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Background In North American countries national guidelines have strongly recommended formula over breastmilk for people with HIV because of concern for HIV transmission. However, data from resource-limited settings suggest the risk is less than 1% among virally suppressed people. Information regarding breastfeeding experience in high resource settings is lacking. Methods A retrospective multi-site study was performed for individuals with HIV who breastfed from 2014-2022 in the United States (8 sites) and Canada (3 sites). Descriptive statistics were used for data analysis. Results Among the 72 cases reported, most had been diagnosed with HIV and were on antiretroviral therapy (ART) prior to the index pregnancy and had undetectable viral loads at delivery. Most commonly reported reasons for choosing to breastfeed were health benefits, community expectations, and parent-child bonding. Median duration of breastfeeding was 24 weeks (range 1 day to 72 weeks). Regimens for infant prophylaxis and protocols for testing of infants and birthing parents varied widely among institutions. No neonatal transmissions occurred among the 94% of infants for whom results were available >= 6 weeks after weaning. Conclusions This study describes the largest cohort to date of people with HIV who breastfed in North America. Findings demonstrate high variability among institutions in policies, infant prophylaxis, and infant and parental testing practices. The study describes challenges in weighing the potential risks of transmission with personal and community factors. Finally, this study highlights the relatively small numbers of patients living with HIV who chose to breastfeed at any one location, and the need for further multi-site studies to identify best care practices.

OBJECTIVE: Little is known about the prevalence and treatment of premature and early menopause among people with HIV. We described premature and early menopause and subsequent hormonal treatment in a longitudinal cohort of women living with or at risk for HIV in the US. METHODS: Data from the Women’s Interagency HIV Study between 2008 and 2020 were analyzed to describe premature and early menopause among cohort participants under the age of 51. RESULTS: Of 3,059 eligible women during the study period, 1% (n=35) underwent premature menopause before age 41, 3% (n=101) underwent menopause between ages 41 and 46, and 21% (n=442) underwent menopause between ages 46 and 50, inclusive. Of participants who experienced menopause before age 41, between age 41 and 45, and between ages 46 and 50, 51%, 24%, and 7% (respectively) received either menopausal hormone therapy or hormonal contraception. CONCLUSION: These findings suggest that disparities in receipt of recommended hormone therapy for premature and early menopause may contribute, in part, to evident health disparities, such as cardiovascular disease, osteoporosis, and overall mortality. They also suggest a substantial need for education among people experiencing early menopause and their providers, with the goal of improving access to hormone therapy based on guidelines to address health disparities and minimize future health consequences.

OBJECTIVE Fetal tissue research has driven significant medical advances but remains publicly contentious in the United States. The views of pregnant individuals in the United States regarding the donation of fetal tissue offer an important and previously unexplored perspective on this issue. METHODS We conducted a secondary analysis of data from two separate, broader qualitative studies. Pregnant and recently pregnant individuals (N=79) from clinical sites at the University of North Carolina at Chapel Hill, Johns Hopkins University, and Massachusetts General Hospital were interviewed individually using a semi-structured guide addressing a range of issues related to infectious disease research and pregnancy, including the acceptability of fetal tissue research. Interviews were transcribed, coded, and analyzed for emergent themes. RESULTS Among this sample of predominantly Black (61%), reproductive-aged pregnant and recently pregnant participants, the majority (72%) generally supported fetal tissue research. The following three themes were identified: choice, respect, and meaning. Respondents discussed the deeply personal nature of decisions surrounding fetal tissue research, emphasizing the importance of informed consent and respect for the person's emotional state when approaching for consent. The ways in which participants regarded how to respectfully handle fetal tissue also shaped views about the acceptability of donation, both for and against. For many participants, fetal tissue donation to research represented one way of ascribing meaning to pregnancy termination or loss. CONCLUSION Among this diverse sample of pregnant and recently pregnant individuals, most were supportive of fetal tissue donation for research. A better understanding of pregnant individuals' views on this topic may lead to policies and practices that are congruent with the needs and values of people facing decisions regarding the disposition of fetal remains.

Persistent human papillomavirus infection is the central cause of cervical cancer, the leading cause of cancer death among women worldwide. Clear evidence from both randomized trials and population based studies shows that vaccination against human papillomavirus reduces the incidence of cervical pre-cancer. These data suggest that the vaccine reduces the incidence of cervical cancer. However, human papillomavirus vaccine coverage is inadequate in all countries, especially in low and middle income countries where disease burden is highest. Supply side strategies to improve coverage include increasing the availability of low cost vaccines, school located delivery, single dose vaccine schedules, and development of vaccines that do not need refrigeration. Demand side strategies include enhancing provider recommendations, correcting misinformation, and public awareness campaigns. The near elimination of cervical cancer is achievable through increased uptake of human papillomavirus vaccination and efforts to increase screening for cervical cancer, especially when enacted to reduce disparities in across the world.

