A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine.

BACKGROUND: Intrapartum single-dose (SD) nevirapine (NVP) reduces perinatal transmission of human immunodeficiency virus (HIV) infection but selects for NVP-resistant virus, which compromises subsequent NVP-based therapy. A 1-week "tail" of lamivudine and zidovudine after SD-NVP decreases the risk of resistance. We hypothesized that increasing the duration or potency of the tail would further reduce this risk to <10%, using a sensitive assay to measure resistance. METHODS: HIV-infected pregnant Thai women with a CD4 cell count >250 cells/µL, most receiving zidovudine, were randomized at 28-38 weeks gestation to receive 1 of 3 intrapartum and postpartum regimens: (A) zidovudine plus enteric-coated didanosine plus lopinavir and ritonavir for 7 days, (B) zidovudine plus enteric-coated didanosine for 30 days, or (C) regimen 1 for 30 days. The incidence of NVP resistance mutations at day 10 or week 6 post partum in each arm was compared with that of a historical comparison group who received prenatal zidovudine and SD-NVP. NVP resistance was identified by consensus sequencing and a sensitive oligonucleotide ligation assay (OLA). RESULTS: At entry, the 169 participants had a median CD4 cell count of 456 cells/µL and an HIV load of 3.49 log(10) copies/mL. The incidence of mutations in each of the 3 P1032 arms was 0% by sequencing and 1.8%, 7.1%, and 5.3% by OLA in arms A, B, and C, respectively, compared with 13.4% by sequencing and 29.4% by OLA in the comparison group (P < .001 for each study arm vs comparison group). Grade 4 anemia developed in 1 woman. CONCLUSIONS: A 7-day tail of highly active combination therapy or 1 month of dual therapy after SD-NVP prevents most NVP resistance to minimal toxicity. CLINICAL TRIALS REGISTRATION: The IMPAACT P1032 Clinical Trial is NCT00109590, and the PHPT-2 Clinical Trial is NCT00398684.

A Framework for the Virtual Medical Interview Process: Considerations for the Applicant and the Interviewer.

Background: Videoconferencing platforms are being used for the purposes of interviewing in academic medicine because of the coronavirus disease 2019 pandemic. We present considerations applicable to interviewers and interviewees in the virtual space, with a focus on medical school and residency applicants. Methods: We reviewed the literature regarding the virtual interview process for medical school and residency by searching PubMed using the following keywords and terms: "interview," "academic medicine," "medical school application," "residency application," "virtual interviews," and "videoconferencing." Our search identified 701 results, from which we selected 36 articles for review. Results: The garnered information focuses on strategies for optimizing the virtual interview process from the standpoint of both the interviewer and the interviewee. We discuss the advantages and disadvantages of the virtual interview process and present recommendations. Conclusion: While the future of the interview process for medical school and residency is uncertain, virtual interviewing is a common and growing practice that will continue to be at least part of the medical interview process for years to come. Interviewers and interviewees should prepare to adapt to the evolving changes in the process.

Rapid HIV testing and obstetrical characteristics of women with unknown HIV serostatus at time of labor and delivery.

OBJECTIVE: To describe the obstetrical characteristics of women without prenatal care and/or undocumented human immunodeficiency virus (HIV) serostatus who presented for delivery and to assess the usefulness of rapid HIV screening in these women. MATERIALS AND METHODS: The study design was a retrospective analysis. Demographics, labor, delivery characteristics, and pregnancy outcomes of women without prenatal care and/or unknown HIV serostatus were reviewed. RESULTS: Three hundred fifty parturients met the inclusion criteria: 15.2% presented at complete cervical dilation, 48.6% with cervical dilation of at least 5 cm, and 43.1% with ruptured membranes. Twenty-two percent of parturients delivered within 1 hour of admission, 47.6% delivered within 4 hours of admission, and 5.5% delivered prior to arrival to the hospital. With the lengthy admission process and procurement of zidovudine from the pharmacy requiring at least 1 hour at best, 27.5% would not have the benefit of intrapartum zidovudine treatment. Single Use Diagnostic System HIV-1 rapid test was reactive and confirmed in 7 women (2.5%). CONCLUSION: Rapid HIV screening is a useful tool for guiding immediate obstetrical management and coordinated care for the neonate. In some circumstances, the full benefit of rapid HIV detection will not be realized due to advanced labor, ruptured members, or delivery prior to arrival.

