Effectiveness of twice-weekly pyrimethamine-sulfadoxine as primary prophylaxis of Pneumocystis carinii pneumonia and toxoplasmic encephalitis in patients with advanced HIV infection.

The safety and efficacy of a fixed 25 mg pyrimethamine-500 mg sulfadoxine combination supplemented with 15 mg folinic acid twice a week as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) and toxoplasmic encephalitis was evaluated in 106 patients infected with the human immunodeficiency virus. All patients had a CD4+ T-lymphocyte count of less than 100 cells/microl at study entry. Efficacy in this single-arm open-label prospective study was analyzed on an as-treated basis. No patient received highly active antiretroviral treatment, including protease inhibitors or non-nucleoside reverse transcriptase inhibitors, while on study medication. PCP developed in four patients, one of whom had been noncompliant. No PCP episode occurred in the first year. Probabilities of freedom from PCP were 0.97 (95%CI, 0.92-1) after 24 months and 0.93 (95%CI, 0.84-1) after 36 months. Of 74 (69.8%) patients positive for anti-toxoplasma IgG antibodies, one noncompliant patient developed toxoplasmic encephalitis after 24 months. Allergic reactions were observed in 18 (17%) patients and resulted in permanent discontinuation in 7 (6.6%) patients. One (0.9%) patient who had continued prophylaxis despite progressive hypersensitivity reactions developed a serious adverse reaction (Stevens-Johnson syndrome). The median survival of study participants was 29 months, with relentless progression of AIDS accounting for most deaths. The prophylaxis regimen studied appeared safe and effective for primary prophylaxis of PCP and toxoplasmic encephalitis. Severe adverse events can likely be prevented by discontinuation of prophylaxis at the time allergic reactions are noted. Rechallenge frequently results in tolerance. Efficacy and safety compare favorably with previously studied regimens. This simple prophylactic regimen may provide a convenient alternative for patients failing or intolerant to approved regimens.

Effectiveness of the macrolide clarithromycin in the treatment of Mycobacterium avium complex infection in HIV-infected patients.

In a randomized double-blind study, nine mycobacteremic patients with AIDS-related disseminated Mycobacterium avium complex (MAC) infection received clarithromycin or placebo in addition to a basic regimen that included isoniazid, ethambutol and clofazimine. All four patients receiving clarithromycin showed blood culture conversion and clinical response. Of the five patients treated without clarithromycin, two showed resolution of mycobacteremia and clinical response, while another two died without having shown response. The remaining patient deteriorated until a switch from placebo to clarithromycin led to blood culture conversion and rapid clinical improvement. After finishing six weeks of intensive treatment, clarithromycin was given in an open maintenance phase to all patients, initially in combination with rifabutin for 24 weeks and then alone. One patient had a relapse of MAC infection while receiving clarithromycin alone. The relapse was associated with acquired resistance to the drug. Clarithromycin appears to be a promising component of multi-drug therapy for patients with MAC infection. Monotherapy can lead to drug resistance.

[Resistance testing of M. avium-intracellulare and M. tuberculosis of AIDS patients with new drugs and drug combinations]. / Resistenztestung von M. avium-intracellulare und M. tuberculosis von AIDS-Patienten mit neuen Medikamenten und Medikamentenkombinationen.

The minimal inhibitory concentration (MIC) of rifabutin for M. tuberculosis was 0.006 to 0.06 micrograms/ml, and 0.12 to 0.25 micrograms/l for clofazimine. Accordingly, M. tuberculosis is inhibited by concentrations of these two medications that are far lower than the levels normally found in the serum. In the case of M. avium, the MIC of the new drugs such as rifabutin and clofazimine are, in contrast to the MICs for M. tuberculosis, merely of the order of the achievable serum concentrations. The minimum bactericidal concentrations of these two substances are much higher than the bacteriostatic concentrations, which probably explains the frequent therapeutic failures, while in the case of ciprofloxacin, the prevailing situation is much more favourable. The growth of all M. avium strains is inhibited (= sensitive) when elevated concentrations (double "breakpoint" concentrations) of a triple-drug combination comprising rifampicin, ethambutol and ciprofloxacin, or a combination of ethambutol, rifampicin, ciprofloxacin and prothionamid are tested at "normal breakpoint" concentrations.