Objectives: In the spring of 2020, Chatham County of North Carolina became a COVID-19 rural epicenter for SARS-CoV-2 infection. During this time seroprevalence of SARS-CoV-2 among adults in Chatham County was as high as 9%.5 The objective of this study was to measure the incidence of SARS-CoV-2 viral infection among pregnant patients seeking care at two rural federally qualified health centers in Chatham County. Methods: This was a retrospective cohort study of mothers and neonates who (1) received prenatal care at the above-mentioned medical clinics between March 2020 and July 2020 and (2) received nasopharyngeal SARS-CoV-2 PCR testing as a part of their prenatal care. Data were collected from outpatient and inpatient records beginning at first prenatal visit until first postpartum visit. Neonatal data were collected from time of birth until first well child visit. Descriptive Statistics are reported. Results: Fifty-one patients who received prenatal care at the study sites were tested for SARS-CoV-2. Hospital records were available from 48 deliveries. A total of 17 (33%) of 51 women tested positive for SARS-CoV-2 virus. Eleven patients had positive tests at prenatal testing; 3 tested positive at delivery, and 3 tested positive during the postpartum period, within 6 weeks of delivery. Two out of the three neonates born to mothers who tested positive at delivery were tested at 24-48 hours of life and neither tested positive. Two of three infants tested after hospital discharge but prior to the first well child visit had positive test results. Race/ethnicity were as follows: Hispanic/Latina (90.0%), Non-Hispanic white (2.0%), Black/African American (3.9%) and Asian (3.9%). Thirty-five women (68.6%) were identified as having no insurance, 10 women (19.6%) had Medicaid or other federal or state supported program, and 5 (9.8%) had private insurance. Conclusions: One-third of this cohort of pregnant patients in a rural setting in a COVID pandemic hotspot in NC tested positive for SARs-CoV-2 infection, significantly higher than the population seroprevalence at the time.

Persons with HIV can receive mixed messages about the safety of breastfeeding. We sought to assess if they felt coerced to formula feed when counseled about practices to reduce HIV transmission. Persons with HIV who had given birth were eligible to complete a survey to describe their experiences with infant feeding counseling and if they felt coerced to formula feed. An Iowa Infant Feeding Attitude Scale (IIFAS) assessed attitudes towards breastfeeding. Qualitative analyses were performed on narrative responses. One hundred surveys were collected from sites in Georgia, North Carolina, Pennsylvania, and South Carolina. The mean IIFAS score (

To measure maternal/fetal SARS-CoV-2 antibody levels.A prospective observational study of eligible parturients admitted to the hospital for infant delivery was conducted between April and September 2020. SARS-CoV-2 antibody levels were measured in maternal and umbilical cord specimens using an in-house ELISA based on the receptor-binding domain (RBD) of the spike protein. Among SARS-CoV-2 seropositive patients, spike RBD antibody isotypes (IgG, IgM, and IgA) and ACE2 inhibiting antibodies were measured.In total, 402 mothers were enrolled and spike RBD antibodies in 388 pregnancies were measured (336 maternal and 52 cord specimens). Of them, 19 were positive (15 maternal, 4 cord) resulting in a seroprevalence estimate of 4.8% (95% confidence interval 2.9-7.4). Of the 15 positive maternal specimens, all had cord blood tested. Of the 15 paired specimens, 14 (93.3%) were concordant. Four of the 15 pairs were from symptomatic mothers, and all four showed high spike-ACE2 blocking antibody levels, compared to only 3 of 11 (27.3%) from asymptomatic mothers.A variable antibody response to SARS-CoV-2 in pregnancy among asymptomatic infections compared to symptomatic infections was found, the significance of which is unknown. Although transfer of transplacental neutralizing antibodies occurred, additional research is needed to determine how long maternal antibodies can protect the infant against SARS-CoV-2 infection.

OBJECTIVE: To evaluate the associations of HIV infection with preterm birth (PTB), and of HIV antiretroviral therapy (ART) with PTB. METHODS: We analysed singleton live-born pregnancies among women from 1995 to 2019 in the Women’s Interagency HIV Study, a prospective cohort of US women with, or at risk for, HIV. The primary exposures were HIV status and ART use before delivery [none, monotherapy or dual therapy, or highly active antiretroviral therapy (HAART)]. The primary outcome was PTB < 34 weeks, and, secondarily, < 28 and < 37 weeks. We analysed self-reported birth data, and separately modelled the associations between HFV and PTB, and between ART and PTB, among women with HIV. We used modified Poisson regression, and adjusted for age, race, parity, tobacco use and delivery year, and, when modelling the impact of ART, duration from HIV diagnosis to delivery, nadir CD4 count, and pre-pregnancy viral load and CD4 count. RESULTS: We analysed 488 singleton deliveries (56% exposed to HIV) to 383 women. The risk of PTB < 34 weeks was similar among women with and without HIV, but the risk of PTB < 37 weeks was higher [32% vs. 23%; adjusted risk ratio (aRR) = 1.43; 95% confidence interval (CI): 1.07–1.91] among women with HIV. The risk of PTB < 34 weeks was lower among women with HIV receiving HAART than among those receiving no ART (7% vs. 26%; aRR:0.19; 95% CI: 0.08–0.44). The associations between HAART and PTB < 28 and < 37 weeks were similar. CONCLUSIONS: Antiretroviral therapy exposure was associated with a decreased risk of PTB among a US cohort of women with HIV. Given the growing concerns about ART and adverse pregnancy outcomes, this finding that ART may be protective for PTB is reassuring.

Considerable strides have been made in reducing the rate of perinatal human immunodeficiency virus (HIV) transmission within the United States and around the globe. Despite this progress, preventable perinatal HIV transmission continues to occur. Adherence to HIV screening and treatment recommendations preconception and during pregnancy can greatly reduce the risk of perinatal HIV transmission. Early and consistent usage of highly active antiretroviral therapy (ART) can greatly lower the HIV viral load, thus minimizing HIV transmission risk. Additional intrapartum interventions can further reduce the risk of HIV transmission. Although the current standard is to recommend abstinence from breastfeeding for individuals living with HIV in settings where there is safe access to breast milk alternatives (such as in the United States), there is guidance available on counseling and risk-reduction strategies for individuals on ART with an undetectable viral load who elect to breastfeed.

