficiency viral (HIV) infection as well as substantial drug-drug interactions. Methadone metabolism is affected by cytochrome P450 (CYP) 3A4 inhibitors or inducers. Because ritonavir can induce CYP3A, it can decrease methadone plasma levels. An HIV-infected patient receiving methadone maintenance experienced withdrawal symptoms after ritonavir, saquinavir, and stavudine were added to his regimen; the most likely cause was ritonavir.

Medication adherence in patients with HIV infection: a comparison of two measurement methods.

Two measurements of adherence, patient self-report and electronic measurement by the Medication Event Monitoring System (MEMS), were compared in a 3-month adherence study of 44 HIV-infected patients who had been placed on regimens that included protease inhibitors (PIs). The dose percentage and degree of clinically significant dosing time fluctuation were calculated monthly. The mean dose percentage by self-report versus MEMS was 97.5% versus 90.3% during month 1 of adherence monitoring, 96.5 versus 90.1% during month 2, and 98.4% versus 92.8% during month 3. Thirty-two percent of patients taking PIs and 21% of patients taking nucleoside analogues demonstrated clinically significant dosing time fluctuation. Our data confirm that self-reports of adherence overestimate true adherence behavior, and patients' self-reports of dosing times may not accurately reflect their deviation from those times.

Electronic compliance assessment of antifungal prophylaxis for human immunodeficiency virus-infected women.

Several prophylactic medications for opportunistic or recurrent infections are used in human immunodeficiency virus-infected individuals. Essential to the efficacy evaluation of these agents is the accurate reporting of medication compliance. We hypothesized that poor patient compliance with thrice-weekly fluconazole prophylaxis would correlate with the occurrence of clinical events. Fluconazole compliance was monitored electronically by using the Medication Event Monitoring Systems with 19 women receiving fluconazole at 50 mg thrice weekly for prophylaxis of recurrent mucocutaneous candidiasis. During 202 patient-months of follow-up, eight breakthrough episodes of mucocutaneous candidiasis developed in four women; compliance data were available for seven of these episodes. At 6 months of therapy, more women with greater than or equal to 80% compliance were disease free compared with women with less than 80% compliance (P < 0.05; the Fisher exact test). These data suggest that documentation of medication compliance is essential in studies of chronic prophylaxis in human immunodeficiency virus-infected patients to properly evaluate drug efficacy and to avoid erroneous conclusions concerning drug failure.

Pseudomonas bacteremia precipitated by ticlopidine-induced neutropenia.

OBJECTIVE: To report a case of ticlopidine-induced neutropenia resulting in Pseudomonas bacteremia. CASE SUMMARY: An 83-year-old white man developed febrile neutropenia 5 days after initiation of ticlopidine therapy. At presentation, the patient's white blood cell count was 1.1 x 10(9)/L with an absolute neutrophil count (ANC) of 0. Ticlopidine was discontinued and the patient was treated empirically with ceftazidime, gentamicin, and filgrastim. The patient's blood cultures were positive for Pseudomonas aeruginosa. By day 6 of antibiotic and fllgrastim therapy, he was clinically improved and the ANC was 17 040 x 10(6) cells/L. The filgrastim and intravenous antibiotics were discontinued and oral ciprofloxacin was started. CONCLUSIONS: Ticlopidine-induced neutropenia can occur suddenly and may result in a serious infection, such as bacteremia.

Alopecia associated with zidovudine therapy.

Alopecia has been described in patients infected with the human immunodeficiency virus (HIV). Zidovudine reportedly influences hair growth in these patients, causing regrowth or thickening. A 33-year-old HIV-infected man developed alopecia areata after beginning zidovudine therapy. The alopecia reversed after the drug was discontinued.

2',3'-didehydro-3'-deoxythymidine (d4T) in patients with AIDS or AIDS-related complex: a phase I trial.

2',3'-didehydro-3'-deoxythymidine (d4T) is a pyrimidine analogue and inhibitor of reverse transcriptase with potent in vitro activity against human immunodeficiency virus (HIV). A phase I trial of d4T was conducted in 41 HIV-infected patients, 12 with AIDS and 29 with AIDS-related complex (ARC). Thirty-six patients were evaluatable. The maximum tolerated dose was 2 mg/kg/day. The dose-limiting toxicity was sensory peripheral neuropathy, which occurred in 20 patients (55%). Four patients (11%) developed hepatotoxicity. Five (14%) developed anemia requiring a transfusion but not discontinuation of drug. The mean +/- SE plasma elimination half-life at all dose levels was 1.2 +/- 0.09 h. Increased or stable absolute CD4 counts were seen in most patients. The majority of patients with detectable serum p24 antigen levels had a persistent decrease by 6 months. d4T is a promising drug for patients with AIDS or ARC. This clinical trial is continuing to determine the minimal effective dose.