Dolutegravir and pregnancy outcomes including neural tube defects in the USA during 2008-20: a national cohort study.

BACKGROUND: A study from Botswana identified an increased risk of neural tube defects (NTDs) in infants of mothers with HIV who were treated with dolutegravir around the time of conception. We aimed to examine associations of dolutegravir use with NTDs and pregnancy loss using large health-care claims databases from the USA, a country with folic acid fortification of food. METHODS: In this cohort study, we analysed health-care claims data, recorded in the Merative MarketScan commercial database (MarketScan data) and Centers for Medicare & Medicaid Services Medicaid database (Medicaid data) from Jan 1, 2008, to Dec 31, 2020. We identified pregnancies with enrolment during their entire duration among women aged 15-49 years and we estimated time of conception. For each pregnancy, we determined HIV status and periconceptional exposure to dolutegravir or other antiretroviral agents. We estimated and compared the incidence rate of NTDs, stillbirths, and pregnancy loss (ie, spontaneous or induced abortions) by type of periconceptional antiretroviral exposure. We calculated adjusted risk ratios of the adverse outcomes using Poisson models adjusting for demographic and clinical factors. FINDINGS: Of 4 489 315 pregnancies in MarketScan data and 14 405 861 pregnancies in Medicaid data that had full enrolment, we identified 69 pregnancies in MarketScan data and 993 pregnancies in Medicaid data that were associated with HIV and periconceptional dolutegravir exposure. For women without HIV, the NTD rate was 4·1 per 10 000 live births (95% CI 3·9-4·3) in MarketScan and 5·7 per 10 000 live births (5·6-5·8) in Medicaid. No NTD cases were found among those with dolutegravir or non- dolutegravir antiretroviral drug exposure in the MarketScan data; only one NTD case was identified among women with dolutegravir, and three among women with non-dolutegravir antiretroviral exposure in Medicaid. After adjusting for covariates, there were no significant differences in risk ratios of NTD between groups with periconceptional dolutegravir or non-dolutegravir antiretroviral exposure and the group without HIV. However, compared with women without HIV, the risk of pregnancy loss was higher among women exposed to antiretroviral therapy: for dolutegravir exposure the adjusted risk ratio was 1·73 (95% CI 1·20-2·49) in MarketScan data and 1·41 (1·30-1·54) in Medicaid data; for non-dolutegravir antiretroviral exposure the adjusted risk ratio was 1·23 (1·10-1·37) in MarketScan data and 1·11 (1·07-1·15) in Medicaid data. INTERPRETATION: We studied the largest US cohort of women with periconceptional or early-pregnancy dolutegravir exposure. Our results do not show an increased risk of NTDs in exposed infants in the USA. Administrative databases can be used, with rigorous methodology, to study correlates of rare outcomes, such as NTDs, and to monitor for adverse pregnancy outcomes in women who receive antiretrovirals. FUNDING: US Centers for Disease Control and Prevention.

Trends in contraceptive use according to HIV status among privately insured women in the United States.

