The Use of Therapy Dogs in the Pediatric COVID-19 Vaccination at the University of Puerto Rico Medical Sciences Campus.

Pet ownership and therapy dogs as companion animals and emotional support have potential health benefits. We report the experiences at a COVID-19 vaccination center after authorizing children's vaccines. When the Pfizer-BioNTech vaccine for children aged 5 to 11 years was authorized for emergency use, we adapted the center's space to receive children, adding cartoon posters and balloons and using children's adhesive bandages, among others. Located at a Campus with six health professional schools, medical students dressed as storybook or movie characters. Children were asked to make drawings during the post vaccination observation period. We incorporated therapy dogs as part of our strategy for a child-friendly center during vaccination activities. Parents expressed that the COVID-19 immunization seemed to be better accepted by children as the dogs in the center entertained them. Many children were in close contact with the dogs while receiving the shots, caressing them, or having the small dogs on their laps. Children's drawings reflected colors, flowers, families, images of happiness, dogs with their names, their own pets, and superhero characters. There were no negative images of syringes, injections, or germs. To our knowledge, this was the only vaccine center in Puerto Rico that implemented therapy dogs as a strategy to create a friendly environment for COVID 19 immunization efforts targeted for children. Based on this experience, we encourage the use of therapy dogs in other immunization activities and will further gather prospective data in the future.

Perioperative Evaluation of Arterial and Venous Whole Blood in the Lamb (Ovis aries) Fontan Model.

Whole blood analysis can evaluate numerous parameters, including pH, pCO2, pO2, HCO3 - , base excess, glucose, electrolytes, lactate, blood urea nitrogen, creatinine, bilirubin, and hemoglobin. This valuable tool enables clinicians to make more informed decisions about patient care. However, the current body of literature describing perioperative whole blood analysis in Dorset sheep (Ovis aries) is small, so clinicians lack adequate information to guide their decision-making when evaluating test results. We evaluated arterial and venous whole blood pH, bicarbonate, pCO2, lactate, creatinine, and blood urea nitrogen before and for the first 24 hours after surgery in 2 cohorts of male and female Ovis arie s undergoing one of 2 major cardiovascular procedures, a Single-Stage Fontan or an inferior vena cava to pulmonary artery extracardiac conduit implantation (IP-ECC). The cohort undergoing a Single-Stage Fontan, which is the more complex procedure, exhibited greater deviation from baseline measurements than did the cohort undergoing the IP-ECC for lactate, bicarbonate, and creatinine. The cohort undergoing the IP-ECC showed no significant deviation from baseline for any parameters, potentially indicating a better safety margin than expected when compared with the Single-Stage Fontan. Together, these results indicate the clinical value of arterial and venous whole blood measurements in perioperative management of sheep and can provide a reference for clinicians managing sheep after significant cardiovascular procedures.

Fetal growth assessed via ultrasound in relation to maternal HIV infection status and antiretroviral regimens.

OBJECTIVE: To evaluate effects of maternal HIV and antiretroviral treatment (ART) on intrauterine fetal growth. DESIGN: Prospective cohort studies of HIV and ZIKA infection among women living with HIV (WLHIV) and women not living with HIV (WNLHIV) conducted in Brazil and the US from 2016 to 2020. METHODS: We evaluated fetal growth via repeated ultrasounds and calculated z scores for fetal growth measures using Intergrowth-21st standards among women with singleton pregnancies. Adjusted linear mixed models were fit for each fetal growth z score by HIV status. Among WLHIV, we compared fetal growth z scores by the most common maternal ART regimens, stratified by timing of ART initiation. RESULTS: We included 166 WLHIV and 705 WNLHIV; none had Zika infection. The z scores were similar for WLHIV and WNLHIV for femur length (latest third trimester median = 1.08) and estimated fetal weight (median ≈0.60); adjusted mean differences in fetal weight z scores by HIV status were less than 0.1 throughout gestation. Other fetal growth measurements were lower for WLHIV than WNLHIV early in gestation but increased more rapidly over gestation. Among WLHIV not on ART at conception, adjusted mean z scores were generally similar across regimens initiated during pregnancy but somewhat lower for atazanavir-based regimens for biparietal diameter compared with efavirenz-based or raltegravir-based regimens. Among WLHIV on ART at conception, mean z scores were similar across ART regimens. CONCLUSION: Within our cohorts, fetal growth was lower in WLHIV than WNLHIV early in gestation but similar by the end of gestation, which is reassuring. Among WLHIV, fetal growth measures were generally similar across ART regimens evaluated.

