Craig B. Borkowf

Estimating per-act HIV transmission risk: a systematic review

Background:Effective HIV prevention programs rely on accurate estimates of the per-act risk of HIV acquisition from sexual and parenteral exposures. We updated the previous risk estimates of HIV acquisition from parenteral, vertical, and sexual exposures, and assessed the modifying effects of factors including condom use, male circumcision, and antiretroviral therapy. Methods:We conducted literature searches to identify new studies reporting data regarding per-act HIV transmission risk and modifying factors. Of the 7339 abstracts potentially related to per-act HIV transmission risk, three meta-analyses provided pooled per-act transmission risk probabilities and two studies provided data on modifying factors. Of the 8119 abstracts related to modifying factors, 15 relevant articles, including three meta-analyses, were included. We used fixed-effects inverse-variance models on the logarithmic scale to obtain updated estimates of certain transmission risks using data from primary studies, and employed Poisson regression to calculate relative risks with exact 95% confidence intervals for certain modifying factors. Results:Risk of HIV transmission was greatest for blood transfusion, followed by vertical exposure, sexual exposures, and other parenteral exposures. Sexual exposure risks ranged from low for oral sex to 138 infections per 10 000 exposures for receptive anal intercourse. Estimated risks of HIV acquisition from sexual exposure were attenuated by 99.2% with the dual use of condoms and antiretroviral treatment of the HIV-infected partner. Conclusion:The risk of HIV acquisition varied widely, and the estimates for receptive anal intercourse increased compared with previous estimates. The risk associated with sexual intercourse was reduced most substantially by the combined use of condoms and antiretroviral treatment of HIV-infected partners.

Triple-Antiretroviral Prophylaxis to Prevent Mother-To- Child HIV Transmission through Breastfeeding—The Kisumu Breastfeeding Study, Kenya: A Clinical Trial

Timothy Thomas and colleagues report the results of the Kisumu breastfeeding study (Kenya), a single-arm trial that assessed the feasibility and safety of a triple-antiretroviral regimen to suppress maternal HIV load in late pregnancy.

Effect of a Brief Video Intervention on Incident Infection among Patients Attending Sexually Transmitted Disease Clinics

Background Sexually transmitted disease (STD) prevention remains a public health priority. Simple, practical interventions to reduce STD incidence that can be easily and inexpensively administered in high-volume clinical settings are needed. We evaluated whether a brief video, which contained STD prevention messages targeted to all patients in the waiting room, reduced acquisition of new infections after that clinic visit. Methods and Findings In a controlled trial among patients attending three publicly funded STD clinics (one in each of three US cities) from December 2003 to August 2005, all patients (n = 38,635) were systematically assigned to either a theory-based 23-min video depicting couples overcoming barriers to safer sexual behaviors, or the standard waiting room environment. Condition assignment alternated every 4 wk and was determined by which condition (intervention or control) was in place in the clinic waiting room during the patients first visit within the study period. An intent-to-treat analysis was used to compare STD incidence between intervention and control patients. The primary endpoint was time to diagnosis of incident laboratory-confirmed infections (gonorrhea, chlamydia, trichomoniasis, syphilis, and HIV), as identified through review of medical records and county STD surveillance registries. During 14.8 mo (average) of follow-up, 2,042 patients (5.3%) were diagnosed with incident STD (4.9%, intervention condition; 5.7%, control condition). In survival analysis, patients assigned to the intervention condition had significantly fewer STDs compared with the control condition (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.84 to 0.99). Conclusions Showing a brief video in STD clinic waiting rooms reduced new infections nearly 10% overall in three clinics. This simple, low-intensity intervention may be appropriate for adoption by clinics that serve similar patient populations. Trial registration: http://www.ClinicalTrials.gov (#NCT00137670).

