RESUMO
In 188 HIV-infected children receiving efavirenz, a lower mid-dose (C12) was associated with a higher risk of HIV-1 viral load >400 copies/mL (P = 0.03). Simulations for a normalized population receiving US Food and Drug Administration weight-band dosing predicted that 15% of children would have a C12 below target threshold (<1.0 mg/L) with a 23% risk of viral replication.
Assuntos
Benzoxazinas/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Inibidores da Transcriptase Reversa/sangue , Carga Viral/efeitos dos fármacos , Alcinos , Benzoxazinas/farmacocinética , Benzoxazinas/farmacologia , Benzoxazinas/uso terapêutico , Criança , Estudos de Coortes , Ciclopropanos , Feminino , HIV-1/efeitos dos fármacos , Humanos , Masculino , Inibidores da Transcriptase Reversa/farmacocinética , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêuticoRESUMO
BACKGROUND: HIV-infected infants have high risk of death in the first two years of life if untreated. WHO guidelines recommend early infant HIV diagnosis (EID) of all HIV-exposed infants and immediate antiretroviral therapy (ART) in HIV-infected children under 24-months. We assessed the cost-effectiveness of this strategy in HIV-exposed non-breastfed children in Thailand. METHODS: A decision analytic model of HIV diagnosis and disease progression compared: EID using DNA PCR with immediate ART (Early-Early); or EID with deferred ART based on immune/clinical criteria (Early-Late); vs. clinical/serology based diagnosis and deferred ART (Reference). The model was populated with survival and cost data from a Thai observational cohort and the literature. Incremental cost-effectiveness ratio per life-year gained (LYG) was compared against the Reference strategy. Costs and outcomes were discounted at 3%. RESULTS: Mean discounted life expectancy of HIV-infected children increased from 13.3 years in the Reference strategy to 14.3 in the Early-Late and 17.8 years in Early-Early strategies. The mean discounted lifetime cost was $17,335, $22,583 and $29,108, respectively. The cost-effectiveness ratio of Early-Late and Early-Early strategies was $5,149 and $2,615 per LYG, respectively as compared to the Reference strategy. The Early-Early strategy was most cost-effective at approximately half the domestic product per capita per LYG ($4,420 in Thailand 2011). The results were robust in deterministic and probabilistic sensitivity analyses including varying perinatal transmission rates. CONCLUSION: In Thailand, EID and immediate ART would lead to major survival benefits and is cost- effective. These findings strongly support the adoption of WHO recommendations as routine care.
Assuntos
Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/economia , Fármacos Anti-HIV/uso terapêutico , Análise Custo-Benefício , Feminino , Infecções por HIV/economia , Humanos , Lactente , Recém-Nascido , Expectativa de Vida , Masculino , Modelos Teóricos , TailândiaRESUMO
BACKGROUND: Despite implementation of universal infant hepatitis B (HB) vaccination, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) still occurs. Limited data are available on the residual MTCT of HBV in human immunodeficiency virus (HIV)-HBV co-infected women. OBJECTIVES: We assessed the prevalence of HBV infection among HIV-infected pregnant women and the rate of residual MTCT of HBV from HIV-HBV co-infected women and analyzed the viral determinants in mothers and their HBV-infected children. STUDY DESIGN: HIV-1 infected pregnant women enrolled in two nationwide perinatal HIV prevention trials in Thailand were screened for HB surface antigen (HBsAg) and tested for HBeAg and HBV DNA load. Infants born to HBsAg-positive women had HBsAg and HBV DNA tested at 4-6 months. HBV diversity within each HBV-infected mother-infant pair was analyzed by direct sequencing of amplified HBsAg-encoding gene and cloning of amplified products. RESULTS: Among 3312 HIV-1 infected pregnant women, 245 (7.4%) were HBsAg-positive, of whom 125 were HBeAg-positive. Of 230 evaluable infants born to HBsAg-positive women, 11 (4.8%) were found HBsAg and HBV DNA positive at 4-6 months; 8 were born to HBeAg-positive mothers. HBV genetic analysis was performed in 9 mother-infant pairs and showed that 5 infants were infected with maternal HBV variants harboring mutations within the HBsAg "a" determinant, and four were infected with wild-type HBV present in highly viremic mothers. CONCLUSIONS: HBV-MTCT still occurs when women have high HBV DNA load and/or are infected with HBV variants. Additional interventions targeting highly viremic women are thus needed to reduce further HBV-MTCT.
