Ryan E. Wiegand

Understanding disparities in HIV infection between black and white MSM in the United States.

Objective:We evaluated several hypotheses for disparities in HIV infection between black and white MSM in the United States, including incarceration, partner HIV status, circumcision, sexual networks, and duration of infectiousness. Design:The 2008 National HIV Behavioral Surveillance System (NHBS), a cross-sectional survey conducted in 21 US cities. Methods:MSM were interviewed and tested for HIV infection. For MSM not previously diagnosed with HIV infection, we used logistic regression to test associations between newly diagnosed HIV infection and incarceration history, partner HIV status, circumcision status, and sexual networks (older partners, concurrency, and partner risk behaviors). For HIV-infected MSM, we assessed factors related to duration of infectiousness. Results:Among 5183 MSM not previously diagnosed with HIV infection, incarceration history, circumcision status, and sexual networks were not independently associated with HIV infection. Having HIV-infected partners [adjusted odds ratio (AOR) = 1.9, 95% confidence interval (CI) = 1.2–3.0] or partners of unknown status (AOR = 1.4, CI = 1.1–1.7) were associated with HIV infection. Of these two factors, only one was more common among black MSM – having partners of unknown HIV status. Among previously diagnosed HIV-positive MSM, black MSM were less likely to be on antiretroviral therapy (ART). Conclusion:Less knowledge of partner HIV status and lower ART use among black MSM may partially explain differences in HIV infection between black and white MSM. Efforts to encourage discussions about HIV status between MSM and their partners and decrease barriers to ART provision among black MSM may decrease transmission.

Barriers and Facilitators to Maternal Communication with Preadolescents about Age-Relevant Sexual Topics

The present study examined factors that promote parent–child discussions about sex topics. A sample of 1,066 dyads of African American mothers and their 9–12-year-old children participated completing computer-administered surveys. After controlling for all other covariates, mother’s sexual communication responsiveness (i.e., knowledge, comfort, skills, and confidence) was the most consistent predictor of discussions. Mothers with higher responsiveness had significantly increased odds of discussions about abstinence, puberty, and reproduction, based on both mother and child reports. In addition, child’s age, pubertal development, readiness to learn about sex, and being female were positively associated with an increase in the odds of discussions in most models. Findings indicate that encouraging parents to talk with their children early may not be sufficient to promote parent–child sex discussions. Parents also need the knowledge, comfort, skills, and confidence to communicate effectively and keep them from avoiding these often difficult and emotional conversations with their children.

An Intervention to Reduce HIV Risk Behavior of Substance-Using Men Who Have Sex with Men: A Two-Group Randomized Trial with a Nonrandomized Third Group

In a randomized trial of a behavioral intervention among substance-using men who have sex with men, aimed at reducing sexual risk behavior, Mansergh and colleagues fail to find evidence of a reduction in risk from the intervention.

Effectiveness of Intermittent Preventive Treatment With Sulfadoxine-Pyrimethamine During Pregnancy on Maternal and Birth Outcomes in Machinga District, Malawi

BACKGROUND Malaria during pregnancy is associated with low birth weight and increased perinatal mortality, especially among primigravidae. Despite increasing prevalence of malarial parasite resistance to sulfadoxine-pyrimethamine (SP), SP continues to be recommended for intermittent preventive treatment in pregnancy (IPTp). METHODS Women without human immunodeficiency virus infection were enrolled upon delivery. Data on the number of SP doses received during pregnancy were recorded. The primary outcome was placental infection demonstrated by histologic analysis. Secondary outcomes included malaria parasitemia (in peripheral, placental, cord blood specimens) at delivery and composite birth outcome (small for gestational age, preterm delivery, or low birth weight). RESULTS.: Of 703 women enrolled, 22% received <2 SP doses. Receipt of ≥ 2 SP doses had no impact on histologically confirmed placental infection. IPTp-SP was associated with a dose-dependent protective effect on composite birth outcome in primigravidae, with an adjusted prevalence ratio of 0.50 (95% confidence interval [CI], .30-.82), 0.30 (95% CI, .19-.48), and 0.18 (95% CI, .05-.61) for 1, 2, and ≥ 3 doses, respectively, compared with 0 doses. CONCLUSIONS IPTp-SP did not reduce the frequency of placental infection but was associated with improved birth outcomes. Few women received no SP, so the true effect of IPTp-SP may be underestimated. Malawian pregnant women should continue to receive IPTp-SP, but alternative strategies and antimalarials for preventing malaria during pregnancy should be investigated.

Epidemiology of and impact of insecticide spraying on Chagas disease in communities in the Bolivian Chaco.