Acknowledging and addressing the gender disparity in pre-exposure prophylaxis use for HIV prevention.

Objective: One in four persons living with HIV in the USA is a woman. While the annual HIV diagnoses for 2019 decreased by approximately 9% when compared with 2015, this decrease was seen in men, while the rates remained stable for women. Pre-exposure prophylaxis (PrEP) is one major biomedical tool that could benefit women at risk of HIV. However, women only account for approximately 5% of PrEP users annually. The objective of this study is to identify and address the gender disparity in PrEP use. Methods: This study used epidemiological data from the AIDSVu database to confirm the presence of a gender disparity in PrEP use across the USA. Cross-sectional data from 2019 showed that PrEP use was significantly higher in men, which suggested the existence of a disparity. The PrEP-to-Need ratio was then used to examine the trends in PrEP use relative to the rate of HIV infections, from 2012 to 2019, and to confirm the existence of the gender disparity in PrEP use. Key findings: There is a marked gender disparity in PrEP use. This disparity is widening and therefore demands more attention to women at risk of HIV. Some recommendations for addressing the disparity include the following: raising awareness, capacity building for providers, scaling up efforts to better reach women at risk of HIV and additional research to understand the drivers of the disparity. Conclusions: Policy makers could therefore prioritize the health outcomes of women by promoting research and education aimed at extending PrEP offerings to effectively reach women.

Pregnant Women's Experiences during Hurricane Maria: Impact, Personal Meaning, and Health Care Needs.

During a disaster, pregnant women are considered among the most vulnerable. BACKGROUND: On 20 September 2017, the Caribbean was hit by a category 4 hurricane. The purpose of the study was to explore the impact on pregnant women during and after the hurricane regarding access to health care, social services, and support systems. METHODS: In-depth interviews were conducted to 10 women that were pregnant during the event. Qualitative inquiry based on the Interpretative Phenomenological Analysis framework was used to interpret the narratives. RESULTS: Five major themes emerged: meaning of living through a disaster, fear, the dual burden of protecting themselves and their unborn baby, disruption in health care, and coping mechanisms. Despite the negative feelings, most participants experienced positive transformations. They narrated how they stayed calm and coped in order to protect their pregnancy. Their overall evaluation of the healthcare system was positive. The support of friends and family was crucial pre and post-disaster. CONCLUSIONS: The interviews provided a wealth of firsthand information of women experiencing a natural disaster while pregnant. The findings underscore the need to incorporate emotional support in the preparedness and response plans for pregnant women. Educating, empowering, and incorporating families and communities is vital in these efforts.

Elimination of the Perinatal Transmission of HIV and Syphilis in Puerto Rico and Sustained Success since 2007: Convergence of Science, Women-Centered Care, and Policy.

OBJECTIVE: There have been significant successes in the fight against HIV/AIDS due to the access to rapid HIV testing, interventions to reduce the mother-to-child transmission (MTCT) risk, potent and effective antiviral medications, and other biomedical prevention strategies. The purpose of this work is to demonstrate that Puerto Rico eliminated Mother-to-Child Transmission of HIV (MTCT) following the 2017 World Health Organization (WHO) criteria for validating the elimination of MTCT and Syphilis. METHODS: Existing epidemiological data from Puerto Rico was used to document the elimination of MTCT and Syphilis. Data to calculate the indicators was obtained from the various divisions of the Puerto Rico Department of Health, including vital statistics, surveillance data, and programmatic outcomes. RESULTS: Puerto Rico eliminated MTCT and syphilis, according to the WHO indicators, earlier than other countries. We can trace the outcomes to 1994 using the incidence rate of perinatally-acquired HIV of <50/100,000; to 2007 using HIV perinatal transmission rates for non-breastfeeding countries (<2%), to 2008 using 90% of women receiving ART at delivery, and to 2005 using the incidence rate of congenital syphilis of <50/100,000. CONCLUSION: Not only have we eliminated the MTCT of HIV and syphilis, but the efforts have been sustained since 2000. The elimination of transmission of infectious diseases requires the intersection of scientific feasibility, coordinated interventions, and political will, successfully attained in Puerto Rico.

