ABSTRACT
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.
Subject(s)
Anti-HIV Agents/pharmacology , HIV Infections/virology , HIV Reverse Transcriptase/genetics , HIV-1/drug effects , Pregnancy Complications, Infectious/virology , Zidovudine/pharmacology , Anti-HIV Agents/therapeutic use , Cohort Studies , Drug Resistance, Microbial/genetics , Female , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV-1/genetics , HIV-1/physiology , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Mutation , New York/epidemiology , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/epidemiology , Prevalence , RNA, Viral/blood , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use , Viral Load , Zidovudine/therapeutic useABSTRACT
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.
Subject(s)
Genetic Variation , HIV Infections/physiopathology , HIV Infections/virology , HIV-1/classification , HIV-1/genetics , Disease Progression , Evolution, Molecular , Gene Products, env/genetics , Genes, env , HIV Envelope Protein gp120/genetics , Heteroduplex Analysis , Humans , Infant , Infant, Newborn , Peptide Fragments/genetics , Polymerase Chain ReactionABSTRACT
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.