Measuring ART Adherence Among Young Adults with Perinatally Acquired HIV: Comparison Between Self-report, Telephone-Based Pill Count, and Objective Pharmacologic Measures.

Tenofovir diphosphate (TVF-DP) can be quantified in red blood cells (RBCs) and dried blood spots (DBS) and can objectively measure ART adherence and predict viral suppression. Data on the association of TFV-DP with viral load are very limited in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV), as are data comparing TFV-DP to other measures of ART adherence, such as self-report and unannounced telephone pill count. Viral load and ART adherence (self-report, TFV-DP and unannounced telephone pill count) were assessed and compared among 61 AYAPHIV recruited from an ongoing longitudinal study (CASAH) in New York City.

Gestational diabetes in women living with HIV in Botswana: lower rates with dolutegravir- than with efavirenz-based antiretroviral therapy.

BACKGROUND: There are few data on the prevalence of gestational diabetes (GDM) in pregnant women living with HIV (WLHIV) in sub-Saharan Africa, particularly those using integrase strand transfer inhibitors such as dolutegravir (DTG). METHODS: We prospectively enrolled pregnant WLHIV and pregnant women without HIV ≥18 years old in Gaborone, Botswana, excluding those with pre-existing diabetes. We screened for GDM using a 75 g oral glucose tolerance test (OGTT) performed at 24-28 weeks' gestation or at the earliest prenatal visit for those presenting after 28 weeks. Logistic regression models were fitted to assess the association between maternal HIV infection and GDM. Subgroup analyses were performed among WLHIV to assess the association between maternal antiretroviral therapy (ART) in pregnancy [DTG vs. efavirenz (EFV) with tenofovir/emtricitabine] and GDM. RESULTS: Of 486 pregnant women, 66.5% were WLHIV, and they were older than women without HIV (median age 30 vs. 25 years, P < 0.01). Among WLHIV, 97.8% had an HIV-1 RNA level < 400 copies/mL at enrolment. Overall, 8.4% had GDM with similar rates between WLHIV and those without HIV (9.0% vs. 7.4%). The WLHIV receiving DTG-based ART had a 60% lower risk for GDM compared with those on EFV-based ART (adjusted odds ratio = 0.40, 95% CI: 0.18-0.92) after adjusting for confounders. CONCLUSIONS: Pregnant WLHIV on ART in Botswana were not at increased risk of GDM compared with women without HIV. Among WLHIV, the risk of GDM was lower with DTG- than with EFV-based ART. Further studies with larger cohorts are warranted to confirm these findings.

Construct Validity Supports Use of a Novel, Tablet-Based Neurocognitive Assessment for Adolescents and Young Adults Affected by Perinatal HIV from Vulnerable Communities in the United States.

Construct validity of novel tablet-based neurocognitive tests (in the NeuroScreen app) measuring processing speed, working memory, and executive functioning in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV) and perinatal HIV-exposure without infection (PHEU) was examined. Sixty-two AYA (33 PHIV, 29 PHEU) were recruited from an ongoing longitudinal study (CASAH) in New York City. Medium to large and statistically significant correlations were found between NeuroScreen and gold standard, paper-and-pencil tests of processing speed, working memory, and executive functioning. Results provide partial support for NeuroScreen as an alternative to cumbersome paper-and-pencil tests for assessing neurocognition among HIV-affected AYA.

Longitudinal trajectories of neurocognitive test performance among individuals with perinatal HIV-infection and -exposure: adolescence through young adulthood.

There are an estimated 2.1 million youth less than 15 years of age living with HIV globally (the majority perinatally HIV-infected [PHIV]) and millions more perinatally HIV-exposed uninfected (PHEU) youth who are expected to survive through adolescence and into adulthood. Transitioning from adolescence to young adulthood requires adaptation to more demanding social interactions, academic pressures, and individual responsibilities which place distinct demands on neurocognitive functions. This study examined longitudinal trajectories of neurocognitive test performance in the domains of processing speed (PS), working memory (WM), and executive functioning (EF) among PHIV and demographically similar PHEU from adolescence through young adulthood. Data for this paper come from four time points, spanning approximately 10 years, within the Child and Adolescent Self-Awareness and Health Study (CASAH). Youth age ranged from 15 to 29 years. Longitudinal linear mixed effect models were computed for each test. Few differences in performance were found on tests of EF and WM between PHIV and PHEU youth as they aged, though PHEU youth showed significantly better PS as they aged than PHIV youth. Future research is needed to understand these vulnerable youth's neurocognitive trajectories as a function of HIV infection and -exposure, biological functions and psychosocial stressors.

