Barbara Weiser

Dose-limiting toxicity of rifabutin in AIDS-related complex: syndrome of arthralgia/arthritis.

We studied the tolerance of humans to rifabutin, a rifamycin with antimycobacterial and in vitro anti-HIV activity. Sixteen subjects with AIDS-related complex were treated for 4–66 weeks with stepwise increasing oral doses of rifabutin from 300 to 2400 mg/day. The highest dose attained was twice that previously reported for humans. Serum and cerebrospinal fluid levels of drug were detected by high-pressure liquid chromatography. A reversible syndrome of arthritis/arthralgia, not previously described, was seen in most (nine out of 10) of those given doses exceeding 1050 mg/day. Uveitis and aphthous stomatitis developed at doses of approximately 1800 mg in two of those with joint manifestations. Typical manifestations of Reiters syndrome were not seen in any patient. An orange-tan skin pigmentation was almost universal. Other toxicities resembled those previously associated with rifampin. Serum levels did not approach those found to inhibit HIV significantly in vitro. No consistent antiviral or immunological effects were observed; even at the highest doses, rifabutin did not appear to inhibit cellular immunity. Rifabutin was well tolerated at daily doses blow 1 g.

Ventricular tachycardia in two patients with AIDS receiving ganciclovir (DHPG).

We report two cases of patients who developed ventricular tachycardia while receiving intravenous infusions of ganciclovir [9-(1,3-dihydroxy-2-propoxy)methylguanine, DHPG]. Worsening cytomegalovirus infection prompted renewal of ganciclovir therapy under close cardiac monitoring in one of these patients, and ventricular tachycardia recurred. The close temporal relationship between administration of the drug and onset of the arrhythmias in conjunction with the absence of other factors known to predispose to arrhythmias suggest that ganciclovir may have played a role in the development of arrhythmias in these patients. The clinical courses of the patients are discussed, as are autopsy results.

Long HIV-1 incubation periods and dynamics of transmission within a family.

The incubation period of human immunodeficiency virus type 1 (HIV-1) infection was studied in a family of five in which vertical and heterosexual transmission occurred from one index case. This investigation documented incubation periods of longer than 12 years in a mother and her daughter; although neither has symptoms, both are definitely infected and have very low CD4(+)-lymphocyte counts. The study confirmed the predictions of incubation periods longer than 10 years in a small proportion of infected individuals. It provides evidence that vertically HIV-1-infected teenagers can be expected to appear in the population.

Efficacy of rifabutin in the treatment of AIDS-related complex.

We performed a phase 1–2 antiviral dose escalation trial of rifabutin, a rifamycin antibiotic with anti-HIV-1 activity in vitro. We followed 16 men with AIDS-related complex (ARC) for a mean duration of 29 weeks; the maximum toxicity-limited dose of rifabutin was 2400 mg/day, which was achieved in two patients. There was some evidence of anti-HIV-1 activity in two patients, one of whom had an improvement in immune status, but 11 of the 16 patients showed a deterioration in either virologic or immunologic status. The majority of the patients under study remained clinically stable during the trial, but there was clinical deterioration in the three who entered with CD4 cell counts of less than 100 x 106/l. On the basis of this trial, rifabutin as a single antiviral agent does not appear to be beneficial to ARC patients.