Partial Treatment Interruption of Protease Inhibitor-Based Highly Active Antiretroviral Therapy Regimens in HIV-Infected Children
Division of Infectious Diseases, Department of Pediatrics, Jacobi Medical Center and Albert Einstein College of Medicine, 1400 Pelham Parkway, Bronx, NY, USA.JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 03/2006; 41(3):298-303. DOI: 10.1097/01.qai.0000197078.41150.0d
Treatment guidelines for HIV-infected children recommend using combinations of reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). Successful suppression of HIV replication and adherence to these regimens are often suboptimal because of multiple factors. For patients with detectable viremia and limited treatment options, therapy simplification consisting of RTIs, referred to as partial treatment interruption (PTI), may represent a temporizing option. We describe a cohort of 26 HIV-infected children who underwent treatment simplification by discontinuing the PI and continuing therapy with 2 or more RTIs. The subjects, who were identified retrospectively, were followed for a period of 24 to 96 weeks. Data collected included clinical information, viral load, and CD4T lymphocyte percentage (CD4%) at baseline and 24, 48, and 96 weeks after PTI. Twenty-six, 21, and 11 patients were evaluated at 24, 48, and 96 weeks, respectively. No child had Centers for Disease Control and Prevention-defined disease progression, and there were no significant changes in viral loads (P > 0.5) across all study intervals after interruption of the PIs. Although most children maintained a CD4% > 15%, comparisons of CD4% at 24 and 48 weeks demonstrated a statistically significant decrease compared with baseline. Therapy simplification by PTI may provide a practical option in patients intolerant of or failing PI-based highly active antiretroviral therapy.
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ABSTRACT: The treatment and prognosis of pediatric HIV infection in the developed world has been transformed with the introduction of highly active antiretroviral therapy. Perinatally infected children are now living into adulthood, changing the face of this epidemic from one of pessimism to one of hope. However, this transformation has brought with it many unforeseen challenges. In this review, we attempt to highlight key issues in the management of HIV-infected children, such as adherence, treatment strategies, drug resistance, and toxicities. We trust that the experience that we have accumulated can be successfully implemented in countries where treatment is urgently needed.
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ABSTRACT: This review sets out to overview treatment interruption in chronic HIV-1 infection: what treatment interruption promised, results from recent trials, and what the future holds. Recent studies have produced mixed results; several trials have been prematurely halted, whereas others have reported more positive outcomes. One consistent finding has been the identification of the CD4 T-cell count nadir as a critical parameter in determining the outcome of treatment interruption. The use of treatment interruption is still controversial, but it is becoming clear that certain individuals could benefit, and partial treatment interruption strategies warrant further investigation.
Article: Partial treatment interruptions[Show abstract] [Hide abstract]
ABSTRACT: Many patients with drug-resistant HIV and limited therapeutic options for complete suppression are maintained on a stable partially suppressive regimen. Although this approach is associated with durable clinical benefit (compared with no therapy), it can result in the accumulation of drug-resistance mutations and the development of drug-related toxicities. Several strategies aimed at maintaining the partial activity of therapy while reducing drug exposure have recently been investigated. Findings from these studies have provided important insights into how drugs work in the presence of drug-resistant viremia. Nucleoside analogues often continue to exert potent antiviral activity against viruses exhibiting evidence of genotypic and phenotypic drug resistance. Protease inhibitors and fusion inhibitors select for mutations that often confer complete resistance in vivo; these mutations, however, reduce viral fitness (as measured in the absence of drug) and may reduce virulence/pathogenicity. Nonnucleoside reverse transcriptase inhibitors generally lack any beneficial activity once drug-resistant mutations have emerged. Although these approaches are not recommended for routine clinical practice, they have provided the requisite proof-of-concept to motivate larger controlled randomized trials. More importantly, findings from these studies have generated a number of important insights that can be valuable when considering 'when to switch', 'how to switch' and 'how to wait'.
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