Early postpartum pharmacokinetics of lopinavir initiated intrapartum in Thai women.

Lopinavir (LPV) exposure is reduced during the third trimester of pregnancy. We report the pharmacokinetics of standard LPV-ritonavir dosing (400/100 mg twice daily) in the immediate and early postpartum period when initiated during labor. In 16 human immunodeficiency virus-infected Thai women, the median (range) LPV area under the concentration-time curve and maximum and minimum concentrations in plasma were 99.7 (66.1 to 180.5) microg x h/ml, 11.2 (8.0 to 17.5) microg/ml, and 4.6 (1.7 to 12.5) microg/ml, respectively, at 41 (12 to 74) h after delivery. All of the women attained adequate LPV levels through 30 days postpartum. No serious adverse events were reported.

Rapid human immunodeficiency virus testing in obstetric outpatient settings: the MIRIAD study.

OBJECTIVE: To evaluate the acceptability and feasibility of rapid human immunodeficiency virus testing in obstetric outpatient settings. STUDY DESIGN: The Mother-Infant Rapid Intervention at Delivery (MIRIAD) study was a prospective, multicenter study. Women were offered rapid and conventional human immunodeficiency virus testing if they presented to outpatient settings late in pregnancy with undocumented human immunodeficiency virus status. We compared median times between conventional and rapid testing and between rapid point-of-care and rapid laboratory-based testing. RESULTS: Among eligible women who were offered participation, 90% accepted testing. The median time from blood draw to result available was faster for rapid testing (25 minutes) than conventional testing (23 hours; P < .0001). For rapid tests, point-of-care testing was faster than laboratory-based testing (24 minutes vs 35 minutes; P < .0001). Almost 96% of rapid test results were available within 1 hour. CONCLUSION: Rapid human immunodeficiency virus testing is acceptable, feasible, and provides results far sooner than conventional testing in obstetric outpatient settings.

Primary human immunodeficiency virus infection during pregnancy detected by repeat testing.

OBJECTIVE: The purpose of this study was to describe characteristics of pregnant women with newly acquired human immunodeficiency virus (HIV) infection that was identified by repeat testing. STUDY DESIGN: The Centers for Disease Control and Prevention-sponsored Mother-Infant Rapid Intervention at Delivery (MIRIAD) study, which was conducted in 6 US cities, encouraged repeat HIV testing during pregnancy to identify primary infections. RESULTS: Fifty-four HIV-infected women were identified. Four primary HIV infections were recognized, with median estimated seroconversion at 22 weeks of gestation. All 4 women denied new sex partners, alcohol, and illegal drug use during pregnancy. Three of the 4 mother-infant pairs received antiretroviral medications. One infant was infected perinatally, with positive HIV DNA polymerase chain reaction at birth. Questionnaire data identified 2 additional women with HIV that was likely acquired during pregnancy (identified by rapid testing at labor and delivery), which suggests that 6 of 54 HIV-infected women (11%) in the MIRIAD study had primary infection during pregnancy. CONCLUSION: Repeat HIV testing in pregnancy can identify opportunities for antiretroviral prophylaxis and should be used in areas of high HIV prevalence.

Rapid human immunodeficiency virus-1 testing on labor and delivery in 17 US hospitals: the MIRIAD experience.

The objective of the study was to evaluate the feasibility, acceptability, and accuracy of rapid human immunodeficiency virus (HIV) testing during labor. The Mother-Infant Rapid Intervention at Delivery (MIRIAD) study was a prospective, multicenter study that offered voluntary, rapid HIV testing to women with undocumented HIV status at 17 hospitals in 6 cities. Of 12,481 eligible women, 74% were approached for participation and 85.5% of those approached accepted rapid HIV testing. Among 7753 women tested, MIRIAD identified 52 (0.7%) HIV-infected women. The time between obtaining the blood sample for the rapid test and reporting the results to the health care provider was shorter for hospitals utilizing point-of-care testing than in hospitals utilizing laboratory-based testing (30 minutes vs 68 minutes; P < .0001), and point-of-care testing strategies were 14 times more likely to have a short turnaround as laboratory testing strategies. Routine rapid testing during labor provides a feasible, acceptable, and accurate way to identify HIV-infected women before delivery.

