Discontinuation of Prophylaxis against<i>Mycobacterium avium</i>Complex Disease in HIV-Infected Patients Who Have a Response to Antiretroviral Therapy

El‐Sadr, Wafaa; Burman, William J.; Grant, Lisa Bjorling; Matts, John P.; Hafner, Richard; Crane, Lawrence R.; Zeh, Doug; Gallagher, Barbara; Mannheimer, Sharon; Martinez, Ana; Gordin, Fred M.

doi:10.1056/nejm200004133421503

Cited by 146 publications

(45 citation statements)

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“…Exploration of factors potentially influencing the occurrence of SBIs was limited by the small number of SBIs, which did not allow for multivariate analyses and restricted the power of the study to detect differences other than very large differences. However, the favorable data from prospective adult studies [14][15][16][17] and the generally low rates of disseminated MAC among children, compared with adults, support the safety of discontinuing prophylaxis for this OI in pediatric populations.…”

Section: Sbi Rates For Hiv-infected Childrenmentioning

confidence: 99%

“…12 However, data for adults suggest that immune reconstitution after HAART allows for the discontinuation of OI and/or PCP prophylaxis. [15][16][17] The results of this study reveal that OI and/or PCP prophylaxis can be discontinued safely for HIV-infected children who demonstrate immune reconstitution (CD4 ϩ cell percentage of Ͼ15%) while receiving stable antiretroviral therapy. There were no associations between developing a SBI and gender, race/ethnicity, age, PI use, or CD4 ϩ cell percentage at study entry or during the follow-up period.…”

mentioning

confidence: 99%

“…[9][10][11] Studies among HIV-infected adults with immune reconstitution after receipt of HAART demonstrated extremely low risks of development of OIs after discontinuation of prophylaxis. [12][13][14][15][16][17] Discontinuation of PCP and MAC prophylaxis among HIV-infected pediatric patients was evaluated in Pediatric AIDS Clinical Trials Group (PACTG) protocol P1008. The study's primary objective was to evaluate the incidence of serious bacterial infections (SBIs) and other OIs (Centers for Disease Control and Prevention [CDC] category C infections) 13 after OI and/or PCP prophylaxis was discontinued for children who achieved immune reconstitution while receiving antiretroviral therapy.…”

mentioning

confidence: 99%

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The Rate of Serious Bacterial Infections Among HIV-Infected Children With Immune Reconstitution Who Have Discontinued Opportunistic Infection Prophylaxis

et al. 2005

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ABSTRACT. Objective. Receipt of highly active antiretroviral therapy is associated with a decrease in the incidence of opportunistic infections (OIs) among HIVinfected adults. The goal of Pediatric AIDS Clinical Trials Group protocol 1008 was to evaluate prospectively the incidence of serious bacterial infections (SBIs) and other OIs after discontinuation of OI and/or Pneumocystis jiroveci pneumonia (PCP) prophylaxis among HIV-infected pediatric subjects who experienced immune reconstitution while receiving stable antiretroviral therapy.Methods. HIV-infected children and adolescents, 2 to 21 years of age, who had received OI and/or PCP prophylaxis for >6 months were enrolled if they had sustained responses (>16 weeks before study entry) to antiretroviral therapy, with CD4 ؉ cell percentages of >20% for patients >6 years of age or >25% for patients 2 to 6 years of age. Prophylaxis was discontinued at entry. To identify whether any correlation existed between functional immune reconstitution and protection from OIs, subjects were immunized with the hepatitis A virus vaccine. The association between the humoral immune response and the likelihood of developing an OI was evaluated.Results. A total of 235 HIV-infected subjects from 43 participating sites had a median follow-up period of 132 weeks, yielding 547 person-years of observation. Twenty SBIs were observed among 19 subjects, resulting in an incidence rate of 3.66 SBIs per 100 person-years (95% confidence interval: 2.24 -5.66 SBIs per 100 person-years). Sixteen of the events were presumed bacterial pneumonia, with 4 proven SBIs. One participant experienced 2 separate pneumonia episodes, of presumed bacterial cause. Ten subjects who developed SBIs had baseline CD4 ؉ cell counts of >750 cells per mm 3 , and 15 had CD4 ؉ cell percentages of >25% at the time of their SBIs. Two subjects died as a result of non-SBI-related causes. There were no statistically significant differences in changes over time in CD4 ؉ cell counts or CD4 ؉ cell percentages between subjects who experienced primary end points and those who did not. There was no evidence that baseline protease inhibitor use, gender, race/ethnicity, age, or CD4 ؉ cell count or percentage affected the time to development of a SBI.Conclusions. OI or PCP prophylaxis can be withdrawn safely for HIV-infected pediatric patients who experience CD4 ؉ cell recovery while receiving stable antiretroviral therapy. More studies are needed to assess the association between antibody responses to neoantigens and the development of SBIs. Because HIV infection progresses and leads to a profound depletion of CD4 ϩ T lymphocytes, quantification of CD4 ϩ cells has become established as the major criterion for the institution of antimicrobial prophylaxis for opportunistic infections (OIs). 1 Several studies have demonstrated the efficacy of prophylaxis for such infections, and national guidelines have been established for standards of practice for the treatment of high-risk HIV-infected infants, children, adolescents, and adults. [2...

