Susan Holman

The Women's Interagency HIV Study: an Observational Cohort Brings Clinical Sciences to the Bench

The Womens Interagency HIV Study (WIHS) is an ongoing long-term observational study of 3,772 women who are either infected with human immunodeficiency virus (HIV) or considered to be at risk for acquiring HIV. Since 1994, the WIHS (pronounced like “wise”) has developed a large database and specimen repository that serve as resources for WIHS investigators as well as for nonaffiliated researchers working on HIV-related or HIV coinfection issues. The purpose of this report is to update researchers on the progress of the WIHS and to provide information on WIHS resources, the methods by which they were obtained, and background for any new potential researchers interested in conducting collaborative research through shared use of these resources.

Domestic Violence and Childhood Sexual Abuse in HIV-Infected Women and Women at Risk for HIV

OBJECTIVES The purpose of this study was to determine the prevalence and effect of domestic violence and childhood sexual abuse in women with HIV or at risk for HIV infection. METHODS Participants with HIV or at risk for HIV infection enrolled in the Womens Interagency HIV Study. Childhood sexual abuse; all physical, sexual, and coercive violence by a partner; HIV serostatus; demographic data; and substance use and sexual habits were assessed. RESULTS The lifetime prevalence of domestic violence was 66% and 67%, respectively, in 1288 women with HIV and 357 uninfected women. One quarter of the women reported recent abuse, and 31% of the HIV-seropositive women and 27% of the HIV-seronegative women reported childhood sexual abuse. Childhood sexual abuse was strongly associated with a lifetime history of domestic violence and high-risk behaviors, including using drugs, having more than 10 male sexual partners and having male partners at risk for HIV infection, and exchanging sex for drugs, money, or shelter. CONCLUSIONS Our data support the hypothesis of a continuum of risk, with early childhood abuse leading to later domestic violence, which may increase the risk of behaviors leading to HIV infection.

MOTHER-TO-INFANT TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1: ASSOCIATION WITH PREMATURITY OR LOW ANTI-gp120

In a prospective study of pregnant women infected with human immunodeficiency virus type 1 (HIV-1) in Brooklyn, New York, USA, 16 (29%) of 55 evaluable infants were infected with HIV-1. 9 infants had paediatric acquired immunodeficiency syndrome, 6 had less severe clinical manifestations of HIV-1 infection, and 1 was symptom-free but was seropositive for HIV-1 beyond 15 months of age. The 10 infants born at 37 weeks of gestation or earlier were at higher risk of HIV-1 infection than infants born at 38 weeks of gestation or later (60% vs 22%) but the median age at appearance of disease was approximately 5 months in both groups. The HIV-1 transmission rate was not associated with predelivery levels of maternal T cells, anti-p24, or neutralising antibodies but it was higher, among full-term infants, for those with mothers in the lowest third of the distribution of anti-gp120 levels (53%). On immunoblot, transmitting mothers lacked a gp120 band but not other bands. Protection was not associated with antibody to recombinant peptides from the hypervariable region of the major neutralising gp120 epitope, and the anti-gp120 endpoint dilution titre was similar in transmitting and non-transmitting mothers. Mothers of uninfected full-term infants appear to confer immunological protection against HIV-1 infection of their offspring by way of a high-affinity antibody to a gp120 epitope, whose specificity has importance for vaccine development and possibly perinatal immunotherapy.

Measuring Retention in HIV Care: The Elusive Gold Standard

Background:Measuring retention in HIV primary care is complex, as care includes multiple visits scheduled at varying intervals over time. We evaluated 6 commonly used retention measures in predicting viral load (VL) suppression and the correlation among measures. Methods:Clinic-wide patient-level data from 6 academic HIV clinics were used for 12 months preceding implementation of the Centers for Disease Control and Prevention/Health Resources and Services Administration (CDC/HRSA) retention in care intervention. Six retention measures were calculated for each patient based on scheduled primary HIV provider visits: count and dichotomous missed visits, visit adherence, 6-month gap, 4-month visit constancy, and the HRSA HIV/AIDS Bureau (HRSA HAB) retention measure. Spearman correlation coefficients and separate unadjusted logistic regression models compared retention measures with one another and with 12-month VL suppression, respectively. The discriminatory capacity of each measure was assessed with the c-statistic. Results:Among 10,053 patients, 8235 (82%) had 12-month VL measures, with 6304 (77%) achieving suppression (VL <400 copies/mL). All 6 retention measures were significantly associated (P < 0.0001) with VL suppression (odds ratio; 95% CI, c-statistic): missed visit count (0.73; 0.71 to 0.75, 0.67), missed visit dichotomous (3.2; 2.8 to 3.6, 0.62), visit adherence (3.9; 3.5 to 4.3,0.69), gap (3.0; 2.6 to 3.3, 0.61), visit constancy (2.8; 2.5 to 3.0, 0.63), and HRSA HAB (3.8; 3.3 to 4.4, 0.59). Measures incorporating “no-show” visits were highly correlated (Spearman coefficient = 0.83–0.85), as were measures based solely on kept visits (Spearman coefficient = 0.72–0.77). Correlation coefficients were lower across these 2 groups of measures (range = 0.16–0.57). Conclusions:Six retention measures displayed a wide range of correlation with one another, yet each measure had significant association and modest discrimination for VL suppression. These data suggest there is no clear gold standard and that selection of a retention measure may be tailored to context.

