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.

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.

Zika Virus Infection in Pregnancy: Maternal, Fetal, and Neonatal Considerations.

An infection with the Zika virus (ZIKV) is usually mild, with nonspecific symptoms and most often asymptomatic. However, because of its causal relationship with severe congenital malformations, the ZIKV epidemic became an imperative for mobilization, renewed strategies for vector control, and biomedical research. A congenital Zika syndrome (CZS) has been characterized with 5 distinctive features that focus on brain development abnormalities (including microcephaly and brain calcifications), retinal manifestations, and defects on extremities including congenital contractures and hypertonia. The CZS could be just "the tip of the iceberg", pending the documentation of a spectrum of disease that could manifest later in life, from mild dysfunction to severe disease. It will be a matter of time for neurodevelopmental abnormalities, learning disabilities, and other unknown but yet-to-be-described outcomes to be associated with intrauterine ZIKV infection. In addition, ZIKV infection during pregnancy has been associated with other adverse outcomes. Reports mostly include ZIKV-affected pregnancies, and it will be difficult to clearly establish causality without appropriate control groups. We are summarizing some of the known or reported consequences of such infection during pregnancy. Women of reproductive age and particularly pregnant women are the most vulnerable to the adverse consequences of the ZIKV epidemic. Vector control programs need to be expanded to curtail new infections. Research is needed to develop safe and effective treatments, a preventive or therapeutic vaccine, and specific and sensitive tests and to diagnose and identify correlates of long-term immunity. Vaccines and treatments should be safe to be used in pregnancy. To do nothing would allow thousands of pregnant women to expose their fetuses to an infection that causes birth defects and other problems. Prenatal diagnosis technology development is necessary to be able to predict or diagnose adverse fetal outcomes related to ZIKV. Moreover, these tests should be used in a manner similar to the testing/screening method for neural tube defects and common chromosomal anomalies during prenatal care.

Preference of Oral Tenofovir Disoproxil Fumarate/Emtricitabine Versus Rectal Tenofovir Reduced-Glycerin 1% Gel Regimens for HIV Prevention Among Cisgender Men and Transgender Women Who Engage in Receptive Anal Intercourse with Men.

Oral pre-exposure prophylaxis (PrEP) can prevent HIV transmission. Yet, some may prefer not to take systemic daily medication. MTN-017 was a 3-period, phase 2 safety and acceptability study of microbicide gel applied rectally either daily or before and after receptive anal intercourse (RAI), compared to daily oral tablet. At baseline, cisgender men and transgender women who reported RAI (N = 187) rated the daily oral regimen higher in overall liking, ease of use, and likelihood of future use than the gel regimens. After trying all three, 28% liked daily oral the least. Gel did not affect sexual enjoyment (88%) or improved it (7-8%). Most partners had no reaction to gel use. Ease of gel use improved significantly between the first and the last few times of daily use. A rectal gel used before and after RAI may constitute an attractive alternative to daily tablet. Experience with product use may increase acceptability.

Measuring Knowledge of Cancer Screening and Prevention Strategies in HIV Healthcare Professionals.

OBJECTIVE: Due to advances in the care of people living with HIV/AIDS (PLWHA), life expectancy significantly increased, putting this group vulnerable to age-related comorbidities, such as cancer. The objective of this study was to describe the knowledge of cancer screening (cervical, breast, anal, colon, prostate) and other cancer prevention strategies (HPV vaccination, HPV testing) among HIV care professionals in Puerto Rico (PR). METHODS: Cross-sectional study using a sample of 104 HIV healthcare professionals in PR. Descriptive analyses were used to characterize the study sample. Logistic regression analysis was used to determine the relation of sociodemographic and work-related factors with cancer screening knowledge. RESULTS: On average, the healthcare professionals interviewed had been working for more than 10 years with the HIV/AIDS population (11.5±7.6 years). Multivariate analysis showed that physicians had a higher likelihood of having extensive knowledge of cervical (OR=3.96; 95% CI=1.23, 12.77) and anal cancer (OR=9.4; 95% CI=2.2, 41.0) screening than other healthcare professionals. For anal cancer in particular, as the number of years a given participant had been working with people living with HIV/AIDS increased, the likelihood that this participant would have extensive knowledge of anal cancer screening significantly increased (10% year). CONCLUSION: Health education interventions, tailored to healthcare professionals who recently finished their formal education should be developed in HPV-related cancers. Such training would improve cancer prevention and control efforts, thereby benefitting the HIV population in Puerto Rico.

