Perinatal HIV Prevention Research Articles

Statewide Implementation of Universal Third-Trimester Repeat HIV Testing in Illinois.

This article aims to assess statewide uptake of HIV repeat testing in the first 2 years after the implementation of an amendment to the Illinois Perinatal HIV Prevention Act (IPHPA) mandating universal repeat HIV testing in the third trimester. This is a retrospective, population-based study of all birthing individuals in Illinois (2018-2019). Data were collected using the state-mandated closed system of perinatal HIV test reporting. We evaluated the incidence of mother-infant pairs with negative early tests and repeat third-trimester tests (RTTTs) performed in adherence with the law, as well as the timing of the performance of the RTTTs (outpatient vs. inpatient). Chi-square tests of trend by quarter were performed to ascertain sustainability. Of 138,805 individuals delivered in 2018, 80.6% presented with early test and RTTTs. In 2018, outpatient RTTTs improved from 71.8% (quarter 1) to 85.1% (quarter 4; p < 0.001). In 2018, the proportion of mother-infant dyads who received testing that was adherent to the IPHPA Amendment was 92.1, 95.5, 96.7, and 96.4% in quarters 1 through 4, respectively (p < 0.001). In 2019, outpatient RTTTs performance remained high (87.4%) and stable (p = 0.06). In 2019, 99.9% of mother-infant dyads had testing adherent to the mandate in quarters 1 through 4 (p = 0.39). Of individuals who presented without RTTTs, 93.5% (2018) and 98.8% (2019) underwent inpatient testing before delivery. Implementation of RTTTs in Illinois was rapid, successful, and sustained in its first 2 years. Public health methodologies from Illinois may benefit other states implementing RTTT programs. · In 2018, Illinois enacted statewide RTTT for HIV among all parturients.. · In 2019, over 99% of mother-infant dyads had documentation of both early and repeat HIV testing before hospital discharge.. · Implementation of repeat third-trimester HIV testing in Illinois was rapid, successful, and sustained in its first 2 years.. · Public health methodologies from Illinois may benefit other states implementing similar programs..

The Vital Role of Public Health Nurses in Perinatal HIV Prevention and Elimination.

Perinatal HIV transmission remains a significant public health challenge, with an estimated 160,000 children newly infected with HIV each year. Public health nurses play a critical role in the prevention and elimination of perinatal HIV transmission through targeted interventions such as identification of pregnant women with HIV, referral and linkage to care, provision of antiretroviral therapy, and follow-up and retention in care for both mothers and infants. However, significant barriers to successful implementation exist, including stigma and discrimination, limited access to healthcare services, socioeconomic factors, and limited resources. Addressing these barriers will require a multifaceted approach that includes policy changes, community engagement, and targeted support and resources for affected families. In this review article, we provide an overview of the epidemiology of perinatal HIV transmission, current strategies for prevention and elimination, and the vital role of public health nurses in these efforts. We will also discuss the barriers to the successful implementation of public health nurse interventions and the future directions for research and practice in this field. Ultimately, the goal of perinatal HIV prevention and elimination can only be achieved through a sustained and collaborative effort across multiple sectors and stakeholders, with public health nurses playing a crucial role in this effort.

Evaluation of State-Mandated Third Trimester Repeat HIV Testing in a Large Tertiary Care Center.

The Illinois Perinatal HIV Prevention Act was passed to ensure universal HIV testing once during pregnancy and was extended in 2018 to add third trimester repeat HIV screening. The objectives of this analysis were to describe uptake of, and patient factors associated with, third trimester repeat HIV testing at a high-volume birthing center. This is a retrospective cohort study of people who delivered at a single tertiary care hospital in Illinois during 2018. Women who delivered before 27 weeks, had an intrauterine fetal demise, a known diagnosis of HIV, or no HIV test during pregnancy were excluded. Repeat testing was defined as an HIV test at or after 27 weeks' gestation after an earlier negative HIV test during the same pregnancy. The primary outcome was the proportion of people who received repeat testing prior to delivery. Bivariable analyses were performed to identify patient characteristics associated with documentation of repeat HIV testing. Of 12,053 people eligible for inclusion, 3.4% (n = 414) presented without a documented third trimester repeat HIV test. The proportion of people with repeat testing improved from 80 to >99% in the first year. Patient factors were largely not associated with testing performance although multiparous people were more likely to have documented repeat testing. Rapid implementation of third trimester repeat HIV testing was achieved without disparity. Patient factors were largely not associated with testing performance which reinforces the goal of a universal screen to test all people equitably and effectively without bias. · Little is known about adherence to repeat third trimester HIV testing in pregnancy.. · Universal third trimester HIV screening was implemented with high uptake and without disparity.. · Protocolization of repeat HIV testing in pregnancy may reduce bias compared to risk based-screening..

