Biomedical subjects

Lawrence H Moulton

Publications and source records attributed to Lawrence H Moulton.

At least 19 recordsLinked to original sources

PubMed2025

Bivalent RSV Prefusion F Protein-Based Vaccine for Preventing Cardiovascular Hospitalizations in Older Adults: A Prespecified Analysis of the DAN-RSV Trial.

IMPORTANCE: Respiratory syncytial virus (RSV) infection is linked to elevated cardiovascular risk, particularly in individuals with preexisting cardiovascular disease (CVD). A bivalent RSV prefusion F protein (RSVpreF) vaccine was recently approved for preventing RSV-related lower respiratory tract illness, but its effectiveness against cardiovascular outcomes has not been evaluated in a randomized trial. OBJECTIVE: To investigate the vaccine effectiveness of RSVpreF compared with no vaccine against cardiovascular outcomes among adults aged 60 years or older. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of the DAN-RSV trial, a pragmatic, open-label, individually randomized clinical trial conducted in Denmark during the 2024-2025 winter season. The first participant was enrolled on November 18, 2024. Adults aged 60 years or older were eligible for inclusion regardless of comorbidity status. INTERVENTIONS: Participants were randomized 1:1 to receive RSVpreF (n = 65 642) or no vaccine (n = 65 634). MAIN OUTCOMES AND MEASURES: Hospitalization for any cardiorespiratory disease was a prespecified secondary outcome, and hospitalizations for any CVD, heart failure, myocardial infarction, stroke, and atrial fibrillation were prespecified exploratory outcomes. Outcomes were assessed from 14 days after booked study visit through May 31, 2025. Vaccine effectiveness was calculated as 1 - incidence rate ratio, expressed as a percentage. RESULTS: Of 131 276 participants included (mean age, 69.4 [SD, 6.5] years; 50.3% male), 28 662 (21.8%) had preexisting CVD. All-cause cardiorespiratory hospitalization incidence was lower in the RSVpreF group compared with the control group (26.3 vs 29.2 events per 1000 participant-years [PY]; absolute rate reduction, 2.90 [95% CI, 0.10-5.71] per 1000 PY; vaccine effectiveness, 9.9% [95% CI, 0.3%-18.7%]; P = .04). There was no significant interaction by baseline CVD status (CVD at baseline: vaccine effectiveness, 5.0% [95% CI, -11.2% to 16.7%]; no CVD at baseline: vaccine effectiveness, 15.2% [95% CI, 2.2%-27.1%]; P = .27 for interaction). For the RSVpreF group vs control group, respectively, incidence rates of all-cause cardiovascular hospitalization were 16.4 vs 17.7 events per 1000 PY (vaccine effectiveness, 7.4% [95% CI, -5.5% to 18.8%]; P = .24), and incidence rates of stroke were 3.0 vs 3.8 events per 1000 PY (vaccine effectiveness, 19.4% [95% CI, -8.6% to 40.4%]; P = .14). There were also no statistically significant between-group differences for myocardial infarction, heart failure hospitalization, and atrial fibrillation. CONCLUSIONS AND RELEVANCE: In adults aged 60 years or older, all-cause cardiorespiratory hospitalization was significantly lower with RSVpreF than with no vaccine. The findings suggest potential downstream cardiorespiratory benefits of RSV immunization, although the effect on all-cause cardiovascular hospitalization was not statistically significant. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06684743.

Aged↗

PubMed2006

Nonmedical exemptions to school immunization requirements: secular trends and association of state policies with pertussis incidence.