Results From a Randomized Controlled Trial of a Peer-Mentoring Intervention to Reduce HIV Transmission and Increase Access to Care and Adherence to HIV Medications Among HIV-Seropositive Injection Drug Users

Background:There is a lack of effective behavioral interventions for HIV-positive injection drug users (IDUs). We sought to evaluate the efficacy of an intervention to reduce sexual and injection transmission risk behaviors and to increase utilization of medical care and adherence to HIV medications among this population. Methods:HIV-positive IDUs (n = 966) recruited in 4 US cities were randomly assigned to a 10-session peer mentoring intervention or to an 8-session video discussion intervention (control condition). Participants completed audio computer-assisted self-interviews and had their blood drawn to measure CD4 cell count and viral load at baseline and at 3-month (no blood), 6-month, and 12-month follow-ups. Results:Overall retention rates for randomized participants were 87%, 83%, and 85% at 3, 6, and 12 months, respectively. Participants in both conditions reported significant reductions from baseline in injection and sexual transmission risk behaviors, but there were no significant differences between conditions. Participants in both conditions reported no change in medical care and adherence, and there were no significant differences between conditions. Conclusions:Both interventions led to decreases in risk behaviors but no changes in medical outcomes. The characteristics of the trial that may have contributed to these results are examined, and directions for future research are identified.

Effectiveness of Non-nucleoside Reverse-Transcriptase Inhibitor-Based Antiretroviral Therapy in Women Previously Exposed to a Single Intrapartum Dose of Nevirapine: A Multi-country, Prospective Cohort Study

In a comparative cohort study, Jeffrey Stringer and colleagues investigate the risk of ART failure in women who received single-dose nevirapine for PMTCT, and assess the duration of increased risk.

Sphingolipids as biomarkers of fumonisin exposure and risk of esophageal squamous cell carcinoma in China

AbstractObjective: Ecologic studies of esophageal squamous cell carcinoma (ESCC) have reported an association with consumption of maize contaminated with Fusarium verticillioides, which produce fungal toxins referred to as fumonisins. Fumonisins disrupt sphingolipid metabolism and serum sphingolipids have been proposed as biomarkers of fumonisin exposure. We conducted a prospective nested case–control study to examine the relationship between serum sphingolipids and ESCC incidence. Methods: Cases and controls were selected from a large prospective trial conducted in Linxian, Peoples Republic of China. Ninety-eight ESCC cases were randomly selected from the 639 incident ESCC ascertained during the initial 5.25 years of follow-up; 185 controls were also randomly selected based on the distribution of cases among six age and sex strata. Concentrations of sphinganine and sphingosine were determined by high-performance liquid chromatography in serum collected at the study baseline. Results: No significant associations were found between serum sphingosine, sphinganine, or the sphinganine/sphingosine ratio and ESCC incidence in conditional and unconditional logistic regression models with adjustment for age, sex, tobacco use, and alcohol use. Conclusion: Our study is the first prospective study to assess the relationship between sphingolipid levels, as biomarkers of fumonisin exposure, and cancer incidence. We found no significant association between sphingolipid levels and risk of ESCC.

HIV sexual transmission risk among serodiscordant couples: assessing the effects of combining prevention strategies.

Background:The number of strategies to prevent HIV transmission has increased following trials evaluating antiretroviral therapy (ART), preexposure prophylaxis (PrEP) and male circumcision. Serodiscordant couples need guidance on the effects of these strategies alone, and in combination with each other, on HIV transmission. Methods:We estimated the sexual risk of HIV transmission over 1-year and 10-year periods among male–male and male–female serodiscordant couples. We assumed the following reductions in transmission: 80% from consistent condom use; 54% from circumcision in the negative male partner of a heterosexual couple; 73% from circumcision in the negative partner of a male–male couple; 71% from PrEP in heterosexual couples; 44% from PrEP in male–male couples; and 96% from ART use by the HIV-infected partner. Findings:For couples using any single prevention strategy, a substantial cumulative risk of HIV transmission remained. For a male–female couple using only condoms, estimated risk over 10 years was 11%; for a male–male couple using only condoms, estimated risk was 76%. ART use by the HIV-infected partner was the most effective single strategy in reducing risk; among male–male couples, adding consistent condom use was necessary to keep the 10-year risk below 10%. Conclusion:Focusing on 1-year and longer term transmission probabilities gives couples a better understanding of risk than those illustrated by data for a single sexual act. Long-term transmission probabilities to the negative partner in serodiscordant couples can be high, though these can be substantially reduced with the strategic use of preventive methods, especially those that include ART.

