Deborah Kacanek

Safety of tenofovir use during pregnancy: Early growth outcomes in HIV-exposed uninfected infants

Objective:To evaluate the association of tenofovir disoproxil fumarate (TDF) use during pregnancy with early growth parameters in HIV-exposed, uninfected (HEU) infants. Design:US-based prospective cohort study of HEU children to examine potential adverse effects of prenatal TDF exposure. Methods:We evaluated the association of maternal TDF use during pregnancy with small for gestational age (SGA); low birth weight (LBW, <2.5 kg); weight-for-age z-scores (WAZ), length-for-age z-scores (LAZ), and head circumference-for-age (HCAZ) z-scores at newborn visit; and LAZ, HCAZ, and WAZ at age 1 year. Logistic regression models for LBW and SGA were fit, adjusting for maternal and sociodemographic factors. Adjusted linear regression models were used to evaluate LAZ, WAZ, and HCAZ by TDF exposure. Results:Of 2029 enrolled children with maternal antiretroviral information, TDF was used by 449 (21%) HIV-infected mothers, increasing from 14% in 2003 to 43% in 2010. There was no difference between those exposed to combination regimens with vs. without TDF for SGA, LBW, and newborn LAZ and HCAZ. However, at age 1 year, infants exposed to combination regimens with TDF had significantly lower adjusted mean LAZ and HCAZ than those without TDF (LAZ: −0.17 vs. −0.03, P = 0.04; HCAZ: 0.17 vs. 0.42, P = 0.02). Conclusion:TDF use during pregnancy was not associated with increased risk for LBW or SGA. The slightly lower mean LAZ and HCAZ observed at age 1 year in TDF-exposed infants are of uncertain significance but underscore the need for additional studies of growth outcomes after TDF use during pregnancy.

Incident depression symptoms are associated with poorer HAART adherence: a longitudinal analysis from the Nutrition for Healthy Living Study.

Objective:To determine the relationship between incident depression symptoms and suboptimal adherence to HIV highly active antiretroviral therapy (HAART). Methods:Participants in a cohort study of persons with HIV on HAART with at least 4 consecutive semiannual study visits were included (n = 225). Incident depression was defined as having 2 visits with a negative depression screening test followed by 2 visits with a positive test. Comparison group participants had 4 consecutive visits with a negative depression screening test. Suboptimal adherence was defined as missing >5% of HAART doses in the past 7 days. We compared suboptimal adherence rates in those with and without incident depression symptoms and estimated the relative risk and 95% confidence intervals of suboptimal adherence at visit 4 in those adherent at baseline (n = 177), controlling for sociodemographic, behavioral, and clinical variables. Results:Twenty-two percent developed depression symptoms. Those developing depression symptoms had higher rates of suboptimal adherence at follow-up (45.1% vs. 25.9%, P < 0.01). Among those with optimal baseline adherence, those with incident depression were nearly 2 times more likely to develop suboptimal adherence (Adjusted relative risk =1.8, 95% confidence interval =1.1 to 3.0) at follow-up. Conclusion:Incident depression symptoms were associated with subsequent suboptimal HAART adherence. Ongoing aggressive screening for, and treatment of, depression may improve HAART outcomes.

Combination antiretroviral use and preterm birth.

BACKGROUND Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth. METHODS The Pediatric HIV/AIDS Cohort Study networks Surveillance Monitoring for ART Toxicities study is a US-based cohort of human immunodeficiency virus (HIV)-exposed uninfected children. We evaluated maternal ARV use during pregnancy and the risk of any type of preterm birth (ie, birth before 37 completed weeks of gestation), the risk of spontaneous preterm birth (ie, preterm birth that occurred after preterm labor or membrane rupture, without other complications), and the risk of small for gestational age (SGA; ie, a birth weight of <10th percentile for gestational age). Multivariable logistic regression models were used to evaluate the association of ARVs and timing of exposure, while adjusting for maternal characteristics. RESULTS Among 1869 singleton births, 18.6% were preterm, 10.2% were spontaneous preterm, and 7.3% were SGA. A total of 89% used 3-drug combination ARV regimens during pregnancy. In adjusted models, the odds of preterm birth and spontaneous preterm birth were significantly greater among mothers who used protease inhibitors during the first trimester (adjusted odds ratios, 1.55 and 1.59, respectively) but not among mothers who used nonnucleoside reverse-transcriptase inhibitor or triple-nucleoside regimens during the first trimester. Combination ARV exposure starting later in pregnancy was not associated with increased risk. No associations were observed between SGA and exposure to combination ARV regimens. CONCLUSIONS Protease inhibitor use early in pregnancy may be associated with increased risk for prematurity.

