A simulation model of human immunodeficiency virus (HIV) disease, which incorporated French data on the progression of HIV disease in the absence of antiretroviral therapy and on cost, was used to determine the clinical impact and cost-effectiveness of different strategies for the prevention of opportunistic infections in French patients who receive highly active antiretroviral therapy (HAART). Compared with use of no prophylaxis, use of trimethoprim-sulfamethoxazole (TMP-SMX) increased per-person lifetime costs from euro 185,600 to euro 187,900 and quality-adjusted life expectancy from 112.2 to 113.7 months, for an incremental cost-effectiveness ratio of euro 18,700 per quality-adjusted life-year (euro/QALY) gained. Compared with use of TMP-SMX alone, use of TMP-SMX plus azithromycin cost euro 23,900/QALY gained; adding fluconazole cost an additional euro 54,500/QALY gained. All strategies that included oral ganciclovir had cost-effectiveness ratios that exceeded euro 100,000/QALY gained. In the era of HAART, on the basis of French data, prophylaxis against Pneumocystis carinii pneumonia, toxoplasmic encephalitis, and Mycobacterium avium complex bacteremia is cost-effective. Prophylaxis against fungal and cytomegalovirus infections is less cost-effective than are other therapeutic options for HIV disease and should remain of lower priority. [Clin Infect Dis 2003;36(1):86-96.]
Three dose levels of the protease inhibitor (PI) atazanavir (200, 400, and 500 mg once daily) were compared with nelfinavir (750 mg three times daily) when given both as monotherapy and in combination with didanosine and stavudine in 420 antiretroviral-naive subjects infected with HIV-1. Subjects received monotherapy for two weeks, followed by combination therapy for 46 weeks. After 48 weeks, mean change from baseline in HIV RNA (-2.57 to -2.33 log copies/mL), the proportion of subjects with HIV RNA 3) were comparable across treatment groups. Diarrhea was two to three times more common in the nelfinavir group (61 percent of subjects) than in the atazanavir groups (23 percent to 30 percent of subjects, <.0001 versus nelfinavir), and jaundice occurred only in atazanavir-treated subjects (6 percent, 6 percent, and 12 percent in the 200-, 400-, and 500-mg groups, respectively) (<.03 for all atazanavir regimens versus nelfinavir). Mean percent change from baseline in fasting low-density lipoprotein (LDL) cholesterol was significantly less in the atazanavir groups (-7 percent to 4 percent) than in the nelfinavir group (31 percent) (<.0001). In conclusion, once-daily atazanavir is a potent, safe, and well tolerated PI that rapidly and durably suppresses HIV RNA and durably increases CD4 cell count in antiretroviral-naive subjects. Through 48 weeks, atazanavir was not associated with clinically relevant increases in total cholesterol, fasting LDL cholesterol, or fasting triglycerides. In comparison, nelfinavir was associated with prompt, marked, and sustained elevations in these parameters of a magnitude that suggests they are clinically relevant. [J Acquir Immune Defic Syndr 2003;32(1):18-29.]
The steady-state pharmacokinetics and pharmacodynamics of two oral doses of lopinavir-ritonavir (lopinavir/r; 400/100 and 533/133 mg) twice daily (BID) when dosed in combination with efavirenz, plus two nucleoside reverse transcriptase inhibitors, were assessed in a phase II, open-label, randomized, parallel arm study in 57 multiple protease inhibitor-experienced but non-nucleoside reverse transcriptase inhibitor-naive human immunodeficiency virus (HIV)-infected subjects. All subjects began dosing of lopinavir/r at 400/100 mg BID; subjects in one arm increased the lopinavir/r dose to 533/133 mg BID on day 14. When codosed with efavirenz, the lopinavir/r 400/100 mg BID regimen resulted in lower lopinavir concentrations in plasma, particularly Cmin, than were observed in previous studies of lopinavir/r administered without efavirenz. Increasing the lopinavir/r dose to 533/133 mg increased the lopinavir area under the concentration-time curve over a 12-h dosing interval (AUC(12)), Cpredose, and C min by 46, 70, and 141%, respectively. The increase in lopinavir Cmax (33 percent) did not reach statistical significance. Ritonavir AUC(12), Cmax, Cpredose, and Cmin values were increased 46 percent to 63 percent. The lopinavir predose concentrations achieved with the 533/133-mg BID dose were similar to those observed with lopinavir/r 400/100 mg BID in the absence of efavirenz. Results from univariate logistic regression analyses identified lopinavir and efavirenz inhibitory quotient (IQ) parameters, as well as the baseline lopinavir phenotypic susceptibility, as predictors of antiviral response (HIV RNA Antimicrob Agents Chemother 2003;47(1):350-9.]
In persons with acquired immunodeficiency syndrome (AIDS), Cryptosporidium parvum causes a prolonged, severe diarrheal illness to which there is no effective treatment, and the risk of developing cryptosporidiosis from drinking tap water in non-outbreak settings remains uncertain. To test the hypothesis that drinking tap water was associated with developing cryptosporidiosis, we conducted a matched case-control study among persons with AIDS in San Francisco. Among patients reported to the San Francisco AIDS Registry from May 1996 through September 1998, we compared patients who developed cryptosporidiosis to those who did not. Cases were individually matched to controls based on age, sex, race/ethnicity, CD4 T lymphocyte count, date of CD4 count, and date of case diagnosis. Population attributable fractions (PAFs) were calculated. The study consisted of 49 cases and 99 matched controls. In the multivariable analysis with adjustments for confounders, tap water consumption inside and outside the home at the highest exposure categories was associated with the occurrence of cryptosporidiosis (inside the home: odds ratio (OR), 6.76; 95 percent CI 1.37 to 33.5, and outside the home: OR 3.16; 95 percent CI 1.23 to 8.13). The PAF was 85 percent; that is, the proportion of cases of cryptosporidiosis in San Francisco AIDS patients attributable to tap water consumption could have been as high as 85 percent. Although the results from this observational study cannot be considered definitive, until there is more data, we recommend persons with AIDS, especially those with compromised immune systems, consider avoiding tap water. [BMC Public Health 2003;3(1):2.]
Back to the January 2003 issue of IAPAC Monthly.