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.

Recruitment of Caribbean female commercial sex workers at high risk of HIV infection.

OBJECTIVE: To evaluate novel eligibility criteria and outreach methods to identify and recruit women at high risk of HIV-1 infection in the Caribbean. METHODS: A prospective cohort study was conducted in 2009-2012 among 799 female commercial sex workers in the Dominican Republic, Haiti, and Puerto Rico. Minimum eligibility criteria included exchange of sex for goods, services, or money in the previous 6 months and unprotected vaginal or anal sex with a man during the same period. Sites used local epidemiology to develop more stringent eligibility criteria and recruitment strategies. Participants were asked questions about HIV/AIDS and their level of concern about participating in an HIV vaccine trial. Logistic regression modeling was used to assess predictors of prevalent HIV infection and willingness to participate in a future HIV vaccine study. RESULTS: HIV prevalence at screening was 4.6%. Crack cocaine use [odds ratio (OR) = 4.2, 95% confidence interval (CI) (1.8-9.0)] was associated with and having sex with clients in a hotel or motel [OR = 0.5, CI (0.3-1.0)] was inversely associated with HIV infection. A total of 88.9% of enrolled women were definitely or probably willing to participate in a future HIV vaccine trial. CONCLUSIONS: This study indicated that local eligibility criteria and recruitment methods can be developed to identify and recruit commercial sex workers with higher HIV prevalence than the general population who express willingness to join an HIV vaccine trial.

Biomedical HIV prevention strategies: state of the art and implications for public health policy in the Caribbean.

Recent advances in the field of biomedical prevention have induced optimism among both the scientific community and the public in general. The discussion of the research evidence is complemented with a discussion of the implications of this evidence for the Caribbean, highlighting the issues and controversies that should be considered in order to encourage and advance the responsible consideration of biomedical strategies. Traditionally, HIV prevention strategies have been characterized as predominantly behavior, social or biomedical. In practice, however, some strategies defy classification: even when they rely on technological or pharmaceutical elements, they have to be adopted by a society and the individuals within it. Moreover, whatever the strategy used, it will have to be distributed, implemented and made available through health care systems or other means. And its cost will be absorbed by specific funders or by society in general. Given the current historical context of the HIV/AIDS epidemic and the array of strategies required to control it, these distinctions (biomedical vs. behavior) can hinder the collaborations required to provide the needed combinations of strategies. The efficacy of the diverse strategies range from: 99% for programs to prevent MTCT, 63% for pre-exposure prophylaxis (PrEP), 96% for treatment as prevention, 39% for vaginal microbicides (54% with good adherence), post exposure prophylaxis (PEP), 31% for a vaccine and 53-60% for medical voluntary adult circumcision. To curtail and eliminate the HIV/AIDS epidemic in the future, expansion and scaled-up implementation of combinations of such strategies will be needed.

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.

Sex-based outcomes of darunavir-ritonavir therapy: a single-group trial.

BACKGROUND: Women account for an increasing proportion of patients with HIV-1 but remain underrepresented in antiretroviral clinical trials. OBJECTIVE: To evaluate sex-based differences in efficacy and adverse events in treatment-experienced, HIV-positive women and men receiving darunavir-ritonavir therapy over 48 weeks. DESIGN: Multicenter, open-label, phase 3b study designed to enroll a high proportion of women, with sample size determined on the basis of a noninferiority design with a maximum allowable difference of 15% in virologic response favoring men. (ClinicalTrials.gov registration number: NCT00381303) SETTING: 65 sites in the United States, Puerto Rico, and Canada. PATIENTS: 287 women and 142 men. INTERVENTION: Patients received darunavir-ritonavir, 600/100 mg twice daily, plus an investigator-selected optimized background regimen. MEASUREMENTS: Virologic response (HIV RNA <50 copies/mL using a time-to-loss of virologic response [TLOVR] algorithm) and adverse events were assessed over 48 weeks. RESULTS: 67% of patients were women; 84% of patients were black or Hispanic. A higher proportion of women discontinued treatment than men (32.8% vs. 23.2%; P = 0.042); more women than men discontinued treatment for reasons other than virologic failure. Response rates in women and men at week 48 were 50.9% and 58.5%, respectively (intention-to-treat TLOVR), and 73.0% and 73.5%, respectively (TLOVR censored for patients who withdrew for reasons other than virologic failure). The absolute difference in response, based on logistic regression and adjusted for baseline log(10) viral load and CD4(+) cell count, was -9.6 percentage points (95% CI, -19.9 to 0.7 percentage points; P = 0.067) for intention-to-treat TLOVR and -3.9 percentage points (CI, -13.9 to 6.0 percentage points; P = 0.438) for TLOVR population that censored patients who withdrew for reasons other than virologic failure. Adverse events were similar between the sexes. The most common grade 2 to 4 adverse events that were considered at least possibly treatment related in women and men were nausea (5.2% and 2.8%, respectively), diarrhea (4.5% and 4.9%, respectively), and rash (2.1% and 2.8%, respectively). LIMITATION: Baseline characteristics differed between sexes. CONCLUSION: Nonsignificant, sex-based differences in response were found during the 48-week study; however, these differences were probably due to higher discontinuation rates in women, suggesting that additional efforts are needed to retain women in clinical trials.

