ABSTRACT
BACKGROUND: Lymph nodes serve as reservoirs for the replication of human immunodeficiency virus (HIV) type 1. Comparison of serial measurements of virus burden in lymph nodes and peripheral blood after a change in antiretroviral therapy may provide insights into pathogenic mechanisms and permit a more accurate assessment of a therapeutic response. STUDY DESIGN: Nevirapine was added to the drug regiment of eight children with HIV infection treated with the combination of zidovudine and didanosine who had increasing levels of serum p24 antigen. Lymph node biopsies were performed at entry and after 12 weeks of therapy. RESULTS: Neither CD4 counts nor p24 antigen level correlated with the degree of viremia as measured by ribonucleic acid copy numbers in plasma. Correlations were found between HIV DNA copy number in peripheral blood mononuclear cells and HIV DNA copy number in lymph nodes (p = 0.02), as well as between peripheral blood CD4 counts and lymph node architecture. The HIV signals in the lymph nodes conformed to the anatomic organization of apical light zones in the germinal centers; however, in more advanced disease stages, organized germinal centers disappeared as evidence by a decline in the extent of the follicular dendritic network. CONCLUSIONS: Lymph node biopsies in this small number of HIV-infected children revealed a progressive loss of an organized architecture, especially of the follicular dendritic network. This correlated with a progressive loss of CD4+ cells but not with other measures of disease stage, including viral load, as measured by ribonucleic acid copy numbers.
Subject(s)
HIV Infections/virology , HIV-1/isolation & purification , Lymph Nodes/virology , Antiviral Agents/therapeutic use , Biopsy , CD4 Lymphocyte Count , Child , Child, Preschool , DNA, Viral/analysis , Didanosine/administration & dosage , Drug Therapy, Combination , Female , HIV Core Protein p24/blood , HIV Infections/drug therapy , HIV Infections/immunology , Humans , In Situ Hybridization , Infant , Lymph Nodes/pathology , Male , Nevirapine , Pyridines/administration & dosage , Viremia , Zidovudine/administration & dosageABSTRACT
OBJECTIVE: To evaluate immunologic and virologic correlates of vertical transmission of human immunodeficiency virus type 1 (HIV-1). DESIGN: Case-control study. PATIENTS: Women who were prospectively enrolled in a natural history study of HIV-1 infection in women and infants. Sixteen HIV-1-infected women whose infants became infected were matched by CD4+ cell percentage and use of zidovudine during pregnancy with women whose infants did not become infected. MEASUREMENTS: Maternal autologous neutralizing antibody, virus load determined by RNA-polymerase chain reaction (RNA-PCR), and virus phenotype. RESULTS: Most women in both groups had low titers of autologous neutralizing antibody, and no difference in neutralizing titers was observed (range, < 4 to 181 in both groups). The HIV-1 copy number in maternal plasma was not significantly different in the two groups but was inversely correlated with maternal CD4+ cell percentage (p < 0.005). Five women in the transmitting group and four in the non-transmitting group had syncytium-inducing (SI) phenotype virus. Two infected infants had SI phenotype virus. The SI phenotype virus was associated with a greater HIV-1 copy number in maternal plasma (p < 0.05) and an increase in the mortality rate for the infants (p < 0.01). CONCLUSIONS: In women matched for CD4+ cell percentage, low titers of autologous neutralizing antibody, high virus load, and SI phenotype virus were not associated with an increased risk of transmission of HIV-1 to their infants.
Subject(s)
Acquired Immunodeficiency Syndrome/transmission , HIV Antibodies/analysis , HIV-1 , Infectious Disease Transmission, Vertical , Acquired Immunodeficiency Syndrome/mortality , CD4 Lymphocyte Count , Female , HIV Core Protein p24/analysis , HIV-1/genetics , HIV-1/immunology , HIV-1/isolation & purification , Humans , Infant , Phenotype , Polymerase Chain Reaction , RNA, Viral/analysisABSTRACT
OBJECTIVE: To determine the safety, tolerance, pharmacokinetics, and antimycobacterial activity of orally administered clarithromycin in children with acquired immunodeficiency syndrome and disseminated Mycobacterium avium complex (MAC) infection. DESIGN: Phase I study with a 10-day pharmacokinetic phase followed by a 12-week continuation therapy phase. PATIENTS: Twenty-five patients with a median age of 8.3 years were enrolled. Ten were receiving zidovudine and 13 were receiving didanosine at the time of enrollment. INTERVENTION: Clarithromycin suspension was administered to each patient at one of three dose levels: 3.75, 7.5, and 15 mg/kg per dose every 12 hours. Clarithromycin and antiretroviral pharmacokinetics were measured during single-drug and concurrent-drug administration. Clinical and laboratory monitoring was performed biweekly. MEASUREMENTS AND MAIN RESULTS: Clarithromycin was well tolerated at all dose levels. Plasma clarithromycin concentrations increased proportionately with increasing doses, and significant pharmacokinetic interactions were not observed during concurrent administration with zidovudine or didanosine. Decreases in mycobacterial load in blood were observed only at the highest clarithromycin dose level. Decreased susceptibility to clarithromycin developed rapidly (within 12 to 16 weeks) in the majority of MAC strains isolated from study patients.