Background Chagas disease control campaigns relying upon residual insecticide spraying have been successful in many Southern American countries. However, in some areas, rapid reinfestation and recrudescence of transmission have occurred. Methodology/Principal Findings We conducted a cross-sectional survey in the Bolivian Chaco to evaluate prevalence of and risk factors for T. cruzi infection 11 years after two rounds of blanket insecticide application. We used a cubic B-spline model to estimate change in force of infection over time based on age-specific seroprevalence data. Overall T. cruzi seroprevalence was 51.7%. The prevalence was 19.8% among children 2–15, 72.7% among those 15–30 and 97.1% among participants older than 30 years. Based on the model, the estimated annual force of infection was 4.3% over the two years before the first blanket spray in 2000 and fell to 0.4% for 2001–2002. The estimated annual force of infection for 2004–2005, the 2 year period following the second blanket spray, was 4.6%. However, the 95% bootstrap confidence intervals overlap for all of these estimates. In a multivariable model, only sleeping in a structure with cracks in the walls (aOR = 2.35; 95% CI = 1.15–4.78), age and village of residence were associated with infection. Conclusions/Significance As in other areas in the Chaco, we found an extremely high prevalence of Chagas disease. Despite evidence that blanket insecticide application in 2000 may have decreased the force of infection, active transmission is ongoing. Continued spraying vigilance, infestation surveillance, and systematic household improvements are necessary to disrupt and sustain interruption of infection transmission.

The A581G Mutation in the Gene Encoding Plasmodium falciparum Dihydropteroate Synthetase Reduces the Effectiveness of Sulfadoxine-Pyrimethamine Preventive Therapy in Malawian Pregnant Women

BACKGROUND The A581 G: mutation in the gene encoding Plasmodium falciparum dihydropteroate synthase (dhps), in combination with the quintuple mutant involving mutations in both dhps and the gene encoding dihydrofolate reductase (dhfr), the so-called sextuple mutant, has been associated with increased placental inflammation and decreased infant birth weight among women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) during pregnancy. METHODS Between 2009 and 2011, delivering women without human immunodeficiency virus infection were enrolled in an observational study of IPTp-SP effectiveness in Malawi. Parasites were detected by polymerase chain reaction (PCR); positive samples were sequenced to genotype the dhfr and dhps loci. The presence of K540 E: in dhps was used as a marker for the quintuple mutant. RESULTS Samples from 1809 women were analyzed by PCR; 220 (12%) were positive for P. falciparum. A total of 202 specimens were genotyped at codon 581 of dhps; 17 (8.4%) harbored the sextuple mutant. The sextuple mutant was associated with higher risks of patent infection in peripheral blood (adjusted prevalence ratio [aPR], 2.76; 95% confidence interval [CI], 1.82-4.18) and placental blood (aPR 3.28; 95% CI, 1.88-5.78) and higher parasite densities. Recent SP use was not associated with increased parasite densities or placental pathology overall and among women with parasites carrying dhps A581 G: . CONCLUSIONS IPTp-SP failed to inhibit parasite growth but did not exacerbate pathology among women infected with sextuple-mutant parasites. New interventions to prevent malaria during pregnancy are needed urgently.

Performance of using multiple stepwise algorithms for variable selection.

Some research studies in the medical literature use multiple stepwise variable selection (SVS) algorithms to build multivariable models. The purpose of this study is to determine whether the use of multiple SVS algorithms in tandem (stepwise agreement) is a valid variable selection procedure. Computer simulations were developed to address stepwise agreement. Three popular SVS algorithms were tested (backward elimination, forward selection, and stepwise) on three statistical methods (linear, logistic, and Cox proportional hazards regression). Other simulation parameters explored were the sample size, number of predictors considered, degree of correlation between pairs of predictors, p-value-based entrance and exit criteria, predictor type (normally distributed or binary), and differences between stepwise agreement between any two or all three algorithms. Among stepwise methods, the rate of agreement, agreement on a model including only those predictors truly associated with the outcome, and agreement on a model containing the predictors truly associated with the outcome were measured. These rates were dependent on all simulation parameters. Mostly, the SVS algorithms agreed on a final model, but rarely on a model with only the true predictors. Sample size and candidate predictor pool size are the most influential simulation conditions. To conclude, stepwise agreement is often a poor strategy that gives misleading results and researchers should avoid using multiple SVS algorithms to build multivariable models. More research on the relationship between sample size and variable selection is needed.

Circumcision status and HIV infection among MSM: reanalysis of a Phase III HIV vaccine clinical trial.