Nevirapine‐associated hepatotoxicity was not predicted by CD4 count ≥250 cells/μL among women in Zambia, Thailand and Kenya

Objective The aim of the study was to determine risk factors for developing severe hepatotoxicity (grade 3 or 4 hepatotoxicity) and rash‐associated hepatotoxicity (rash with ≥grade 2 hepatotoxicity) among women initiating nevirapine‐based antiretroviral therapy (ART).

Carotenoids, vitamin A and risk of adenomatous polyp recurrence in the polyp prevention trial.

One trial reported beta‐carotene supplementation was protective of adenomatous polyp recurrence in nonsmokers. We now examine the relation of serum and dietary carotenoids and vitamin A to adenomatous polyp recurrence in a subcohort of 834 participants in a low fat, high fiber, high fruit and vegetable dietary intervention, the Polyp Prevention Trial. Multivariate odds ratio (OR) and 95% confidence intervals (CI) of polyp recurrence were obtained using baseline or the average (first 3 years of the trial) carotenoid and vitamin A values after adjustment for covariates. Compared to the lowest quartile of baseline alpha‐carotene concentrations, the OR of multiple polyp recurrence for the highest quartile was 0.55 (95% CI = 0.30–0.99) and the OR of right‐sided recurrence was 0.60 (95% CI = 0.37–0.95). Baseline dietary intakes of alpha‐carotene and vitamin A from food with/without supplements were inversely associated with any recurrence (pfor linear trend = 0.03‐ alpha‐carotene; p = 0.004 and p = 0.007 ‐intakes of vitamin A). Compared to the lowest quartile of averaged beta‐carotene concentrations, the OR of multiple adenomas for the highest quartile was 0.40 (95% CI = 0.22–0.75) with an inverse trend (p = 0.02). The risk was inversely related to averaged: alpha‐carotene concentrations and right‐sided polyps; alpha‐carotene intake and recurrence of any, multiple and right‐sided polyps; beta‐carotene intake and multiple adenoma recurrence; vitamin A from food (with supplements) and each adverse endpoint. Thus, alpha‐carotene and vitamin A may protect against recurrence in nonsmokers and nondrinkers or be indicative of compliance or another healthy lifestyle factor that reduces risk.

Attitudes toward Family Planning among HIV-Positive Pregnant Women Enrolled in a Prevention of Mother-To-Child Transmission Study in Kisumu, Kenya

Background Preventing unintended pregnancies among HIV-positive women through family planning (FP) reduces pregnancy-related morbidity and mortality, decreases the number of pediatric HIV infections, and has also proven to be a cost-effective way to prevent mother-to-child HIV transmission. A key element of a comprehensive HIV prevention agenda, aimed at avoiding unintended pregnancies, is recognizing the attitudes towards FP among HIV-positive women and their spouse or partner. In this study, we analyze FP attitudes among HIV-infected pregnant women enrolled in a PMTCT clinical trial in Western Kenya. Methods and Findings Baseline data were collected on 522 HIV-positive pregnant women using structured questionnaires. Associations between demographic variables and the future intention to use FP were examined using Fishers exact tests and permutation tests. Most participants (87%) indicated that they intended to use FP. However, only 8% indicated condoms as a preferred FP method, and 59% of current pregnancies were unintended. Factors associated with positive intentions to use FP were: marital status (p = 0.04), having talked to their spouse or partner about FP (p<0.001), perceived spouse or partner approval of FP (p<0.001), previous use of a FP method (p = 0.006), attitude toward the current pregnancy (p = 0.02), disclosure of a sexually transmitted infection (STI) diagnosis (p = 0.03) and ethnic group (p = 0.03). Conclusion A significant gap exists between future FP intentions and current FP practices. Support and approval by the spouse or partner are key elements of FP intentions. Counseling services should be offered to both members of a couple to increase FP use, especially given the high number of unplanned pregnancies among HIV-positive women. Condoms should be promoted as part of a dual use method for HIV and STI prevention and for contraception. Integration of individual and couple FP services into routine HIV care, treatment and support services is needed in order to avoid unintended pregnancies and to prevent mother-to-child HIV transmission.