HIV-1 in genital tract and plasma of women: Compartmentalization of viral sequences, coreceptor usage, and glycosylation

Worldwide, 90% of HIV-1 infections are transmitted heterosexually. Because the genital mucosa are the sites of initial contact with HIV-1 for most exposed individuals, study of the virus from the genital tract is critical for the development of vaccines and therapeutics. Previous analyses of HIV-1 in various tissues have documented compartmentalization of viral genomes. Whether compartmentalization was associated with viral phenotypic differences or immune status, however, was not well understood. We compared HIV-1 gp120 env sequences from the genital tract and plasma of 12 women. Eight women displayed compartmentalized HIV-1 RNA genomes, with viral sequences from each site that were clearly discrete, yet phylogenetically related. The remaining four exhibited env sequences that were intermingled between the two sites. Women with compartmentalized HIV-1 genomes had higher CD4+ cell counts than those displaying intermingled strains (P = 0.02). Intrapatient HIV-1 recombinants comprising sequences that were characteristic of both sites were identified. We next compared viral phenotypes in each compartment. HIV-1 coreceptor usage was often compartmentalized (P ≤ 0.01). The number of N-linked glycosylation sites, associated with neutralization resistance, also differed between compartments (P < 0.01). Furthermore, disparities between the density of gp120 glycosylations in each compartment correlated with higher CD4+ counts (P = 0.03). These data demonstrate that the genital tract and plasma can harbor populations of replicating HIV-1 with different phenotypes. The association of higher CD4+ cell counts with compartmentalization of viral genomes and density of gp120 glycosylations suggests that the immune response influences the development of viral genotypes in each compartment. These findings are relevant to the prevention and control of HIV-1 infection.

C-reactive protein is an independent predictor of mortality in women with HIV-1 infection.

The relationship of C-reactive protein (CRP) to mortality was assessed in 209 HIV-1–infected women after adjusting for age, body mass index (BMI), serum albumin, CD4 cell lymphocyte count, and HIV-1 RNA. During the follow-up period of up to 5 years (median = 45 months) there were 49 deaths. CRP at study enrollment was measured using a low sensitivity assay. CRP levels were only weakly correlated (Pearson correlation coefficient r < .2) with other predictors of mortality. CRP was a powerful predictor of mortality (p < .01) after adjusting for age, BMI, serum albumin, CD4 cell lymphocytes, and HIV-1 RNA. The relative hazard associated with an elevated CRP level, independent of the covariates noted above, varied from 3.4- to 13.6-fold depending on how CRP values were grouped. CRP may be a useful and inexpensive predictor of HIV disease mortality in women.

Enhanced Personal Contact With HIV Patients Improves Retention in Primary Care: A Randomized Trial in 6 US HIV Clinics

