Immune activation is a hallmark of human immunodeficiency virus type 1 (HIV-1) infection and impacts innate and adaptive immunity. Individuals coinfected with HIV-1 and hepatitis C virus (HCV) may have increased immune activation early in HIV disease because of a high HCV antigen load in tissues such as the liver. We evaluated T cell markers of activation and maturation in women with or without HIV-1 infection, by HCV antibody and HCV RNA status. We found increased percentages of activated CD8(+) T cells (i.e., CD8(+)HLA-DR(+)38(+) cells and CD8(+)CD28(+)HLA-DR(+) cells) but not of CD4(+) T cells among women who tested positive for HIV-1, HCV antibody, and HCV RNA, compared with HIV-1-positive women who tested negative for HCV antibody. Because CD8(+) T cell activation is related to HIV-1 disease progression, these data may have implications for the medical management of patients coinfected with HIV-1 and HCV.

Maternal perinatal depression (PND) may interfere with effective perinatal HIV care. In order to begin examining the prevalence and characteristics of PND in HIV-infected women, we analyzed data from the medical records of all HIV-infected women who had received perinatal care in the Maternal-Child and Adolescent Center for Infectious Diseases and Virology at LAC=USC Medical Center from 1997 through 2006. Data from 273 individual women (328 live births) were analyzed. Demographic, medical history, psychosocial, pregnancyrelated, and HIV-related factors measured during the perinatal period were examined for an association with PND using multivariate logistic regression with generalized estimating equations to account for the withinsubject correlation due to multiple births per mother. The overall prevalence of PND was 30.8%. Multivariate analysis showed that PND was significantly associated with substance abuse during pregnancy (odds ratio [OR] ¼ 2.81, 95% confidence interval [CI]: 1.35-5.82) and past history of psychiatric illness (OR ¼ 3.72, 95% CI: 2.06-6.71). Compared to mothers with CD4 nadir greater than 500 cells=mm 3 , mothers with a CD4 nadir during pregnancy #200 cells=mm 3 were 3.1 times more likely to experience PND (OR ¼ 3.01, 95% CI: 1.32-6.88). Women who had antiretroviral (ARV) medications adherence problems during pregnancy were more likely to experience PND than women who were adherent (OR ¼ 2.14, 95% CI: 1.08-4.23). These preliminary results suggest that rates of PND among HIV-infected women are substantial. We conclude that pregnant HIV-infected women should be routinely screened for PND. Prospective studies examining the bio-psycho-social markers of PND in HIV-infected women are indicated.

Background Cervicovaginal HIV level (CV-VL) influences HIV transmission. Plasma viral load (PVL) correlates with CV-VL but discordance is frequent. We evaluated how PVL, behavioral, immunologic and local factors/conditions individually and collectively correlate with CV-VL. Methods CV-VL was measured in cervicovaginal lavage fluid (CVL) over 976 person-visits for 481 HIV-infected women in a longitudinal cohort study. We correlated identified factors with CV-VL at individual person-visits and detectable/undetectable PVL strata by univariate and multivariate linear regression, and with shedding pattern (never, intermittent, persistent ≥3 shedding-visits) in 136 women with ≥3 visits by ordinal logistic regression. Results 450/959 (46.9%) of person-visits with available PVL were discordant. 435/959 (45.3%) had detectable PVL with undetectable CV-VL and 15/959 (1.6%) undetectable PVL with detectable CV-VL. Lower CV-VL correlated with HAART usage (P=0.01). Higher CV-VL correlated with higher PVL (P<0.001), inflammation-associated cellular changes (P=0.03), cervical ectopy (P=0.009), exudate (P=0.005), and trichomoniasis (P=0.03). In multivariate analysis of the PVL-detectable stratum, increased CV-VL correlated with the same factors and friability (P=0.05), while with undetectable PVL, decreased CV-VL correlated with HAART use (P=0.04). In longitudinal analysis, never (40.4%) and intermittent (44.9%) shedding were most frequent. Higher-frequency shedders were more likely to have higher initial PVL (OR=2.47/log10 increase), HSV-2 seropositivity (OR=3.21) and alcohol use (OR=2.20). Conclusions While PVL correlates strongly with CV-VL, discordance is frequent. When PVL is detectable, cervicovaginal inflammatory conditions correlate with increased shedding. However, genital shedding is sporadic and not reliably predicted by associated factors. HAART, by reducing PVL, is the most reliable means of reducing cervicovaginal shedding.

Objective Evaluate a social network approach to develop an adolescent cohort for HIV vaccine preparedness and investigate characteristics that influence recruitment. Methods We summarize baseline data from a prospective cohort study that included four sessions over six months. Fifty-nine HIV-infected adolescent and adult patients of a family-based HIV clinic named significant others and indicated willingness to involve them in this study. Sixty-two adolescent and adult significant others not known to be HIV-infected were enrolled. Logistic regression was used to estimate factors associated with willingness. Results Participants identified 624 social network members including 276 (44%) adolescents. Network member's awareness of the index's HIV-positivity (P<0.01) and older age (P=0.05) affected willingness. Respondents were less willing to invite drug-risk alters (P=0.006). Adolescents were willing to invite more adolescents than were adults (P<.0001). Adolescents <18 years old reported fewer sexual and drug-using risk behaviors than expected. Conclusions HIV-infected patients are willing to recruit their social networks provided concerns about disclosure of HIV status are addressed. Using social networks to identify and recruit adolescent populations is appropriate and feasible for vaccine preparedness activities, future vaccine trials, and other prevention programs, but procedures are needed to selectively identify and retain high-risk youth.

Background Mucosal tissues represent major targets for HIV transmission, but differ in susceptibility and reservoir function by unknown mechanisms. Methods In a cross-sectional study, HIV RNA and infectious virus were compared between oral and genital compartments and blood in HIV-infected women, in association with clinical parameters, co-pathogens and putative innate and adaptive HIV inhibitors. Results HIV RNA was detectable in 24.5% of women from all 3 compartments, whereas 45% had RNA in only one or two sites. By comparison, infectious HIV, present in blood of the majority, was rare in mucosal sites. Innate mediators, SLPI and TSP, were highest in mucosae. Highly active antiretroviral therapy (HAART) was associated with an 80% decreased probability of shedding. Multivariate logistic regression models revealed that mucosal HIV RNA was associated with higher plasma RNA, infectious virus, and total mucosal IgA, but not IgG. There was a 37-fold increased probability of detecting RNA in both genital and oral specimens (P=0.008;P=0.02, respectively) among women in highest vs lowest IgA tertiles. Conclusions Mucosal sites exhibit distinct characteristics of infectious HIV, viral shedding and responses to therapy, dependent upon both systemic and local factors. Of the putative innate and adaptive mucosal defense factors examined, only IgA was associated with HIV RNA shedding. However, rather than being protective, there was a striking increase in probability of detectable HIV RNA shedding in women with highest total IgA.