Association of Chronic Myelogenous (Basophilic) Leukemia and the BCR/ABL Mutation in a Yucatan Barrow (Sus scrofa domestica).

Background: Chronic myelogenous leukemia (CML) is a clonal proliferative disorder of the myeloid, megakaryocyte, and erythroid lineages. The onset and subsequent progression of CML is well-described in humans. There is comparably little information surrounding CML progression in veterinary species, including Yucatan miniature swine that are common for preclinical pharmaceutical and device testing. In humans, more than 90% of CML cases are associated with a chromosomal translocation that results in the Philadelphia gene (BCR/ABL mutation). In this report, the presence of the Philadelphia gene in a Yucatan burrow was confirmed in white blood cells collected prior to onset of clinical signs with primers designed from the human BCR/ABL sequence. Case Presentation: A 24 month old, 70 kg, Yucatan barrow received a prefabricated bovine cortical bone xenograft following a unilateral zygomatic ostectomy for a preclinical study. Complete blood count and serum chemistries were performed prior to and 28, 53, 106, and 129 days after facial surgery. Fifty three days after surgery, a bone marrow biopsy was performed due to anorexia, severe basophilia, and mild anemia. A finding of a moderate increase in basophilic precursors in bone marrow cytology was followed by lymphocyte immunophenotyping via flow cytometry and RT-PCR amplification of the Philadelphia gene in white blood cell samples from the affected barrow and an unaffected barrow in the same treatment group. Bone marrow, lymph node, liver, spleen, lung, kidney, and adrenal gland lesions of mostly myeloblasts were identified after the affected barrow died 146 days after surgery. Flow cytometry confirmed lymphopenia and suggested basophilia, and RT-PCR established the presence of the BCR/ABL gene. Conclusions: The information in this report confirms the presence of the BCR/ABL mutation and documents progression of chronic myelogenous (basophilic) leukemia from a chronic phase to a terminal blast crisis in an adult Yucatan barrow. The natural occurrence and progression of CML associated with the BCR/ABL mutation in miniature swine establishes potential for future porcine models of human CML. The information also establishes a genetic test to confirm porcine CML to prevent inadvertent attribution of clinical signs to treatment complications during preclinical testing.

Pharmacogenetic interactions between antiretroviral drugs and vaginally administered hormonal contraceptives.

OBJECTIVE: In AIDS Clinical Trials Group study A5316, efavirenz lowered plasma concentrations of etonogestrel and ethinyl estradiol, given as a vaginal ring, while atazanavir/ritonavir increased etonogestrel and lowered ethinyl estradiol concentrations. We characterized the pharmacogenetics of these interactions. METHODS: In A5316, women with HIV enrolled into control (no antiretrovirals), efavirenz [600 mg daily with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)], and atazanavir/ritonavir (300/100 mg daily with NRTIs) groups. On day 0, a vaginal ring was inserted, releasing etonogestrel/ethinyl estradiol 120/15 µg/day. Intensive plasma sampling for antiretrovirals was obtained on days 0 and 21, and single samples for etonogestrel and ethinyl estradiol on days 7, 14, and 21. Seventeen genetic polymorphisms were analyzed. RESULTS: The 72 participants in this analysis included 25, 24 and 23 in the control, efavirenz, and atazanavir/ritonavir groups, respectively. At day 21 in the efavirenz group, CYP2B6 genotype was associated with increased plasma efavirenz exposure (P = 3.2 × 10), decreased plasma concentrations of etonogestrel (P = 1.7 × 10), and decreased ethinyl estradiol (P = 6.7 × 10). Compared to controls, efavirenz reduced median etonogestrel concentrations by at least 93% in CYP2B6 slow metabolizers versus approximately 75% in normal and intermediate metabolizers. Efavirenz reduced median ethinyl estradiol concentrations by 75% in CYP2B6 slow metabolizers versus approximately 41% in normal and intermediate metabolizers. CONCLUSION: CYP2B6 slow metabolizer genotype worsens the pharmacokinetic interaction of efavirenz with hormonal contraceptives administered by vaginal ring. Efavirenz dose reduction in CYP2B6 slow metabolizers may reduce, but will likely not eliminate, this interaction.