Background: Primary high-risk human papillomavirus (hr-HPV) testing of self-collected cervico-vaginal swabs could increase cervical cancer screening coverage, although triage strategies are needed to reduce unnecessary colposcopies. We evaluated the use of extended hr-HPV genotyping of self-collected samples for cervical cancer screening. Methods: We recruited women ages 25–65 years at two colposcopy clinics in North Carolina between November 2016 and January 2019, and obtained self-collected cervico-vaginal samples, provider-collected cervical samples, and cervical biopsies from all enrolled women. Self- and provider-collected samples were tested for 14 hr-HPV genotypes using the Onclarity Assay (Becton Dickinson). We calculated hr-HPV genotype–specific prevalence and assessed agreement between results in self- and provider-collected samples. We ranked the hr-HPV genotypes according to their positive predictive value (PPV) for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or higher (CIN2+). Results: A total of 314 women participated (median age, 36 years); 85 women (27%) had CIN2+. More women tested positive for any hr-HPV on self-collected (76%) than on provider-collected samples (70%; P = 0.009) with type-specific agreement ranging from substantial to almost perfect. HPV-16 was the most common genotype in self-collected (27%) and provider-collected samples (20%), and HPV-16 prevalence was higher in self- than provider-collected samples (P < 0.001). In self- and provider-collected samples, HPV-16 had the highest PPV for CIN2+ detection. Conclusions: Overall sensitivity for CIN2+ detection was similar for both sample types, but the higher HPV-16 prevalence in self-collected samples could result in increased colposcopy referral rates. Impact: Additional molecular markers might be helpful to improve the triage of women who are hr-HPV positive on self-collected samples.

Introduction The multiple mini interview (MMI) has been incorporated into the holistic review process in the selection of students to US medical schools. The MMI has been used to evaluate interpersonal and intrapersonal attributes which are deemed as necessary for future physicians. We hypothesized that there would be little difference in overall MMI evaluation data compared with traditional interview ratings. Methods The University of North Carolina School of Medicine developed an interview process that included a traditional interview and MMI format during the 2019 admissions cycle. Evaluation data along with key demographic variables for 608 MD program applicants were analyzed using descriptive and inferential statistical analyses. Results The MMI format slightly favored female over male applicants (p = 0.002) but did not select for or against applicants based on age, race/ethnicity, underserved/rural area upbringing, or indicators of disadvantage. Out of 608 applicants, 356 (59%) completed a post-interview survey in which the experience was positively rated. Discussion Based on our experience, the use of a hybrid model of traditional interviews complemented with MMI stations provided greater details in the assessment of medical school applicants while obtaining equivalent data and acceptability amongst applicants.

Background: We compared women's acceptability of urine and cervico-vaginal sample self-collection for high-risk (oncogenic) human papillomavirus (hrHPV) testing and assessed whether acceptability v...

Background: Characterizing estradiol among women with HIV may have implications for breast cancer and cardiovascular disease risk but has not been adequately explored. We quantified differences in total (E2), free (FE2) estradiol, and sex hormone binding globulin (SHBG) by HIV and viral suppression status. Methods: Women from a substudy (2003–2006) within the Women's Interagency HIV Study (IRB approved at each participating site) were included if they reported: a period in the last six months, were not pregnant/breastfeeding, no oophorectomy, and no exogenous hormone use in the prior year. Serum was collected on days 2–4 of the menstrual cycle. We assessed differences in biomarkers at 25th, 50th, and 75th percentiles by HIV and viral suppression status using weighted quantile regression. Results: Among 643 women (68% with HIV) median age was 37 years. All E2 percentiles were significantly (p

Historically, individuals with HIV have reported feeling coerced during contraceptive counseling or experienced forced sterilization. The purpose of this study was to assess perceptions of coercion related to counseling and influence on postpartum contraceptive choice among individuals with HIV.This is a mixed methods study conducted in Georgia, North Carolina, Pennsylvania, and South Carolina between March 2020 and June 2021. Participants completed a survey to assess their experiences with contraception counseling and perceived coercion. An Interpersonal Quality of Family Planning (IQFP) care score was calculated to assess quality of counseling. Qualitative analyses were performed on narrative responses. Bivariate and regression analyses were used to evaluate factors associated with perceived coercion and IQFP scores.100 surveys were collected. The median age of respondents was 29 (IQR 24-35). The median IQFP score was 53 (IQR 44-55) and 45 % of individuals had a maximum IQFP score of 55. Most individuals (96 %) report that a provider "did a good job" explaining contraceptive options and 26 % report their provider's preference affected their contraceptive choice to some degree. Few (11 %) respondents felt pressured to use long-acting reversible contraception postpartum. This perceived coercion was more likely when a provider suggested a specific contraceptive method, aOR 6.1 [95 % CI 1.1-33.1] and such specific provider suggestions were reported by one-third of respondents.While perceived coercion was reported by few individuals with HIV, it was strongly associated with the provider making a specific method suggestion. Disproportionate provider influence in the final contraceptive decision occurred in one-quarter of individuals. More research is needed to discern to what extent provider preference compromises patient autonomy in shared decision-making.

Background Over the past 40 years, the physician supply of North Carolina (NC) grew faster than the total population. However, the distribution of physicians between urban and rural areas increased, with many more physicians in urban areas. In rural counties, access to care and health disparities remain concerning. As a result, the medical school implemented pipeline programs to recruit more rural students. This study investigates the results of these recruitment efforts. Methodology Descriptive analyses were conducted to compare the number and percentage of rural and urban students from NC who applied, interviewed, and were accepted to the University of North Carolina's School of Medicine (UNC SOM). The likely pool of rural applicants was based on the number of college-educated 18-34-year-olds by county. Results Roughly 10.9% of NC's population of college-educated 18-34-year-olds live in rural counties. Between 2017 and 2019, 9.3% (n = 225) of UNC SOM applicants were from a rural county. An increase of just 14 additional rural applicants annually would bring the proportion of rural UNC SOM applicants in alignment with the potential applicant pool in rural NC counties. Conclusions Our model of analysis successfully calculated the impact of recruitment efforts to achieve proportional parity in the medical school class with the rural population of the state. Addressing rural physician workforce needs will require multiple strategies that affect different parts of the medical education and healthcare systems, including boosting college completion rates in rural areas. This model of analysis can also be applied to other pipeline programs to document the success of the recruitment efforts.