Characteristics and management of HIV-1-infected pregnant women enrolled in a randomised trial: differences between Europe and the USA.

BACKGROUND: Rates of mother-to-child transmission of HIV-1 (MTCT) have historically been lower in European than in American cohort studies, possibly due to differences in population characteristics. The Pediatric AIDS Clinical Trials Group Protocol (PACTG) 316 trial evaluated the effectiveness of the addition of intrapartum/neonatal nevirapine in reducing MTCT in women already receiving antiretroviral prophylaxis. Participation of large numbers of pregnant HIV-infected women from the US and Western Europe enrolling in the same clinical trial provided the opportunity to identify and explore differences in their characteristics and in the use of non-study interventions to reduce MTCT. METHODS: In this secondary analysis, 1350 women were categorized according to enrollment in centres in the USA (n = 978) or in Europe (n = 372). Factors associated with receipt of highly active antiretroviral therapy and with elective caesarean delivery were identified with logistic regression. RESULTS: In Europe, women enrolled were more likely to be white and those of black race were mainly born in Sub-Saharan Africa. Women in the US were younger and more likely to have previous pregnancies and miscarriages and a history of sexually transmitted infections. More than 90% of women did not report symptoms of their HIV infection; however, more women from the US had symptoms (8%), compared to women from Europe (4%). Women in the US were less likely to have HIV RNA levels <400 copies/ml at delivery than women enrolling in Europe, and more likely to receive highly active antiretroviral therapy, and to start therapy earlier in pregnancy. The elective caesarean delivery rate in Europe was 61%, significantly higher than that in the US (22%). Overall, 1.48% of infants were infected and there was no significant difference in the rate of transmission between Europe and the US despite the different approaches to treatment and delivery. CONCLUSION: These findings confirm that there are important historical differences between the HIV-infected pregnant populations in Western Europe and the USA, both in terms of the characteristics of the women and their obstetric and therapeutic management. Although highly active antiretroviral therapy predominates in pregnancy in both settings now, population differences are likely to remain. TRIAL REGISTRATION: NCT00000869.

Initial and repeat testing for chlamydia during pregnancy.

OBJECTIVE: This study was done to evaluate the prevalence of chlamydia in late pregnancy after an initial negative test. METHODS: This retrospective cohort study reports prenatal patients entering care between January 1998 and May 2000 at an inner city community based clinic (n = 752). Patients were evaluated if results of initial and late tests (34 weeks gestational age) for chlamydia were known. Charts were abstracted for demographic and pregnancy-related factors. Analysis for categorized data was by chi-squares and odds ratios. Continuous data were analyzed by t-test. Significance was accepted if p < 0.05. RESULTS: The prevalence of chlamydia was 17.8%, with 3.9% having only the second test positive. Treatment failure and/or reinfection were found in 13.3%. Factors correlated with chlamydial carriage include: age 19 years (p < 0.001), gonorrheal carriage (p < 0.001), lower gravidity (p < 0.01), lower parity (p < 0.05), and never having married (p < 0.001). Logistic regression identified gonorrheal carriage and age 19 years as important for both initial and late chlamydial cervicitis. Marital status was important for initial tests only. CONCLUSIONS: In our high-risk population, repeat testing for chlamydia in late pregnancy was found appropriate.

The challenges of informed consent for rapid HIV testing in labor.

