We have measured the surface expression of the HIV-1 coreceptors CCR5 and CXCR4 on CD4+ T cells and monocytes from cord and adult blood. The expression of CCR5 was largely restricted to the memory (CD45RAlow) subset, whereas CXCR4 was expressed on both memory and naive (CD45RAhigh) T cells. The paucity of memory CD4+ T cells in cord blood means that CCR5-positive cells are relatively uncommon, so the overall extent of CCR5 expression was reduced in cord blood, compared with adult blood. IL-2 activation of CD4+ T cells from both cord and adult bloods caused a substantial increase in CCR5 expression, but moderately decreased CXCR4 expression. PHA stimulation increased CCR5 expression slightly, but only on naive cells. Monocytes expressed both CCR5 and CXCR4 at levels that differed little between cord and adult blood.
The transmission of perinatal hepatitis C virus (HCV) infection was studied retrospectively in 62 infants born to 54 HCV- and human immunodeficiency virus (HIV)-coinfected women enrolled in a prospective natural history study of HIV transmission. Infant HCV infection was assessed by nested RNA polymerase chain reaction. The overall rate of vertical HCV transmission was 16.4% (9/62). Most HCV-infected children did not develop antibodies to HCV. The rate of HCV infection was higher among HIV-infected infants (40%) than among HIV-uninfected infants (7.5%; odds ratio, 8.2; P = .009). This difference in transmission was not related to differences in maternal HCV load, as measured by branched DNA assay, or mode of delivery. Why HIV-infected infants of HCV- and HIV-coinfected women have significantly higher rates of perinatal HCV transmission remains to be elucidated. The rate of HCV transmission in HIV-uninfected infants of HCV- and HIV-coinfected women is similar to that reported for infants born to HIV-seronegative mothers.
Opportunistic infections such as pulmonary tuberculosis (TB) increase local HIV-1 replication and mutation. As AIDS progresses, alteration of the HIV-1 gp120 V3 sequence is associated with a shift in viral coreceptor use from CCR5 (CD195) to CXCR4 (CD184). To better understand the effect of HIV/TB coinfection, we screened transcripts from bronchoalveolar lavage cells with high density cDNA arrays and found that CXCR4 mRNA is increased in patients with TB. Surprisingly, CXCR4 was predominately expressed on alveolar macrophages (AM). Mycobacterium tuberculosis infection of macrophages in vitro increased CXCR4 surface expression, whereas amelioration of disease reduced CXCR4 expression in vivo. Bronchoalveolar lavage fluid from TB patients had elevated levels of CCL4 (macrophage inflammatory protein-1β), CCL5 (RANTES), and CX3CL1 (fractalkine), but not CXCL12 (stromal-derived factor-1α). We found that M. tuberculosis infection of macrophages in vitro increased viral entry and RT of CXCR4, using HIV-1, but not of CCR5, using HIV-1. Lastly, HIV-1 derived from the lung contains CD14, suggesting that they were produced in AM. Our results demonstrate that TB produces a permissive environment for replication of CXCR4-using virus by increasing CXCR4 expression in AM and for suppression of CCR5-using HIV-1 by increasing CC chemokine expression. These changes explain in part why TB accelerates the course of AIDS. CXCR4 inhibitors are a rational therapeutic approach in HIV/TB coinfection.
Despite the recent approval of lamivudine for the treatment of children with chronic hepatitis B virus (HBV) infection, there is insufficient information on the kinetics of HBV clearance and the factors that predict a favorable treatment response to lamivudine in this population. In a small retrospective study of 16 HBV-infected children treated with lamivudine, we examined changes in virus load and other factors associated with hepatitis B e antigen (HBeAg) clearance. High pretherapy alanine aminotransferase level, low serum HBV DNA load, and age at the start of treatment were independently associated with HBeAg clearance. HBeAg clearance was also associated with the achievement of specific levels of virus suppression, and failure to achieve those levels was associated with the development of lamivudine resistance. Additional studies are necessary to provide better indications and guidelines for the treatment of children with chronic HBV infection.
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