Correction to: International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol.

Following publication of the original article [1], the author mentioned that two additional NIH staff were involved in the development of the protocol who did not receive recognition in the Acknowledgments section in their published article.

Cognitive Development of Infants Exposed to the Zika Virus in Puerto Rico.

Importance: Existing research has established a causal link between Zika virus (ZIKV) infection and severe birth defects or consequent health impairments; however, more subtle cognitive impairments have not been explored. Objective: To determine whether infants of mothers with at least 1 positive ZIKV test show differences in cognitive scores at ages 3 to 6 months and ages 9 to 12 months. Design, Setting, and Participants: This cross-sectional study recruited infants enrolled in existing ZIKV study cohorts associated with the Maternal-Infant Studies Center and the Puerto Rico Clinical and Translational Research Consortium at the University of Puerto Rico and from the broader San Juan metropolitan area. The study took place at the Puerto Rico Clinical and Translational Research Consortium at the University of Puerto Rico. Participants were recruited through convenience sampling if their mothers underwent ZIKV testing prenatally and were at the target ages during the study period. Infants who were born preterm (<36 weeks' gestational age), with low birth weight (<2500 g), or with a known genetic disorder were excluded. Infants were tested from ages 3 to 6 months or ages 9 to 12 months from May 2018 to April 2019. Data analysis was performed from March to April 2019. Exposures: Zika virus status was measured prenatally and in the early postnatal period using real-time polymerase chain reaction or a ZIKV IgM antibody capture enzyme-linked immunosorbent assay. Main Outcomes and Measures: The infants' development was assessed using the Mullen Scales of Early Learning (translated to Spanish and adapted for Puerto Rico), and assessors were blinded to each infant's ZIKV status. Results: A total of 65 study participants were included. The mean (SD) age of the infants at the time of cognitive testing was 8.98 (3.19) months. Most of the infants were white (55 [84.6%]) and Puerto Rican (64 [98.5%]); 38 of the infants were male (58.5%). General cognitive and domain-specific scores did not differ significantly between prenatally ZIKV-positive and ZIKV-negative infants except for receptive language score (mean difference = 5.52; t = 2.10; P = .04). Exposure to ZIKV (B = -5.69; ß = -0.26 [95% CI -11.01 to -0.36]; P = .04) and a measure of Hurricane Maria exposure (time without water, B = -0.05; ß = -0.27 [95% CI, -0.10 to -0.01]; P = .03) were both independently and significantly associated with receptive language scores after adjusting for key confounders. Conclusions and Relevance: Although infants exposed to ZIKV prenatally showed unaffected motor and visually mediated cognitive development, they did show deficits in receptive language scores. Receptive language skills were also associated with the degree of exposure to Hurricane Maria, with those who spent more time without water after the hurricane having lower receptive language scores.

Antiretroviral therapy and vaginally administered contraceptive hormones: a three-arm, pharmacokinetic study.

