Snapshots of the Literature

Comparison of Three Regimens for Treatment of Mild to Moderate Pneumocystis carinii Pneumonia in Patients with AIDS [Safrin S, et al. Ann Intern Med 1996;124:792]: This is ACTG trial 108 comparing trimethoprim-sulfamethoxazole, dapsone-trimethoprim and clindamycin-primaquine for the treatment of P. carinii pneumonia in patients with an (A-a)O2 gradient of <45 mm Hg. Treatment failure at day 21 was defined as death, requirement for intubation, change in therapy for reasons other than toxicity, lack of resolution of baseline signs and symptoms, or an increase in A-a gradient of >20 mm Hg. There were 181 patients evaluated. Comparison between groups showed no statistically significant differences in rates of survival,therapeutic failure or dose-limiting toxicity. Hepatotoxicity, indicated by elevation of serum aminotransferase levels exceeding five times baseline levels, was significantly more frequent with TMP-SMX. Hematologic toxicity with neutropenia, anemia, thrombocytopenia or methemoglobinemia was significantly more frequent with the clindamycin-primaquine regimen. Therapeutic failure rates for the three regimens at day 21 ranged from 6.9% (clindamycin-primaquine) to 11.9% (dapsone-trimethoprim). The rate of dose-limiting toxicity ranged from 24% (dapsone-trimethoprim) to 36% (TMP-SMX). Rash was the most frequent dose limiting toxicity in all three groups. The overall mortality rate was 4.4%. The authors concluded that the choice of treatment for patients with mild to moderate PCP may ultimately depend on anticipated side effects. In patients with hepatic insufficiency, alternatives to TMP-SMX should be considered, and it may be preferable to treat patients with baseline myelosuppression with a regimen other than clindamycin-primaquine.

Comparison of Sputum Induction and Fiberoptic Bronchoscopy in the Diagnosis of Tuberculosis [Anderson C, et al. Am J Respir Crit Care Med 1995;152:1570]: The authors compared sputum induction with bronch- oscopy for detection of M. tuberculosis in 101 patients with suspected TB who had negative sputum smears or who could not produce an expectorated sample. In 27 patients eventually diagnosed with TB, there were 19 positive cultures from bronchoscopy compared to 20 from induced sputa. The yield of acid-fast organisms detected on smears was low in both groups: five from bronchoscopy and seven from induced sputa. The yield by culture was different for the two procedures in individual patients since only 14 had positive results from both procedures. The authors conclude that induced sputum is preferred because it is less expensive and less invasive, but bronchoscopy will increase the yield by about 20% if both procedures are performed.

Serologic Response to Treatment of Syphilis in Patients with HIV Infection [Yinnon AM, et al. Arch Intern Med 1996;156:321]: The authors compared serologic response in 52 patients with HIV infection and syphilis and 52 with syphilis and negative HIV serology. The groups were matched by age, sex, race, RPR titer and stage of syphilis. There were 26 matched patients with early syphilis and 26 with late syphilis. Early syphilis in patients with HIV infection was usually treated with three doses of benzathine penicillin G; the standard treatment for early syphilis in HIV-negative patients was a single dose of benzathine penicillin. Overall, 56% of the HIV-infected patients failed to achieve a four-fold reduction in RPR titer at six months compared to 38% in the HIV-negative patients (p = 0.06). At 12 months the rates were 44% and 29%, respectively (p = 0.07). These differences in response rates reached statistical significance in patients with RPR titers of 1:32 or less (p <0.005). There were no apparent distinguishing clinical features for non-responders. The authors concluded that HIV-infected patients with syphilis are less likely to demonstrate serologic improvement after recommended treatment with penicillin.

Antiretroviral Therapy for HIV Infection in 1996: Recommendations of an International Panel [Carpenter CC, et al. JAMA 1996;276:146]: The recommendations are from a 13-member panel representing the International AIDS Society-U.S.A. by group consensus in January 1996 with revisions by group consensus through May 1996.

When to initiate treatment:

• Symptomatic disease: all patients.
  
  
• Asymptomatic with CD4 cell count <500/mm3: treat all patients, but some would reserve this for patients with CD4 cell counts <350/mm3 and/or HIV RNA levels above 5-10,000 copies/ml.
  
  
• Asymptomatic with CD4 cell count >500/mm3: therapy recommended for patients with HIV RNA levels exceeding 30,000-50,000 copies/ml or a rapidly declining CD4 cell count.

Recommended initial regimen:AZT plus ddI, AZT plus ddC, AZT plus 3TC or ddI monotherapy.

When to switch:

• Treatment failure: indicated by increase in viral load (return toward or within 0.3-0.5 log of pretreatment levels), decrease in CD4 cell count or clinical progression.
  
  
• Toxicity, intolerance or non-adherence.
  
  
• Current use of a suboptimal treatment regimen such as AZT monotherapy.