CONTEXT: School immunization requirements have played a major role in controlling vaccine-preventable diseases in the United States. Most states offer nonmedical exemptions to school requirements (religious or personal belief). Exemptors are at increased risk of acquiring and transmitting disease. The role of exemption policies may be especially important for pertussis, which is endemic in the United States. OBJECTIVE: To determine if (1) the rates of nonmedical exemptions differ and have been increasing in states that offer only religious vs personal belief exemptions; (2) the rates of nonmedical exemptions differ and have been increasing in states that have easy vs medium and easy vs difficult processes for obtaining exemptions; and (3) pertussis incidence is associated with policies of granting personal belief exemptions, ease of obtaining exemptions, and acceptance of parental signature as sufficient proof of compliance with school immunization requirements. DESIGN, SETTING, AND PARTICIPANTS: We analyzed 1991 through 2004 state-level rates of nonmedical exemptions at school entry and 1986 through 2004 pertussis incidence data for individuals aged 18 years or younger. MAIN OUTCOME MEASURES: State-level exemption rates and pertussis incidence. RESULTS: From 2001 through 2004, states that permitted personal belief exemptions had higher nonmedical exemption rates than states that offered only religious exemptions, and states that easily granted exemptions had higher nonmedical exemption rates in 2002 through 2003 compared with states with medium and difficult exemption processes. The mean exemption rate increased an average of 6% per year, from 0.99% in 1991 to 2.54% in 2004, among states that offered personal belief exemptions. In states that easily granted exemptions, the rate increased 5% per year, from 1.26% in 1991 to 2.51% in 2004. No statistically significant change was seen in states that offered only religious exemptions or that had medium and difficult exemption processes. In multivariate analyses adjusting for demographics, easier granting of exemptions (incidence rate ratio = 1.53; 95% confidence interval, 1.10-2.14) and availability of personal belief exemptions (incidence rate ratio = 1.48; 95% confidence interval, 1.03-2.13) were associated with increased pertussis incidence. CONCLUSIONS: Permitting personal belief exemptions and easily granting exemptions are associated with higher and increasing nonmedical US exemption rates. State policies granting personal belief exemptions and states that easily grant exemptions are associated with increased pertussis incidence. States should examine their exemption policies to ensure control of pertussis and other vaccine-preventable diseases.

Adolescent↗

PubMed2006

Effects of infant sex on mother-to-child transmission of HIV-1 according to timing of infection in Zimbabwe.

We examined the relationship between sex and the risk of intrauterine, intrapartum and postnatal HIV transmission among 4495 infants born to HIV-infected mothers in Harare, Zimbabwe. Intrauterine transmission was 8.6%, and consistent with other studies was higher among girl than boy infants (AOR 1.53; 95% CI 1.23-1.91). Unlike previous studies, we observed no independent effect of infant sex on intrapartum or breastfeeding-associated HIV transmission. Sex-specific postnatal prevention strategies are not warranted in this population.

Adult↗

PubMed2006

Contributions of Native Americans to the global control of infectious diseases.

For over a half of a century, Native American populations have participated in numerous studies regarding the epidemiology, prevention and treatment of infectious diseases. These studies have resulted in measures to prevent morbidity and mortality from many infectious diseases. The lessons learned from these studies and their resultant prevention or treatment interventions have been applied around the world, and have had a major impact in the reduction of global childhood morbidity and mortality.

Humans↗

PubMed2006

A SAS macro for constrained randomization of group-randomized designs.

Group-randomized study designs are useful when individually-randomized designs either are not possible, or will not be able to estimate the parameters of interest. Group-randomized trials often have small number of experimental units or groups and strong geographically-induced between-unit correlation, thereby increasing the chance of obtaining a "bad" randomization outcome. It has been suggested to highly constrain the design through restriction to those allocations that meet specified criteria based on certain covariates available at the baseline. We describe a SAS macro that allocates treatment conditions in a two-arm stratified group-randomized design that ensures balance on relevant covariates. The application of the macro is illustrated using two examples of group-randomized designs.

AIDS Vaccines↗

PubMed2006

HIV incidence among post-partum women in Zimbabwe: risk factors and the effect of vitamin A supplementation.