BACKGROUND: Drug-drug interactions between orally administered antiretroviral therapy (ART) and hormones released from an intravaginal ring are not known. We hypothesised that ART containing either efavirenz or ritonavir-boosted atazanavir would alter plasma concentrations of vaginally administered etonogestrel and ethinylestradiol but that ART concentrations would be unchanged during use of an intravaginal ring. METHODS: We did a parallel, three-group, pharmacokinetic evaluation at HIV clinics in Asia (two sites), South America (five), sub-Saharan Africa (three), and the USA (11) between Dec 30, 2014, and Sept 12, 2016. We enrolled women with HIV who were either ART-naive (control group; n=25), receiving efavirenz-based ART (n=25), or receiving atazanavir-ritonavir-based ART (n=24). Women receiving ART were required to be on the same regimen for at least 30 days, with 400 copies or less per mL of plasma HIV-1 RNA; women not receiving ART had CD4 counts of 350 cells per µL or less. We excluded participants who had a bilateral oophorectomy or conditions that were contraindicated in the intravaginal ring product labelling. An intravaginal ring releasing etonogestrel and ethinylestradiol was inserted at entry (day 0). Single plasma samples for hormone concentrations were collected on days 7, 14, and 21 after intravaginal ring insertion. The primary outcome was the plasma concentration of etonogestrel and ethinylestradiol on day 21. Etonogestrel and ethinylestradiol concentrations were compared between each ART group and the control group by geometric mean ratio (GMR) with 90% CIs and Wilcoxon rank-sum test. As secondary outcomes, efavirenz or ritonavir-boosted atazanavir concentrations were assessed by 8-h intensive pharmacokinetic sampling at entry before intravaginal ring insertion and before intravaginal ring removal on day 21. Antiretroviral areas under the concentration-time curve (AUC0-8 h) were compared before and after intravaginal ring insertion by GMR (90% CI) and Wilcoxon signed-rank test. This study is registered with ClinicalTrials.gov, number NCT01903031. FINDINGS: Between Dec 30, 2014, and Sept 12, 2016, we enrolled 84 participants in the study; ten participants were excluded from the primary hormone analysis. 74 participants met the primary endpoint: 25 in the control group, 25 in the efavirenz group, and 24 in the atazanavir group. On day 21 of intravaginal ring use, participants receiving efavirenz had 79% lower etonogestrel (GMR 0·21, 90% CI 0·16-0·28; p<0·0001) and 59% lower ethinylestradiol (0·41, 0·32-0·52; p<0·0001) concentrations compared with the control group. By contrast, participants receiving ritonavir-boosted atazanavir had 71% higher etonogestrel (1·71, 1·37-2·14; p<0·0001), yet 38% lower ethinylestradiol (0·62, 0·49-0·79; p=0·0037) compared with the control group. The AUC0-8 h of efavirenz or atazanavir did not differ between the groups. INTERPRETATION: Hormone exposure was significantly lower when an intravaginal ring contraceptive was combined with efavirenz-based ART. Further studies designed to examine pharmacodynamic endpoints, such as ovulation, when intravaginal ring hormones are combined with efavirenz are warranted. FUNDING: National Institutes of Health, through the AIDS Clinical Trials Group and the International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health.

International prospective observational cohort study of Zika in infants and pregnancy (ZIP study): study protocol.

BACKGROUND: Until recently, Zika virus (ZIKV) infections were considered mild and self-limiting. Since 2015, they have been associated with an increase in microcephaly and other birth defects in newborns. While this association has been observed in case reports and epidemiological studies, the nature and extent of the relationship between ZIKV and adverse pregnancy and pediatric health outcomes is not well understood. With the unique opportunity to prospectively explore the full spectrum of issues related to ZIKV exposure during pregnancy, we undertook a multi-country, prospective cohort study to evaluate the association between ZIKV and pregnancy, neonatal, and infant outcomes. METHODS: At research sites in ZIKV endemic regions of Brazil (4 sites), Colombia, Guatemala, Nicaragua, Puerto Rico (2 sites), and Peru, up to 10,000 pregnant women will be recruited and consented in the first and early second trimesters of pregnancy and then followed through delivery up to 6 weeks post-partum; their infants will be followed until at least 1 year of age. Pregnant women with symptomatic ZIKV infection confirmed by presence of ZIKV RNA and/or IgM for ZIKV will also be enrolled, regardless of gestational age. Participants will be tested monthly for ZIKV infection; additional demographic, physical, laboratory and environmental data will be collected to assess the potential interaction of these variables with ZIKV infection. Delivery outcomes and detailed infant assessments, including physical and neurological outcomes, will be obtained. DISCUSSION: With the emergence of ZIKV in the Americas and its association with adverse pregnancy outcomes in this region, a much better understanding of the spectrum of clinical outcomes associated with exposure to ZIKV during pregnancy is needed. This cohort study will provide information about maternal, fetal, and infant outcomes related to ZIKV infection, including congenital ZIKV syndrome, and manifestations that are not detectable at birth but may appear during the first year of life. In addition, the flexibility of the study design has provided an opportunity to modify study parameters in real time to provide rigorous research data to answer the most critical questions about the impact of congenital ZIKV exposure. TRIAL REGISTRATION: NCT02856984 . Registered August 5, 2016. Retrospectively registered.