Sexual Risk Behavior Among Youth With Perinatal HIV Infection in the United States: Predictors and Implications for Intervention Development

BACKGROUND Factors associated with initiation of sexual activity among perinatally human immunodeficiency virus (HIV)-infected (PHIV(+)) youth, and the attendant potential for sexual transmission of antiretroviral (ARV) drug-resistant HIV, remain poorly understood. METHODS We conducted cross-sectional and longitudinal analyses of PHIV(+) youth aged 10-18 years (mean, 13.5 years) enrolled in the US-based Pediatric HIV/AIDS Cohort Study between 2007 and 2009. Audio computer-assisted self-interviews (ACASI) were used to collect sexual behavior information. RESULTS Twenty-eight percent (95% confidence interval [CI], 23%-33%) (92/330) of PHIV(+) youth reported sexual intercourse (SI) (median initiation age, 14 years). Sixty-two percent (57/92) of sexually active youth reported unprotected SI. Among youth who did not report history of SI at baseline, ARV nonadherence was associated with sexual initiation during follow-up (adjusted hazard ratio, 2.87; 95% CI, 1.32-6.25). Youth living with a relative other than their biological mother had higher odds of engaging in unprotected SI than those living with a nonrelative. Thirty-three percent of youth disclosed their HIV status to their first sexual partner. Thirty-nine of 92 (42%) sexually active youth had HIV RNA ≥5000 copies/mL after sexual initiation. Viral drug resistance testing, available for 37 of these 39 youth, identified resistance to nucleoside reverse transcriptase inhibitors in 62%, nonnucleoside reverse transcriptase inhibitors in 57%, protease inhibitors in 38%, and all 3 ARV classes in 22%. CONCLUSIONS As PHIV(+) youth become sexually active, many engage in behaviors that place their partners at risk for HIV infection, including infection with drug-resistant virus. Effective interventions to facilitate youth adherence, safe sex practices, and disclosure are urgently needed.

HIV and STD risk behavior among 18- to 25-year-old men released from U.S. prisons: provider perspectives.

Ninety-seven service providers, representing 83 agencies, were interviewed about sexual and drug use HIV/STD risk behaviors and their determinants among young men who have been released from prison. Providers believed that men frequently practiced sexual risk behavior, often in conjunction with substance use. Individual determinants of risk behavior primarily focused on “making up for lost time,” being a man, degree of HIV/STD knowledge and vulnerability, desire to escape, and future orientation. Peers, partners, and family were portrayed as strong interpersonal influences on risk behavior, both positively and negatively. The dominant contextual determinant of risk behavior was the co-occurrence of sex and drug use. Structural determinants of reduced risk included stable housing, economic sufficiency, and positive community support for safer behavior (e.g., drug treatment access, needle exchange). The findings highlight the need for comprehensive, transitional case management for young men as they reintegrate into the community, including HIV/STD prevention.

A Qualitative Study of Substance Use and Sexual Behavior Among 18- to 29-Year-Old Men While Incarcerated in the United States

The article describes men’s perceptions of and experience with substance use and sexual behavior during incarceration. Grounded theory content analyses were performed on qualitative interviews conducted with 80 men, aged 18 to 29, in four U.S. states. Participants believed that drugs were easily available in prison. Half reported using substances, primarily marijuana or alcohol, while incarcerated. Key themes included the role of correctional personnel in the flow of substances in prison and the economic significance of substance traffic king. With regard to sexual behavior, most men acknowledged that it occurred but were hesitant to talk in-depth about it. There was a strong belief in “don’t look, don’t tell,” and sex in prison was often associated with homo sexual behavior or identity. Sex during incarceration was reported by 12 men, mostly with female partners. Participants were pessimistic about HIV/STD/hepatitis prevention efforts inside correctional facilities. These findings highlight the need for risk reduction programs for incarcerated men.

Patterns and Predictors of Adherence to Diaphragm Use in a Phase III Trial in Sub-Saharan Africa: A Trajectory Analysis.

Background:We examined diaphragm adherence among 2429 women randomized to the intervention arm (diaphragm + gel + condoms) in Methods for Improving Reproductive Health in Africa, a phase III trial of the diaphragm for HIV prevention in Zimbabwe and South Africa. Methods:Women were followed for a median of 7 quarterly visits (range: 1-8 quarterly visits) during which diaphragm adherence was assessed. We conducted trajectory analyses to identify behavioral groups associated with specific diaphragm adherence patterns. Multivariate multinomial logistic regression was used to identify baseline characteristics associated with higher probability of being in a particular trajectory group. Results:Diaphragm uptake was very high (3.1% never used diaphragms). However, diaphragm adherence was reported at only 49% of visits. Women were clustered into 4 diaphragm adherence groups based on their highest estimated group membership probability: low adherers (31.0%), decreasing adherers (28.9%), increasing adherers (9.3%), and high adherers (30.8%). Women classified as high adherers (as compared with low adherers) were more likely to be older [adjusted odds ratio (AOR) = 1.09, 95% confidence interval (CI): 1.07 to 1.11] and to report baseline condom adherence (AOR = 2.00, 95% CI: 1.47 to 2.71). They were less likely to have high-risk behavior (AOR = 0.51; 95% CI: 0.37 to 0.71) and to have high-risk partners (AOR = 0.58; 95% CI: 0.43 to 0.78). They were most likely to be from the Zimbabwe site (AOR = 2.82; 95% CI: 1.89 to 4.20) and least likely to be from the Johannesburg site (AOR = 0.51; 95% CI: 0.37 to 0.77). Conclusion:This analytic approach could help to identify high compliers for enrollment in future HIV prevention trials or the types of participants who may need intensive adherence counseling during follow-up.