OBJECTIVE: To test whether post-partum vitamin A supplementation can reduce incident HIV among post-partum women and identify risk factors for HIV incidence. DESIGN: Randomized, placebo-controlled trial METHODS: Between November 1997 and January 2001, 14,110 women were randomly administered 400,000 IU vitamin A or placebo within 96 h post-partum. HIV incidence was monitored among 9562 HIV-negative women. RESULTS: Cumulative incidence was 3.4% [95% confidence interval (CI), 3.0-3.8] and 6.5% (95% CI, 5.7-7.4) over 12 and 24 months post-partum, respectively. Vitamin A supplementation had no impact on incidence [hazard ratio (HR), 1.08; 95% CI, 0.85-1.38]. However, among 398 women for whom baseline serum retinol was measured, those with levels indicative of deficiency (< 0.7 micromol/l, 9.2% of those measured) were 10.4 (95% CI, 3.0-36.3) times more likely to seroconvert than women with higher concentrations. Furthermore, among women with low serum retinol, vitamin A supplementation tended to be protective against incidence (HR, 0.29; 95% CI, 0.03-2.60; P = 0.26), although not significantly so, perhaps due to limited statistical power. Severe anaemia (haemoglobin < 70 g/l) was associated with a 2.7-fold (95%CI, 1.2-6.1) greater incidence. Younger women were at higher risk of HIV infection: incidence declined by 5.7% (2.8-8.6) with each additional year of age. CONCLUSION: Among post-partum women, a single large-dose vitamin A supplementation had no effect on incidence, although low serum retinol was a risk factor for seroconversion. Further investigation is required to determine whether vitamin A supplementation of vitamin-A-deficient women or treatment of anaemic women can reduce HIV incidence.

Adolescent↗

PubMed2006

The potential impact of enhanced diagnostic techniques for tuberculosis driven by HIV: a mathematical model.

OBJECTIVE: To explore the potential impact of enhanced tuberculosis (TB) diagnostic techniques as a TB control strategy in an adult population with high HIV prevalence. DESIGN: A compartmental difference-equation model of TB/HIV was developed using parameter estimates from the literature. METHODS: The impact of five TB control interventions (rapid molecular testing, mycobacterial culture, community-wide and HIV-targeted active case finding, and highly active antiretroviral therapy) on TB incidence, prevalence, and mortality was modeled in a steady-state population with an HIV prevalence of 17% and annual TB incidence of 409 per 100 000. Sensitivity analyses assessed the influence of each model parameter on the interventions' mortality impact. RESULTS: Enhanced diagnostic techniques (rapid molecular testing or culture) are each projected to reduce TB prevalence and mortality by 20% or more, an impact similar to that of active case-finding in 33% of the general community and greater than the effect achievable by case-finding or antiretroviral treatment efforts in HIV-positive patients alone. The projected impact of enhanced diagnostics on TB incidence (< 10% reduction) is smaller. The impact of TB diagnostics is sensitive to the quality of existing diagnostic standards and the level of access to diagnostic services, but is robust across a wide range of population parameters including HIV and TB incidence. CONCLUSIONS: Enhanced TB diagnostic techniques may have substantial impact on TB morbidity and mortality in HIV-endemic regions. As TB rates continue to increase in these areas, enhanced diagnostic techniques merit further consideration as TB control strategies.

AIDS-Related Opportunistic Infections↗

PubMed2006

Effects of a single large dose of vitamin A, given during the postpartum period to HIV-positive women and their infants, on child HIV infection, HIV-free survival, and mortality.

BACKGROUND: Low maternal serum retinol level is a risk factor for mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). Multiple-large-dose vitamin A supplementation of HIV-positive children reduces mortality. The World Health Organization recommends single-large-dose vitamin A supplementation for postpartum women in areas of prevalent vitamin A deficiency; neonatal dosing is under consideration. We investigated the effect that single-large-dose maternal/neonatal vitamin A supplementation has on MTCT, HIV-free survival, and mortality in HIV-exposed infants. METHODS: A total of 14,110 mother-infant pairs were enrolled < or =96 h after delivery, and both mother and infant, mother only, infant only, or neither received vitamin A supplementation in a randomized, placebo-controlled trial with a 2 x 2 factorial design. All but 4 mothers initiated breast-feeding. A total of 4495 infants born to HIV-positive women were included in the present analysis. RESULTS: Neither maternal nor neonatal vitamin A supplementation significantly affected postnatal MTCT or overall mortality between baseline and 24 months. However, the timing of infant HIV infection modified the effect that supplementation had on mortality. Vitamin A supplementation had no effect in infants who were polymerase chain reaction (PCR) positive [corrected] for HIV at baseline. In infants who were PCR negative at baseline and PCR positive at 6 weeks, neonatal supplementation reduced mortality by 28% (P=.01), but maternal supplementation had no effect. In infants who were PCR negative at 6 weeks, all 3 vitamin A regimens were associated with ~2-fold higher mortality (P< or =.05). CONCLUSIONS: Targeted vitamin A supplementation of HIV-positive children prolongs their survival. However, postpartum maternal and neonatal vitamin A supplementation may hasten progression to death in breast-fed children who are PCR negative at 6 weeks. These findings raise concern about universal maternal or neonatal vitamin A supplementation in HIV-endemic areas.

