A Study on the Rate of Opportunistic (AIDS-Related) Infections Among HIV-Positive Children Who Have Stopped Taking Their OI Preventive Medications
Condition: HIV Infections
MeSH terms: Infections; Communicable Diseases; Opportunistic Infections
Study type: Interventional

Summary: 
      The purpose of this study is to find out if it is safe for HIV-positive children who are
      responding well to their anti-HIV treatment to stop taking medications that prevent
      AIDS-related infections (opportunistic infections) such as pneumonia and other bacterial
      infections. This is an observational study, meaning children will only be monitored to see if
      they develop any infections.

      Children have been receiving medications to prevent complications of HIV infection, such as
      Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC) disease, or other
      bacterial infections. It is common for HIV-positive patients with low CD4 counts to receive
      these preventive medications. However, these drugs can have serious side effects, they are
      expensive, and it is possible for bacteria resistant to the drugs to grow. For these reasons,
      it may be beneficial to the child to stop taking these preventive medications if he/she has
      been on anti-HIV (antiretroviral) therapy and has improved CD4 counts. This study will look
      at how many children who stop taking their medications develop opportunistic infections.
    

Detailed description: 
      Due to the strong correlation between a significant decrease in CD4 count and the frequency
      and magnitude of OIs such as Pneumocystis carinii pneumonia (PCP), Mycobacterium avium
      complex (MAC), and severe bacterial infections, CD4 count has become the major criterion for
      initiating antimicrobial prophylaxis for OIs. However, despite the benefits of these
      antimicrobial drugs, all are associated with adverse side effects, and patients with
      reconstituted immune systems following antiretroviral therapy may be receiving prophylaxis
      unnecessarily. Benefits to stopping prophylaxis include: (1) elimination of adverse effects
      from drugs; (2) reduction in drug costs; and (3) removal of selective pressure for the
      development of drug-resistant microbes. These benefits must be weighed against the
      disadvantages, however, such as more frequent determinations of CD4 counts to assure
      maintenance of immunocompetence, more frequent occurrence of serious OIs otherwise
      preventable with prophylaxis in patients lost to follow-up, and possible occurrence of
      atypical PCP because of prior exposure to anti-PCP drugs. [AS PER AMENDMENT 04/26/02: The
      extent of complete immune restitution has not yet been defined. An important corollary of an
      incomplete immune recovery is that vaccination schedules might need to be adjusted to obtain
      optimal responses in HIV-infected patients on highly active antiretroviral therapy (HAART).
      Therefore, a third dose of hepatitis A virus vaccine will be administered.]

      After pre-entry and entry laboratory studies, patients are followed every 8 weeks until the
      last patient has completed 104 weeks of study observation. Hepatitis A vaccination is
      administered at entry and Week 24 to measure responses to neoantigen. [AS PER AMENDMENT
      04/26/02: All patients (except those co-enrolled in P1024 on or after November 1, 2001) who
      have received 2 doses of hepatitis A virus vaccine during the study will be offered an
      opportunity to enroll in Step II of P1008. Patients in Step II receive a third dose of
      hepatitis A vaccination at Week 104 or later. Additional blood samples are taken 8 weeks
      later for antibody detection and peripheral blood mononuclear cell (PBMC) cryopreservation.]
      All serious bacterial infections that are Grade 3 or higher and OI events are recorded and
      compared to historical event rates. Virologic and immunologic marker studies are done in all
      patients and correlated with the risk of developing serious bacterial infections or OI
      events. Patients are considered to have reached an endpoint if they develop PCP, 2 serious
      bacterial infections, other Category C OI diagnoses, or CD4% less than 15% and re-initiation
      of PCP prophylaxis.
    

Intervention name(s): Hepatitis A Vaccine (Inactivated)
Intervention type(s): Biological
Primary purpose: Treatment
Keywords: Viral Vaccines; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Hepatitis A Virus, Human