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The initial site of exposure to human immunodeficiency virus (HIV)-1 during heterosexual transmission occurs in the genital tract. Although the majority of immunological studies have focused on the immune response to HIV-1 at the systemic level, our understanding of tissue-specific immunity is deficient. The goal of the present study was to characterize T cell populations found in the cervix of women shown to be resistant to infection by HIV-1. Levels of both systemic and cervical mucosal lymphocytes were compared between HIV-1-resistant, HIV-1-uninfected, and HIV-1-infected commercial sex workers (CSWs) as well as HIV-1-uninfected non-CSW control subjects at low risk for exposure. The HIV-1-resistant CSWs had increased cervical CD4+ and CD8+ T cell counts, compared with the HIV-1-uninfected CSWs; importantly, these increases were not reflected in the systemic lymphocyte compartment. There was a 2-fold increase in CD4+ T cell counts in the HIV-1-resistant CSWs, compared with both the HIV-1-infected and the HIV-1-uninfected CSWs. Expression of the HIV-1 coreceptors CCR5 and CXCR4 was also determined, and cytokine and β chemokine levels in the genital mucosa were assessed. The HIV-1-resistant CSWs had a 10-fold increase in RANTES expression, compared with the HIV-1-uninfected CSWs. This is the first study to show elevated levels of β chemokines and CD4+ T cells in the genital tracts of women who are exposed to HIV-1 and yet are uninfected. [ABSTRACT FROM AUTHOR]

Focuses on a study which determined the influence of human lymphocyte antigen supertype A2/6802 on HIV type 1 transmission in HIV positive mothers and children in Kenya. Methods; Results; Discussion.

Unlabelled: OBJECTIVES To compare sociodemographic profiles, child care, child feeding practices and growth indices of children born to HIV-1 seropositive and seronegative mothers.Methods: A cohort study of 234 children (seropositive and seronegative) born to HIV-1 seropositive mothers and 139 children born to seronegative mothers in Pumwani Maternity Hospital which serves a low-income population in Nairobi, Kenya from December 1991 and January 1994.Results: With few exceptions, at the time of their birth children in all three cohorts had parents with similar characteristics, lived in similar housing in similar geographical areas, had their mothers as their primary care givers, had similar feeding practices and similar growth status and patterns. However, the HIV-1 seropositive mothers were slightly younger (23.8 years vs. 25.0 years, P < 0.01), if married they were less likely to be their husband's first wife (79% vs. 91%, P = 0.02) and more likely to have a one-room house (75% vs. 63%, P = 0.04). All three cohorts had mean Z-scores in length-for-age and in weight-for-height within the normal range (>/= 2.0 Z-scores) from birth to 21 months with the exception of the length-for-age of the seropositive children at the 18-month visit. In all cohorts length-for-age became more compromised than weight-for-length, dropping to about -1.45 Z-score by 21 months; in contrast, weight-for-length dropped to about -0.5 Z-score by this age. The only statistically significant differences in growth indices among the three cohorts were between the two cohorts of seronegative children: those with seronegative mothers were less compromised in length-for-age at 1.5 months (mean Z-score = -0.19 vs. -0.48, P < 0.05) and more compromised in weight-for-length at 6 months (mean Z-score = 0.10 vs. 0.45, P < 0.05) and at 18 months (mean Z-score = -0.73 vs. -0.16, P < 0.05). 27-34% were exclusively breastfed at 1.5 months; 52-61% consumed solid foods in addition to breast milk by 2.5 months.Conclusions: Low-income HIV-1 seropositive- and seronegative-born children were from families with similar characteristics and similar housing environments. Similar growth patterns in the cohorts suggest that the challenging environment and the choice of weaning foods had an impact on all three cohorts. The aggressive care given the children with HIV-1 seropositive mothers and their children may have reduced the progression and impact of HIV-1 disease on the growth of the seropositive children. Further research is needed to corroborate our findings to be certain that our results are not affected by loss to follow-up bias: we lost the same proportion in all three cohorts but cannot verify that the children we lost had the same growth patterns as those who remained in the study. [ABSTRACT FROM AUTHOR]

APOBEC3G is an important innate immune molecule that causes human immunodeficiency virus type 1 (HIV-1) hypermutation, which can result in detrimental viral genome mutations. The Vif protein of wild-type HIV-1 counteracts APOBEC3G activity by targeting it for degradation and inhibiting its incorporation into viral particles. Additional APOBEC cytidine deaminases have been identified, such as APOBEC3F, which has a similar mode of action but different sequence specificity. A relationship between APOBEC3F/G and HIV disease progression has been proposed. During HIV-1 sequence analysis of the vpu/env region of 240 HIV-infected subjects from Nairobi, Kenya, 13 drastically hypermutated proviral sequences were identified. Sequences derived from plasma virus, however, lacked hypermutation, as did proviral vif. When correlates of disease progression were examined, subjects with hypermutated provirus were found to have significantly higher CD4 counts than the other subjects. Furthermore, hypermutation as estimated by elevated adenine content positively correlated with CD4 count for all 240 study subjects. The sequence context of the observed hypermutation was statistically associated with APOBEC3F/G activity. In contrast to previous studies, this study demonstrates that higher CD4 counts correlate with increased hypermutation in the absence of obvious mutations in the APOBEC inhibiting Vif protein. This strongly suggests that host factors, such as APOBEC3F/G, are playing a protective role in these patients, modulating viral hypermutation and host disease progression. These findings support the potential of targeting APOBEC3F/G for therapeutic purposes. [ABSTRACT FROM AUTHOR]