Long-term experience with combination antiretroviral therapy that contains nelfinavir for up to 7 years in a pediatric cohort
ABSTRACT We sought to provide long-term data on the clinical, immunologic, and virologic response to highly active antiretroviral therapy in infants and children who are naive to protease inhibitors.
HIV-1-infected children who were naive to protease inhibitors were treated with a combination of nelfinavir and 2 nucleoside reverse transcriptase inhibitors (stavudine and lamivudine) in an observational, prospective, single-center study. Virologic failure-free survival was assessed by Kaplan-Meier analyses. The increase in CD4+ T cells during follow-up was estimated with a generalized linear model incorporating repeated measurements.
Thirty-nine HIV-1-infected children were included and followed for a median period of 227 weeks (interquartile range: 108-275 weeks). The virologic failure-free survival rate was 74%, 66%, 58%, and 54% after 48, 96, 144, and 240 weeks, respectively. Children who experienced virologic failure in 48 weeks (or 96 weeks) were younger at baseline compared with the responders (0.8 vs 5.3 years). Eighteen children remained on the regimen for >5 years. All children, including the nonresponders, showed a sustained immunologic response. Grades 3 to 4 toxicity was observed in 2 patients only. Eleven developed clinically evident lipodystrophy.
Combination therapy can be used safely in infants and children over a long period. Young age is strongly associated with virologic failure. Although the virologic response declined, immunologic parameters and clinical improvement were sustained up to 7 years, at the expense of lipodystrophy.
Full-textDOI: · Available from: Frank Van Leth, Aug 23, 2015
- SourceAvailable from: seen.esJournal of Parenteral and Enteral Nutrition 11/2009; 33(6):588-606. DOI:10.1177/0148607109346276 · 3.14 Impact Factor
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ABSTRACT: R SpecialIssue ecently, a report suggested that the epidemic of human immune deficiency virus (HIV) infection may have reached its peak. Although the number of new cases is reducing, the number of people living with HIV has not decreased as the patients survive in this era in which effective antiretroviral therapy has been widely accessible. The knowledge about HIV disease has never been this immense. The challenges facing us have changed from treating the dying diseased cases complicated with opportunistic infections to dealing with the problems related to long-term treatment including life-long adhe-rence, drug adverse effects, drug resistance, and the need for a newer generation with less toxic drugs. In children, additional challenges are related to adolescent problems. This review summarizes the challenging issues of this era in treating HIV-infected children. The overview disease burden In 2009, there were 33.3 million people living with HIV worldwide, of which 5-10% were children. 1 The majority of them are living in Sub-Saharan Africa. In Thailand, an estimated 400,000 infected people with HIV were reported in 2009, of which approximately 15,000-20,000 were children. Nearly all of them were acquired perinatally. The prevalence of HIV infection among pregnant women in Thailand has declined from 1.74% in 1999 to 0.64% in 2009. After the implementation of a nation-wide prevention-of-mother-to-child-transmission (PMTCT) program, the rate of perinatal transmission has decreased from 25% to 2-4%. 2 Diagnosis of HIV infection in perinatally HIV-exposed infants Virologic assay, either HIV DNA-PCR or RNA-PCR assay, can be used for diagnosis of HIV infection in infants. Because of the maternally transferred anti-HIV antibody, the serologic test causes a false positive in uninfected young infants. The PCR is recommended to be performed at least 2 times at age 1-2 months and 4-6 months. At age 12-18 months of age, the HIV antibody test should always be performed to confirm the diagnosis regardless of the results of prior virologic tests. HIV infection can be definitely diagnosed by the presence of HIV antibody in children aged ≥ 18 months. Definitive exclusion of HIV infection can be made by no clinical or virologic evidence of HIV infection plus one of the fol-lowing criteria: 1) at least two negative HIV PCR assays which are performed at age ≥ 1 month and ≥ 4 months, 2) at least two negative HIV antibody tests at ≥ 6 months of age, 3) one negative HIV PCR at age ≥ 4 months and absence of HIV antibody after 6 months of age. 3 Management of HIV-infected children: the current Thai guidelines HIV-infected children require routine care and an-ticipatory guidance similar to normal children. All HIV-infected children should be immunized with the same schedule as uninfected children except that children with severe immune suppression (CD4 percentage < 15% or CD4 count < 200 cells/mm 3) or severely symptomatic disease status should not receive live-attenuated vaccine such as mumps-measles-rubella or varicella vaccine. Moreover, all HIV-exposed infants with unknown infection status from 4-6 weeks of age, should receive chemoprophylaxis against Pneumocystis jiroveci pneumonia (PCP) until HIV infection can be excluded. Cotrimoxazole is the drug of choice. Likewise, infected children younger than 12 months or those with CD4 < 15%; or < 200 cells/mm 3 in children older than 5 years, should also receive PCP prophylaxis. This is because the risk of PCP development is quite high in HIV-infected infants < 12 months regardless of their CD4 levels. Highly active antiretroviral therapy (HAART) has been the principle of treatment of HIV infection. HAART normalizes immunologic function, prevents opportunistic infection and mortality. With HAART, HIV has been changed from a deadly disease to a chronic disease in which patients can live a very normal life. HAART is generally composed of three drugs from at least two classes. The aims of antiretroviral therapy are to minimize viral load, maintain viral suppression, preserve immune function, maintain normal growth and development, and improve the quality of life.
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ABSTRACT: In Africa, facing the scaling-up of HAART, there is an urgent need to monitor accurately the long-term benefits of these lifelong treatments. Survival and immuno-virological response were assessed for 78 children in the ANRS 1244/1278 Children's cohort (Abidjan, Côte d'Ivoire) who were enrolled from October 2000 for treatment with HAART and followed to September 2004. Initial HAART consisted of two nucleoside reverse transcriptase inhibitors with either nelfinavir (NFV) or efavirenz (EFV). For the comparison of immunological and virological responses, CD4 cell counts and HIV-1 RNA viral load were assessed by performing time-point specific and longitudinal data analysis. At baseline, the median CD4 cell percentage was 7.5% and the median HIV-1 RNA viral load was 5.37 log10 copies/ml. The survival probability was high (0.86 at month 42; 95% confidence interval, 0.77-0.92) with no difference according to whether the HAART regimen contained NFV or EFV. At 36 and 42 months of follow-up, an immune recovery was observed with median CD4 cell percentages reaching 23.1% and 24.8%, respectively, with no difference according to the HAART regimen (longitudinal data analysis). At the same time points, a sustained viral suppression was also obtained, with undetectable viral load achieving in 46.5% and 45.0%, respectively, regardless of whether the HAART regimen. This study demonstrates the durability of both clinical and biological response to HAART in African children.AIDS 12/2006; 20(18):2315-9. DOI:10.1097/QAD.0b013e328010943b · 6.56 Impact Factor