Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients.

The safety, tolerability, and antiviral activity of atevirdine (ATV), a nonnucleoside reverse transcriptase inhibitor, were studied in a phase I/II clinical trial (ACTG 187) of patients with CD4 counts < or =500/mm3. In all, 34 HIV-1-infected patients were randomized to receive ATV for 12 weeks in doses chosen to achieve one of three serum trough levels: 5 to 13 microM, 14 to 22 microM, or 23 to 31 microM. Rash was the most common adverse event, with a grade 3 or 4 rash occurring in 4 patients. No significant change from baseline in HIV-1 plasma RNA mean copy number was detected at week 4 (+0.09 log10 copies/ml; p = .30). However, some evidence indicated moderate antiviral activity at week 4, based on median changes in CD4 count (+23/mm3; p = .05), and viral peripheral blood mononuclear cell (PBMC) titer (-0.68 log10) copies/ml; p = .03). In addition, 2 of 4 patients with detectable baseline serum p24 antigen showed declines of >50%. HIV-1 resistance to ATV was detected in 41% of patients and was most commonly associated with RT mutations K103N and Y181C. In contrast, the Y181C mutation was not detected in ATV-resistant isolates obtained from patients enrolled in ACTG 199, a study of ATV given in combination with zidovudine. Under the conditions of this study, ATV failed to demonstrate significant antiretroviral activity. However, transient in vivo activity might have been obscured by rapid development of resistance coupled with inadequate sampling at early time points following initiation of ATV therapy.

Phase I study of atevirdine, a nonnucleoside reverse transcriptase inhibitor, in combination with zidovudine for human immunodeficiency virus type 1 infection. ACTG 199 Study Team.

Twenty patients were enrolled in a phase I clinical trial of atevirdine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), given in combination with zidovudine for treatment of human immunodeficiency virus type 1 (HIV-1) infection. Fifteen patients had received no previous antiretroviral therapy. HIV-1 isolates obtained at 6-week intervals were tested for sensitivity to atevirdine and zidovudine. Two patients developed a rash within 2 weeks of enrollment, and 1 of these developed concomitant fever and hepatitis. No hematopoietic, neurologic, or pancreatic toxicities were observed. Atevirdine had considerable initial interpatient pharmacokinetic variability. Forty-seven percent of patients treated with atevirdine plus zidovudine had increased CD4 lymphocyte counts, and HIV isolates from 62% of patients remained sensitive to atevirdine after 24 weeks of therapy. Atevirdine plus zidovudine was well-tolerated. Additional studies should be done to determine the role of atevirdine in the therapy for HIV infection.

Treatment of condyloma acuminatum with three different interferons administered intralesionally. A double-blind, placebo-controlled trial.

STUDY OBJECTIVE: To determine the efficacy and toxicity of intralesionally administered interferons in the treatment of condyloma acuminatum. DESIGN: Randomized, double-blind, and placebo-controlled study. SETTING: Outpatient clinics at university medical centers. PATIENTS: Seventy-nine patients with biopsy-proved condyloma acuminatum that was refractory to conventional therapy were enrolled in the study. INTERVENTIONS: Alpha-2b, alpha-nl-, and beta-interferons were used. One wart on each patients was injected three times per week for 4 weeks with either 1 x 10(6) units of interferon or placebo. MEASUREMENTS AND MAIN RESULTS: Forty-seven percent of warts injected with interferon resolved completely, compared with 22% of placebo-injected warts (P = 0.009). In addition, more recipients of interferon had a complete resolution of uninjected lesions. No differences in rates of response were noted among the different interferon groups. Approximately one third of interferon-injected warts recurred, compared with none of four placebo-injected warts. Intralesionally administered interferon was nontoxic and well tolerated, although transient pain on injection was observed frequently. CONCLUSIONS: Intralesional administration of each of these three interferons appears to be useful in treating condyloma acuminatum. However, the frequent recurrence of disease and the failure of many lesions to resolve indicate that different regimens, such as longer courses of therapy or different routes of administration, should be evaluated to maximize beneficial effects of interferon for treating this common sexually transmitted disease.

Isolation of Chlamydia trachomatis from men with urethritis: relative value of one vs. two swabs and influence of concomitant gonococcal infection.

Two successive urethral swabs were used to obtain specimens for culture of Neisseria gonorrhoeae and Chlamydia trachomatis from 136 heterosexual men with urethritis. The first swab was used to culture N. gonorrhoeae and then C. trachomatis; the second was used to culture C. trachomatis only. C. trachomatis cultures from the second swab were positive more often (30 of 31 pairs) than were cultures from the first swab (22 of 31 pairs) (P less than .05). In addition, cultures from swab 2 had greater numbers of inclusions per coverslip more frequently (23 of 31 pairs) than did cultures from the first swab (six of 31 pairs) (P = .003). Numbers of chlamydial inclusions per coverslip were lower in specimens positive for both C. trachomatis and N. gonorrhoeae than in specimens positive for C. trachomatis only (P less than .02). In addition, the presence of N. gonorrhoeae in a specimen adversely affected the quality of the McCoy cell monolayer. In 17 of 21 instances of monolayer toxicity, cultures for N. gonorrhoeae were positive (P less than .01). These results demonstrate that when specimens from men with urethritis are cultured for N. gonorrhoeae and C. trachomatis, use of a second swab will improve rates of recovery of C. trachomatis. Material present in specimens that contain N. gonorrhoeae may adversely affect rates of isolation of C. trachomatis.

Single-dose cefuroxime axetil in the treatment of uncomplicated gonorrhea: a controlled trial.

One hundred eighty-four patients were enrolled in a randomized study that evaluated the efficacy and toxicity of a single dose of orally administered cefuroxine axetil in the treatment of men and women with uncomplicated gonorrhea. Sixty-two patients received cefuroxine axetil alone, 62 received cefuroxine axetil and probenecid, and 60 received amoxicillin plus probenecid. Cure rates in the three groups were 98%, 98%, 96%, respectively. Only 2% of patients who received cefuroxine axetil alone complained of nausea, as compared with 11% of those who received a regimen that contained probenecid (P less than .05). The results show that cefuroxime axetil is effective and nontoxic in the treatment of uncomplicated gonococcal infections in adults.