Dietary Supplements↗

PubMed2006

Mortality and morbidity among postpartum HIV-positive and HIV-negative women in Zimbabwe: risk factors, causes, and impact of single-dose postpartum vitamin A supplementation.

BACKGROUND: Vitamin A deficiency is common among women in resource-poor countries and is associated with greater mortality during HIV. METHODS: Fourteen thousand one hundred ten mothers were tested for HIV and randomly administered 400,000 IU vitamin A or placebo at less than 96 hours postpartum. The effects of vitamin A and HIV status on mortality, health care utilization, and serum retinol were evaluated. RESULTS: Four thousand four hundred ninety-five (31.9%) mothers tested HIV positive. Mortality at 24 months was 2.3 per 1000 person-years and 38.3 per 1000 person-years in HIV-negative and HIV-positive women, respectively. Vitamin A had no effect on mortality. Tuberculosis was the most common cause of death, and nearly all tuberculosis-associated deaths were among HIV-positive women. Among HIV-positive women, vitamin A had no effect on rates of hospitalization or overall sick clinic visits, but did reduce clinic visits for malaria, cracked and bleeding nipples, pelvic inflammatory disease, and vaginal infection. Among HIV-negative women, serum retinol was responsive to vitamin A, but low serum retinol was rare. Among HIV-positive women, serum retinol was largely unresponsive to vitamin A, and regardless of treatment group, the entire serum retinol distribution was shifted 25% less than that of HIV-negative women 6 weeks after dosing. CONCLUSIONS: Single-dose postpartum vitamin A supplementation had no effect on maternal mortality, perhaps because vitamin A status was adequate in HIV-negative women and apparently unresponsive to supplementation in HIV-positive women.

Adult↗

PubMed2006

Prevalence and risk factors for reproductive tract infections among women in rural Vietnam.

The objective of this study was to estimate prevalence and risk factors of reproductive tract infections (RTIs) among women in Haiphong, Vietnam. In October 1998, 197 women aged 18-49 were recruited into a community-based, cross-sectional study. Of the 197 women, 95 (49.5%) were diagnosed with > or = 1 endogenous reproductive tract infections (RTI) and 7 (3.6%) with > or = 1 sexually transmitted disease (STD). In three separate multivariate analyses, age <30 years (OR = 2.5; 95% CI = 1.1, 5.8), residential mobility (OR = 2.3; 95% CI = 1.1, 4.9), self reported genital itch/discharge (OR = 2.1; 95% CI = 1.1, 4.1), and reported belief that RTI symptoms were shameful (OR = 2.5; 95% CI = 1.2, 5.0) were associated with bacterial vaginosis (BV); low education was associated with candida (OR = 2.6; 95% CI = 1.0, 6.7); > or = 1 abortion was associated with > or = 1 STD (OR = 9.2; 95% CI = 1.1, 427). The prevalence of STDs was low but the prevalence of endogenous infections was high. Abortion is a proxy for other factors, such as high risk sexual behavior in either the woman or her partner. Given the low prevalence STD in this area of Vietnam, clinical case management of women presenting with RTI symptoms should focus on treatment of the more common endogenous infections, candida and BV.

Adolescent↗

PubMed2005

Early exclusive breastfeeding reduces the risk of postnatal HIV-1 transmission and increases HIV-free survival.

