A randomized trial of the discontinuation of primary and secondary prophylaxis against Pneumocystis carinii pneumonia after highly active antiretroviral therapy in patients with HIV infection. Grupo de Estudio del SIDA 04/98.
BACKGROUND
Prophylaxis against Pneumocystis carinii pneumonia is indicated in patients with human immunodeficiency virus (HIV) infection who have less than 200 CD4 cells per cubic millimeter and in those with a history of P. carinii pneumonia. However, it is not clear whether prophylaxis can be safely discontinued after CD4 cell counts increase in response to highly active antiretroviral therapy.


METHODS
We conducted a randomized trial of the discontinuation of primary or secondary prophylaxis against P. carinii pneumonia in HIV-infected patients with a sustained response to antiviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and plasma HIV type 1 (HIV-1) RNA level of less than 5000 copies per milliliter for at least three months. Prophylactic treatment was restarted if the CD4 cell count declined to less than 200 per cubic millimeter.


RESULTS
The 474 patients receiving primary prophylaxis had a median CD4 cell count at entry of 342 per cubic millimeter, and 38 percent had detectable HIV-1 RNA. After a median follow-up period of 20 months (758 person-years), there had been no episodes of P. carinii pneumonia in the 240 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 0.85 episode per 100 person-years). For the 113 patients receiving secondary prophylaxis, the median CD4 cell count at entry was 355 per cubic millimeter, and 24 percent had detectable HIV-1 RNA. After a median follow-up period of 12 months (123 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.5 episodes per 100 person-years).


CONCLUSIONS
In HIV-infected patients receiving highly active antiretroviral therapy, primary and secondary prophylaxis against P. carinii pneumonia can be safely discontinued after the CD4 cell count has increased to 200 or more per cubic millimeter for more than three months.
Lopez Bernaldo de Quiros
J C
JC
Hospital Universitario Gregorio Marañón, Madrid, Spain. juanclopez@retemail.es
Miro
J M
JM
Peña
J M
JM
Podzamczer
D
D
Alberdi
J C
JC
Martínez
E
E
Cosin
J
J
Claramonte
X
X
Gonzalez
J
J
Domingo
P
P
Casado
J L
JL
Ribera
E
E
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000517:prevention & control*; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy / Q000517:prevention & control*; D012367:RNA, Viral / Q000097:blood; D018709:Statistics, Nonparametric; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use*
D000890:Anti-Infective Agents; D012367:RNA, Viral; D015662:Trimethoprim, Sulfamethoxazole Drug Combination