RESUMO
From 1997 through 1999, the prevalence of the zidovudine resistance mutation T215Y was 9.7% among pregnant women, and the human immunodeficiency virus type 1 (HIV-1) load in those with resistant virus was higher than that measured in women with wild-type HIV-1. All mutations were noted in women with zidovudine experience, which suggests that monotherapy may not be adequate prophylaxis for vertical transmission of HIV-1 infection in the current era.
Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/virologia , Transcriptase Reversa do HIV/genética , HIV-1/efeitos dos fármacos , Complicações Infecciosas na Gravidez/virologia , Zidovudina/farmacologia , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Resistência Microbiana a Medicamentos/genética , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , HIV-1/genética , HIV-1/fisiologia , Humanos , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Mutação , New York/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologia , Prevalência , RNA Viral/sangue , Inibidores da Transcriptase Reversa/farmacologia , Inibidores da Transcriptase Reversa/uso terapêutico , Carga Viral , Zidovudina/uso terapêuticoRESUMO
The evolution of HIV-1 quasispecies in patients during the first year of life was investigated in 10 vertically infected infants, using heteroduplex analysis of the V3-V5 region of env. Four subjects, who showed little viral evolution during the period of the study, had rapid progression of disease and early loss of CD4(+) cells. The remaining six subjects, who were slow progressors, evolved new viral variants within 6 months, and in one case by 1 month of age. Of the four patients who were PCR positive at birth, one was infected with multiple HIV-1 variants. These results show that in HIV-infected children, multiple variants may initiate infection and early quasispecies diversification is associated with a favorable clinical outcome.
Assuntos
Variação Genética , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Progressão da Doença , Evolução Molecular , Produtos do Gene env/genética , Genes env , Proteína gp120 do Envelope de HIV/genética , Análise Heteroduplex , Humanos , Lactente , Recém-Nascido , Fragmentos de Peptídeos/genética , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: To determine the long-term immunologic and virologic effects of highly active antiretroviral therapy (HAART) in children with AIDS. DESIGN: A prospective observational study. SETTING: Two pediatric HIV clinics. PARTICIPANTS: Twenty-five protease-inhibitor naive HIV-infected children (aged 2-18 years) with advanced disease (CD4 < or =6%). INTERVENTION: HAART (one protease inhibitor and one or more nucleoside analogs). Diphtheria and tetanus immunization in six patients after 18 months of therapy. MAIN OUTCOME MEASURES: Changes in percentage of CD4 cells and plasma HIV-1 RNA levels; post-treatment assays of lymphoproliferative responses to recall antigens; CD4 cell memory phenotype. RESULTS: Median duration of follow-up was 18.8 months (range, 7.5-28 months). At baseline the CD4 cell percentage was 2% (range, 0-6%), this increased significantly to 16% (range, 3-48%) above baseline at 12 months (P = 0.002). The mean maximum CD4 cell increase was 20.7% (range 4-48%) which corresponds to 657x10(6) cells/l (range, 30-2240x10(6) cells/l) above baseline. By contrast, the median viral load was not significantly lower at 12 months than at baseline (P = 0.34), and only 25% of the patients had sustained undetectable viral load. Of the reconstituted CD4 cells 70% were naive, and none of the subjects had lymphoproliferative responses to tetanus and diphtheria although 40% did develop responses to Candida, an environmental antigen. A single immunization with diphtheria and tetanus toxoid produced lymphoproliferative responses to tetanus in three out of six patients. CONCLUSIONS: HAART was associated with sustained increases in CD4 cell counts, despite a high incidence of 'virologic failure'. CD4 counts and the proportion of naive cells were higher than have been reported in adults, which may be a reflection of greater thymic activity in children. Memory cell clones for antigens encountered in the past which are not prevalent before therapy could not be expanded without additional antigenic exposure.