OBJECTIVES: The promotion of exclusive breastfeeding (EBF) to reduce the postnatal transmission (PNT) of HIV is based on limited data. In the context of a trial of postpartum vitamin A supplementation, we provided education and counseling about infant feeding and HIV, prospectively collected information on infant feeding practices, and measured associated infant infections and deaths. DESIGN AND METHODS: A total of 14 110 mother-newborn pairs were enrolled, randomly assigned to vitamin A treatment group after delivery, and followed for 2 years. At baseline, 6 weeks and 3 months, mothers were asked whether they were still breastfeeding, and whether any of 22 liquids or foods had been given to the infant. Breastfed infants were classified as exclusive, predominant, or mixed breastfed. RESULTS: A total of 4495 mothers tested HIV positive at baseline; 2060 of their babies were alive, polymerase chain reaction negative at 6 weeks, and provided complete feeding information. All infants initiated breastfeeding. Overall PNT (defined by a positive HIV test after the 6-week negative test) was 12.1%, 68.2% of which occurred after 6 months. Compared with EBF, early mixed breastfeeding was associated with a 4.03 (95% CI 0.98, 16.61), 3.79 (95% CI 1.40-10.29), and 2.60 (95% CI 1.21-5.55) greater risk of PNT at 6, 12, and 18 months, respectively. Predominant breastfeeding was associated with a 2.63 (95% CI 0.59-11.67), 2.69 (95% CI 0.95-7.63) and 1.61 (95% CI 0.72-3.64) trend towards greater PNT risk at 6, 12, and 18 months, compared with EBF. CONCLUSION: EBF may substantially reduce breastfeeding-associated HIV transmission.

AIDS Serodiagnosis↗

PubMed2005

Factors associated with refusal of childhood vaccines among parents of school-aged children: a case-control study.

BACKGROUND: The rate of nonmedical exemptions to school immunization requirements has been increasing, and children with exemptions have contributed to outbreaks of vaccine-preventable diseases. OBJECTIVES: To determine why parents claim nonmedical exemptions and to explore differences in perceptions of vaccines and vaccine information sources between parents of exempt and fully vaccinated children. DESIGN: Case-control study. SETTING: Colorado, Massachusetts, Missouri, and Washington. PARTICIPANTS: Surveys were mailed to the parents of 815 exempt children (cases) and 1630 fully vaccinated children (controls randomly selected from the same grade and school) recruited from 112 private and public elementary schools. Surveys were completed by 2435 parents (56.1%). MAIN OUTCOME MEASURES: Parental reports. RESULTS: Most children (209 [75.5%] of 277) with nonmedical exemptions received at least some vaccines. The most common vaccine not received was varicella (147 [53.1%] of 277 exempt children). The most common reason stated for requesting exemptions (190 [69%] of 277) was concern that the vaccines might cause harm. Parents of exempt children were significantly more likely than parents of vaccinated children to report low perceived vaccine safety and efficacy, a low level of trust in the government, and low perceived susceptibility to and severity of vaccine-preventable diseases. Parents of exempt children were significantly less likely to report confidence in medical, public health, and government sources for vaccine information and were more likely to report confidence in alternative medicine professionals than parents of vaccinated children. CONCLUSION: Continued efforts must be made to educate parents about the utility and safety of vaccines, especially parents requesting nonmedical exemptions to school immunization requirements.

Adult↗

PubMed2005

Effect of postpartum maternal or neonatal vitamin A supplementation on infant mortality among infants born to HIV-negative mothers in Zimbabwe.