Twenty years of Prevention of Mother to Child HIV Transmission: research to implementation at a national referral hospital in Uganda.

Over 90% of new paediatric HIV infections are acquired through mother to child transmission. Prevention of mother to child HIV transmission (PMTCT) research in sub-Saharan Africa informed WHO guidelines which enabled implementation of PMTCT programs globally. To describe Makerere University-Johns Hopkins University (MU-JHU) perinatal HIV prevention research and implementation of the Mulago National Referral Hospital (MNRH) PMTCT program. Perinatal HIV prevention studies conducted at MU-JHU between 1997-2016 were summarized. Program aggregated data was extracted and analyzed using STATA 15. In 1999, the HIVNET 012 study demonstrated that single-dose nevirapine (sdNVP) to the mother at onset of labor and to her newborn, reduced MTCT by nearly 50%. In 2016, the PROMISE study documented the safety and efficacy of ART during pregnancy and breastfeeding period. Program implementation at MNRH started in 2000. Uptake of HIV testing increased from 70% to 99% from 2006 onwards. sd NVP was the initial ARV regimen but by 2012, MOH recommended Option B+(triple therapy). MTCT rates reduced from 16.9% in 2001 to 2.3% in 2020. Perinatal HIV prevention clinical trials conducted at MU-JHU provided evidence to inform WHO PMTCT guidelines. MNRH program evaluation demonstrated the significant decline in MTCT rates over the last two decades.

Effect of Integrase Strand Transfer Inhibitor use on Time to HIV Viral Suppression and Viral Suppression before Delivery

Integrase strand transfer inhibitors (INSTIs) are a preferred antiretroviral (ARV) class for the prevention of perinatal HIV during pregnancy due to their ability to rapidly suppress HIV viral load and high barrier to resistance. We sought to determine if pregnant women with HIV on ARV regimens containing INSTIs achieve viral suppression faster than women taking non-INSTI ARV regimens. We sought to determine if there were differences in viral suppression at delivery between INSTI and non-INSTI regimens as well as individual INSTI drugs.

Impact of Integrase Strand Transfer Inhibitors use during Pregnancy on Viral Suppression at Delivery and Infant Outcomes: a Statewide Retrospective Cohort Study

Integrase strand transfer inhibitors (INSTIs) are a preferred antiretroviral (ARV) class for the prevention of perinatal HIV during pregnancy due to their ability to suppress HIV viral load rapidly and their high barrier to drug resistance. Our primary objective was to determine if pregnant women with HIV on ARV regimens containing INSTIs were more likely to have an undetectable HIV RNA viral load at delivery. Our secondary outcome was to determine if maternal INSTIs use increased the risk of preterm birth or low birth weight infants.

Prevention of Perinatal HIV Transmission in an Area of High HIV Prevalence in the United States