BACKGROUND: Although increasing attention has been focused on the adequacy of the informed consent process for participation in research studies, there has been little systematic evaluation of the process, particularly when consent is obtained in the labor and delivery setting. The Mother Infant Rapid Intervention at Delivery (MIRIAD) study is an ongoing multisite study initiated by the Centers for Disease Control and Prevention (CDC) designed to evaluate the feasibility of offering 24-hour counseling and voluntary rapid HIV testing and antriretroviral therapy when indicated to women with unknown HIV status who are in labor. METHODS: To address concerns about obtaining informed consent from women in labor, we have completed focus groups, conducted a pilot of the informed consent process among women in labor, developed flip-charts to enhance comprehension, and plan an ongoing evaluation of the informed consent process throughout the course of the MIRIAD study. RESULTS: In the pilot study, approximately 70% of women were able to state in their own words the purpose and benefits of the research study. Substantially fewer women (25%) were able to state one or more risks of the study. CONCLUSIONS: We hope that the MIRIAD study will make a valuable contribution by defining best approaches for informed consent and will provide guidance when it is necessary to obtain consent from laboring women for crucial interventions.

Rapid HIV-1 testing during labor: a multicenter study.

CONTEXT: Timely testing of women in labor with undocumented human immunodeficiency virus (HIV) status could enable immediate provision of antiretroviral prophylaxis. OBJECTIVES: To determine the feasibility and acceptance of rapid HIV testing among women in labor and to assess rapid HIV assay performance. DESIGN, SETTING, AND PATIENTS: The Mother-Infant Rapid Intervention At Delivery (MIRIAD) study implemented 24-hour counseling and voluntary rapid HIV testing for women in labor at 16 US hospitals from November 16, 2001, through November 15, 2003. A rapid HIV-1 antibody test for whole blood was used. MAIN OUTCOME MEASURES: Acceptance of HIV testing; sensitivity, specificity, and predictive value of the rapid test; time from blood collection to patient notification of results. RESULTS: There were 91,707 visits to the labor and delivery units in the study, 7381 of which were by eligible women without documentation of HIV testing. Of these, 5744 (78%) women were approached for rapid HIV testing and 4849 (84%) consented. HIV-1 test results were positive for 34 women (prevalence = 7/1000). Sensitivity and specificity of the rapid test were 100% and 99.9%, respectively; positive predictive value was 90% compared with 76% for enzyme immunoassay (EIA). Factors independently associated with higher test acceptance included younger age, being black or Hispanic, gestational age less than 32 weeks, and having had no prenatal care. Lower acceptance was associated with being admitted between 4 pm and midnight, particularly on Friday nights, but this may be explained in part by fewer available personnel. Median time from blood collection to patient notification of result was 66 minutes (interquartile range, 45-120 minutes), compared with 28 hours for EIA (P<.001). CONCLUSIONS: Rapid HIV testing is feasible and delivers accurate and timely test results for women in labor. It provides HIV-positive women prompt access to intrapartum and neonatal antiretroviral prophylaxis, proven to reduce perinatal HIV transmission, and may be particularly applicable to higher-risk populations.

Prevalence of HIV among women entering labor who accepted or declined voluntary counseling and testing.

OBJECTIVE: To assess whether there was a difference in HIV seroprevalence between eligible women who declined and those who agreed to participate in a study of voluntary counseling and testing among women entering labor with unknown HIV status in South Africa. METHODS: Anonymous cord blood specimens were collected-as dried blood spots-from all women approached for participation in a cluster-randomized trial. No patient identifiers were included on the cord blood specimens. The dried blood spots were analyzed for HIV antibody via enzyme immunoassay and western blotting. RESULTS: Of 7238 women screened for study participation, 1041 (14.4%) had undocumented HIV status; of these women, 542 were eligible for inclusion and 343 enrolled. Based on 513 evaluable samples, the overall seroprevalence was 13.3% (95% confidence interval [CI], 10.4-16.5), which was similar to the 13.1% (95% CI, 9.7-17.2) seroprevalence among the 343 enrolled women. CONCLUSION: Seroprevalence among eligible women was similar to that among enrolled women, which indicates that study participation did not select for a group with an HIV seroprevalence substantially different from that among women who declined to enroll.

Various viral compartments in HIV-1-infected mothers contribute to in utero transmission of HIV-1.

