for Opportunistic Infections
İİİİ from Jules Levin
Due to increases in CD4s under certain circumstance patients are able to stop certain OI prophylaxis. A number of preliminary relatively short term studies have shown this. These studies were originally presented at AIDS Conferences over the past 1.5 years. Initially at ICAAC 1999 and at 2000 Human Retrovirus Conference. NATAP reported this presentations from the conferences immediately upon our web site (links to articles below) and in our subsequent NATAP Reports newsletters. The current issue of the New England Journal Of Medicine published two of these studies with an editorial addressing the ability to stop OI prophylaxis in patients on primary & secondary prophylaxis for PCP. Secondary is when you already have had a bout with PCP and primary is when you never had a bout. The two articles are attached in pdf and the editorial is attached also. Below are the original articles on the NATAP web site and in the newsletter with the links to read the articles on the web site. Also below are the two abstracts, which is a summary, from the New England Journal of Medicine. Below is a link to an article written by Fred Valentine, an immunologist and head of the ACTU at NYU/Bellevue, discussing the immune system.
Preliminary Studies Reported at 7th Retrovirus Conference 2000 show it's safe to discontinue prophylaxis for MAC and cryptococcal meningitis in carefully selected patients with CD4 increases. This is due to HAART induced immunity improvement sufficient to prevent OIs.
It Safe to Discontinue Secondary Prophylaxis for PCP in HIV-Infected Patients
Treated with HAART?
(written 3/20/2000; data presented at Retrovirus Conference 2000)
Prohylaxis Revised with Update From IDSA Nov12-15
(written 9/28/99 from ICAAC & IDSA)
Primary Prophylaxis Against Pneumocystis CariniiPneumonia in HIV-1oInfected
Adults Treated with Combination Antiretroviral Therapy
This study reported in the current issue of NEJM suggests a person is relatively safe in stopping PCP prophylaxis if their CD4 count rises to above 200 (CD4 count in study was 324) after starting HAART. But there is still a risk of getting PCP. Bactrim still may protect against toxo. Following the abstract below are a few points of concern to bear in mind.
Study of MAC Azithromycin Prophylaxis Discontinuation
-for individuals who never had MAC previously and their CD4s increased on anti-retroviral therapy (1999 ICAAC)
the Immune System
(Printed in NATAP Reports newsletter) written by Fred Valentine, MD
Randomized Trial of the Discontinuation of Primary and Secondary Prophylaxis
against Pneumocystis carinii Pneumonia after Highly Active Antiretroviral Therapy
in Patients with HIV Infection
İİİİ Juan C. Lopez Bernaldo de Quiros, Jose M. Miro, Jose M. Pena, Danielİ Podzamczer, Juan C. Alberdi, Esteban Martinez, Jaime Cosin, Xavierİ Claramonte, Juan Gonzalez, Pere Domingo, Jose L. Casado, Esteban Ribera, the Grupo de Estudio del SIDA 04/98.
Full version in PDF format
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 antiretroviral therapy, defined by a CD4 cell count of 200 or more per cubic millimeter and aİ 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 (388 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 (65 person-years), there had been no episodes of P. carinii pneumonia in the 60 patients who discontinued prophylaxis (95 percent confidence interval, 0 to 4.57 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. (N Engl J Med 2001;344:159-67.)
of Secondary Prophylaxis against Pneumocystis carinii Pneumonia in Patients
with HIV Infection Who Have a Response to Antiretroviral Therapy
İİİİ Bruno Ledergerber, Amanda Mocroft, Peter Reiss, Hansjakob Furrer, Ole Kirk, Markus Bickel, Caterina Uberti-Foppa, Christian Pradier, Antonella d'Arminio Monforte, Margriet M.E. Schneider, Jens D. Lundgren, for Eight European Study Groups
Full version in PDF format
Background. Patients with human immunodeficiency virus (HIV) infection and a history of Pneumocystis carinii pneumonia are at high risk for relapse if they are not given secondary prophylaxis. Whether secondary prophylaxis against P. carinii pneumonia can be safely discontinued inİ patients who have a response to highly active antiretroviral therapy is not known.
Methods. We analyzed episodes of recurrent P. carinii pneumonia in 325 HIV-infected patients (275 men and 50 women) in eight prospective European cohorts. Between October 1996 and January 2000, these patients discontinued secondary prophylaxis during treatment with at least threeİ anti-HIV drugs after they had at least one peripheral-blood CD4 cell count of more than 200 cells per cubic millimeter.
Results. Secondary prophylaxis was discontinued at a median CD4 cell count of 350 per cubic millimeter; the median nadir CD4 cell count hadİ been 50 per cubic millimeter. The median duration of the increase in the CD4 cell count to more than 200 per cubic millimeter after discontinuation of secondary prophylaxis was 11 months. The median follow-up period after discontinuation of secondary prophylaxis was 13 months, yielding a total of 374 person-years of follow-up; for 355 of these person-years, CD4 cell counts remained at or above 200 per cubic millimeter. No cases of recurrent P. carinii pneumonia were diagnosed during this period; the incidence was thus 0 per 100 patient-years (99 percent confidence interval, 0 to 1.2 per 100 patient-years, on the basis of the entire follow-up period, and 0 to 1.3 per 100 patient-years, on the basis of the follow-up period during which CD4 cell counts remained at or above 200 per cubic millimeter).
Conclusions. It is safe to discontinue secondary prophylaxis against P. carinii pneumonia in patients with HIV infection who have an immunologic response to highly active antiretroviral therapy. (N Engl J Med 2001;344:168-74.)
The life expectancy of patients with human immunodeficiency virus (HIV) infection has dramatically improved, (1,2,3,4) and the risk of opportunistic infections, including Pneumocystis carinii pneumonia, has markedly declined in industrialized countries since 1996 (1,5) because of the widespread use of highly active antiretroviral therapy. This decline has suggested that highly active antiretroviral therapy results in clinically important immune reconstitution. The absolute risk of the progression of HIV disease was markedly lower in patients who had an increase in CD4 cell counts in peripheral blood to more than 200 per cubic millimeter than in patients who had no such increase. (6) The degree of protection conferred could have been overestimated in these studies, because the majority of patients continued to use standard prophylactic medication against various opportunistic infections, including P. carinii pneumonia. However, several studies have subsequently indicated that the reduction in the risk of primary P. carinii pneumonia is maintained after the discontinuation of specific chemoprophylaxis. (7,8,9,10) These findings resulted in recommendations for the discontinuation of primary prophylaxis against P. carinii pneumonia in patients who have a response to antiretroviral therapy. (11)
The risk of recurrence of P. carinii pneumonia is substantially higher than the risk of primary P. carinii pneumonia. (12) This increase in risk is almost certainly due to the fact that the immune system is more profoundly compromised in patients in whom pneumonia has already developed, and to the presence of residual P. carinii organisms in the lungs despite a clinical response to therapy. (13) Thus, recommendations regarding the safety of discontinuing primary prophylaxis cannot simply be extrapolated to the discontinuation of secondary prophylaxis.
We therefore analyzed data on eight European cohorts of HIV-infected patients who had been successfully treated for an episode of P. carinii pneumonia, whose CD4 cell count had risen to more than 200 per cubic millimeter, and who subsequently discontinued chemoprophylaxis against recurrent P. carinii pneumonia.