Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Discontinuation of prophylaxis for Pneumocystis carinii pneumonia was safe after highly active antiretroviral therapy

PDF

ACP J Club. 2001 Jul-Aug;135:26. doi:10.7326/ACPJC-2001-135-1-026


Source Citation

Lopez Bernaldo de Quiros JC, Miro JM, Peña JM, et al., and the Grupo de Estudio del SIDA 04/98. 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. N Engl J Med. 2001 Jan 18;344:159-67. [PubMed ID: 11172138] (All 2001 articles were reviewed for relevancy, and abstracts were last revised in 2007.)


Abstract

Question

In patients with HIV infection, can primary and secondary prophylaxis for Pneumocystis carinii pneumonia (PCP) be safely discontinued if antiretroviral therapy has improved immune function and CD4+ cell counts remain ≥ 200 cells/mm3?

Design

Randomized {allocation concealed*}†, unblinded*, controlled trial with mean follow-up of 20 months (primary prophylaxis group) and 12 months (secondary prophylaxis group).

Setting

19 public hospitals in Spain.

Patients

587 patients, of whom 474 (median age 36 y, 73% men) were in the primary prophylaxis group and 113 (median age 37 y, 76% men) were in the secondary group (previous PCP). Inclusion criteria were HIV infection and previous CD4+ cell counts < 200/mm3 or PCP, current prophylaxis for PCP, sustained response to highly active antiretroviral therapy (HAART) (current CD4+ cell count ≥ 200/mm3and a plasma HIV-1 RNA level < 5000 copies/mL for > 3 months), and Karnofsky score > 80. Exclusion criteria were age < 18 years, pregnancy, or poor adherence to antiretroviral therapy. Follow-up was 97% (primary) and 100% (secondary).

Intervention

In the primary prophylaxis group, 240 patients were allocated to discontinue prophylaxis and 234 were allocated to continue. In the secondary prophylaxis group, 60 patients were allocated to discontinue prophylaxis and 53 to continue. If the CD4+ count fell to < 200/mm3, prophylaxis was started again.

Main outcome measure

Incidence of PCP.

Main results

No cases of PCP developed in any group in either the primary or secondary prophylaxis analyses. For both primary and secondary prophylaxis, the study groups did not differ for any outcomes, including infections, adverse effects, and CD4+ cell counts.

Conclusion

Discontinuation of primary and secondary prophylaxis for Pneumocystis carinii pneumonia, if antiretroviral therapy had improved immune function and CD4+ cell counts had remained ≥ 200 cells/mm3, was associated with no new cases of PCP in patients with HIV infection.

*See Glossary.

†Information supplied by author.

Sources of funding: Grupo de Estudio del SIDA de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica (GESIDA/SEIMC); National AIDS Plan Secretariat of the Spanish Ministry of Health; DuPont Pharma Laboratories.

For correspondence: Dr. J.C. Lopez Bernaldo de Quiros, Division of Infectious Diseases, Hospital Gregorio Marañón, Dr. Esquerdo 46, 28007 Madrid, Spain. FAX 349-158-685-92.


Revised Commentary 2007

In the 1980s, PCP was an expected complication of HIV infection. PCP prophylaxis to prevent the first episode and lifelong suppression to prevent secondary recurrence were standard practices. Managing HIV infection is now directed toward disease modification by using HAART, which controls HIV replication and increases CD4+ cell counts, rather than prophylaxis for patients against opportunistic complications. What are the implications of this improved immune function on common events?

Lopez Bernaldo de Quiros and colleagues have addressed this question by clarifying when primary and secondary prophylaxis can be safely discontinued. Their results are supported by a recent study of primary prophylaxis (1) and secondary prophylaxis data from an observational database study (2).

Evidence supports discontinuing primary and secondary PCP prophylaxis when CD4+ counts are ≥ 200 cells/mm3 for ≥ 3 months on highly active antiretroviral therapy. Situations in which we do not have sufficient evidence to discontinue PCP prophylaxis include patients with oral candidiasis or ongoing weight loss or those receiving cytotoxic chemotherapy or long-term corticosteroids.

This information supports current guidelines that prophylaxis for opportunistic infections can be discontinued when there has been immune reconstitution. (3) Prophylaxis should, however, be restarted in patients who do not have sustained responses to antiretroviral therapy. Clinicians should monitor patients and their CD4+ cell counts and may reapply the same criteria for resuming prophylaxis as were initially used.

Andrew McIvor, MD
University of TorontoToronto, Ontario, Canada


Updated References 2007

1. Furrer H, Egger M, Opravil M, et al. Discontinuation of primary prophylaxis against Pneumocystis carinii pneumonia in HIV-1 infected adults treated with combination antiretroviral therapy. N Engl J Med. 1999;340:1301-6. [PubMed ID: 10219064]

2. Lederberger B, Mocroft A, Reiss P, et al. Discontinuation of secondary prophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection who have a response to antiretroviral therapy. N Engl J Med. 2001; 344:168-74. [PubMed ID: 11188837]

3. Kaplan JE, Masur H, Holmes KK; Infectious Disease Society of America. Guidelines for preventing opportunistic infections among HIV-infected persons – 2002. Recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep. 2002;41(RR-8):1-52. [PubMed ID: 12081007]