Perinatal HIV transmission occurs in utero or intrapartum. The mechanisms and timing of transmission are not clearly understood. To compare the genetic sequences of the V3 envelope region of infant's plasma HIV to that of the mother's plasma, peripheral blood mononuclear cells (PBMC) and vaginal secretions, and correlate with timing of transmission. All 3 infants had a positive HIV PCR in the first days of life, thus classified as in utero infections. In the first mother-infant pair, two different variants were present in the infant, one correlating with maternal PBMC virus and highly homologous to virus from vaginal secretions and the other identical to sequences in maternal plasma. In the second pair, the infant plasma virus was similar to that of maternal PBMC. In the third pair, the cord blood and infant plasma virus were highly similar to maternal vaginal virus. The presence of more than one HIV variant from the maternal blood and from the vaginal compartment in the cord blood of infants presumably infected in utero could point to more than one episode of transmission or, alternatively, to transmission of PBMC virus.

Rapid intrapartum or postpartum HIV testing at a midwife obstetric unit and a district hospital in South Africa.

OBJECTIVE: To compare the prepartum and postpartum feasibility and acceptance of voluntary counseling and rapid testing (VCT) among women with unknown HIV status in South Africa. METHODS: Eligible women were randomized according to the calendar week of presentation to receive VCT either while in labor or after delivery. RESULTS: Of 7238 women approached, 542 (7.5%) were eligible, 343 (63%) were enrolled, and 45 (13%) were found to be HIV infected. The proportions of eligible women who accepted VCT were 66.8% (161 of 241) in the intrapartum arm and 60.5% (182 of 301) in the postpartum arm, and the difference of 6.3% (95% CI, -1.8% to 14.5%) was not significant. The median times (44 and 45 minutes) required to conduct VCT were also similar in the 2 arms. In the intrapartum arm, all women in true labor received their test results before delivery and all those found to be HIV positive accepted prophylaxis with nevirapine before delivery. CONCLUSIONS: Rapid testing in labor wards for women with an unknown HIV status is feasible and well accepted, and allows for a more timely antiretroviral prophylaxis than postpartum testing.

Correlates of prenatal HIV testing in women with undocumented status at delivery.

OBJECTIVE: To determine factors associated with prenatal HIV testing in women who accepted rapid testing at delivery. METHODS: The mother-infant rapid intervention at delivery (MIRIAD) protocol offered counseling and voluntary HIV testing in six US cities including New York City (NYC). These hospitals are required to document the HIV status of pregnant women or their infants. From January 2002 to January 2005, 653 HIV-negative women were interviewed post-partum. RESULTS: 63% of women reported prior HIV testing during the index pregnancy, although their results were not available at delivery. Multivariate logistic modeling identified receipt of prenatal care and delivery in NYC as being associated with having been offered prenatal HIV testing. In a model restricted to women receiving medical care, emergency department (ED) use and delivery outside of NYC were associated with not having been offered testing. In a model restricted to women who were offered prenatal testing, acceptance was associated with delivery outside of NYC. CONCLUSIONS: Improved documentation of prenatal test results, expanded prenatal testing in non-traditional settings like EDs, and routine voluntary "opt-out" testing during pregnancy may further reduce perinatal HIV transmission.

Women identified with HIV at labor and delivery: testing, disclosing and linking to care challenges.

OBJECTIVE: To determine if women with undocumented HIV status in late pregnancy or at labor and delivery who are rapidly tested and identified as HIV infected have high-risk behaviors and psychosocial obstacles hindering postpartum follow-up. METHODS: Consenting participants (women with undocumented HIV status and > or =24 weeks gestational age (GA) and imminent delivery or > or =34 weeks GA) in 6 cities were rapidly tested and interviewed. HIV-positive women were offered follow-up. RESULTS: From 2001-2005, 54 HIV-infected women were identified: median age 26 years; 91% African American; 11 (20%) lost custody of their infants; 30 (56%) knew they or their partner were HIV-infected, but had no antenatal HIV care; 25 met criteria for starting antiretroviral therapy. Comparison between 48 HIV-infected and 130 HIV-negative women, tested and interviewed at the same hospitals, showed HIV-infected women more likely to be African American (P < .01) and report no prenatal care (P < .001), use street drugs (P < .01), have unstable residency (P < .05), not live with the father of their infant (P < .001), and have children in foster care (P < .01). Sixteen women (30%) and 17 (31%) infants did not remain in follow-up study due to relocation, child protective custody, and psychosocial issues including frequent substance use. CONCLUSION: Over half of HIV-infected women knew they or their partner were infected with HIV, but did not initially disclose their status. Increased support services and substance abuse treatment are critical to facilitate better continuity of care for these socially marginalized women.