Cost and cost-effectiveness of transitioning to universal initiation of lifelong antiretroviral therapy for all HIV-positive pregnant and breastfeeding women in Swaziland.

OBJECTIVES: To assess the costs and cost-effectiveness of transitioning from antiretroviral therapy (ART) initiation based on CD4 cell count and WHO clinical staging ('Option A') to universal ART ('Option B+') for all HIV-infected pregnant and breastfeeding women in Swaziland. METHODS: We measured the total costs of prevention of mother-to-child HIV transmission (PMTCT) service delivery at public sector facilities with empirical cost data collected at three points in time: once under Option A and again twice after transition to the Option B+ approach. The cost per woman treated per month includes recurrent costs (personnel, overheads, medication and diagnostic tests) and capital costs (buildings, furniture, start-up costs and training). Cost-effectiveness was estimated from the health services perspective as the cost per woman retained in care through 6 months postpartum. This analysis is nested within a larger stepped-wedge evaluation, which demonstrated a 26% increase in maternal retention after the transition to Option B+. RESULTS: Across the five sites, the total cost for PMTCT during the study period (from August 2013 to October 2015, in 2015 US$) was $868,426 for Option B+ and $680 508 for Option A. The cost per woman treated per month was $183 for a woman on ART under Option B+, and $127 and $118 for a woman on ART and zidovudine (AZT), respectively, under Option A. The weighted average cost per woman treated on Option B+ was $826 compared to $525 under Option A. The main cost drivers were the start-up costs, additional training provided and staff time spent on PMTCT tasks for Option B+. The incremental cost-effectiveness ratio was estimated at $912 for every additional mother retained in care through six months postpartum. CONCLUSIONS: The cost and cost-effectiveness outcomes from this study indicate that there is a robust economic case for pursuing the Option B+ approach in Swaziland and similar settings such as South Africa. Furthermore, these costs can be used to aid decision making and budgeting, for similar settings transitioning to test and treat strategy.

HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa.

OBJECTIVES: Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. METHODS: We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. RESULTS: A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre-ART VL, 4.0 log10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL ≤ 1000 and ≤ 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL < 50, 50-1000 and > 1000 copies/mL at delivery, respectively (P < 0.001). CONCLUSIONS: High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention.

The Impact of Oxygen on Bacterial Enteric Pathogens.

Bacterial enteric pathogens are responsible for a tremendous amount of foodborne illnesses every year through the consumption of contaminated food products. During their transit from contaminated food sources to the host gastrointestinal tract, these pathogens are exposed and must adapt to fluctuating oxygen levels to successfully colonize the host and cause diseases. However, the majority of enteric infection research has been conducted under aerobic conditions. To raise awareness of the importance in understanding the impact of oxygen, or lack of oxygen, on enteric pathogenesis, we describe in this review the metabolic and physiological responses of nine bacterial enteric pathogens exposed to environments with different oxygen levels. We further discuss the effects of oxygen levels on virulence regulation to establish potential connections between metabolic adaptations and bacterial pathogenesis. While not providing an exhaustive list of all bacterial pathogens, we highlight key differences and similarities among nine facultative anaerobic and microaerobic pathogens in this review to argue for a more in-depth understanding of the diverse impact oxygen levels have on enteric pathogenesis.

HIV-associated neurodevelopmental delay: prevalence, predictors and persistence in relation to antiretroviral therapy initiation and viral suppression.