BACKGROUND: There is limited information on the patterns and trends of contraceptive use among women living with HIV, compared with noninfected women in the United States. Further, little is known about whether antiretroviral therapy correlates with contraceptive use. Such information is needed to help identify potential gaps in care and to enhance unintended pregnancy prevention efforts. OBJECTIVE: We sought to compare contraceptive method use among HIV-infected and noninfected privately insured women in the United States, and to evaluate the association between antiretroviral therapy use and contraceptive method use. STUDY DESIGN: We used a large US nationwide health care claims database to identify girls and women ages 15-44 years with prescription drug coverage. We used diagnosis, procedure, and National Drug Codes to assess female sterilization and reversible prescription contraception use in 2008 and 2014 among women continuously enrolled in the database during 2003 through 2008 or 2009 through 2014, respectively. Women with no codes were classified as using no method; these may have included women using nonprescription methods, such as condoms. We calculated prevalence of contraceptive use by HIV infection status, and by use of antiretroviral therapy among those with HIV. We used multivariable polytomous logistic regression to calculate unadjusted and adjusted odds ratios and 95% confidence intervals for female sterilization, long-acting reversible contraception, and short-acting hormonal contraception compared to no method. RESULTS: While contraceptive use increased among HIV-infected and noninfected women from 2008 through 2014, in both years, a lower proportion of HIV-infected women used prescription contraceptive methods (2008: 17.5%; 2014: 28.9%, compared with noninfected women (2008: 28.8%; 2014: 39.8%, P < .001 for both). Controlling for demographics, chronic medical conditions, pregnancy history, and cohort year, HIV-infected women compared to HIV-noninfected women had lower odds of using long-acting reversible contraception (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86 compared to no method) or short-acting hormonal contraception method (adjusted odds ratio, 0.59; 95% confidence interval, 0.50-0.70 compared to no method). In 2014, HIV-infected women using antiretroviral therapy were significantly more likely to use no method (76.8% vs 64.1%), and significantly less likely to use short-acting hormonal contraception (11.0% vs 22.7%) compared to HIV-infected women not using antiretroviral therapy. Those receiving antiretroviral therapy had lower odds of using short-acting hormonal contraception compared to no method (adjusted odds ratio, 0.45; 95% confidence interval, 0.32-0.63). There was no significant difference in female sterilization by HIV status or antiretroviral therapy use. CONCLUSION: Despite the safety of reversible contraceptives for women with HIV, use of prescription contraception continues to be lower among privately insured HIV-infected women compared to noninfected women, particularly among those receiving antiretroviral therapy.

Impact of Health Insurance Type on Trends in Newborn Circumcision, United States, 2000 to 2010.

OBJECTIVES: We explored how changes in insurance coverage contributed to recent nationwide decreases in newborn circumcision. METHODS: Hospital discharge data from the 2000-2010 Nationwide Inpatient Sample were analyzed to assess trends in circumcision incidence among male newborn birth hospitalizations covered by private insurance or Medicaid. We examined the impact of insurance coverage on circumcision incidence. RESULTS: Overall, circumcision incidence decreased significantly from 61.3% in 2000 to 56.9% in 2010 in unadjusted analyses (P for trend = .008), but not in analyses adjusted for insurance status (P for trend = .46) and other predictors (P for trend = .55). Significant decreases were observed only in the South, where adjusted analyses revealed decreases in circumcision overall (P for trend = .007) and among hospitalizations with Medicaid (P for trend = .005) but not those with private insurance (P for trend = .13). Newborn male birth hospitalizations covered by Medicaid increased from 36.0% (2000) to 50.1% (2010; P for trend < .001), suggesting 390,000 additional circumcisions might have occurred nationwide had insurance coverage remained constant. CONCLUSIONS: Shifts in insurance coverage, particularly toward Medicaid, likely contributed to decreases in newborn circumcision nationwide and in the South. Barriers to the availability of circumcision should be revisited, particularly for families who desire but have less financial access to the procedure.

Eliminating preventable HIV-related maternal mortality in sub-Saharan Africa: what do we need to know?

INTRODUCTION: HIV makes a significant contribution to maternal mortality, and women living in sub-Saharan Africa are most affected. International commitments to eliminate preventable maternal mortality and reduce HIV-related deaths among pregnant and postpartum women by 50% will not be achieved without a better understanding of the links between HIV and poor maternal health outcomes and improved health services for the care of women living with HIV (WLWH) during pregnancy, childbirth, and postpartum. METHODS: This article summarizes priorities for research and evaluation identified through consultation with 30 international researchers and policymakers with experience in maternal health and HIV in sub-Saharan Africa and a review of the published literature. RESULTS: Priorities for improving the evidence about effective interventions to reduce maternal mortality and improve maternal health among WLWH include better quality data about causes of maternal death among WLWH, enhanced and harmonized program monitoring, and research and evaluation that contributes to improving: (1) clinical management of pregnant and postpartum WLWH, including assessment of the impact of expanded antiretroviral therapy on maternal mortality and morbidity, (2) integrated service delivery models, and (3) interventions to create an enabling social environment for women to begin and remain in care. CONCLUSIONS: As the global community evaluates progress and prepares for new maternal mortality and HIV targets, addressing the needs of WLWH must be a priority now and after 2015. Research and evaluation on maternal health and HIV can increase collaboration on these 2 global priorities, strengthen political constituencies and communities of practice, and accelerate progress toward achievement of goals in both areas.