Brief Report: Routine Use of Oral PrEP in a Phase 2 Rectal Microbicide Study of Tenofovir Reduced-Glycerin 1% Gel (MTN-017).

BACKGROUND: As daily oral preexposure prophylaxis (PrEP) becomes standard for HIV prevention, routine use of PrEP is likely to increase within clinical trials of novel preventive agents. We describe the prevalence and characteristics of participants reporting nonstudy oral PrEP use within Microbicide Trials Network-017 (MTN-017), a phase 2 trial of a rectal microbicide. SETTING AND METHODS: One hundred ninety-five HIV-uninfected men who have sex with men and transgender women were enrolled and followed in MTN-017 across 8 sites in the United States, Thailand, South Africa, and Peru from 2013 to 2015. Nonstudy oral PrEP use was recorded on case report forms and progress notes. Characteristics of PrEP users and non-PrEP users were compared using tests of statistical significance. RESULTS: Overall, 11% of participants reported nonstudy oral PrEP use, all from the San Francisco (SF) site, accounting for 58% (22/38) of participants enrolled in SF. There was a higher median number of sex partners reported in the past 8 weeks before enrollment among oral PrEP users vs. nonusers (7 vs. 2, P = 0.02). Most PrEP users (18/22, 82%) began PrEP treatment during screening/after enrollment, and most (19/22, 86%) decided to continue oral PrEP after study completion. CONCLUSION: Nonstudy oral PrEP use in the first phase 2 study of tenofovir reduced-glycerin 1% gel was high at a single site in SF where community PrEP availability and use was expanding. Investigators should consider the evolving context of nonstudy oral PrEP use across trial sites when designing and interpreting trials of novel biomedical prevention modalities.

Pregnancy and Zika: The Quest for Quality Care and Reproductive Justice.

On February 1, 2016, the World Health Organization (WHO) declared the ZIKV virus outbreak a Public Health Emergency of International Concern (PHEIC). Pregnant women and their infants, are vulnerable to the impact of this vector-borne illness (mosquito) and sexually transmitted viral infection. The uncertainty surrounding the possibility of congenital anomalies due to ZIKV infection during pregnancy bring a renewed debate about the rights of women to control their reproductive decisions. Current strategies, resources and services aimed at prevention priorities fall short of responding to a clear framework regarding sexual reproductive health, rights and justice. A comprehensive approach to reproduction, in times of Zika, needs to empower women of reproductive age and their families to make decisions and to act on those decisions. This paper highlights the contributions of the Maternal-Infant Studies Center (CEMI-Spanish Acronym) in close collaboration with the Department of Obstetrics and Gynecology of the University of the Puerto Rico School of Medicine and the University Hospital in providing comprehensive health care to pregnant women with ZIKV or at risk of ZIKV, at the very onset of the epidemic. CEMI approaches the care of pregnant women from a reproductive justice perspective, integrating clinical services, education, research, and advocacy. Transformación Prenatal (Centering Group Prenatal Care, GPC) currently implemented at the Puerto Rico University Hospital High Risk Clinics has been pivotal to achieve this aim. Based on the health professionals' experiences and women's testimonies, we articulate a set of principles and key actions that would benefit women, their family and children.

Congenital Zika Syndrome in Puerto Rico, Beyond Microcephaly, A Multiorgan Approach.

OBJECTIVE: Zika virus (ZIKV) infection was identified in Puerto Rico on December 2015, and the outbreak encouraged us to characterize clinical manifestations and laboratory findings of intrauterine exposed infants. METHODS: Retrospective medical record review of infants born to mothers with confirmed ZIKV infection during pregnancy was performed from January 2016-June 2017. We included patients admitted to UPH Neonatal Intensive Care Unit or referred for follow-up at UPH High Risk Clinics. The database was approved by the University of Puerto Rico, Medical Sciences Campus, IRB. RESULTS: 191 infants born to ZIKV positive mothers during pregnancy were identified. Normal head sonogram was found in 93% of the normo cephalic infants. Ocular findings were reported in 50% of the patients with microcephaly and 31% of the normo-cephalics. Fifteen newborns (7.8%) presented with microcephaly, of which 73% showed calcifications in head sonogram, and had severe anomalies on brain MRI. Auditory brainstem response test was performed on all newborns, 80% were within normal limits. CONCLUSION: Among the group of infants born to mothers with Zika positive test 4% had microcephaly. Of concern to us is the fact that 31% of normo cephalic infants had ocular manifestations and 7% of them had findings on head sonogram. While microcephaly is the severest form of Congenital Zika Syndrome, ocular manifestations might characterize the spectrum of disease. These findings reiterate the importance of detailed neonatal evaluations of exposed infants.