In 2014, the US Department of Health and Human Services modified the perinatal HIV management guidelines suggesting that women are considered low risk if they are living with HIV on antiretroviral therapy (ART) with HIV RNA ≤1000 copies per mL in late pregnancy and near delivery. In this population, it no longer recommended to administer maternal intrapartum intravenous zidovudine. In addition, for low-risk HIV-exposed infants (HEI), prophylaxis recommendation is 4 weeks of zidovudine after birth, whereas for high-risk HEI, it is 6 weeks of either a dual or triple therapy with zidovudine. This study was designed to help understand the use of these new perinatal HIV prevention interventions by evaluating the risk of perinatal HIV transmission in mother–infant pairs in a high HIV prevalence US area.In this study, researchers included 551 HIV-exposed infants (HEI) and 542 mothers living with HIV in the Washington, District of Columbia, area who were evaluated at Special Immunology Services in Children’s National Hospital between January 2013 and December 2017.A retrospective cohort analysis of these mother–infant pairs was completed, assessing a number of characteristics but, most notably, antiretroviral treatment during the pregnancy, HIV viral load at delivery, intrapartum zidovudine, delivery type (cesarean delivery versus vaginal), antiretroviral prophylaxis regimen for infant, antiretroviral prophylaxis duration for infant, and final HIV status of infant.The majority of mothers received antiretrovirals (95.5%), had HIV RNA ≤1000 copies per mL before delivery (81.9%), and received intrapartum zidovudine (65.5%). The majority of all HEIs were low risk (82.6); among these low-risk HEIs, slightly over one-half were delivered via cesarean delivery, and 62.9% received intrapartum zidovudine. In the study population, 9 infants acquired HIV perinatally and were all in the high-risk category, and not all of these infants were on dual or triple therapy with zidovudine.In this study, the researchers highlighted that the newer perinatal HIV recommendations have not been completely adopted because they showed 62.9% of the low-risk patients received intrapartum zidovudine, despite it no longer being recommended. Furthermore, of the 9 infants who acquired HIV perinatally, they were all considered high risk, but 6 were not on a dual or triple therapy. Certain factors can affect the decision to initiate combination antiretroviral therapy; however, in this study, it is suggested there were possible missed opportunities for use of this treatment as a prevention of perinatal HIV transmission.As the field of HIV and perinatal treatment of mother–infant pairs evolves and new recommendations emerge, it is essential the medical community strives to follow these recommendations as closely as possible to decrease perinatal HIV transmission. Adhering to the recommendations would minimize the medication exposures to those low-risk patients, while optimizing the antiretroviral regimen for high-risk HEIs, leading to the lowest perinatal HIV-transmission possible.

Ethically designing research to inform multidimensional, rapidly evolving policy decisions: Lessons learned from the PROMISE HIV Perinatal Prevention Trial.

Research in rapidly evolving policy contexts can lead to the following ethical challenges for sponsors and researchers: the study's standard of care can become different than what patients outside the study receive, there may be political or other pressure to move ahead with unproven interventions, and new findings or revised policies may decrease the relevance of ongoing studies. These ethical challenges are considerable, but not unprecedented. In this article, we review the case of a multinational, randomized, controlled perinatal HIV prevention trial, the "PROMISE" (Promoting Maternal Infant Survival Everywhere) study. PROMISE compared the relative efficacy and safety of interventions to prevent mother to child transmission of HIV. The sponsor engaged an independent international ethics panel to address controversy about the study's standard of care and relevance as national and international guidelines changed. This ethics panel concluded that continuing the PROMISE trial as designed was ethically permissible because: (1) participants in all arms received interventions that were effective, and there was insufficient evidence about whether one intervention was more effective or safer than the other, and (2) data from PROMISE could be useful for a diverse range of stakeholders. In general, trials designed to inform rapidly evolving policy issues should develop mechanisms to revisit social value while recognizing that the value of research varies for diverse stakeholders with legitimate reasons to weigh evidence differently. We conclude by providing four reasons that trials may depart from the standard of care after a change in policy, while remaining ethically justifiable, and by suggesting how to improve existing trial oversight mechanisms to address evolving social value.

Missed Opportunities for HIV Prevention in Perinatal Care Settings in the United States.

Universal opt-out HIV screening in pregnancy is an essential intervention toward eliminating perinatal HIV transmission in the US. However, it fails to identify pregnant people who are HIV negative at the time of testing but are at ongoing risk for HIV acquisition. Those of us involved in caring for women living with HIV are acutely aware of the many diagnoses of HIV that might have been prevented if only a partner had been tested for HIV or preexposure prophylaxis (PrEP) had been offered to a patient. This perspective article will review current recommendations and evidence-based interventions to evaluate missed opportunities for HIV prevention in US perinatal care settings. We identified three barriers to implementation of HIV prevention strategies during pregnancy and breastfeeding: (1) HIV risk for women is underestimated and poorly defined in clinical practice; (2) Partner testing is challenging and implementation studies in the US are lacking; and (3) PrEP remains underutilized. In March 2020, the National Perinatal HIV Hotline convened a group of clinicians and researchers specializing in perinatal HIV care to a case-based discussion of missed opportunities in perinatal HIV prevention. From our review of the literature via PubMed search as well as expert opinions gathered in this discussion, we make recommendations for addressing these barriers.