Complications of cesarean deliveries among HIV-infected women in the United States.

OBJECTIVE: To compare rates of complications associated with cesarean delivery in HIV-infected and HIV-uninfected women in the United States and to investigate trends in such complications across four study cycles spanning the implementation of HAART in the United States (1995-1996, 2000-2001, 2005-2006, 2010-2011). DESIGN: The Nationwide Inpatient Sample from the Healthcare Cost and Utilization Project is the largest all-payer hospital inpatient care database in the United States; when weighted to account for the complex sampling design, nationally representative estimates are derived. After restricting the study sample to women aged 15-49 years, our study sample consisted of approximately 1 090 000 cesarean delivery hospitalizations annually. METHODS: Complications associated with cesarean deliveries were categorized as infection, hemorrhage, or surgical trauma, based on groups of specific International Classification of Diseases 9th revision codes. Length of hospitalization, hospital charges, and in-hospital deaths were also examined. RESULTS: The rate of complications significantly decreased during the study periods for HIV-infected and HIV-uninfected women. However, rates of infectious complications and surgical trauma associated with cesarean deliveries remained higher among HIV-infected, compared with HIV-uninfected women in 2010-2011, as did prolonged hospital stay and in-hospital deaths. Length of hospitalization decreased over time for cesarean deliveries of HIV-infected women to a greater extent compared with HIV-uninfected women. CONCLUSION: In the United States, rates of cesarean delivery complications decreased from 1995 to 2011. However, rates of infection, surgical trauma, hospital deaths, and prolonged hospitalization are still higher among HIV-infected women. Clinicians should remain alert to this persistently increased risk of cesarean delivery complications among HIV-infected women.

Relationship between social cognitive theory constructs and self-reported condom use: assessment of behaviour in a subgroup of the Safe in the City trial.

OBJECTIVES: Previous studies have found social cognitive theory (SCT)-framed interventions are successful for improving condom use and reducing sexually transmitted infections (STIs). We conducted a secondary analysis of behavioural data from the Safe in the City intervention trial (2003-2005) to investigate the influence of SCT constructs on study participants' self-reported use of condoms at last intercourse. METHODS: The main trial was conducted from 2003 to 2005 at three public US STI clinics. Patients (n=38,635) were either shown a 'safer sex' video in the waiting room, or received the standard waiting room experience, based on their visit date. A nested behavioural assessment was administered to a subsample of study participants following their index clinic visit and again at 3 months follow-up. We used multivariable modified Poisson regression models to examine the relationships among SCT constructs (sexual self-efficacy, self-control self-efficacy, self-efficacy with most recent partner, hedonistic outcome expectancies and partner expected outcomes) and self-reported condom use at last sex act at the 3-month follow-up study visit. RESULTS: Of 1252 participants included in analysis, 39% reported using a condom at last sex act. Male gender, homosexual orientation and single status were significant correlates of condom use. Both unadjusted and adjusted models indicate that sexual self-efficacy (adjusted relative risk (RRa)=1.50, 95% CI 1.23 to 1.84), self-control self-efficacy (RRa=1.67, 95% CI 1.37 to 2.04), self-efficacy with most recent partner (RRa=2.56, 95% CI 2.01 to 3.27), more favourable hedonistic outcome expectancies (RRa=1.83, 95% CI 1.54 to 2.17) and more favourable partner expected outcomes (RRa=9.74, 95% CI 3.21 to 29.57) were significantly associated with condom use at last sex act. CONCLUSIONS: Social cognitive skills, such as self-efficacy and partner expected outcomes, are an important aspect of condom use behaviour. TRIAL REGISTRATION NUMBER: clinicaltrials.gov (NCT00137370).