Initial and repeated screening for gonorrhea during pregnancy.

BACKGROUND AND GOAL: Late pregnancy rescreening is advised for at-risk patients, but data supporting this recommendation are lacking. The intent of this study was to determine the value of a late-pregnancy test for gonorrhea after a negative initial test at the beginning of prenatal care. STUDY DESIGN: A retrospective chart review of clinic records over a 29-month period identified patients with a positive DNA direct assay for gonorrhea either initially or at 34 weeks. RESULTS: Of 751 women, 38 (5.1%) had gonorrhea diagnosed at their first testing; 19 women (2.5%) were positive only at their second screening. For one patient, both tests were positive. CONCLUSION: Repeating screening for gonorrhea at 34 weeks in a high-prevalence population is warranted.

Maternal toxicity and pregnancy complications in human immunodeficiency virus-infected women receiving antiretroviral therapy: PACTG 316.

OBJECTIVE: The purpose of this study was to evaluate rates of maternal toxicity, pregnancy complications, and peripartum morbidity by type and duration of antiretroviral therapy (ART) during pregnancy. STUDY DESIGN: The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 316 (PACTG 316) study evaluated the addition of intrapartum/neonatal nevirapine to background ART to reduce perinatal transmission of human immunodeficiency virus-1 (HIV-1). For this secondary analysis, women were categorized into one of six groups on the basis of ART during pregnancy (monotherapy [monoRx], combination without protease inhibitor [PI], combination with PI), and start time (early: before or during first trimester; late: second or third trimester). RESULTS: One thousand four hundred seven women were included: 288 monoRx late, 34 monoRx early, 327 combo, no PI late, 175 combo, no PI early, 320 combo, PI late, and 263 combo, PI early. Symptoms and laboratory abnormalities of moderate grade or more occurred in less than 5% of women. Only gestational diabetes (highest in combo PI early) varied significantly by therapy group. CONCLUSION: In HIV-infected women receiving prenatal care and ART, adverse events were uncommon.

The impact of race/ethnicity on mother-to-child HIV transmission in the United States in Pediatric AIDS Clinical Trials Group Protocol 316.

The present analysis was designed to determine whether race/ethnicity was independently associated with mother-to-child HIV-1 transmission risk in subjects enrolled in a trial of 2-dose intra-partum nevirapine in combination with standard antiretroviral therapy and to determine what factors, including race/ethnicity, predicted maternal viral suppression at the time of delivery. Women enrolled in Pediatric AIDS Clinical Trials Group (PACTG) 316 from sites in the United States and Puerto Rico were included. Distribution of selected maternal disease and treatment characteristics was assessed by race/ethnicity category. Logistic regression models were fit to evaluate possible association of factors with HIV transmission and with viral load at delivery. Variables associated with the outcome at P < 0.05 level were retained in the final models. Of 1052 women randomized at PACTG sites, 891 were included in the present analysis: 572 (64%) were black; 206 (23%) were Hispanic; and 113 (13%) were white. All women who had infected infants were black or Hispanic (11/572 and 3/206, respectively), whereas none of the women identified as white had an infected infant (0/113). This difference was not statistically significant (P = 0.54). White women had higher entry CD4 cell counts and lower HIV-1 RNA at delivery than women of other races/ethnicities. Black and Hispanic women were more likely than white women to start therapy during their current pregnancy but did not initiate prenatal care later. In bivariate models that included antiretroviral type and variables that had values of P < or = 0.25 in univariate analysis, time of antiretroviral initiation, time of prenatal care initiation, and race/ethnicity each retained significance in predicting viral suppression at delivery. Race/ethnicity remained predictive of viral suppression at delivery in a multivariate model incorporating all of these variables (P = 0.01). Higher HIV-1 RNA and lower CD4 cell counts in women identified as black or Hispanic have significant implications for the health of these women and their newborns. Race/ethnicity is significant in predicting viral suppression at the time of delivery.