Intimate partner violence and condom and diaphragm nonadherence among women in an HIV prevention trial in southern Africa.

Background:We longitudinally examined the effect of intimate partner violence (IPV) on condom and diaphragm nonadherence among women in the Methods for Improving Reproductive Health in Africa study, a phase III HIV prevention trial in southern Africa. Methods:Recent IPV (fear of violence, emotional abuse, physical violence, or forced sex, in past 3 months), condom nonadherence, and diaphragm nonadherence were assessed at baseline, 12 month, and exit visits (up to 24 months). The association between IPV and (1) condom nonadherence or (2) diaphragm nonadherence across visits was modeled using Generalized Estimating Equations adjusting for potential confounders. Results:Of 4505 participants, 55% reported recent IPV during their trial participation. Women reported fearing violence (41%), emotional abuse (38%), being physically assaulted (16%), and forced sex (15%) by their regular male partner. IPV was associated with condom nonadherence in both study arms [adjusted odds ratio (AOR): 1.41, 95% confidence interval (CI): 1.24 to 1.61 (control arm) and AOR: 1.47, 95% CI: 1.28 to 1.69, (intervention arm)] and with diaphragm nonadherence (AOR 1.24, 95% CI: 1.06 to 1.45) adjusting for age, study sites, number of sex partners, and knowledge of male partner infidelity. Modeling effects of each form of IPV separately on nonadherence outcomes yielded similar results. Conclusions:Prevalence of recent IPV was high and associated with condom and diaphragm nonadherence during the trial. Counseling in prevention trials should proactively address IPV, for its own sake, and in product and risk-reduction counseling. Strategies to encourage mens positive involvement in product use and prevent IPV perpetration should be considered.

Degrees of disclosure: a study of women's covert use of the diaphragm in an HIV prevention trial in sub-Saharan Africa.

In sub-Saharan Africa more women are infected with HIV/AIDS than men and new prevention methods are urgently needed. One major attribute of female-initiated HIV prevention methods is that they can be used covertly, without a male partners knowledge. Using mixed methods, we explored the predictors and dimensions of covert use of the diaphragm in a randomized controlled trial that tested its effectiveness for HIV prevention. The Methods for Improving Reproductive Health in Africa (MIRA) trial was conducted in Zimbabwe and South Africa, and data collection took place between September 2003 and January 2007. This study is a secondary analysis of quantitative and qualitative data from participants randomized to the intervention group, and their male partners. It includes survey data from 2316 women (mean age=28.3), 14 focus group discussions (FGD) conducted with 104 women, and 7 FGD and 10 in-depth interviews with 37 male partners. The median follow-up for trial participation was 21 months (range: 12-24). At their final visit, approximately 9% of women had never disclosed to their primary partners that they were using the diaphragm (covert use). In multivariate analysis, predictors of covert use included being older, not co-habiting with the partner, having a partner who did not use condoms, and being from South Africa. Qualitative analysis revealed that covert use was not dichotomous, but ranged along a continuum, which we categorized into five levels (i.e. full disclosure; mostly open use; occasional covert use; mostly covert use; and completely covert use). We discuss the critical role of the option of covert use for many women in the context of an HIV prevention trial, as well as gender power dynamics which may influence womens decisions about disclosure.

Screening for sexually transmitted diseases and hepatitis in 18-29-year-old men recently released from prison: feasibility and acceptability

Men entering prisons have high rates of sexually transmitted disease (STD), hepatitis, and HIV. This study sought to determine the acceptability and feasibility of screening for STD and hepatitis in young men released from prison. Participants were interviewed six months after release and offered free screening. Of 42 (56%) eligible men who participated in the qualitative interview, 33 (79%) provided at least a blood or urine specimen. Eight of 33 (24%) men tested had chlamydia, trichomoniasis, hepatitis B or C virus (HBV or HCV). Three of 32 (9%) had chlamydia, three of 32 (9%) had trichomoniasis, two of 28 (7%) had prior syphilis, and two of 28 (7%) had HCV. Of 28 tested for HBV, six (21%) were immune, two (7%) had chronic infection, and 20 (71%) were susceptible. Barriers to screening included lack of forewarning, inconvenience, and insufficient incentive. In conclusion, screening for STD and hepatitis among former inmates can be acceptable and feasible. Forewarning, reducing the time burden, and providing monetary incentives may increase screening rates.