BACKGROUND: Young infants are at risk of vitamin A deficiency. Supplementation of breastfeeding mothers improves the vitamin A status of their infants, but there are no data regarding its effect on infant mortality, and data on the effect of directly supplementing infants during the first few weeks of life are conflicting. OBJECTIVE: The objective was to measure the effect on infant mortality of supplementing neonates and their HIV-negative mothers with single, large doses of vitamin A during the immediate postpartum period. DESIGN: A randomized, placebo-controlled, 2-by-2 factorial design trial was conducted in 14,110 mothers and their infants; 9208 of the mothers were HIV-negative at delivery, remained such during the postpartum year, and were retained in the current analysis. The infants were randomly assigned within 96 h of delivery to 1 of 4 treatment groups: mothers and infants received vitamin A (Aa), mothers received vitamin A and infants received placebo (Ap), mothers received placebo and infants received vitamin A (Pa), and both mothers and infants received placebo (Pp). The vitamin A dose in the mothers was 400,000 IU and in the infants was 50,000 IU. The mother-infant pairs were followed to 12 mo. RESULTS: Hazard ratios (95% CI) for 12 mo mortality among infants in the maternal-supplemented and infant-supplemented groups were 1.17 (0.87, 1.58) and 1.08 (0.80, 1.46), respectively. Hazard ratios (95% CI) for the Aa, Ap, and Pa groups compared with the Pp group were 1.28 (0.83, 1.98), 1.27 (0.82, 1.97), and 1.18 (0.76, 1.83), respectively. These data indicate no overall effect. Serum retinol concentrations among a subsample of women were similar to reference norms. CONCLUSION: Postpartum maternal or neonatal vitamin A supplementation may not reduce infant mortality in infants of HIV-negative women with an apparently adequate vitamin A status.

Adult↗

PubMed2005

Evaluation of non-specific effects of infant immunizations on early infant mortality in a southern Indian population.

OBJECTIVE: The aim of this study was to assess the relationship between receipt of routine childhood immunizations and infant mortality before 6 months of age. METHODS: This was an observational study of 10,274 infants, in a randomized trial of vitamin A supplementation, who received the study dose and survived to at least 1 week of age. The primary outcome was mortality before 6 months of age, analysed in Cox regression models as a function of vaccine receipt and gender. RESULTS: Receipt of Bacille Calmette Guerin (BCG) or diphtheria, tetanus, polio (DTP) vaccine was associated with significant reductions of one-half to two-thirds of mortality hazards; among girls, those who received both BCG and DTP experienced higher mortality than those who received only one of the two vaccines (hazards ratio 2.4; 95% confidence interval 1.2-5.0). CONCLUSION: The reduced mortality rate associated with receipt of BCG or DTP may be due to both biological and selection factors; the analyses regarding the combined effect of these vaccines and gender need to be replicated in other settings.

BCG Vaccine↗

PubMed2005

Exemptions to school immunization requirements: the role of school-level requirements, policies, and procedures.

OBJECTIVES: Our goal was to determine whether school-level variability in implementation of immunization requirements is associated with the likelihood of a child having received an exemption to school immunization requirements. METHODS: We surveyed 1000 school immunization personnel in Colorado, Massachusetts, Missouri, and Washington. We explored associations between school implementation of immunization requirements and the likelihood of a child having an exemption using logistic regression models. RESULTS: School policies associated with an increased likelihood of children having exemptions included lack of provision of written instructions for completing the school immunization requirement before enrollment, administrative procedures making it easier to claim an exemption, and granting of philosophical exemptions. In the 2 states we surveyed where philosophical exemptions are not authorized (Massachusetts and Missouri), 17.0% and 18.1% of schools reported permitting philosophical exemptions. CONCLUSIONS: Inconsistencies in the interpretation and implementation of school immunization laws contribute to variability in rates of exemptions. School policies should be reviewed to ensure consistency with the intent of state laws.

Child↗

PubMed2004

Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: A 60-year follow-up study.

CONTEXT: The duration of protection from tuberculosis of BCG vaccines is not known. OBJECTIVE: To determine the long-term duration of protection of a BCG vaccine that was previously found to be efficacious. DESIGN: Retrospective record review using Indian Health Service records, tuberculosis registries, death certificates, and supplemental interviews with trial participants. SETTING AND PARTICIPANTS: Follow-up for the period 1948-1998 among American Indians and Alaska Natives who participated in a placebo-controlled BCG vaccine trial during 1935-1938 and who were still at risk of developing tuberculosis. Data from 1483 participants in the BCG vaccine group and 1309 in the placebo group were analyzed. MAIN OUTCOME MEASURES: Efficacy of BCG vaccine, calculated for each 10-year interval using a Cox regression model with time-dependent variables based on tuberculosis events occurring after December 31, 1947 (end of prospective case finding). RESULTS: The overall incidence of tuberculosis was 66 and 138 cases per 100 000 person-years in the BCG vaccine and placebo groups, respectively, for an estimate of vaccine efficacy of 52% (95% confidence interval, 27%-69%). Adjustments for age at vaccination, tribe, subsequent BCG vaccination, chronic medical illness, isoniazid use, and bacille Calmette-Guérin strain did not substantially affect vaccine efficacy. There was slight but not statistically significant waning of the efficacy of BCG vaccination over time, greater among men than women. CONCLUSION: In this trial, BCG vaccine efficacy persisted for 50 to 60 years, suggesting that a single dose of an effective BCG vaccine can have a long duration of protection.