Socioeconomic disadvantage as a social determinant of teen childbearing in the U.S.

OBJECTIVES: We reviewed the literature focused on socioeconomic influences on teen childbearing and suggested directions for future research and practice related to this important indicator of teen sexual health. METHODS: We conducted an electronic search of Medline, ERIC, PsychLit, and Sociological Abstracts databases for articles published from January 1995 to November 2011. Selected articles from peer-reviewed journals included original quantitative analyses addressing socioeconomic influences on first birth among teen women in the U.S. Articles were abstracted for key information, ranked for quality according to the U.S. Preventive Services Task Force guidelines, assessed for bias, and synthesized. RESULTS: We selected articles with a range of observational study designs. Risk for bias varied across studies. All 12 studies that considered socioeconomic factors as influences on teen childbearing (vs. moderators or mediators of other effects) reported at least one statistically significant association relating low socioeconomic status, underemployment, low income, low education levels, neighborhood disadvantage, neighborhood physical disorder, or neighborhood-level income inequality to teen birth. Few reports included any associations contradicting this pattern. CONCLUSIONS: This review suggests that unfavorable socioeconomic conditions experienced at the community and family levels contribute to the high teen birth rate in the U.S. Future research into social determinants of sexual health should include multiple levels of measurement whenever possible. Root causes of teen childbearing should be evaluated in various populations and contexts. Interventions that address socioeconomic influences at multiple levels could positively affect large numbers of teens and help eliminate disparities in teen childbearing.

Contraceptive availability during an emergency response in the United States.

This article provides the evidence for contraceptive need to prevent unintended pregnancy during an emergency response, discusses the most appropriate types of contraceptives for disaster situations, and details the current provisions in place to provide contraceptives during an emergency response.

Trends in hospitalizations with psychiatric diagnoses among HIV-infected women in the USA, 1994-2004.

Psychiatric illnesses commonly co-occur with HIV infection and such illnesses have been linked to women's poorer medication adherence and suicide. Using hospital discharge data from the 1994-2004 Nationwide Inpatient Sample, we conducted this study to describe hospitalizations with psychiatric diagnoses from 1994 through 2004 and evaluate the association of specific psychiatric disorders among hospitalized HIV-infected women in the USA with their lack of adherence to medical treatment and suicide attempt. Multivariable logistic regression analyses were used to examine trends in hospitalizations with psychiatric diagnoses among nonpregnant HIV-infected women and the association between specific disorders and women's lack of adherence to medical treatment and suicide attempt. Between 1994 and 2004, the estimated number of all hospitalizations among nonpregnant HIV-infected women increased by 8%, while the number of hospitalizations with a psychiatric diagnosis in this population increased by 73%. After adjusting for demographic factors and alcohol/substance abuse, we found that HIV-infected women were more likely to be hospitalized for mood (odds ratio (OR): 2.35; 95% confidence interval (CI): 1.93-2.88), anxiety (OR: 2.24, 95%CI: 1.74-2.88), and psychotic (OR: 1.45, 95%CI: 1.10-1.90) disorders in 2004 than in 1994. There was a significant association of alcohol/substance abuse with mood, adjustment, anxiety, personality, and psychotic disorders. Noncompliance with medical treatment was significantly associated with psychotic disorders, whereas suicide attempt/self-inflicted injury was significantly associated with mood, adjustment, anxiety, personality, and psychotic disorders. The number of hospitalizations with a psychiatric diagnosis among HIV-infected women in the USA has increased substantially. As HIV-infected women live longer, these results highlight the need for targeted public health interventions to address mental health issues in this population.