Objective:Determine whether male circumcision would be effective in reducing HIV transmission among men who have sex with men (MSM). Design:Retrospective analysis of the VAXGen VAX004 HIV vaccine clinical trial data. Methods:Survival analysis was used to associate time to HIV infection with multiple predictors. Unprotected insertive and receptive anal sex predictors were highly correlated, thus separate models were run. Results:Four thousand eight hundred and eighty-nine participants were included in this reanalysis; 86.1% were circumcised. Three hundred and forty-two (7.0%) men became infected during the study; 87.4% were circumcised. Controlling for demographic characteristics and risk behaviors, in the model that included unprotected insertive anal sex, being uncircumcised was not associated with incident HIV infection [adjusted hazards ratio (AHR) = 0.97, confidence interval (CI) = 0.56–1.68]. Furthermore, while having unprotected insertive (AHR = 2.25, CI = 1.72–2.93) or receptive (AHR = 3.45, CI = 2.58–4.61) anal sex with an HIV-positive partner were associated with HIV infection, the associations between HIV incidence and the interaction between being uncircumcised and reporting unprotected insertive (AHR = 1.78, CI = 0.90–3.53) or receptive (AHR = 1.26, CI = 0.62–2.57) anal sex with an HIV-positive partner were not statistically significant. Of the study visits when a participant reported unprotected insertive anal sex with an HIV-positive partner, HIV infection among circumcised men was reported in 3.16% of the visits (80/2532) and among uncircumcised men in 3.93% of the visits (14/356) [relative risk (RR) = 0.80, CI = 0.46–1.39]. Conclusions:Among men who reported unprotected insertive anal sex with HIV-positive partners, being uncircumcised did not confer a statistically significant increase in HIV infection risk. Additional studies with more incident HIV infections or that include a larger proportion of uncircumcised men may provide a more definitive result.

Impact of Sulfadoxine-Pyrimethamine Resistance on Effectiveness of Intermittent Preventive Therapy for Malaria in Pregnancy at Clearing Infections and Preventing Low Birth Weight

BACKGROUND Owing to increasing sulfadoxine-pyrimethamine (SP) resistance in sub-Saharan Africa, monitoring the effectiveness of intermittent preventive therapy in pregnancy (IPTp) with SP is crucial. METHODS Between 2009 and 2013, both the efficacy of IPTp-SP at clearing existing peripheral malaria infections and the effectiveness of IPTp-SP at reducing low birth weight (LBW) were assessed among human immunodeficiency virus-uninfected participants in 8 sites in 6 countries. Sites were classified as high, medium, or low resistance after measuring parasite mutations conferring SP resistance. An individual-level prospective pooled analysis was conducted. RESULTS Among 1222 parasitemic pregnant women, overall polymerase chain reaction-uncorrected and -corrected failure rates by day 42 were 21.3% and 10.0%, respectively (39.7% and 21.1% in high-resistance areas; 4.9% and 1.1% in low-resistance areas). Median time to recurrence decreased with increasing prevalence of Pfdhps-K540E. Among 6099 women at delivery, IPTp-SP was associated with a 22% reduction in the risk of LBW (prevalence ratio [PR], 0.78; 95% confidence interval [CI], .69-.88; P < .001). This association was not modified by insecticide-treated net use or gravidity, and remained significant in areas with high SP resistance (PR, 0.81; 95% CI, .67-.97; P = .02). CONCLUSIONS The efficacy of SP to clear peripheral parasites and prevent new infections during pregnancy is compromised in areas with >90% prevalence of Pfdhps-K540E. Nevertheless, in these high-resistance areas, IPTp-SP use remains associated with increases in birth weight and maternal hemoglobin. The effectiveness of IPTp in eastern and southern Africa is threatened by further increases in SP resistance and reinforces the need to evaluate alternative drugs and strategies for the control of malaria in pregnancy.

The Effect of Indoor Residual Spraying on Malaria and Anemia in a High-Transmission Area of Northern Uganda

Indoor residual spraying (IRS) with insecticide is now recommended for malaria control in high-transmission settings. However, concerns about insecticide resistance have increased. We conducted a cross-sectional household survey in high-transmission northern Uganda in two districts previously sprayed with pyrethroids before documentation of pyrethroid resistance and at least one round of carbamates and in one contiguous district that was not sprayed. Parasitemia prevalence among children < 5 years of age was lower in the two IRS districts compared with the non-sprayed district: 37.0% and 16.7% versus 49.8%, P < 0.001. Anemia prevalence was also significantly lower in the two IRS districts: 38.8% and 36.8% versus 53.0%, P < 0.001. Multivariable Poisson regression models indicated that a child living in a sprayed district had a 46% and 32% lower risk of parasitemia and anemia, respectively, than a child in a non-sprayed district (P < 0.001). Carefully managed IRS can significantly reduce malaria burden in high-transmission settings.