Background Primary human papillomavirus (HPV) screening (PHS) utilizes oncogenic human papillomavirus (oncHPV) testing as the initial cervical cancer screening method and typically, if positive, additional reflex-triage (eg, HPV16/18-genotyping, Pap testing). While US guidelines support PHS usage in the general population, PHS has been little studied in women living with HIV (WLWH). Methods We enrolled n = 865 WLWH (323 from the Women’s Interagency HIV Study [WIHS] and 542 from WIHS-affiliated colposcopy clinics). All participants underwent Pap and oncHPV testing, including HPV16/18-genotyping. WIHS WLWH who tested oncHPV[+] or had cytologic atypical squamous cells of undetermined significance or worse (ASC-US+) underwent colposcopy, as did a random 21% of WLWH who were oncHPV[−]/Pap[−] (controls). Most participants additionally underwent p16/Ki-67 immunocytochemistry. Results Mean age was 46 years, median CD4 was 592 cells/µL, 95% used antiretroviral therapy. Seventy WLWH had histologically-determined cervical intraepithelial neoplasia grade 2 or greater (CIN-2+), of which 33 were defined as precancer (ie, [i] CIN-3+ or [ii] CIN-2 if concurrent with cytologic high grade squamous intraepithelial lesions [HSILs]). PHS had 87% sensitivity (Se) for precancer, 9% positive predictive value (PPV), and a 35% colposcopy referral rate (Colpo). “PHS with reflex HPV16/18-genotyping and Pap testing” had 84% Se, 16% PPV, 30% Colpo. PHS with only HPV16/18-genotyping had 24% Colpo. “Concurrent oncHPV and Pap Testing” (Co-Testing) had 91% Se, 12% PPV, 40% Colpo. p16/Ki-67 immunochemistry had the highest PPV, 20%, but 13% specimen inadequacy. Conclusions PHS with reflex HPV16/18-genotyping had fewer unnecessary colposcopies and (if confirmed) could be a potential alternative to Co-Testing in WLWH.

Background Over the past 40 years, North Carolina’s physician supply grew faster than the total population, but the maldistribution of physicians between urban and rural areas increased. In rural counties, access-to-care and health disparities remain concerning. Method Descriptive analyses were conducted to compare the number and percentage of rural and urban students from North Carolina (NC) who applied, interviewed, and were accepted to the University of North Carolina’s School of Medicine. The likely pool of rural applicants was based on the number of college-educated 18-34-year-olds by county. Results Roughly 10.9% of NC’s population of college-educated 18-34-year-olds live in rural counties. Between 2017–2019, 9.3% (n = 225) of UNC SOM applicants were from a rural county. Conclusion An increase of just 14 additional rural applicants annually would bring the proportion of rural UNC SOM applicants in alignment with the potential applicant pool in rural NC counties. Addressing NC’s rural physician workforce needs will require multiple strategies that affect different parts of the medical education and health care systems, including boosting college completion rates in rural areas.

Objective To map the cervical cancer screening cascade among women living with HIV attending a public-sector cytology screening program in Johannesburg, South Africa. Methods We conducted a retrospective cohort study of routinely collected clinical data captured in an electronic medical record system. Women (≥18 years) living with HIV with an abnormal Pap result between January 2013 and May 2018 were included. The proportion of women who received follow-up consistent with extant clinical guidelines, stratified by their initial Pap smear result, was examined. Results The study included 2072 women: 1384 (66.8%) with a low-risk Pap result, 681 (32.9%) with a high-risk Pap result, and 7 (0.3%) with suspected cancer. Only 174 (25.6%) women with a high-risk Pap result underwent guideline-indicated management within 18 months. Among women with a low-risk Pap result, 375 (27.1%) received follow-up within 1 year; the cumulative incidence of follow-up increased to 63.1% at 3 years. All women with suspected cancer either received a colposcopic biopsy or were referred for further treatment. Conclusion Attrition among South African women living with HIV who attended cervical screening in an urban public-sector program was high. Developing tailored interventions to address bottlenecks in the care cascade and improve cervical screening outcomes will be central to eliminating cervical cancer.

OBJECTIVE The aim of this study was to evaluate postpartum HIV care outcomes. DESIGN A prospective clinical cohort of women with HIV and a live birth at the University of North Carolina, 1996-2014. METHODS We estimated two stages of the HIV care continuum in the first 24 months postpartum: care retention (at least two visits per year, ≥90 days apart) and viral suppression (HIV RNA

Infection by human papillomavirus (HPV) type 16, the most oncogenic HPV type, was found to be the least affected by HIV-status and CD4 count of any of the approximately 13 oncogenic HPV types. This relative independence from host immune status has been interpreted as evidence that HPV16 may have an innate ability to avoid the effects of immunosurveillance. However, the impact of immune status on other individual HPV types has not been carefully assessed. We studied type-specific HPV infection in a cohort of 2,470 HIV-positive (HIV[+]) and 895 HIV-negative (HIV[−]) women. Semi-annually collected cervicovaginal lavages were tested for >40 HPV types. HPV type-specific prevalence ratios (PRs), incidence and clearance hazard ratios (HRs), were calculated by contrasting HPV types detected in HIV[+] women with CD4 < 200 to HIV[−] women. HPV71 and HPV16 prevalence had the weakest associations with HIV-status/CD4 count of any HPV, according to PRs. No correlations between PRs and HPV phylogeny or oncogenicity were observed. Instead, higher HPV type-specific prevalence in HIV[−] women correlated with lower PRs (ρ = −0.59; p = 0.0001). An alternative (quadratic model) statistical approach (P(HIV+) = a*P(HIV−) + b*P(HIV−)(2); R(2) = 0.894) found similar associations (p = 0.0005). In summary, the most prevalent HPV types in HIV[−] women were the types most independent from host immune status. These results suggest that common HPV types in HIV[−] women may have a greater ability to avoid immune surveillance than other types, which may help explain why they are common.

