A Randomized Trial of Point-of-Care Early Infant Human Immunodeficiency Virus (HIV) Diagnosis in Zambia.

BACKGROUND: Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART). METHODS: We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months. RESULTS: Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22-30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6-2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15-34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16-43%) infants in the POC group vs 7 (19%; 6-32%) in the SOC group (RR: 1.56; .7-3.50). CONCLUSIONS: POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes. CLINICAL TRIALS REGISTRATION: This trial is registered at https://clinicaltrials.gov (NCT02682810).

Maternal Decision-Making and Uptake of Health Services for the Prevention of Mother-to-Child HIV Transmission: A Secondary Analysis.

Objectives We investigated whether a woman's role in household decision-making was associated with receipt of services to prevent mother-to-child HIV transmission (PMTCT). Methods We conducted a secondary analysis of the PEARL study, an evaluation of PMTCT effectiveness in Cameroon, Cote d'Ivoire, South Africa, and Zambia. Our exposure of interest was the women's role (active vs. not active) in decision-making about her healthcare, large household purchases, children's schooling, and children's healthcare (i.e., four domains). Our primary outcomes were self-reported engagement at three steps in PMTCT: maternal antiretroviral use, infant antiretroviral prophylaxis, and infant HIV testing. Associations found to be significant in univariable logistic regression were included in separate multivariable models. Results From 2008 to 2009, 613 HIV-infected women were surveyed and provided information about their decision-making roles. Of these, 272 (44.4%) women reported antiretroviral use; 281 (45.9%) reported infant antiretroviral prophylaxis; and 194 (31.7%) reported infant HIV testing. Women who reported an active role were more likely to utilize infant HIV testing services, across all four measured domains of decision-making (adjusted odds ratios [AORs] 2.00-2.89 all p < .05). However, associations between decision-making and antiretroviral use-for both mother and infant-were generally not significant. An exception was active decision-making in a woman's own healthcare and reported maternal antiretroviral use (AOR 1.69, p < 0.05). Conclusions for Practice Associations between decision-making and PMTCT engagement were inconsistent and may be related to specific characteristics of individual health-seeking behaviors. Interventions seeking to improve PMTCT uptake should consider the type of health-seeking behavior to better optimize health services.

Racial bias in cesarean decision-making.

BACKGROUND: Category II fetal heart tracing noted during continuous external fetal monitoring is a frequent indication for cesarean delivery in the United States despite its somewhat subjective interpretation. Black patients have higher rates of cesarean delivery and higher rates for this indication. Racial bias in clinical decision-making has been demonstrated throughout medicine, including in obstetrics. OBJECTIVE: We sought to examine if racial bias affects providers' decisions about cesarean delivery for an indication of category II fetal heart tracings. STUDY DESIGN: We constructed an online survey study consisting of 2 clinical scenarios of patients in labor with category II tracings. Patient race was randomized to Black and White; the vignettes were otherwise identical. Participants had the option to continue with labor or to proceed with a cesarean delivery at 3 decision points in each scenario. Participants reported their own demographics anonymously. This survey was distributed to obstetrical providers via email, listserv, and social media. Data were analyzed using chi-square tests at each decision point in the overall sample and in subgroup analyses by various participant demographics. RESULTS: A total of 726 participants contributed to the study. We did not find significant racial bias in cesarean delivery decision-making overall. However, in a scenario of a patient with a previous cesarean delivery, Fisher's exact tests showed that providers <40 years old (n=322; P=.01) and those with <10 years of experience (n=239; P=.050) opted for a cesarean delivery for Black patients more frequently than for White patients at the first decision point. As labor progressed in this scenario, the rates of cesarean delivery equalized across patient race. CONCLUSION: Younger providers and those with fewer years of clinical experience demonstrated racial bias in cesarean delivery decision-making at the first decision point early in labor. Providers did not show racial bias as labor progressed, nor in the scenario with a patient without a previous cesarean delivery. This bias may be the consequence of provider training with the Maternal-Fetal Medicine Unit Network Vaginal Birth After Cesarean Calculator, developed in 2007, and widely used to estimate the probability of successful vaginal birth after a cesarean delivery. This calculator used race as a predictive factor until it was removed in June 2021. Future studies should investigate if this bias persists following this change, while also focusing on interventions to address these findings.

The clinical use of inflammatory markers during pregnancy.

PURPOSE OF REVIEW: There is overwhelming evidence that intrauterine infection and inflammation play an important role in the pathogenesis of spontaneous preterm labor, preterm prelabor rupture of the membranes and fetal injury resulting in long-term sequelae. Early diagnosis of subclinical infection and inflammation may therefore aid clinicians institute interventions focusing on such adverse outcomes. RECENT FINDINGS: Biomarkers of intrauterine inflammation such as interleukin-6, although sensitive, are not specific. Thus, decision to deliver remote from term because of intrauterine infection and/or inflammation should be based on clinical signs and/or bacterial culture or Gram stain of amniotic fluid. In patients with preterm contractions and intact membranes, the risk of delivery is 1% within the week following a negative fetal fibronectin in cervicovaginal secretions. This aids to decide whether antenatal steroids should be administered to patients presenting with preterm contractions between 24 and 34 weeks' gestation. Biomarkers in cervical secretions and amniotic fluid identify those who may benefit from cerclage when the cervix is shortened (<25 mm) and dilated in the second trimester. SUMMARY: So far, few interventions utilizing inflammatory biomarkers have shown clinical benefit. Future efforts should focus on the quest for accurate biomarkers that can be obtained noninvasively and allow early prediction of subclinical disease to initiate appropriate risk-specific intervention.

Point-of-Care Virologic Testing to Improve Outcomes of HIV-Infected Children in Zambia: A Clinical Trial Protocol.

INTRODUCTION: In the absence of early infant diagnosis (EID) and immediate antiretroviral therapy (ART), some 50% of untreated HIV-infected infants die before age 2. Conventional EID requires sophisticated instruments that are typically placed in centralized or reference laboratories. In low-resource settings, centralized systems often lead to result turnaround times of several months, long delays in diagnosis, and adverse outcomes for HIV-infected children. Our clinical trial tests the effectiveness of a new point-of-care (POC) diagnostic technology to identify HIV-infected infants and start providing them life-saving ART as soon as possible. METHODS AND DESIGN: The study uses a randomized, controlled design to test whether the Alere q platform for HIV DNA polymerase chain reaction (PCR) testing improves outcomes of HIV-infected children in Zambia. We aim to enroll 2867 HIV-exposed infants aged 4-12 weeks and to follow those who are HIV infected for 12 months as they receive HIV care at 6 public health facilities in Lusaka. The trial's primary endpoint is the proportion of HIV-infected infants in each study arm who start ART and remain alive, in care, and virally suppressed 12 months after their diagnostic blood draw. DISCUSSION: Our trial will provide evidence for the incremental benefit of implementing a POC EID strategy in low-resource settings where only off-site PCR services are currently available. The results will be useful in guiding future decisions regarding investments in POC virologic testing as part of overall pediatric AIDS mitigation strategies in sub-Saharan Africa. TRIAL REGISTRATION: clinicaltrials.gov NCT02682810.