Adolescents have the capacity to improve their immunologic status with HAART. Lower than expected success in virologic control is related to lack of adherence, and efforts to improve treatment outcome must stress measures to assure adherence to medication.
The PACTG 381 cohort included 120 adolescents infected via high-risk behaviors and treated with at least two NRTIs plus either a protease inhibitor or an efavirenz-containing HAART regimen. After 24 weeks of therapy, only 69 of 118 (59%) evaluable subjects had undetectable viral loads. We now present findings of the study after 3 years of follow-up. Virologic, immunologic, and treatment information were collected from subjects every 12 weeks beyond the first 24 weeks of therapy through 156 weeks. Of the 120 subjects starting HAART, 44 (37%) stayed on study treatment for the 3 years of observation. Twenty-nine (24%) subjects reached and maintained undetectable viral loads. Poorer adherence (p = 0.016), higher baseline viral load (p = 0.010), and CD8 naive counts (p = 0.034) predicted virologic failure. Immunologic measurements improved from entry to the end of follow-up in the subjects with undetectable viral loads. CD4 counts at the end of study were not significantly different from HIV-uninfected youth, but CD4%, CD8 counts and percent, and CD8 activation markers remained significantly different. Adolescents infected with HIV via high-risk behaviors have less than optimal responses to HAART therapy with only 24% achieving and maintaining undetectable viral loads over 3 years. Immunologic improvement was demonstrated and CD4 counts in subjects with virologic control reached levels in HIV-uninfected adolescents. Interventions, especially those focused on adherence, are necessary to improve HAART outcomes in adolescents.
Monocytes differentiated in the presence of phytohemagglutinin P-stimulated T cells could be infected with human cytomegalovirus AD169 and produced low levels of infectious virus. Additional treatment with therapeutic levels of hydrocortisone resulted in a 10to 100-fold increase in infectious virus production. Hydrocortisone-treated cells demonstrated immediate-early protein kinetics similar to that observed with human fibroblasts, whereas a delay of up to 24 h was observed with untreated cells. Late protein production was barely detectable by immunostaining without hydrocortisone treatment. In treated cells, however, late protein was detected and the levels correlated with the number of cells producing infectious virus. This system provides a model for human cytomegalovirus infection of macrophages in humans.
To investigate factors that affect mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1), autologous neutralizing antibody, viral load, and viral tropism were evaluated in 28 pregnant women infected with HIV-1, of whom 8 were transmitters and 20 nontransmitters. One (12%) of 8 transmitters versus 11 (55%) of 20 nontransmitters had autologous neutralizing antibody (P=.04). Plasma levels of HIV-1 RNA and infectious HIV-1 titers (mean+/-SD) in peripheral blood mononuclear cells (PBMC) at delivery did not differ significantly between transmitters and nontransmitters (24, 266+/-10,101 vs. 31,589+/-9128 copies/mL and 29+/-12 vs. 42+/-17 infected cells per 106 PBMC, respectively). However, only transmitters (4 [50%] of 8) were HIV p24 antigen positive. The ability of HIV-1 strains to induce syncytium did not differ between groups (P=.6); however, only non-syncytium-inducing isolates were transmitted. Isolates from 4 (80%) of 5 transmitters versus 2 (18%) of 12 nontransmitters (P=.03) demonstrated increasing replication in macrophages. Thus, lack of autologous neutralizing antibody and increased replication in macrophages were significantly associated with mother-to-infant transmission. In addition, autologous neutralizing antibody was associated with reduced viral load.
Human immunodeficiency virus (HIV) type 1 DNA assay data were obtained at baseline from 111 HIV-1-positive subjects who were treated with nucleosides. Higher baseline DNA level, HIV-1 RNA level, and infectious titer were comparably associated with an increased hazard of disease progression (each P<.03). Only DNA level was significantly associated with survival (adjusted hazard ratio for 1 log(10) higher level, 3.99; 95% confidence interval, 1.44-11.09; P=.008).
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