CONTEXT: HIV infection in infancy may influence the developing brain, leading to adverse neurodevelopmental consequences. OBJECTIVE: We aim to describe neurodevelopmental characteristics of a cohort of HIV-infected infants and young children prior to antiretroviral therapy (ART) initiation and after achieving viral suppression. METHODS: As part of the Neverest 2 trial, 195 HIV-infected children under 2 years of age were assessed using the Ages and Stages Questionnaire (ASQ) prior to ART initiation and at subsequent age-appropriate time points after ART had been started. The ASQ is a simple screening questionnaire used to identify children at risk of neurodevelopmental delays. Questionnaires completed by the parent/caregiver assess neurodevelopmental functioning in five domains: communication, gross motor, fine motor, problem solving and personal-social. RESULTS: Median age pre-ART was 8.8 months (range 2.2-24.9) and 53.9% were male. Mean time to viral suppression was 9.4 months (range 5.9-14.5). Compared with pre-ART better outcomes were reported at time of viral suppression with a lower proportion of children failing the gross motor (31.5% vs. 13%, p = 0.0002), fine motor (21.3% vs. 10.2%, p = 0.017), problem solving (26.9% vs. 9.3%, p = 0.0003) and personal-social (19.6% vs. 7.4%, p = 0.019) domains. However, there was no change in the communication domain (14.8% vs. 12.0%, p = 0.6072). CONCLUSION: Although achieving viral suppression on ART resulted in significant improvements in markers of neurodevelopmental function of young HIV-infected children, potential neurodevelopmental delays still persisted in a large proportion. Further interventions are needed to limit potential disabilities and maximize developmental outcomes.

'There's no place like home': perceptions of home-based HIV testing in Lesotho.

HIV testing has the potential to reduce HIV transmission by identifying and counseling individuals with HIV, reducing risk behaviors, linking persons with HIV to care and earlier treatment, and reducing perinatal transmission. In Lesotho, a high HIV prevalence country in which a large proportion of the population has never tested for HIV, home-based testing (HBT) may be an important strategy to increase HIV testing. We identified factors influencing acceptability of HIV prevention strategies among a convenience sample of 200 pregnant or post-partum Basotho women and 30 Basotho men. We first conducted cross-sectional surveys, followed by key informant interviews with all 30 men and focus group discussions with a sub-set of 62 women. In total, 82% of women reported positive perceptions of HBT; women and men viewed HBT as a potential way to increase testing among men and saw the home as a comfortable, supportive environment for testing and counseling couples and families together. Potential barriers to HBT uptake included concerns about confidentiality, privacy, coercion to test, conflict within the family and fear of HIV/AIDS-associated stigma. Participants emphasized community mobilization and education as important elements of HBT.

The role of thymic stromal lymphopoietin in the immunopathogenesis of atopic dermatitis.

Atopic dermatitis (AD), a skin disease characterized by pruritus and chronic inflammation, results from a complex interplay between environmental and genetic factors. Thymic stromal lymphopoietin (TSLP), an IL-7-like cytokine, is believed to propagate AD lesions through T helper 2 (Th2) polarization. This paper describes the immunologic mechanisms involving TSLP in the generation of allergic disease. Specifically in AD, TSLP has been shown to be an inducer of myeloid dendritic cells, Th2 responses, mast cells, and natural killer T cells, thereby leading to cytokine secretion and the development of AD. We hope that further understanding of the TSLP pathway and its role in the pathogenesis of AD will lead to improved clinical management of AD in the future.

CSACI guidelines for the ethical, evidence-based and patient-oriented clinical practice of oral immunotherapy in IgE-mediated food allergy.