A Randomised Trial of Point-of-Care Early Infant HIV Diagnosis

Background: Early infant diagnosis (EID) of HIV is critical to the care of the 1.3 million infants who are perinatally exposed to the virus each year. Point-of-care (POC) EID provides same-day results and the potential for improved survival through immediate initiation of antiretroviral therapy (ART). Methods: We conducted a pragmatic randomised trial at 6 primary health centres in Lusaka, Zambia. HIV-exposed infants were equally allocated to either: (a) POC EID – on-site testing with the Alere q HIV-1/2 Detect instrument or (b) enhanced standard of care (SOC) EID – off-site testing at a public-sector laboratory. We provided a safety net if off-site EID results did not return within 4 weeks. Infants found to be HIV infected were immediately referred for care in the public sector and followed by the study for 12 months. Our primary outcome was programmatic success, defined as being alive, in care, and virally suppressed (<200 copies/mL) at 12 months. We also compared the time to receipt of result by the facility and by the participant’s parent/guardian. Findings: Between March 2016 and November 2018, we randomised 4,000 HIV-exposed infants at a median age of 6.4 weeks to POC (n=1,989) or enhanced SOC (n=2,011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (IQR: 22-30) days. Most infants randomised to SOC relied on the trial’s diagnostic safety net. Eighty-one (2%, 95% CI: 1.6–2.5%) infants were diagnosed with HIV. Although ART initiation was high overall, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures during follow-up. By 12 months, only 20 of 81 (25%, 95% CI: 15–34%) HIV-infected infants were alive, in care, and virally suppressed: 13 (30%, 95% CI: 16–43%) infants in the POC group vs. 7 (19%, 95% CI: 6–32%) in the enhanced SOC group (RR: 1.56, 95% CI: 0.7–3.50). Interpretation: Outcomes among HIV-infected infants were poor in both randomization groups. Although POC EID eliminated diagnostic delays and accelerated ART initiation, the POC EID strategy did not translate into a statistically significant improvement in programmatic success. Our findings are limited by a lower than anticipated number of HIV-infected infants in the trial, a welcome consequence of the success of Zambia’s perinatal HIV prevention program. Trial Registration: This trial is registered at https://clinicaltrials.gov (NCT02682810). Funding Statement:This research was funded by the U.S. National Institutes of Health (NIH) (U01AI100053). Biostatistical and laboratory support was provided by the UNC Center for AIDS Research, which is supported in part by the NIH (P30AI050410). Additional investigator and trainee support was provided by the NIH for BHC (K24AI120796) and CEF (T32HD075731, D43TW009340). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Ethical approval for the trial (NCT02682810) was granted by the University of Zambia Biomedical Research Ethics Committee (BREC Ref: 010-02-13), the Zambian Ministry of Health, and the University of North Carolina at Chapel Hill Institutional Review Board (IRB Number: 12-1346).

Editorial introductions

Editorial introductions

Reconsidering the Number of Women With HIV Infection Who Give Birth Annually in the United States.

The annual number of women with HIV infection who delivered infants in the United States was estimated to be 8700 in 2006. An accurate, current estimate is important for guiding perinatal HIV prevention efforts. Our objective was to analyze whether the 2006 estimate was consistent with the number of infants with HIV infection observed in the United States and with other data on perinatal HIV transmission. We compared the number of infants born with HIV in 2015 (n = 53) with data on interventions to prevent perinatal HIV transmission (eg, maternal HIV diagnosis before and during pregnancy and prenatal antiretroviral use). We also estimated the annual number of deliveries to women living with HIV by using the number of women of childbearing age living with HIV during 2008-2014 and the estimated birth rate among these women. Finally, we determined any changes in the annual number of infants born to women with HIV from 2007-2015, among 19 states that reported these data. The low number of infants born in the United States with HIV infection and the uptake of interventions to prevent perinatal HIV transmission were not consistent with the 2006 estimate (n = 8700), even with the best uptake of interventions to prevent perinatal HIV transmission. Given the birth rate among women with HIV (estimated at 7%) and the number of women aged 13-44 living with HIV during 2008-2014 (n = 111 273 in 2008, n = 96 363 in 2014), no more than about 5000 women with HIV would be giving birth. Among states consistently reporting the annual number of births to women with HIV, the number declined about 14% from 2008 to 2014. The current annual number of women with HIV infection delivering infants in the United States is about 5000, which is substantially lower than the 2006 estimate. More accurate estimates would require comprehensive reporting of perinatal HIV exposure.