BACKGROUND The aim of the study was to determine whether enhanced personal contact with human immunodeficiency virus (HIV)-infected patients across time improves retention in care compared with existing standard of care (SOC) practices, and whether brief skills training improves retention beyond enhanced contact. METHODS The study, conducted at 6 HIV clinics in the United States, included 1838 patients with a recent history of inconsistent clinic attendance, and new patients. Each clinic randomized participants to 1 of 3 arms and continued to provide SOC practices to all enrollees: enhanced contact with interventionist (EC) (brief face-to-face meeting upon returning for care visit, interim visit call, appointment reminder calls, missed visit call); EC + skills (organization, problem solving, and communication skills); or SOC only. The intervention was delivered by project staff for 12 months following randomization. The outcomes during that 12-month period were (1) percentage of participants attending at least 1 primary care visit in 3 consecutive 4-month intervals (visit constancy), and (2) proportion of kept/scheduled primary care visits (visit adherence). RESULTS Log-binomial risk ratios comparing intervention arms against the SOC arm demonstrated better outcomes in both the EC and EC + skills arms (visit constancy: risk ratio [RR], 1.22 [95% confidence interval {CI}, 1.09-1.36] and 1.22 [95% CI, 1.09-1.36], respectively; visit adherence: RR, 1.08 [95% CI, 1.05-1.11] and 1.06 [95% CI, 1.02-1.09], respectively; all Ps < .01). Intervention effects were observed in numerous patient subgroups, although they were lower in patients reporting unmet needs or illicit drug use. CONCLUSIONS Enhanced contact with patients improved retention in HIV primary care compared with existing SOC practices. A brief patient skill-building component did not improve retention further. Additional intervention elements may be needed for patients reporting illicit drug use or who have unmet needs. CLINICAL TRIALS REGISTRATION CDCHRSA9272007.

Depressive Symptoms in the Immediate Postpartum Period Among Hispanic Women in Three U.S. Cities

The aim of this was to examine rates and determinants of depressive symptomatology in the immediate postpartum period among Hispanic women in the United States. A total of 3952 Hispanic women who had delivered infants (parturients) were interviewed in postpartum wards in Miami, New York City and San Francisco. Symptoms of depression were regressed onto a series of social, psychological, and socioeconomic variables. Results showed that 42.6% of participants were probable cases of depression (CES-D ≥ 16). Depression was negatively associated with perceived level of social support (adjusted OR = 0.59, 95% CI: 0.53–0.67) and health insurance coverage (adjusted OR = 0.68, 95% CI: 0.49–0.95), but not with the degree of acculturation or immigration status. It was found that depressive symptoms are common among Hispanic parturients. Pregnant Hispanic women should be carefully monitored for signs of depression and appropriate preventive measures are needed.

Factors associated with preclinical disability and frailty among HIV-infected and HIV-uninfected women in the era of cART.

BACKGROUND HIV-associated immune injury is hypothesized to increase the risk of preclinical disability and frailty via inflammatory pathways. We investigated the role of CD4+ T cell depletion and clinical AIDS on preclinical disability and frailty in HIV-positive women with a history of combination antiretroviral therapy (cART) and HIV-negative women. METHODS This was a cross-sectional study nested within the Womens Interagency HIV Study (WIHS), a prospective cohort study initiated in 1994 across five U.S. cities. Questionnaires and tests were performed by 573 HIV-negative and 1206 HIV-positive women. Prevalence ratios were computed using regression models. RESULTS Severe CD4+ cell depletion was an independent predictor of slowness, weakness, and frailty in HIV-positive women compared with HIV-negative women. Women with CD4+ counts<100 cells/mm3 were 0.13 seconds slower to complete 4 meters (95% CI 0.06-0.21), 1.25 kg weaker (95% CI -2.31--0.19), and had 2.7 times higher prevalence of frailty (95% CI 1.46-5.01). CONCLUSIONS This study is one of the largest studies to administer performance-based tests to investigate disability and frailty in HIV-positive women. HIV-positive women with intact immune systems and without a history of clinical AIDS were no different from HIV-negative women on tests of slowness, weakness, and frailty phenotype.

Pregnancy outcomes among mothers infected with human immunodeficiency virus and uninfected control subjects

Between June 26, 1985, and Feb. 24, 1989, 101 seropositive pregnant women and 129 seronegative pregnant women from the same prenatal clinics in Brooklyn and the Bronx were recruited into a prospective study of human immunodeficiency virus infection in pregnant women and their offspring. This report details the course of pregnancy and short-term neonatal outcomes of 91 seropositive women and 126 seronegative women who gave birth during the study period. Seropositive mothers were significantly more likely to have sexually transmitted diseases (17.6% vs 7.1%, p = 0.017) and medical complications (43.0% vs 25%, p = 0.006) during pregnancy. No other obstetric complications (e. g., chorioamnionitis, endometritis, toxemia, or placental problems) were associated with serologic status. After controlling for confounding variables (drug use, tobacco use, age of mother, and clinic), we found that the mothers serologic status was not significantly associated with birth weight, gestational age, head circumference, or Apgar scores among live infants. For example, after adjustment on confounders we found that children born to seropositive mothers weighed about 7 gm more than children of seronegative mothers (95% confidence interval, -180 to 194 gm). We conclude that in this population human immunodeficiency virus infection has little demonstrable impact on the status at birth of live neonates.