ABSTRACT
Although expanded access to antiretroviral therapy (ART), and starting lifelong ART as soon as possible after diagnosis of HIV, have dramatically improved survival and reduced morbidity in HIV-infected children and adolescents, ~20% of children will develop virological failure (VF). Children and adolescents may be at higher risk of VF and drug resistance for a number of reasons, including prevention of mother-to-child exposure, reliance on a caregiver to administer ART, poor palatability of paediatric drugs, tuberculosis/HIV co-treatment in protease inhibitor (PI) (mainly lopinavir/ritonavir)-based regimens, and adolescence being associated with poor adherence. In children with VF, if adherence issues are addressed and re-suppression is not achieved, a switch to second- or third-line drugs may be indicated, which is the gold standard in management. However, in the face of ongoing adherence challenges, with potential accumulation of resistance mutations, limited treatment options due to extensive resistance and limited approved paediatric formulations, other strategies have been used. These include continuing a failing PI regimen, switching to a holding regimen (one or more nucleoside reverse transcriptase inhibitors) or discontinuing ART. Lamivudine monotherapy is a common choice when holding regimens are used, on the premise that the lamivudine-associated M184V resistance mutation reduces viral replication and may maintain clinical and immunological stability compared with discontinuing treatment altogether. However, this strategy is generally associated with immunological, and in some cases clinical, decline after starting lamivudine monotherapy. We discuss the pros and cons of using this therapy in children. We also propose guidance for using lamivudine monotherapy, suggesting clinical and immunological criteria for its use. Close monitoring and adherence support are required with this approach. Given many new emerging ART drugs and strategies, lamivudine monotherapy should be administered temporarily, while efforts to improve adherence are implemented. It should not be considered a default option in children with VF.
Subject(s)
Genes, Viral , HIV Infections , HIV , Lamivudine , Adolescent , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Child , Disease Management , Drug Monitoring/methods , Drug Resistance, Viral/drug effects , HIV/drug effects , HIV/genetics , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/physiopathology , HIV Infections/psychology , Humans , Lamivudine/administration & dosage , Lamivudine/adverse effects , Long-Term Care/methods , Long-Term Care/psychology , Medication Adherence/psychology , Mutation , Viral Load/drug effectsABSTRACT
OBJECTIVE: To examine whether body mass index is an independent predictor of cataract. (Body mass index is a standardized measure defined as weight in kilograms divided by the square of the height in meters.) DESIGN: Prospective cohort study, with 5 years of follow-up. PARTICIPANTS: A total of 17,764 US male physicians participating in the Physicians' Health Study, aged 40 to 84 years, who were free of cataract, myocardial infarction, stroke, and cancer at baseline and reported complete information about body mass index and other cataract risk factors. MAIN OUTCOME MEASURE: Incident cataract, defined as a self-report, confirmed by medical record review, first diagnosed after randomization, age-related in origin, and responsible for a decrease in best corrected visual acuity to 20/30 or worse. RESULTS: Incident cataract occurred during follow-up in 370 participants. In proportional hazards models that adjusted for potential confounding variables, body mass index had a strong, graded relationship with risk of cataract. Relative to those with body mass index less than 22, relative risks (95% confidence intervals) associated with body mass index of 22 to less than 25, 25 to less than 27.8, and 27.8 or more were 1.54 (1.04 to 2.27), 1.46 (0.98 to 2.20), and 2.10 (1.35 to 3.25), respectively. Relative to any given level of body mass index, a 2-unit higher level predicted a 12% increase in risk of cataract (95% confidence interval, 5% to 19%). Higher body mass index was especially strongly related to risk of posterior subcapsular and nuclear sclerotic cataracts and was also significantly related to risk of cataract extraction. CONCLUSIONS: In a prospective cohort study of apparently healthy men, higher body mass index, a potentially modifiable risk factor, was a determinant of cataract. The leanest men had the lowest rates, consistent with experimental evidence that restriction of energy intake slows development of cataract. Although precise mechanisms are unclear, the effect of body mass index on cataractogenesis is apparently independent of other risk factors, including age, smoking, and diagnosed diabetes.
