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Tolerabilities of antiretrovirals in paediatric HIV infection
Daniel Avi Lemberg1, Pamela Palasanthiran, Michele Goode
1Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, New South Wales, Australia.
Insights
Antiretroviral drugs for treating HIV-1 in children are generally well-tolerated, with most toxicities affecting the gastrointestinal and hepatic systems. While side effects exist, they rarely prevent effective treatment in pediatric patients.
Area of Science:
- Pediatric Infectious Diseases
- Pharmacology
- Hepatology
Background:
- Limited pediatric data necessitates extrapolation from adult antiretroviral studies.
- Children's unique physiology requires specific consideration, as they are not simply small adults.
- Understanding antiretroviral tolerability in pediatric HIV-1 is crucial for effective management.
Purpose of the Study:
- To review and summarize existing data on the tolerability of antiretrovirals in children with HIV-1.
- To highlight common and significant toxicities associated with various antiretroviral drug classes in pediatric populations.
- To emphasize the importance of factors like taste and formulation availability in pediatric antiretroviral adherence and tolerability.
Main Methods:
- Systematic review of existing reports and literature on antiretroviral tolerability in children.
- Focus on summarizing adverse events and toxicities, excluding efficacy data.
- Analysis of drug class-specific toxicities, including gastrointestinal, hepatic, skin, mitochondrial, hematological, metabolic, and renal effects.
Main Results:
- Antiretrovirals are generally well-tolerated in children, though all carry potential toxicities.
- Gastrointestinal and hepatic systems are most frequently affected.
- Specific drug classes present distinct risks: non-nucleoside reverse transcriptase inhibitors (NNRTIs) with rashes, nucleoside analogues (NAs) with mitochondrial toxicities, and protease inhibitors (PIs) with metabolic issues.
Conclusions:
- While antiretrovirals can cause various toxicities in children, they are typically manageable.
- Gastrointestinal, hepatic, and mitochondrial toxicities are key concerns.
- Despite potential side effects, the availability of pediatric formulations and a broader drug range generally ensure that toxicities do not impede effective antiretroviral therapy in children.
Abstract:
Data on the efficacy and tolerability of antiretrovirals in children are limited as, in contrast to adult studies, large paediatric cohort studies are lacking. Thus, data pertaining to adults are often extrapolated to children despite the acknowledgement that children are not little adults. This review summarises information gathered from existing reports and focuses on the tolerabilities of antiretrovirals in children infected with HIV-1. The efficacy of antiretrovirals is not included in the scope of the discussion. Taste of antiretrovirals should be an important factor when considering the tolerability of antiretrovirals in children. However, antiretroviral options are often limited in young children as only some of the antiretrovirals are available as paediatric formulations. All antiretrovirals have been associated with toxicities in children, but in general, they are relatively well tolerated. The gastrointestinal system including hepatic system is most prone to being affected by these drugs. Skin rashes and hypersensitivity reactions are also associated with antiretroviral use, particularly with the non-nucleoside reverse transcriptase inhibitors. Mitochondrial toxicities that lead to impairment of liver function, pancreatic function and lactic acidosis are associated with most of the nucleoside analogues. Haematological toxicity is often a dose limiting adverse effect especially of the nucleoside analogues, in particular zidovudine. The protease inhibitors are associated with gastrointestinal intolerance (diarrhoea) and metabolic derangements that can lead to hypercholesterolaemia and hypertriglyceridaemia, which in turn and can lead to changes in body habitus. The renal system is also affected by several drugs, the most important of which is indinavir, which has been associated with renal stones and damage to the renal tubules. Fortunately, with lower incidence of major toxicity and with the range of drugs now available for paediatric use, toxicities are usually not a barrier to effect antiretroviral therapy in children.