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Section: Sbi Rates For Hiv-infected Childrenmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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The Rate of Serious Bacterial Infections Among HIV-Infected Children With Immune Reconstitution Who Have Discontinued Opportunistic Infection Prophylaxis

et al. 2005

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“…However, the role of HHV-8in KS formation is not yet fully understood (13,14). According to the results of prophylaxis against these opportunistic infections containing MAC and Pneumocystis carinii, an increase in the CD4+T cell count during HAARTmarks the recovery of cellular-mediated immune responses to opportunistic pathogens (15,16). It is crucial for prophylaxis against opportunistic infections that the CD4+T cell count recovers to more than 100 cells/jiil.…”

Section: Discussionmentioning

confidence: 99%

Successful Treatment with Paclitaxel of Advanced AIDS-associated Kaposi's Sarcoma.

et al. 2002

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Kaposi's sarcoma (KS) is the most prevalent AIDS-associated tumor. Wereport a 44-year-old Japanese manwith advanced AIDS-associated KS, which was spread over bilateral pulmonary parenchyma. He was initially treated with combination chemotherapy with a partial response.Uponthe recurrence of his KStwo months after the completion of the combination chemotherapy, the patient received paclitaxel, which brought about a complete response. Highly active antiretrovial therapy (HAART) was initiated three months before the combination chemotherapy, and the CD4+T-cell count had risen before starting paclitaxel. His clinical course suggests that paclitaxel was highly effective for KS disease control as previously reported, and that immunerestoration with HAART is crucial in the treatment of KS.

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“…There were no controlled studies of the use of azithromycin for treatment of NTM in HIV-negative patients or uncontrolled studies of azithromycin used in HIV-positive patients. As seen in figure 2a [28,38,39,52,53,64,77], there was significant heterogeneity between the controlled studies of toxicity of use of azithromycin for NTM in HIV-infected subjects, although only moderate heterogeneity between studies of SAEs attributed to azithromycin ( fig. 2b [21, 41, 47-49]) in the uncontrolled studies of NTM treatment in HIV-uninfected patients.…”

Section: Serious Adverse Eventsmentioning

confidence: 99%

Efficacy and safety of World Health Organization group 5 drugs for multidrug-resistant tuberculosis treatment

2015

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The efficacy and toxicity of several drugs now used to treat multidrug-resistant tuberculosis (MDR-TB) have not been fully evaluated.We searched three databases for studies assessing efficacy in MDR-TB or safety during prolonged treatment of any mycobacterial infections, of drugs classified by the World Health Organization as having uncertain efficacy for MDR-TB (group 5).We included 83 out of 4002 studies identified. Evidence was inadequate for meropenem, imipenem and terizidone. For MDR-TB treatment, clarithromycin had no efficacy in two studies (risk difference (RD) −0.13, 95% CI −0.40-0.14) and amoxicillin-clavulanate had no efficacy in two other studies (RD 0.07, 95% CI −0.21-0.35). The largest number of studies described prolonged use for treatment of nontuberculous mycobacteria. Azithromycin was not associated with excess serious adverse events (SAEs). Clarithromycin was not associated with excess SAEs in eight controlled trials in HIV-infected patients (RD 0.00, 95% CI −0.02-0.02), nor in six uncontrolled studies in HIV-uninfected patients, whereas six uncontrolled studies in HIV-infected patients clarithromycin caused substantial SAEs ( proportion 0.20, 95% CI 0.12-0.27).For most group 5 drugs we found inadequate evidence of safety for prolonged use or for efficacy for MDR-TB, although macrolides appeared to be safe in prolonged use. @ERSpublications Weak evidence for the efficacy and safety of group 5 drugs for MDR-TB suggests they should be evaluated using RCTs

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Discontinuation of Prophylaxis againstMycobacterium aviumComplex Disease in HIV-Infected Patients Who Have a Response to Antiretroviral Therapy

Abstract: Azithromycin prophylaxis can safely be withheld in HIV-infected patients whose CD4+ cell counts have increased to more than 100 cells per cubic millimeter in response to antiretroviral therapy.

Cited by 146 publications

References 27 publications

The Rate of Serious Bacterial Infections Among HIV-Infected Children With Immune Reconstitution Who Have Discontinued Opportunistic Infection Prophylaxis

The Rate of Serious Bacterial Infections Among HIV-Infected Children With Immune Reconstitution Who Have Discontinued Opportunistic Infection Prophylaxis

Successful Treatment with Paclitaxel of Advanced AIDS-associated Kaposi's Sarcoma.

Efficacy and safety of World Health Organization group 5 drugs for multidrug-resistant tuberculosis treatment

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