To explore the associations of urbanicity with clinical/behavioral outcomes and sociodemographic factors among women living with HIV in the Southern United States, 523 participants of the Women’s Interagency HIV Study were classified into population density quartiles. Rural-Urban Commuting Area codes revealed that 7% resided in areas where >30% commute to urban areas, 2% resided in small towns or rural areas, and 91% resided in varying densities of urban areas. Although women in lower density, mostly suburban areas reported higher socioeconomic indicators such as advanced education and greater annual household income, larger proportions of women in the lowest density quartile (compared to those in more dense and urban areas) perceived discrimination in health care settings and agreed with several internalized HIV stigma scale items. Women in the lower quartiles had higher CD4 counts, while those in the lowest quartile were more likely to have a suppressed HIV viral load, report being employed, and not report a history of drug use or current heavy alcohol use. More research is needed to understand the interplay between population density and mechanisms contributing to HIV control as well as increased internalized stigma and perceived discrimination, along with how to target interventions (including for stigma alleviation) to improve outcomes for individuals with HIV across urban, suburban, and rural areas.

Objective: There are no currently approved options for medical management of cervical intraepithelial neoplasia (CIN) 2/3. This article describes the use of intravaginal 5% 5-fluorouracil (5-FU) fo...

Objective To evaluate the natural history of treated and untreated cervical intraepithelial neoplasia-2 (CIN2) among HIV-positive women. Methods Participants were women enrolled in the Women's Interagency HIV Study between 1994 and 2013. One hundred four HIV-positive women diagnosed with CIN2 before age 46 were selected, contributing 2076 visits over a median of 10 years (interquartile range 5-16). The outcome of interest was biopsy-confirmed CIN2 progression, defined as CIN3 or invasive cervical cancer. CIN2 treatment was abstracted from medical records. Results Most women were African American (53%), current smokers (53%), and had a median age of 33 years at CIN2 diagnosis. Among the 104 HIV-positive women, 62 (59.6%) did not receive CIN2 treatment. Twelve HIV-positive women (11.5%) showed CIN2 progression to CIN3; none were diagnosed with cervical cancer. There was no difference in the median time to progression between CIN2-treated and CIN2-untreated HIV-positive women (2.9 vs. 2.7 years, P = 0.41). CIN2 treatment was not associated with CIN2 progression in multivariate analysis (adjusted hazard ratio 1.82; 95% confidence interval: 0.54 to 7.11), adjusting for combination antiretroviral therapy and CD4 T-cell count. In HIV-positive women, each increase of 100 CD4 T cells was associated with a 33% decrease in CIN2 progression (adjusted hazard ratio 0.67; 95% confidence interval: 0.47 to 0.88), adjusting for CIN2 treatment and combination antiretroviral therapy. Conclusions CIN2 progression is uncommon in this population, regardless of CIN2 treatment. Additional studies are needed to identify factors to differentiate women at highest risk of CIN2 progression.

OBJECTIVE Cervical excision procedures are essential to the care of cervical dysplasia and malignancy. We sought to determine whether learner involvement in cervical excision procedures affects the quality of excision specimen. MATERIALS AND METHODS A retrospective cohort study of cervical cancer patients diagnosed from July 1, 2000, to July 1, 2015, was performed. We included patients who had (1) a cervical excision procedure, either loop electrosurgical excision procedure or cold knife cone, and (2) pathologic information available. Primary outcome was the margin status of the specimen; secondary outcome was the size of the excision specimen including both width and depth. The exposure of interest was trainee participation, defined as resident physicians under the supervision of either a gynecologist or gynecologic oncologist. Descriptive statistics and general linear models were used for analysis. RESULTS Ninety-four patients were identified. Overall, 58% (n = 54) of procedures were performed with trainee involvement. There was no difference in age, body mass index, or specimen width between trainee-performed and nontrainee-performed excisions. There was no significant difference in the status of margins with or without a trainee [44/57 (77%) and 29/37 (78%), respectively, p = .89]. There was a statistically significant difference in median specimen depth between trainee-performed and nontrainee-performed cases (15.4 mm vs 12 mm, p < .02). When adjusting for age, body mass index, excision type, indication, presence of trainee, and type of supervising physician, only the indication and type of excision were associated with greater depth of excision, (p < .01). CONCLUSIONS Trainee involvement in cervical excision procedures does not alter the quality of excision specimen.