Hospitalizations with amphetamine abuse among pregnant women.

OBJECTIVE: To examine trends in pregnancy hospitalizations with a diagnosis of amphetamine or cocaine abuse and the prevalence of associated medical complications. METHODS: Data were obtained from the Nationwide Inpatient Sample. Hospitalization ratios per 100 deliveries for amphetamine or cocaine abuse from 1998 to 2004 were tested for linear trends. Amphetamine-abuse hospitalizations were compared with cocaine-abuse hospitalizations and non-substance-abuse hospitalizations. A chi2 analysis was used to compare hospitalization characteristics. Conditional probabilities estimated by logistic regression were used to calculate adjusted prevalence ratios for each medical diagnosis of interest. RESULTS: From 1998 to 2004, the hospitalization ratio for cocaine abuse decreased 44%, whereas the hospitalization ratio for amphetamine abuse doubled. Pregnancy hospitalizations with a diagnosis of amphetamine abuse were geographically concentrated in the West (82%), and were more likely to be among women younger than 24 years than the cocaine-abuse or non-substance-abuse hospitalizations. Most medical conditions were more prevalent in the amphetamine-abuse group than the non-substance-abuse group. When the substance abuse groups were compared with each other, obstetric diagnoses associated with infant morbidity such as premature delivery and poor fetal growth were more common in the cocaine-abuse group, whereas vasoconstrictive effects such as cardiovascular disorders and hypertension complicating pregnancy were more common in the amphetamine-abuse group. CONCLUSION: As pregnancy hospitalizations with a diagnosis of amphetamine abuse continue to increase, clinicians should familiarize themselves with the adverse consequences of amphetamine abuse during pregnancy and evidence-based guidelines to deal with this high-risk population. LEVEL OF EVIDENCE: III.

Cesarean delivery for HIV-infected women: recommendations and controversies.

Two studies that were published in 1999 demonstrated that cesarean delivery before labor and before the rupture of membranes (elective cesarean delivery) reduces the risk of mother-to-child transmission of the human immunodeficiency virus (HIV). On the basis of these results, the American College of Obstetricians and Gynecologists and the US Public Health Service recommend that HIV-infected pregnant women with plasma viral loads of >1000 copies per milliliter be counseled regarding the benefits of elective cesarean delivery. Since the release of these guidelines, the cesarean delivery rate among HIV-infected women in the United States has increased dramatically. Major postpartum morbidity is uncommon, and cesarean delivery among HIV-infected women is relatively safe and cost-effective. However, a number of important questions remain unanswered, including whether cesarean delivery has a role among HIV-infected women with low plasma viral loads or who receive combination antiretroviral regimens.

Hospitalizations of pregnant HIV-infected women in the United States in the era of highly active antiretroviral therapy (HAART).

Highly active antiretroviral therapy (HAART) has improved the outlook of HIV-infected patients, but it has several side effects, particularly when it is used during pregnancy. Prior to the advent of HAART, HIV-infected women were at increased risk for adverse pregnancy outcomes. This report describes hospital use among pregnant HIV-infected women in the United States in the HAART era and compares hospitalizations for select morbidities in pregnant HIV-infected vs. uninfected women. In 2003, the majority of HIV-infected pregnant women were hospitalized in urban hospitals in the South and had Medicare or Medicaid as the expected payer. HIV-infected pregnant women had longer hospitalizations and incurred higher hospitalization charges than uninfected women. In addition, HIV-infected pregnant women were more likely to be hospitalized for major puerperal sepsis, sexually transmitted infections, urinary tract infections, bacterial infections, liver disorders, and preterm labor/delivery than uninfected women, even after adjusting for sociodemographic factors and comorbid conditions. No significant differences were observed in the rates of preeclampsia and antepartum hemorrhage in the two groups. HIV-infected pregnant women in the United States in the era of HAART remain at higher risk for several morbidities and adverse obstetrical outcomes than uninfected women.

