Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association最新文献

Disturbances of vaginal flora are common among women of reproductive age. In areas of sub-Saharan Africa where the prevalence of HIV is high, the frequency of bacterial vaginosis (BV) is also high. In this study, we assessed the association of BV and other disturbances of vaginal flora with prevalent HIV infection in two cross-sectional studies among pregnant women in urban Malawi. The prevalence of HIV-1 was 23% in 1990 and 30% in 1993. Overall, 30% of the women had BV, 59% had mild or moderate disturbance of vaginal flora, and only 11% had normal vaginal flora. Increasing prevalence of HIV was significantly associated with increasing severity of disturbance of vaginal flora (p < .00001, chi2 trend test). This trend of increased prevalence persisted after controlling for concurrent sexually transmitted diseases (STDs), sexual activity, and socioeconomic factors. After multivariate adjustment for potential confounders, the odds ratio for the association of BV with prevalent HIV infection was 3.0 (95% confidence interval [CI], 2.4-3.8), that of moderate vaginal disturbance with HIV infection was 2.2 (95% CI, 1.7-2.8), and that of mild vaginal disturbance with HIV infection was 1.6 (95% CI, 1.3-2.1). Among women with BV, HIV infection was higher among younger women than older, implying more recent infection. Although these studies were cross-sectional, our data suggest that BV could be associated with increased susceptibility to HIV infection.

HTLV-I is the etiologic agent of adult T-cell leukemia/lymphoma and is associated with tropical spastic paraparesis/HTLV-I-associated myelopathy. Following integration into the host cell genome, HTLV-I replication is regulated by both host and viral mechanisms that control transcription. Low levels of viral transcription (basal transcription) occur before expression of the virally encoded Tax protein (Tax-mediated transcription). Members of the cyclic adenosine monophosphate (cAMP) response element binding (CREB)/activating transcription factor 1 (ATF-1) family of transcription factors bind three 21-bp repeats (Tax-responsive element-1, or TRE-1) within the viral promoter and are important for basal and Tax-mediated transcription. Using mitogen stimulated and quiescent peripheral blood mononuclear cells (PBMC) and Jurkat cells, we compared differences in basal transcription and amounts and binding of transcription factors with TRE-1. We demonstrate that amounts of transcriptionally active phosphorylated CREB protein (P-CREB) differ between activated PBMC and Jurkat cells. Following stimulation, P-CREB levels remain elevated in PBMC for up to 24 hours whereas CREB is dephosphorylated in Jurkat cells within 4 hours following stimulation. The differences in P-CREB levels between PBMC and Jurkat cells were directly correlated with basal transcription of HTLV-I in the two cell types. Using electrophoretic mobility shift assays, we determined that the pattern of band migration differed between the two cell types. These data demonstrate that PBMC differentially regulate basal HTLV-I transcription compared with Jurkat T cells, and this differential regulation is due, in part to differential phosphorylation and binding of CREB/ATF-1 to TRE-1 in the HTLV-I promoter. We demonstrate the utility of using primary lymphocyte models to study HTLV-I transcription in the context of cell signaling and suggest that activated PBMC maintain elevated levels of P-CREB, which promote basal HTLV-I transcription and enhance viral persistence in vivo.

The immunologic and virologic activity of nevirapine in combination with two nucleosides (zidovudine [ZDV] and didanosine [ddI]) was evaluated in antiretroviral-naive patients with a CD4 count <200/mm3 or clinical AIDS. In all, 68 patients were enrolled in a 48-week double-blind, placebo-controlled trial. A group of 32 patients received ZDV + ddI + nevirapine, and 36 patients received ZDV + ddI. Primary efficacy parameters were the activity on HIV-1 RNA and on peripheral blood CD4+ cells, with differences between groups analyzed by the Wilcoxon's nonparametric two-sample test. Baseline RNA was high in both treatment groups (median values, 5.8 and 5.7 log10). RNA and CD4 responses were significantly higher with the triple combination (median RNA reductions, 2.69 versus 1.05 log10 at 24 weeks and 1.97 versus 1.20 log10 at 48 weeks; median CD4 increases, 81 versus 64 cells/mm3 at 24 weeks and 101 versus 27 cells/mm3 at 48 weeks). This study demonstrates that a triple combination of ZDV + ddI + nevirapine used as first-line regimen in antiretroviral-naive patients can induce sustained virologic and immunologic response in patients with low CD4 count or a previous diagnosis of AIDS.

Vitamin A supplementation has been suggested for treatment and prevention of HIV infection. However, some in vitro data indicate that vitamin A may activate HIV. Randomly, 40 HIV-seropositive women of reproductive age were allocated to receive a single oral dose of 9900 micromol (300,000 IU) vitamin A or placebo. Plasma HIV-1 RNA concentration, total lymphocytes, selected lymphocyte subsets and activation markers, and in vitro lymphocyte proliferation to phytohemagglutinin (PHA) and Candida were measured before dosing and at various time points over an 8-week follow-up period. No differences were found between treatment groups in the frequency of signs or symptoms of acute vitamin A toxicity, nor were differences evident in any lymphocyte subset or activation marker at any time during follow-up. Mean and median viral load concentration at each time point and change in viral load from baseline to each follow-up point did not differ between treatment groups. No difference was measured between treatment groups in the proportion of women who responded to PHA or Candida. This study provides no evidence that high dose vitamin A supplementation of HIV-infected women is associated with significant clinical or immunologic adverse effects.

The discovery of inhibition of HIV-1 by selected chemokines and their receptors instills hope in AIDS researchers, especially because a 32-bp deletion in the chemokine receptor CCR5 (delta32-CCR5) provides resistance to HIV infection. A recent report found that the highest delta32-CCR5 frequency is among Ashkenazi Jews (20.93%). In the present study, we have determined by PCR the allelic frequency of delta32-CCR5 in 520 individuals representing a spectrum of ethnic groups living in Israel. The samples were obtained from the Israeli National Laboratory of Genetic Diversity. Our results showed that Ashkenazi Jews, as to be expected, have the highest frequency (10.19%), yet not significantly higher than that which has been reported for whites of European decent. Other ethnic groups, North African Jews, non-Jews, Middle Eastern Jews, and Ethiopian Jews, gave allelic frequencies of 2.08, 1.35, 1.15, and 0, respectively. Thus, the delta32-CCR5 mutation is found in Jews with the same allelic frequency as that found for residents of their countries of origin. Therefore, it appears that the delta32-CCR5 allele has been introduced into Jewish communities world wide through intermarriage and genetic drift.

The prevalence of HIV infection in Brazil is one of the highest in the world. In addition, transfusion-transmitted HIV accounts for 2.3% of all AIDS cases in Brazil. The objective of this study was to evaluate genetic diversity and distribution of HIV-1 strains circulating in the blood-donor population. We characterized 43 seropositive blood units collected from volunteer blood donors residing throughout Rio de Janeiro, Brazil. Viral RNA was extracted from plasma, reverse transcribed, and amplified by nested polymerase chain reaction (PCR) using HIV group M degenerate primers. Genetic heterogeneity was evaluated by direct automated cycle sequencing of the following gene fragments: gag p24 (399 bp), env C2V3 (345 bp), and env gp41 (369 bp). Phylogenetic analysis reflected the complexity of the Brazilian HIV epidemic: the majority of specimens, 33 of 43 (76.7%) were subtype B, and 6 of 43 (14%) were subtype F. The remaining 4 samples (9.3%) involved potential mosaic viruses of subtypes B and F or B and D. This survey is the first to document HIV-1 genetic variation in the Brazilian blood-donor population.