The Zika Virus Infection in Pregnancy: Review and Implications for Research and Care of Women and Infants in Affected Areas.

The world has encountered a new and serious epidemic which has disproportionately affected fetuses and infants. What makes the Zika virus (ZIKV) epidemic such a threat in our times, is that a whole generation can be affected by birth defects caused by a seemingly innocuous maternal infection, which in most cases go unnoticed and undiagnosed. Spreading to over 80 countries and affecting millions, it is associated with severe birth defects known as congenital Zika syndrome (CZS), which include fetal brain development abnormalities (microcephaly and brain calcifications), retinal abnormalities, and contractures and hypertonia of the extremities. Testing strategies are challenging because of the lack of symptoms and cross reactivity with other viral infections. Obstetrical complications include fetal loss and the need for an emergency cesarean delivery. The rate of CZS has been described as ranging from 5 to 6% among cohorts in the US, reaching 11% for 1st trimester exposure. Prolonged viremia during pregnancy has been documented in a few cases, reaching 89 days after the onset of symptoms in one case and 109 days after such onset in another. If the ZIKV can infect, multiply in, and persist in diverse placental cells, then movement across the placenta, the fetal brain, and the maternal peripheral blood is possible. There is a sense of urgency, and we need safe and effective vaccines and treatments, particularly for pregnant women. If we do not expand testing and develop methods for early diagnosis and treatment, thousands of infants will be exposed to a neurotropic virus that causes severe birth defects and that could also affect the lives of those who form the next generation.

Quantitation of anti-Pythium insidiosum antibodies before and after administration of an immunotherapeutic product to healthy dogs.

OBJECTIVE To evaluate the effect of an immunotherapeutic product on concentrations of anti-Pythium insidiosum antibodies in dogs. ANIMALS 7 healthy hound-crossbreds. PROCEDURES Antibody concentrations were evaluated before (day 0) and after administration of the immunotherapeutic product. The immunotherapeutic product was administered on days 0, 7, and 21. Serum was obtained on days 0, 7, 14, 21, 28, 35, 42, 49, and 56. Anti-P insidiosum antibody concentrations were measured and reported as the percentage positivity relative to results for a strongly positive control serum. RESULTS Mean ± SD percentage positivity before administration of the immunotherapeutic product was 7.45 ± 3.02%. There was no significant change in anti-P insidiosum antibody concentrations after administration of the product, with percentage positivity values in all dogs remaining within the range expected for healthy dogs (3% to 15%). CONCLUSIONS AND CLINICAL RELEVANCE Administration of the immunotherapeutic product to healthy dogs in accordance with the manufacturer's suggested protocol did not induce a significant change in anti-P insidiosum antibody concentrations. These results suggested that administration of the immunotherapeutic product may not interfere with postadministration serologic monitoring. However, further investigations will be required to determine whether there is a similar effect in naturally infected dogs.

Pharmacokinetics, Antiviral Activity, and Safety of Rilpivirine in Pregnant Women with HIV-1 Infection: Results of a Phase 3b, Multicenter, Open-Label Study.