Perinatal HIV Service Coordination: Closing Gaps in the HIV Care Continuum for Pregnant Women and Eliminating Perinatal HIV Transmission in the United States.

Eliminating perinatal transmission of HIV and improving the care of childbearing women living with HIV in the United States require public health and clinical leadership. The Comprehensive Care Workgroup of the Elimination of Perinatal HIV Transmission Stakeholders Group, sponsored by the Centers for Disease Control and Prevention, developed a concept of perinatal HIV service coordination (PHSC) and identified 6 core functions through (1) semistructured exploratory interviews with contacts in 11 state or city health departments from April 2011 through February 2012, (2) literature review and summary of data on gaps in services and outcomes, and (3) group meetings from August 2010 through June 2017. We discuss leadership strategies for implementing the core functions of PHSC: strategic planning, access to services, real-time case finding, care coordination, comprehensive care, and data and case reviews. PHSC provides a systematic approach to optimize services and close gaps in perinatal HIV prevention and the HIV care continuum for childbearing women that can be individualized for jurisdictions with varying needs.

Prevention and Treatment of Pediatric HIV Infection

The goal of this paper is to review the prevention of mother-to-child HIV transmission (PMTCT) research that informed World Health Organization (WHO) guidelines for PMTCT and describe the impact of worldwide scale-up of PMTCT programs and antiretroviral therapy (ART) coverage. The impact of these interventions on new pediatric infections and infected children’s morbidity and mortality in sub-Saharan Africa are reviewed. The IMPAACT PROMISE study demonstrated that triple therapy consisting of tenofovir (TDF), lamivudine (3TC), and lopinavir/ritonavir (LPVr) or zidovudine (AZT), 3TC, and LPVr initiated in the first trimester reduced vertical transmission at 2 weeks of age to 0.6% and 0.5%, respectively, supporting the current WHO Option B+ recommendation for PMTCT. However, increased adverse pregnancy outcomes in the AZT- and TDF-based triple therapy arms were reported when compared with the AZT prophylaxis arm (low birth weight [20.4% and 16.9% vs. 8.9%; p = 0.004] and premature deliveries [19.7% and 18.5% vs. 13.5%; p = 0.09], respectively). Implementation of Option B+ for PMTCT has led to significant reductions in vertical transmission rates, including elimination of new pediatric infections in some countries. The WHO declared elimination of mother-to-child HIV transmission (MTCT) in Cuba in 2015 and in Armenia, Belarus, and Thailand in 2016. Globally, new pediatric HIV infections have declined significantly since the introduction of effective antiretroviral regimens for PMTCT. Perinatal HIV prevention clinical trials conducted in sub-Saharan Africa informed WHO PMTCT guidelines which led to implementation of PMTCT programs worldwide, leading to a 47% reduction in new pediatric infections since 2009. Support from The United States President's Emergency Plan for AIDS Relief (PEPFAR), the Global Fund for AIDS, Tuberculosis and Malaria, and UN agencies has enabled scale-up of national PMTCT programs, and increased antiretroviral coverage (47% globally) for infected children has led to a decline in HIV/AIDS-related mortality in children. Implementation strategies that improve retention in care and adherence to ART in pregnant and breastfeeding HIV-infected women is critical to ensure that more countries achieve the elimination of MTCT (eMTCT) targets. Assessing the effectiveness of new antiretroviral drugs, including fixed-dose combinations and long-acting formulations, is key to improving ART adherence and reducing the emergence of viral resistance mutations. In addition, interventions to prevent HIV transmission in adolescents and young adults is critical for reducing new HIV infections worldwide. Innovative interventions to improve adherence to ART are required to further improve the survival of HIV-infected children and adolescents.

What is new in perinatal HIV prevention?