Background Current US cervical cancer screening guidelines recommend screening cessation at the age of 65 years provided women have adequate previous screening and no history of precancer. Women living with HIV are at higher risk of cervical cancer than women living without HIV. Furthermore, limited data exists to quantify the risk of cervical cancer among women who otherwise would qualify for screening cessation. Objective This study aimed to determine whether guidelines recommending women to discontinue cervical cancer screening at the age of 65 years are appropriate for women living with HIV. Study Design Semiannual Papanicolaou testing was performed as part of surveillance visits in the Women’s Interagency HIV Study. Launched in October 1994, the Women’s Interagency HIV Study is a federally funded US multisite cohort study that has enrolled 3678 women living with HIV and 1304 women living without HIV; we included data throughout September 2019 onward. Conventional Papanicolaou tests were collected at scheduled 6-month visits and read centrally according to the 1991 Bethesda System criteria. Results were analyzed among women at least 65 years of age. The primary endpoint was high-grade cytology, including high-grade squamous intraepithelial lesions; atypical glandular cells; atypical squamous cells, cannot exclude high-grade lesions; and malignant cytology. Wilcoxon rank-sum tests were used to compare the continuous variables, and Chi-square tests or the Fisher exact tests were used to compare the categorical variables. The Kaplan-Meier method was used to calculate the cumulative incidence. Poisson regression was used to compare 2 incidence rates. Results Of 169 eligible women (121 women living with HIV and 48 women living without HIV) who contributed 678.4 person-years of observation after reaching the age of 65 years, 2.2% had high-grade cytologic abnormalities. However, no cancer was found. Furthermore, 20 women had previous precancer results, and 74 women had abnormal Papanicolaou test results in the previous decade. Among 50 women (38 women living with HIV and 12 women living without HIV) with a previous hysterectomy and no history of cervical precancer, the cumulative incidence rates of high-grade squamous intraepithelial lesions were 0.6 (95% confidence interval, 0.0–3.2) per 100 person-years for women living with HIV and 0.0 (95% confidence interval, 0.0–8.1) per 100 person-years for women living without HIV (P=.61). Only 48 women (27 women living with HIV and 21 women living without HIV) had cervices and met the current guidelines to discontinue screening; their risk of experiencing high-grade squamous intraepithelial lesions was 2.2 (95% confidence interval, 0.6–5.5) per 100 person-years overall and did not vary by HIV status (2.3 [95% confidence interval, 0.5–6.8] per 100 person-years for women living with HIV and 1.8 [95% confidence interval, 0.0–9.8] per 100 person-years for women living without HIV; P=.81). Conclusion Most women living with HIV do not meet the criteria for cervical cancer screening cessation and will need to continue screening over the age of 65 years; however, women who meet the criteria for screening cessation have risks of high-grade squamous lesions similar to women living without HIV and may choose to discontinue.

The objective was to assess the diagnostic test accuracy of high-risk human papillomavirus (hrHPV) testing of self-collected urine and cervicovaginal samples for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). We recruited a convenience sample of women 25 to 65 years of age who were undergoing clinically indicated colposcopy at two medical centers in North Carolina between November 2016 and January 2019. Women with normal cytology results and positive hrHPV results were also recruited. Urine samples, self-collected cervicovaginal samples, provider-collected cervical samples, and cervical biopsy samples were obtained from all enrolled women. Samples were tested for hrHPV DNA using the Onclarity assay (Becton Dickinson, Sparks, MD). Biopsy samples were histologically graded as CIN2+ or

Women who are late to prenatal care miss opportunities for health interventions and are at increased risk for pregnancy-related complications. Black women have the lowest rates of first trimester care compared with White or Latinx women. We sought to describe barriers to prenatal care experienced by race/ethnicity in a multi-site, prospective cohort. We performed a secondary analysis of the Community Child Health Research Network Study, a multi-site prospective cohort study of pregnant women from 2008 to 2012. Women were recruited at the time of delivery and followed prospectively for 2 years. Participants who experienced a repeat pregnancy in the 2-year follow-up period had a prospective assessment of prenatal care barriers. A multilevel mixed effects Poisson regression was performed to evaluate the association between race/ethnicity and number of prenatal barriers. Of the 298 participants in the sample, 43% of Black, 35% of Latinx, and 23% of White participants reported barriers to prenatal care. After adjustment for confounders, Black and Latinx women reported almost twice as many barriers to prenatal care as White women (adjusted rate ratio 1.89 [1.2, 3.0]; 2.00 [1.1, 3.8], respectively). In our analysis, multiparous Black and Latinx women reported encountering more barriers to prenatal care than White women. Additional reforms and policy change are needed at the clinic, local, and state levels to support women in accessing early quality prenatal care to achieve racial equity in prenatal care.

The scientific and ethical importance of including women of reproductive age in biomedical research is widely acknowledged. Concerns about preventing fetal exposure to research interventions have motivated requirements for contraception among reproductive aged women in biomedical studies-often irrespective of risks and benefits or a woman's actual potential for pregnancy, raising important questions about when such requirements are appropriate. The perspectives of women themselves on these issues are largely unexplored. We conducted 140 interviews, 70 in the U.S. and 70 in Malawi, with women either living with or at-risk for HIV, exploring their views about the practice of requiring contraception in clinical trials. A majority of women interviewed from both countries indicated overall support for the practice, with seven themes characterizing advantages and disadvantages raised: reproductive control, health effects, prevention of fetal harm, burden on women, deferral to authority, autonomy regarding enrollment and birth control method, and relationship concerns. While women in the US frequently raised prevention of fetal harm as a key advantage, many other positives noted by women in both countries were related to contraception use in general, not specific to a trial context. With regard to disadvantages, U.S. women tended to focus on biomedical risks such as side effects and impact on fertility, whereas Malawian women focused on the social risks of contraception requirements, including violations of trust in marital relations and suspicions of potential infidelity. Given the potential benefits and burdens highlighted, contraception in research should be sensitive to actual fetal risk assessments; directed where justified at optimizing effective pregnancy prevention; responsive to women's reproductive preferences; and made available as an ancillary benefit even where risk thresholds do not justify requirement-in order to facilitate trials that are both ethical and robustly oriented around the interests and lives of women who will participate in them.