BCG Vaccine↗

PubMed2004

Behavioral impact, acceptability, and HIV incidence among homosexual men with access to postexposure chemoprophylaxis for HIV.

BACKGROUND: Little is known about the behavioral impact, acceptability, and incidence of HIV infection in persons with easy access to post-sexual exposure prophylaxis (PEP) to prevent HIV. METHODS: Participants were recruited from a well-characterized, high-risk HIV seronegative homosexual male cohort in Rio de Janeiro, Brazil, given a 4-day supply of zidovudine and lamivudine, and instructed to begin PEP immediately after an eligible exposure. For eligible exposures, an additional 24-day supply was provided. Reported behavior, PEP utilization, adverse events, and incident HIV infection were the main study outcomes. The observed and expected incidences of HIV infection were compared. RESULTS: Two hundred subjects were enrolled and followed for a median of 24.2 months. The median age was 28 years. PEP was initiated 109 times by 68 participants (34.0%). In comparison to reported behavior at baseline, reported high-risk sexual activities on average declined over time for both PEP and non-PEP users. There were no serious drug-related adverse events. There were 11 HIV seroconversions, 10 among non-PEP users and 1 that was a PEP failure. The overall seroincidence was 2.9 per 100 person-years (95% CI = 1.4, 5.1). The expected number of new HIV infections and corresponding expected seroincidence based on the risk profile were 11.8 and 3.1, respectively (P > 0.97). The most commonly reported reasons for not initiating PEP among seroconverters were sex with a steady partner and not considering the exposure to be of sufficiently high risk to warrant PEP. CONCLUSION: PEP was safe and did not appear to be associated with increases in reported high-risk behavior in our cohort. Ready access to PEP did not appear to substantially affect HIV transmission, suggesting a limited public health impact of this intervention.

Adult↗

PubMed2004

Timing of mother-to-child transmission of HIV-1 and infant mortality in the first 6 months of life in Harare, Zimbabwe.

OBJECTIVES: To examine the risks of intra-uterine (IU), intra- and early post-partum (IP/ePP) and late post-partum (LPP) mother-to-child transmission (MTCT) of HIV-1 and infant mortality in the first 6 months of life. METHODS: Whole blood was collected in ethylenediaminetetra-acetic acid at birth, 6 weeks, 3 and 6 months from 996 infants born to HIV-1 seropositive mothers. Polymerase chain reaction using Roche DNA amplification assay, version 1.5 (Roche Diagnostics Incorporation, Alameda, California, USA) was used to determine timing of MTCT. Logistic regression models determined risk factors for HIV-1 transmission and survival analyses examined mortality by timing of transmission. RESULTS: Two hundred and forty-nine mothers (30.7%) transmitted HIV-1 infection to their infants by 6 months of age. Eighty-nine infants [9.4%; 95% confidence interval (CI), 7.7-11.5], 104 infants (16.0%; 95% CI, 10.8-21.2) and 21 infants (5.3%; 95% CI, 1.6-12.2) were infected IU, IP/ePP and LPP respectively. Low maternal CD4 cell count and arm circumference were risk factors for IP/ePP transmission. Infant mortality was higher among infected infants than uninfected (P < 0.001, log rank test). Timing of infection, birth weight and maternal CD4 cell counts were important factors in predicting infant death. CONCLUSION: In the first 6 months of life, IU and IP/ePP transmission contributed more than three-quarters of the 30.7% MTCT. Our data, in addition to serving as a historical comparison, may be useful in designing and evaluating the efficacy of short course antiretroviral trials aimed at reducing MTCT in developing countries.

Adult↗