BACKGROUND: Oral immunotherapy (OIT) is an emerging approach to the treatment of patients with IgE-mediated food allergy and is in the process of transitioning to clinical practice. OBJECTIVE: To develop patient-oriented clinical practice guidelines on oral immunotherapy based on evidence and ethical imperatives for the provision of safe and efficient food allergy management. MATERIALS AND METHODS: Recommendations were developed using a reflective patient-centered multicriteria approach including 22 criteria organized in five dimensions (clinical, populational, economic, organizational and sociopolitical). Data was obtained from: (1) a review of scientific and ethic literature; (2) consultations of allergists, other healthcare professionals (pediatricians, family physicians, nurses, registered dieticians, psychologists, peer supporters), patients and caregivers; and patient associations through structured consultative panels, interviews and on-line questionnaire; and (3) organizational and economic data from the milieu of care. All data was synthesized by criteria in a multicriteria deliberative guide that served as a platform for structured discussion and development of recommendations for each dimension, based on evidence, ethical imperatives and other considerations. RESULTS: The deliberative grid included 162 articles from the literature and media reviews and data from consultations involving 85 individuals. Thirty-eight (38) recommendations were made for the practice of oral immunotherapy for the treatment of IgE mediated food allergy, based on evidence and a diversity of ethical imperatives. All recommendations were aimed at fostering a context conducive to achieving objectives identified by patients and caregivers with food allergy. Notably, specific recommendations were developed to promote a culture of shared responsibility between patients and healthcare system, equity in access, patient empowerment, shared decision making and personalization of OIT protocols to reflect patients' needs. It also provides recommendations to optimize organization of care to generate capacity to meet demand according to patient choice, e.g. OIT or avoidance. These recommendations were made acknowledging the necessity of ensuring sustainability of the clinical offer in light of various economic considerations. CONCLUSIONS: This innovative CPG methodology was guided by patients' perspectives, clinical evidence as well as ethical and other rationales. This allowed for the creation of a broad set of recommendations that chart optimal clinical practice and define the conditions required to bring about changes to food allergy care that will be sustainable, equitable and conducive to the well-being of all patients in need.

Implementing family-focused HIV care and treatment: the first 2 years' experience of the mother-to-child transmission-plus program in Abidjan, Côte d'Ivoire.

OBJECTIVES: To describe a family-focused approach to HIV care and treatment and report on the first 2 years experience of implementing the mother-to-child transmission (MTCT)-plus program in Abidjan, Côte d'Ivoire. PROGRAM: The MTCT-plus initiative aims to enroll HIV-infected pregnant and postpartum women in comprehensive HIV care and treatment for themselves and their families. MAIN OUTCOMES: Between August 2003 and August 2005, 605 HIV-infected pregnant or postpartum women and 582 HIV-exposed infants enrolled. Of their 568 male partners reported alive, 52% were aware of their wife's HIV status and 30% were tested for HIV; 53% of these tested partners were found to be HIV-infected and 78% enrolled into the program. Overall only 10% of the women enrolled together with their infected partner. On the other hand, the program involved half of the seronegative men who came for voluntary counselling and testing (VCT) in the care of their families. Of 1624 children <15 years reported alive by their mothers (excluding the last newborn infants of the most recent pregnancy systematically screened for HIV), only 10.8% were brought in for HIV testing, of whom 12.3% were found to be HIV-infected. LESSONS LEARNED AND CHALLENGES: The family-focused model of HIV care pays attention to the needs of families and household members. The program was successful in enrolling HIV women, their partners and infants in continuous follow-up. However engaging partners and family members of newly enrolled women into care involves numerous challenges such as disclosure of HIV status by women to their partners and family members. Further efforts are required to understand barriers for families accessing HIV services as strategies to improve partner involvement and provide access to care for other children in the households are needed in this West African urban setting.

The Tingathe Surge: a multi-strategy approach to accelerate HIV case finding in Malawi.

SETTING: Nineteen health facilities in rural, southeastern Malawi. OBJECTIVE: To describe the implementation and results of a 6-week intervention to accelerate human immunodeficiency virus (HIV) case finding. DESIGN: Six HIV testing strategies were simultaneously implemented. Routinely collected data from Ministry of Health registers were used to determine the number of HIV tests performed and of new cases identified. The weekly averages of the total number of tests and new cases before and during the intervention were compared. Testing by age group and sex was described. The percentage yield of new cases was compared by testing strategy. RESULTS: Of 29 703 HIV tests conducted, 1106 (3.7%) were positive. Of the total number of persons tested, 69.5% were women and 75.5% were aged >15 years. The yield of positive test results was 3.5% among women, 4.3% among men, 4.4% among those aged >15 years and 1.5% among those aged ⩽15 years. The average weekly number of tests increased 106.7% from 3337 to 6896 (P = 0.002). The average weekly number of positive cases identified increased 51.9% from 158 to 240 (P = 0.017). The testing strategy with the highest yield resulted in a 6.0% yield; the lowest was 1.3%. The yield for all strategies, except one, was highest in adult men. CONCLUSION: A multi-strategy approach to HIV testing and counseling can be an effective means of accelerating HIV case finding.