Background There is a knowledge gap on the clinical use of elvitegravir (EVG) during pregnancy and maternal viral suppression. Our objective was to evaluate the effects of EVG use in pregnancy on rates of HIV virologic suppression and perinatal outcomes. Methods We conducted a retrospective, multicenter study of pregnant women living with HIV (WLHIV) who used EVG-containing antiretroviral therapy (ART) between January 2014 and March 2017 at 9 tertiary care centers in the United States. WLHIV were included if they took EVG at any time during pregnancy. We described the characteristics of the WLHIV using EVG during the study period and evaluated the rates of HIV suppression and perinatal outcomes. Results Among 134 pregnant WLHIV who received EVG at any time during pregnancy, viral suppression at delivery (HIV-1 RNA < 40 copies/mL) occurred in 81.3%. In WLHIV who initiated EVG before pregnancy and continued through delivery (n = 68), the rate of viral suppression at delivery was 88.2%. The average gestational age at the time of delivery was 37 weeks 6 days, and the overall rate of preterm birth was 20%. No cases of open neural tube defects were noted in women on EVG at the time of conception (n = 82). The perinatal HIV transmission rate was 0.8%. Conclusions EVG use was associated with high sustained levels of HIV suppression during pregnancy and a low rate of perinatal HIV transmission.

Relatively little is known about the frequency and factors associated with miscarriage among women living with HIV.The objective of the study was to evaluate factors associated with miscarriage among women enrolled in the Women's Interagency HIV Study.We conducted an analysis of longitudinal data collected from Oct. 1, 1994, to Sept. 30, 2017. Women who attended at least 2 Women's Interagency HIV Study visits and reported pregnancy during follow-up were included. Miscarriage was defined as spontaneous loss of pregnancy before 20 weeks of gestation based on self-report assessed at biannual visits. We modeled the association between demographic, behavioral, and clinical covariates and miscarriage (vs live birth) for women overall and stratified by HIV status using mixed-model logistic regression.Similar proportions of women living with and without HIV experienced miscarriage (37% and 39%, respectively, P = .638). In adjusted analyses, smoking tobacco (adjusted odds ratio, 2.0), alcohol use (adjusted odds ratio, 4.0), and marijuana use (adjusted odds ratio, 2.0) were associated with miscarriage. Among women living with HIV, low HIV viral load (4 log10 copies/mL) (adjusted odds ratio, 0.5) and protease inhibitor (adjusted odds ratio, 0.4) vs the nonuse of combination antiretroviral therapy use were protective against miscarriage.We did not find an increased odds of miscarriage among women living with HIV compared with uninfected women; however, poorly controlled HIV infection was associated with increased miscarriage risk. Higher miscarriage risk among women exposed to tobacco, alcohol, and marijuana highlight potentially modifiable behaviors. Given previous concern about antiretroviral therapy and adverse pregnancy outcomes, the novel protective association between protease inhibitors compared with non-combination antiretroviral therapy and miscarriage in this study is reassuring.

OBJECTIVES Self-collection of samples for human papillomavirus (HPV) testing (self-collection) has the potential to increase cervical cancer screening among underscreened women. We assessed attitudes toward at-home HPV self-collection compared with clinic-based Pap testing in this higher-risk population. MATERIALS AND METHODS Participants were low-income women in North Carolina overdue for cervical cancer screening. Women self-collected samples at home, returned samples by mail for HPV testing, and completed phone questionnaires about at-home HPV self-collection. Participants were referred to clinic-based Pap testing and invited to complete a second questionnaire about Pap testing. A cross-sectional questionnaire compared attitudes, experiences, and preferences for self-collection versus Pap testing and assessed predictors of preference for HPV self-collection. RESULTS Half (51%) of 221 women reported a preference for HPV self-collection, 19% preferred Pap testing, and 27% reported no preference. More women reported difficulty finding time to do the Pap test (31%) than the self-test (13%, p = .003) and being afraid of the self-test results (50%) than the Pap test results (36%, p = .02). There were relatively fewer reports of physical discomfort and pain from self-collection than Pap testing (discomfort: 18% self; 48% Pap; pain: 8% self; 30% Pap, p = .001). No differences were found in positive versus negative thoughts about the tests, trust in the tests' safety and accuracy, or willingness to do tests again. CONCLUSIONS Overall positive attitudes toward HPV self-collection compared with Pap testing among underscreened women suggest that self-collection is a promising option to increase cervical cancer screening in this high-risk population.

Background: HIV-positive women are at substantial risk of HPV-associated cervical neoplasia caused by high-risk (HR) HPVs. Methylation of the HPV genome is associated with cervical intraepithelial neoplasia grade 3 (CIN3) in HIV-negative women, yet it is unknown whether this holds true for HIV-positive women. Methods: We designed a case–control study within the Women's Interagency HIV Study (WIHS) cohort comparing HIV-positive CIN3 cases (N = 72) to HIV-positive controls without detectable CIN2+. The unit of analysis and matching was HPV-type infection. Cases with ≥2 HR-HPV types (N = 23; 32%) had a separate control for each HR-HPV type. We developed and utilized next-generation sequencing (NGS) methylation assays for 12 different HR-HPVs, focusing on CpG sites in the L1/L2 regions. Results: Significant case–control differences in individual CpG site methylation levels were observed for multiple alpha-9 (HPV16/31/35/58) and alpha-7 HPV (HPV18/39/45) types, based on dichotomization of tertile levels (T3 vs. T1 and T2). Analyses combining homologous CpG sites [e.g., HPV16-L1-5608/HPV31-L1-5521/HPV35-L2L1-5570; OR = 7.28; 95% confidence interval (CI): 2.75–19.3], and (e.g., HPV18-L1-7062/HPV45-L1-7066; OR = 6.94; 95% CI: 1.23–39.3) were significant in separate case–control comparisons. In cases with multiple HR-HPVs, we tested and confirmed the hypothesis that one HR-HPV type would have higher methylation than other types detected, consistent with there being a single HR-HPV causally related to a lesion. Conclusions: CIN3 is associated with elevated L1/L2 CpG methylation levels in HIV-positive women. Impact: HPV DNA CpG methylation is a promising triage option in HIV-positive women testing positive for HR-HPV types and provides risk attribution in women with multiple HPV type infections.