INTRODUCTION: Physiologic changes during pregnancy may impact the pharmacokinetics of drugs. In addition, efficacy and safety/tolerability concerns have been identified for some antiretroviral agents. METHODS: Human immunodeficiency virus (HIV)-1-infected pregnant women (18-26 weeks gestation) receiving the non-nucleoside reverse transcriptase inhibitor rilpivirine 25 mg once daily were enrolled in this phase 3b, open-label study examining the impact of pregnancy on the pharmacokinetics of rilpivirine when it is given in combination with other antiretroviral agents. Blood samples (collected over the 24-h dosing interval) to assess total and unbound rilpivirine plasma concentrations were obtained during the second and third trimesters (24-28 and 34-38 weeks gestation, respectively) and 6-12 weeks postpartum. Pharmacokinetic parameters were derived using noncompartmental analysis and compared (pregnancy versus postpartum) using linear mixed effects modeling. Antiviral and immunologic response and safety were assessed. RESULTS: Nineteen women were enrolled; 15 had evaluable pharmacokinetic results. Total rilpivirine exposure was 29-31% lower during pregnancy versus postpartum; differences were less pronounced for unbound (pharmacodynamically active) rilpivirine. At study entry, 12/19 (63.2%) women were virologically suppressed; 10/12 (83.3%) women were suppressed at the postpartum visit. Twelve infants were born to the 12 women who completed the study (7 discontinued); no perinatal viral transmission was observed among 10 infants with available data. Rilpivirine was generally safe and well tolerated in women and infants exposed in utero. CONCLUSION: Despite decreased rilpivirine exposure during pregnancy, treatment was effective in preventing mother-to-child transmission and suppressing HIV-1 RNA in pregnant women. Results suggest that rilpivirine 25 mg once daily, as part of individualized combination antiretroviral therapy, may be an appropriate option for HIV-1-infected pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT00855335.

HIV seroconversion during pregnancy and the need for pre-exposure prophylaxis (PrEP).

The reduction in the mother-to-infant transmission of HIV has been among the early successes of care and treatment of women living with HIV. Prenatal HIV counseling and testing, the availability of diverse antiretroviral therapies, elective cesarean section, and the use of formula milk have significantly reduced the mother-to-infant transmission in the USA and Europe. We are presenting two cases of seroconversion during pregnancy, identified during labor and delivery, of women who received risk reduction counseling and serial HIV testing during pregnancy. Because there are no guidelines for (or easy access to) the use of pre-exposure prophylaxis (PrEP) in pregnancy, they were offered other strategies for prevention including risk reduction counseling, condoms, and serial HIV testing. These cases support the use of PrEP during pregnancy. Both infants were negative and the women are currently receiving long-term highly active antiretroviral therapy. One of them recently delivered another infant. After these two women seroconverted, we decided to offer PrEP to all pregnant women presenting for care who report having an HIV positive partner. During the period 2012-2014, we treated ten HIV negative pregnant women who were partners of HIV positive men. Since 2015, we have seen 20 pregnant women in HIV discordant relationships. Of those, seven received PrEP. No seroconversions have been observed among the pregnant women on PrEP. Although small numbers, seroconversion during pregnancy was observed in two of 13 (15%) of the pregnant women in HIV-discordant relationships seen in our clinic, excluding those treated with PrEP. Given the safety data and experience with tenofovir and emtricitabine among pregnant women living with HIV, we believe PrEP should be offered in pregnancy and that guidelines should reflect this option as an additional strategy to reduce risks during pregnancy and to further reduce infant HIV transmission risk.

The birds and the bees: do Puerto Rican mothers and daughters talk about sex?

INTRODUCTION: Effective communication skills that foster responsible sexual decisions are known to have the potential to reduce the risky adolescent sexual behavior. It is well understood that maternal communication is a key element in modifying the adolescent sexual behavior. The objective of this qualitative study was to explore if Puerto Rican mothers of adolescent girls have conversations about sexuality with their daughters and the content of such conversations. METHODS: A total of 22 HIV-seropositive mothers and 22 HIV-seronegative mothers were enrolled. Six focus groups were conducted, sessions were transcribed ad-verbum and coded for specific topics. All qualitative analysis was incorporated into Atlas.ti. RESULTS: Participants in both groups had a similar average age (mean=41 years old); but, the HIV-seropositive mothers were more likely single, less educated and unemployed. Regarding having engaged in conversations about sexuality and the topics covered, however, there were no differences revealed among HIV-seropositive mothers and seronegative mothers. In both groups, mothers understood the importance of these conversations, but most said they were difficult and uncomfortable. CONCLUSION: These findings reinforce the importance of communication between mothers and daughters for the prevention of STIs, HIV/AIDS, and teenage pregnancy in minority populations.Interventions are needed for mother and daughter to improve communication skills, communication about sexuality, and addressing prevention.