The purpose of this review is to describe recent clinical trial, laboratory and observational findings that highlight both the progress that can be achieved in elimination of new pediatric infections in international clinical trial settings among HIV-infected breastfeeding women while also describing recent safety concerns related to currently used antiretroviral regimens. The article will also address the ongoing adherence challenges for HIV-infected mothers in taking their antiretroviral drugs. This information is timely and relevant as new regimens are being considered for both prevention of mother-to-child transmission (PMTCT) of HIV and HIV treatment options worldwide. The main themes described in this article include both efficacy of different antiretroviral therapy (ART) regimens currently being rolled out internationally for PMTCT as well as safety findings from recent research including a large multisite international trial, PROMISE. The findings from the IMPAACT PROMISE trial as well as other recent trial and observational findings suggest that while progress has been steady in reducing PMTCT worldwide, the goal of virtual elimination of pediatric HIV worldwide will require careful attention to optimizing safety of new regimens which are less dependent on maternal daily ART adherence and safer in preventing certain toxicities.

Editorial introductions

Editorial introductions

Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention

(N Engl J Med. 2016;375(18):1726–1737) Although triple-drug antiretroviral therapy (ART) has clear benefits for mothers and infants, studies have shown higher rates of adverse pregnancy outcomes with maternal ART than with regimens containing fewer antiretroviral agents. The Promoting Maternal and Infant Survival Everywhere (PROMISE) trial thus compared the relative efficacy and safety of various open-label antiretroviral strategies and their effect on preventing mother-to-child transmission among asymptomatic HIV-infected pregnant women with high CD4 counts (at least 350 cells/mm3).

HIV: Das Ende der perinatalen Mutter-Kind-Übertragung

Fowler MG et al. Benefits and risks of antiretroviral therapy for perinatal HIV prevention. N Engl J Med 2016 (3) 375:1726–1736

HIV Knowledge Among Pregnant Latinas in Rural South Carolina.

To inform and strengthen culturally-tailored HIV perinatal prevention, we assessed HIV knowledge among pregnant Latinas receiving prenatal care in rural South Carolina. We administered an 11 item HIV knowledge scale (n=171). Women who answered 8 of 11 (73%) items correctly were categorized as having "high" knowledge; <8 items correct was categorized as "low" knowledge. Seventy-six percent of participants had low HIV knowledge; only 37% knew that there is medicine to prevent mother-to-child HIV transmission. In multivariate analyses, high HIV knowledge was more likely among women who had ≥high school education compared with women with elementary school education only (Adjusted Odds Ratio 10.5, 95% Confidence Interval 3.3-33.6). These findings highlight the need for targeted educational interventions to better inform Latinas regarding perinatal HIV prevention and transmission risks. Enhancing efforts with patients and providers is aligned with national goals for HIV prevention and elimination of perinatal transmission.

Perinatal HIV transmission and prevention

Perinatal HIV transmission occurs during pregnancy, labor, delivery or breastfeeding. Maternal factors associated with increased perinatal transmission include timing of infection, immune status, mode of delivery, co-existing sexually transmitted diseases, illicit drug use, increased duration of ruptured membranes, chorioamnionitis, viral load & invasive procedures. Infant risk factors include premature birth, low birth weight, skin & mucous membrane lesions. Preventive measures include anti retroviral therapy, treatment of chorioamnionitis with antibiotics, opting for caesarean section & avoiding breastfeeding. Early appropriate treatment of subclinical chorioamnionitis & virocidal cleaning of birth canal reduces perinatal HIV transmission. Caesarean section before onset of labour & membrane rupture reduces risk of mother–infant transmission by almost 50%. Vertical HIV transmission can occur through breast-feeding mostly during first 6 weeks of life & hence avoiding breastfeeding reduces transmission. Interrupting intrapartum transmission like giving ART in late gestation/ peri-partum & elective caesarean section reduce vertical HIV acquisition. As monotherapy & dual therapy are less effective, current guidelines recommend 2 nucleoside reverse transcriptase inhibitors & either a nonnucleoside reverse transcriptase inhibitor or a protease inhibitor. Perinatal HIV transmission can be reduced through a comprehensive approach including Universal access to prenatal care & routine HIV counselling & testing, access to antiretroviral therapy during pregnancy, at delivery & postpartum, education about treatment options & regimen adherence.