Cervical cancer is currently the fourth leading cause of cancer death among women worldwide, with most cases occurring in low- and middle-income countries. Safe, highly effective vaccines against human papillomavirus (HPV) have been on the market since 2006, yet only 6% of girls worldwide have received this life-saving cancer prevention intervention. International organizations, including PATH, Gavi, and the pharmaceutical companies Merck and GlaxoSmithKline, have provided support to eligible low- and middle-income countries to implement national HPV vaccination programs. Still, glaring disparities in the availability of national HPV vaccination programs and the coverage of the primary target population between the global north and south persist. We illustrate worldwide HPV vaccine implementation and coverage using an online data visualization, which is publicly available and can be used to gain unique insights. We also present three emerging solutions to transform future HPV vaccine delivery in low- and middle-income countries: low-cost generics, single-dose vaccination, and co-administration with other adolescent vaccines. By rapidly expanding access to HPV vaccination to girls everywhere, vaccine-type HPV infections can be virtually eliminated. At high vaccination-coverage levels, more than 80%—or approximately 230 000—of the cervical cancer deaths that occur each year can be averted.

There are approximately 284,500 adolescent and adult women living with human immunodeficiency virus (HIV) in the United States. It is estimated that approximately 8500 of these women give birth annually. While the rate of perinatal transmission in the United States has decreased by more than 90% since the early 1990s, potentially preventable HIV transmission events still occur and cause significant morbidity and mortality.The aim of this review was to summarize the current data regarding perinatal HIV transmission timing and risk factors, current management recommendations, and implications of timing of transmission on patient management.Literature review.This review reiterates that the risk of perinatal HIV transmission can be reduced to very low levels by following current recommendations for screening for HIV in all pregnant women and properly treating HIV-infected mothers, as well as using evidence-based labor management practices.Familiarity with the pathogenesis of HIV transmission is important for obstetric care providers to appropriately manage HIV-infected women in pregnancy, intrapartum, and the postpartum period.

Background Urine testing for high-risk human papillomavirus (HR-HPV) detection could provide a non-invasive, simple method for cervical cancer screening. Objectives We examined whether HR-HPV detection is affected by urine collection time, portion of urine stream, or urine fraction tested, and assessed the performance of HR-HPV testing in urine for detection of cervical intraepithelial neoplasia grade II or worse (CIN2+). Study design A total of 37 female colposcopy clinic attendees, ≥30 years, provided three urine samples: “first void” urine collected at home, and “initial stream” and “mid-stream” urine samples collected at the clinic later in the day. Self- and physician-collected brush specimens were obtained at the same clinic visit. Colposcopy was performed and directed biopsies obtained if clinically indicated. For each urine sample, HR-HPV DNA testing was conducted for unfractionated, pellet, and supernatant fractions using the Trovagene test. HR-HPV mRNA testing was performed on brush specimens using the Aptima HPV assay. Results HR-HPV prevalence was similar in unfractionated and pellet fractions of all urine samples. For supernatant urine fractions, HR-HPV prevalence appeared lower in mid-stream urine (56.8%[40.8–72.7%]) than in initial stream urine (75.7%[61.9–89.5%]). Sensitivity of CIN2+ detection was identical for initial stream urine and physician-collected cervical specimen (89.9%[95%CI = 62.7–99.6%]), and similar to self-collected vaginal specimen (79.1%[48.1–96.6%]). Conclusion This is among the first studies to compare methodologies for collection and processing of urine for HR-HPV detection. HR-HPV prevalence was similar in first void and initial stream urine, and was highly sensitive for CIN2+ detection. Additional research in a larger and general screening population is needed.

Invasive cervical cancer (ICC) is the third most common female malignancy and fourth most common cause of cancer death in women globally1. The risk of ICC is several-fold higher in HIV-positive women than in HIV-negative women, as are the prevalence2–5, incidence, and persistence of oncogenic human papillomavirus (oncHPV)6–14, the infectious cause of most ICC. Although use of effective highly-active antiretroviral therapy (HAART) has been associated with reduced oncHPV prevalence and incidence15 and increased regression of cervical lesions16–19, the overall incidence of ICC has not decreased in HIV-positive women during the HAART era. By increasing survival, HAART may increase lifetime oncHPV infections, allowing accumulation of somatic mutations and epigenetic changes necessary for oncogenesis. Currently, no anti-viral medications are clinically approved to treat cervical HPV infections. In vitro studies have shown that lopinavir (LPV), an HIV-1 protease inhibitor (PI) used in some HAART regimens, may have activity against oncHPV through inhibition of viral oncogene E620, 21. Most recently, an early phase clinical trial conducted in Nairobi, Kenya studied topical application of LPV to the cervix; preliminary results showed that 21 of 23 women initially diagnosed with high-grade disease returned to normal on subsequent Papanicolaou (Pap) smears and showed visible regression of cervical lesions22. We therefore assessed the hypothesis that oral LPV use may be associated with decreased prevalence and increased clearance of oncHPV compared to other antiretroviral (ARV) regimens.

A comparative analysis of cellular and soluble markers of immune activation in HIV-infected women on combination antiretroviral therapy showed that the upper genital tract (UGT) compared to the lower female genital tract was characterized by higher frequencies of potential HIV target cells and increased inflammatory molecules. Despite the activated UGT milieu, HIV RNA could not be detected in paired samples of plasma, cervicovaginal or endometrial lavage. As antiretroviral concentrations were ≥3-fold higher in the endometrium than in the lower genital tract, high antiretroviral penetration and/or metabolism may limit viral replication in the UGT.