Burden of tuberculosis in HIV-positive pregnant women in Cape Town, South Africa.

BACKGROUND: The burden of active tuberculosis (TB) in pregnancy compared with preconception and postpartum is unclear, particularly with universal antiretroviral therapy (ART) initiation in pregnancy. METHODS: We retrospectively compared active TB incidence in the 18 months preconception, during pregnancy and up to 6 months postpartum in human immunodeficiency virus (HIV) positive women attending antenatal care at a primary health care facility in Cape Town from 2013 to 2014. RESULTS: Among 1513 women (4116 person-years [py]), 1489 (98.4%) received lifelong ART in pregnancy, and 79 TB episodes were identified. Unadjusted TB incidence rates (IR) preconception, during pregnancy and postpartum were 2466 (95%CI 1863-3202), 1127 (95% CI 600-1928) and 1447 (95% CI 694-2661) per 100 000 py, respectively. Adjusting for age and CD4 count at first antenatal visit and ART status, TB risk was lower during pregnancy (incidence rate ratio [IRR] 0.17 vs. preconception, 95%CI 0.09-0.31) and increased slightly postpartum (IRR 1.31 vs. pregnancy, 95%CI 0.56-3.07). CONCLUSION: Among HIV-positive women in South Africa, the TB burden preconception, during pregnancy and postpartum was substantial. The risk of TB during pregnancy was lower than preconception, but increased slightly postpartum; this represents missed opportunities for diagnosis, prevention and control. Improved TB prevention strategies and integrated care for HIV-positive women and their children are needed.

Evolution of the human immunodeficiency virus envelope gene is dominated by purifying selection.

The evolution of the human immunodeficiency virus (HIV-1) during chronic infection involves the rapid, continuous turnover of genetic diversity. However, the role of natural selection, relative to random genetic drift, in governing this process is unclear. We tested a stochastic model of genetic drift using partial envelope sequences sampled longitudinally in 28 infected children. In each case the Bayesian posterior (empirical) distribution of coalescent genealogies was estimated using Markov chain Monte Carlo methods. Posterior predictive simulation was then used to generate a null distribution of genealogies assuming neutrality, with the null and empirical distributions compared using four genealogy-based summary statistics sensitive to nonneutral evolution. Because both null and empirical distributions were generated within a coalescent framework, we were able to explicitly account for the confounding influence of demography. From the distribution of corrected P-values across patients, we conclude that empirical genealogies are more asymmetric than expected if evolution is driven by mutation and genetic drift only, with an excess of low-frequency polymorphisms in the population. This indicates that although drift may still play an important role, natural selection has a strong influence on the evolution of HIV-1 envelope. A negative relationship between effective population size and substitution rate indicates that as the efficacy of selection increases, a smaller proportion of mutations approach fixation in the population. This suggests the presence of deleterious mutations. We therefore conclude that intrahost HIV-1 evolution in envelope is dominated by purifying selection against low-frequency deleterious mutations that do not reach fixation.

Molecular analysis of SNF2 and SNF5, genes required for expression of glucose-repressible genes in Saccharomyces cerevisiae.

The SNF2 and SNF5 genes are required for derepression of SUC2 and other glucose-repressible genes of Saccharomyces cerevisiae in response to glucose deprivation. Previous genetic evidence suggested that SNF2 and SNF5 have functionally related roles. We cloned both genes by complementation and showed that the cloned DNA was tightly linked to the corresponding chromosomal locus. Both genes in multiple copy complemented only the cognate snf mutation. The SNF2 gene encodes a 5.7-kilobase RNA, and the SNF5 gene encodes a 3-kilobase RNA. Both RNAs contained poly(A) and were present in low abundance. Neither was regulated by glucose repression, and the level of SNF2 RNA was not dependent on SNF5 function or vice versa. Disruption of either gene at its chromosomal locus still allowed low-level derepression of secreted invertase activity, suggesting that these genes are required for high-level expression but are not directly involved in regulation. Further evidence was the finding that snf2 and snf5 mutants failed to derepress acid phosphatase, which is not regulated by glucose repression. The SNF2 and SNF5 functions were required for derepression of SUC2 mRNA.

Cutting the cost of South African antiretroviral therapy using newer, safer drugs.