Hospitalizations of pregnant HIV-infected women in the USA prior to and during the era of HAART, 1994-2003.

BACKGROUND: The literature on whether HIV infection and its complex antiretroviral treatments confer a higher risk for adverse pregnancy outcomes is controversial. OBJECTIVE: We compared rates of hospitalization for select morbidities among HIV-infected and uninfected pregnant women in the USA. DESIGN AND METHODS: Using data from the 1994-2003 Nationwide Inpatient Sample, we used descriptive statistics and multivariate logistic regression to examine socio-demographic characteristics, morbidity outcomes and time trends. RESULTS: There were approximately 6000 hospitalizations per year of HIV-infected pregnant women in the USA. HIV-infected women were more likely to be hospitalized in urban hospitals, in the South, have Medicaid as the expected payer, have longer hospitalizations and incur higher charges than uninfected women. Hospitalizations for major puerperal sepsis, genitourinary infections, influenza, bacterial infections, preterm labor/delivery, and liver disorders were more frequent among pregnant HIV-infected women than their uninfected counterparts. However, rates of pre-eclampsia and antepartum hemorrhage were not significantly different. While rates of inpatient mortality and various infectious conditions decreased between 1994 and 2003, the rate of gestational diabetes increased among HIV-infected pregnant women. CONCLUSIONS: HIV-infected pregnant women in the USA continue to be at higher risk for morbidity and adverse obstetric outcomes. With the introduction of antiretroviral therapy, rates of most of the conditions examined have either decreased or remained stable, hence current antiretroviral regimens do not seem to be associated with major adverse pregnancy outcomes on a population basis. The increase in gestational diabetes among HIV-infected women may be associated, in part, with antiretroviral therapy and merits further attention.

National estimates of hospital use by children with HIV infection in the United States: analysis of data from the 2000 KIDS Inpatient Database.

OBJECTIVES: The purpose of this research was to describe hospital use patterns of HIV-infected children in the United States. STUDY DESIGN: We analyzed a nationwide, stratified probability sample of 2.5 million hospital discharges of children and adolescents during the year 2000, weighted to 7.3 million discharges nationally. We excluded discharges after hospitalizations related to pregnancy/childbirth and their complications and discharges of neonates <1 month of age and of patients >18 years of age. Diagnoses were identified through the use of the Clinical Classification Software with grouping of related diagnoses. RESULTS: We estimated that there were 4107 hospitalizations of HIV-infected children in 2000 and that these hospitalizations accounted for approximately dollar 100 million in hospital charges and >30000 hospital days. Infections, including sepsis and pneumonia, were among the most frequent diagnoses in such hospitalizations, followed by diagnoses related to gastrointestinal conditions, nutritional deficiencies and anemia, fluid/electrolyte disorders, central nervous system disorders, cardiovascular disorders, and respiratory illnesses. Compared with hospitalizations of non-HIV-infected children, hospitalizations of HIV-infected ones were more likely to be in urban areas, in pediatric/teaching hospitals, and in the Northeast, and the expected payer was more likely to be Medicaid (77.6% vs 37.2%). Compared with children without HIV, those with HIV tended to be older (median age: 9.5 years vs 5.2 years), to have been hospitalized longer (mean: 7.8 days vs 3.9 days), and to have incurred higher hospital costs (mean: dollar 23221 vs dollar 11215); HIV-associated hospitalizations ended in the patient's death more frequently than non-HIV ones (1.8% vs 0.4%), and complications of medical care were also more common (10.8% vs 6.2%). CONCLUSIONS: Infections account for the majority of hospitalizations of HIV-infected children in the United States, although nutritional deficiencies, anemia and other hematologic disorders, gastrointestinal and renal disorders, and complications of medical care are also more common among hospitalized children with HIV than among those without HIV.