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.

A multifaceted mentoring model for minority researchers to address HIV health disparities.

In an era of significant biomedical advances in the treatment of HIV, health disparities still persist. The participation of minority researchers brings new perspectives to health-disparities research. Mentoring is key to this process. We present the multifaceted mentoring model that evolved in the Puerto Rico Comprehensive Center for the Study of HIV Disparities and the Mentoring Institute for HIV and Mental Health. The model includes (1) multi-institutional collaborations, (2) competency development, and (3) cross-disciplinary teams. These aspects of the model provide guidelines for institutions seeking to formalize mentoring programs while addressing the complexities of health disparities. The competency development component is a powerful tool in assessing and supporting the researchers. Further explorations on the applicability of the model are encouraged.

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.

No association between antepartum serologic and genital tract evidence of herpes simplex virus-2 coinfection and perinatal HIV-1 transmission.

OBJECTIVE: The purpose of this study was to assess the risk of perinatal HIV-1 transmission in women who are coinfected with herpes simplex virus-2 (HSV-2). STUDY DESIGN: We performed a nested case-control study of 26 women whose HIV-1 was transmitted to their infants and 52 control subjects whose HIV-1 was not transmitted. We assessed antepartum serologic evidence of HSV-2 by HSV-2 serostatus and genital tract evidence of HSV-2 by presence of HSV-2 DNA. RESULTS: There was no significant association between antepartum serologic evidence of HSV-2 coinfection and the risk of perinatal HIV-1 transmission. There was also no association between antepartum genital tract evidence of HSV-2 coinfection and risk of perinatal HIV-1 transmission. CONCLUSION: Women who were infected with HIV-1 with antepartum serologic and genital tract evidence of HSV-2 coinfection did not appear to have an increased risk of perinatal HIV-1 transmission. However, further investigations are needed to assess HSV-2 reactivation and the risk of perinatal HIV-1 transmission at the time of delivery.

Concerns about HIV and sexually transmitted infection among low-risk and high-risk women, Puerto Rico.

In this study, the RESPECT-2, an HIV risk reduction intervention developed by the Centers for Disease Control and Prevention, was translated into Spanish and culturally adapted to the Puerto Rican population. A new intervention emerged called the RReduC-PR (Risk Reduction Counseling-Puerto Rico). This instrument allows the assessment of sexual behaviors and development of risk reduction plans. Women from three distinct risk behavior groups participated: women recruited from a community-based organization (CBO), which includes street sex workers, crack users, and sexual partners of intravenous drug users; participants from a sexually transmitted infection (STI) clinic; and participants from a family planning clinic (FPC) in Puerto Rico. As part of the RReduC-PR, participants were provided counseling before and after a rapid HIV test to explore their attitudes about sexual behaviors. At baseline, all participants from the FPC reported having monogamous relationships (100%), as compared with the participants from the STI clinic (70%) and those from the CBO (20%). STI risk-reduction behaviors varied by site. Most of the participants acknowledged risk behaviors that may have exposed them to HIV. They did not use condoms, or used them inconsistently, even though acquiring HIV was a great concern for them. Most regarded a positive HIV diagnosis as a negative event. Their attitudes toward an HIV diagnosis varied by site. The groups varied in the perception of risk behaviors, knowledge, and concerns. These findings provide useful information for future risk-reduction interventions with these women.