I. Aerosolized pentamidine vs. Bactrim (Am. J. Crit. Care Med. 151:1068, 1995) for tx:

  1. Multicenter study randomized 367 HIV + adults with PCP (mild-mod. pneumonia & A-a gradient <55mm Hg) to aerosolized pentamidine (600mg QD) vs. Bactrim (IV x 5d or more, then PO)
  2. No sig. difference in mortality measured at 35d
  3. Bactrim group had faster improvement of PaO2 and fewer recurrences at 6mos; more likely to get drug side f/x, though (n/v, rash)

II. Bactrim vs. dapsone-trimethoprim vs. clindamycin-primaquine (Ann. Int. Med 124:792, 1996-JW) for tx:

  1. Multicenter double-blind trial of these 3 oral regimens
  2. 181 pts with AIDS and mild-to-moderate PCP with A-a gradients < 45mm Hg randomized to above regimens to 21d; pts with A-a gradients 35-45 mm Hg also got prednisone
  3. Dose-limiting toxicities occurred in 1/3 of pts; 6% had therpautic failure
  4. No sig. diff in dose-limiting toxicities, therapeutic failure, ability to complete course of therapy among different groups

III. Prophylaxis against PCP pneumonia in pts with HIV

  1. Since 1989 recc'd for CD4 < 200 or oral candidiasis or unexplained fever > 2wks or h/o PCP
  2. May be OK to stop PCP prophylaxis after starting highly effective antiretroviral tx
    1. In 78 pts on "highly--active antiretroviral therapy" with at least 2 CD4 counts > 200 since starting HAART, prophylaxis was withdrawn (and restarted if CD4 fell < 200); no pts developed PCP over avg. 12.7mo f/u (Lancet 353:201, 1999--AFP)
    2. In a cohort of 3,000 HIV+ pts who were on PCP prophylaxis and began combination antiretroviral Rx that included a protease inhibitor and then followed for avg. 2y, the 319pts who stopped primary prophylaxis and 59pts who stopped secondary prophylaxis (median 10mos after protease inhibitor tx begun) had no identified cases of PCP (Lancet 353:1287, 1999--JW)
    3. In 262 pts who had stopped primary PCP prophylaxis after at least 3mos of combination antiretroviral tx and f/u's for 1y, there were no identified cases of PCP. median CD4 at time prophylaxis was stopped was 325/mm3 and medial viral load was 100 copies/ml (NEJM 340:1301, 1999--JW)
    4. Stopping secondary prophylaxis: 587 with good CD4 responses to antiretrovirals randomized to continued PCP prophylaxis  vs. d/c of prophylaxis; no cases of PCP in either group over 19mos of f/u including in 60 pts with h/o prior PCP (NEJM 344:159, 2001--JW)
    5. In a nonrandomized prospective study of 491 HIV-positive pts with CD4 counts > 200/mm3 after starting HAART, 146 of whom were selected by their physicians to d/c PCP prophylaxis, no cases of PCP occurred in either group, over mean 18.2mo f/u (Ann. Int. Med. 132:201, 2000--AFP)
  3. Prophylactic regimens
    1. Trimethoprim-Sulfamethoxazole DS 1 PO QD
      1. Sulfa-trimethoprim DS 1 PO 3x/wk ass'd with similar (non-sig. higher) incidence of PCP c/w 1 PO QD over median 22mo f/u in a randomized trial of 2625 pts with AIDS (Clin. Inf. Dis. 29:775, 1999--JW)
    2. Dapsone 100mg/d
    3. Atovaquone 1.5g/d
      1. 1,057 pts with HIV and CD4 < 200 randomized to Atovaquone 1.5g/d vs. Dapsone 100mg/d; over mean 27mo f/u, no sig. diff. in incidence of PCP (27% w/Atovaquone; 30% w/Dapsone) (NEJM 339:1889, 1998--AFP)
    4. Sulfadoxine 500mg/Pryimethamine 25mg 1 PO Q1Wk as good as sulfa-trimethoprim DS 1 PO QD in a 6mo trial for PCP prophylaxis in a randomized trial of 120 liver transplant pts (non-HIV-positive) (Clin. Inf. Dis. 29:771, 1999--JW)