Antiretrovirals are a significant cost driver for HIV programmes. Current first-line regimens have performed well in real-life programmes, but have a low barrier to virological resistance and still carry toxicity that limits adherence. New drug developments may mean that we have access to safer, more robust and cheaper regimens, but only if the appropriate clinical trials are conducted. We briefly discuss these trials, and demonstrate the large cost savings to the South African HIV programme if these are successful.

Mother-to-child discordance in HLA-G exon 2 is associated with a reduced risk of perinatal HIV-1 transmission.

Definitive genetic parameters correlating with mother-to-child transmission (MCT) of HIV have not been fully established. We screened for the potential correlation between HLA-G variants and MCT, in a cohort of mother-child pairs. Discordance in exon 2 of HLA-G was significantly more common among non-transmitting (93%) than transmitting mother-child pairs (40%). Our results suggest that mother-child pairs both carrying the identical mutation in HLA-G exon 2 may be at higher risk of MCT of HIV-1.

Lack of correlation between maternal antibodies to V3 loop peptides of gp120 and perinatal HIV-1 transmission. The NYC Perinatal HIV Transmission Collaborative Study.

Recent reports have suggested that maternal antibodies to specific epitopes of the variable region 3 (V3 loop) of gp120 of HIV-1 might protect against perinatal transmission. In an attempt to confirm these findings, sera from 34 HIV-1-seropositive mothers, representing 13 episodes of mother-to-infant transmission and 23 episodes of non-transmission (two mothers had two pregnancies each during the study period), were tested for the presence of antibodies to various regions of the gp120 V3 loop. Synthetic peptides were generated from HIV-1MN. Of the four peptides tested by enzyme-linked immunosorbent assay (ELISA), only antibody to the C53 peptide (Env310-322, principal neutralizing determinant) was present in maternal sera. Antibody to the C53 sequence was present in 11 specimens from transmitting mothers and 21 from non-transmitting mothers (84.6 and 91.3%, respectively, P = 0.6). No reactivity was detected against the C51, C57, or C58 peptide sequences, located on the sides of the V3 loop. In an antigen-limited ELISA, only two specimens from transmitting mothers and two specimens from non-transmitting mothers had detectable 'high-affinity' antibodies to C53 at low antigen concentrations (15.4 and 8.7%, respectively; P = 0.6). Our results do not support previous reports that epitope-specific antibodies to the V3 loop peptides protect against perinatal transmission. Further research is required to determine whether any specific maternal humoral response might influence HIV-1 perinatal transmission.

Heterosexual behavior during pregnancy and perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the relationship between maternal heterosexual activity during pregnancy and perinatal transmission of HIV-1. DESIGN: A retrospective analysis of 175 New York City HIV-1-seropositive women enrolled during pregnancy or immediately post-partum from 1986 to 1994 in a prospective cohort study. METHODS: Frequency of heterosexual intercourse and condom use during pregnancy was determined from self-report measures. Unprotected intercourse was defined as follows: 'none', consistent condom use or abstinence; 'moderate', inconsistent condom use and fewer than 80 episodes of intercourse; and 'high', inconsistent condom use and 80 or more episodes. RESULTS: The rate of perinatal HIV-1 transmission was 9.1% (four out of 44) among women with no unprotected intercourse during pregnancy, 22.2% (20 out of 90) among those with moderate frequency, and 39.0% (16 out of 41) among those with high frequency (P < 0.01). The relative risk (RR) of perinatal transmission was higher among women with moderate [RR, 2.4; 95% confidence interval (Cl), 0.9-6.7] and high frequency of unprotected sexual intercourse (RR, 4.3; 95% Cl, 1.6-11.8) compared with women with no unprotected sexual intercourse. When potential covariates (maternal injecting drug use, CD4 lymphocyte count, AIDS, zidovudine use, pelvic inflammatory disease or sexually transmitted disease during pregnancy, delivery mode, and extreme prematurity) were included in a logistic regression model (n = 128), the rate of perinatal transmission remained significantly higher among women with any unprotected sexual intercourse during pregnancy. CONCLUSIONS: Data suggest that unprotected sexual intercourse during pregnancy influences perinatal HIV-1 transmission.