Primary HPV and Molecular Cervical Cancer Screening in US Women Living With Human Immunodeficiency Virus.

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.

Miscarriage among women in the United States Women's Interagency HIV Study, 1994-2017.

BACKGROUND: Relatively little is known about the frequency and factors associated with miscarriage among women living with HIV. OBJECTIVE: The objective of the study was to evaluate factors associated with miscarriage among women enrolled in the Women's Interagency HIV Study. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Cervical cancer incidence after up to 20 years of observation among women with HIV.

To estimate the incidence of invasive cervical cancer (ICC) across up to 21 years of follow-up among women with human immunodeficiency virus (HIV) and to compare it to that among HIV-uninfected women, we reviewed ICC diagnoses from a 20-year multi-site U.S. cohort study of HIV infected and uninfected women who had Pap testing every 6 months. Incidence rates were calculated and compared to those in HIV-negative women. Incidence ratios standardized to age-, sex-, race-, and calendar-year specific population rates were calculated. After a median follow-up of 12.3 years, four ICCs were confirmed in HIV seropositive women, only one in the last 10 years of observation, and none in seronegative women. The ICC incidence rate did not differ significantly by HIV status (HIV seronegative: 0/100,000 person-years vs. HIV seropositive: 19.5/100,000 person-years; p = 0.53). The standardized incidence ratio for the HIV-infected WIHS participants was 3.31 (95% CI: 0.90, 8.47; p = 0.07). Although marginally more common in women without HIV, for those with HIV in a prevention program, ICC does not emerge as a major threat as women age.

Trends of and factors associated with live-birth and abortion rates among HIV-positive and HIV-negative women.

BACKGROUND: Little is known about fertility choices and pregnancy outcome rates among HIV-infected women in the current combination antiretroviral treatment era. OBJECTIVE: We sought to describe trends and factors associated with live-birth and abortion rates among HIV-positive and high-risk HIV-negative women enrolled in the Women's Interagency HIV Study in the United States. STUDY DESIGN: We analyzed longitudinal data collected from Oct. 1, 1994, through Sept. 30, 2012, through the Women's Interagency HIV Study. Age-adjusted rates per 100 person-years live births and induced abortions were calculated by HIV serostatus over 4 time periods. Poisson mixed effects models containing variables associated with live births and abortions in bivariable analyses (P < .05) generated adjusted incidence rate ratios and 95% confidence intervals. RESULTS: There were 1356 pregnancies among 2414 women. Among HIV-positive women, age-adjusted rates of live birth increased from 1994 through 1997 to 2006 through 2012 (2.85-7.27/100 person-years, P trend < .0001). Age-adjusted rates of abortion in HIV-positive women remained stable over these time periods (4.03-4.29/100 person-years, P trend = .09). Significantly lower live-birth rates occurred among HIV-positive compared to HIV-negative women in 1994 through 1997 and 1997 through 2001, however rates were similar during 2002 through 2005 and 2006 through 2012. Higher CD4+ T cells/mm3 (≥350 adjusted incidence rate ratio, 1.39 [95% CI 1.03-1.89] vs <350) were significantly associated with increased live-birth rates, while combination antiretroviral treatment use (adjusted incidence rate ratio, 1.35 [95% CI 0.99-1.83]) was marginally associated with increased live-birth rates. Younger age, having a prior abortion, condom use, and increased parity were associated with increased abortion rates among both HIV-positive and HIV-negative women. CD4+ T-cell count, combination antiretroviral treatment use, and viral load were not associated with abortion rates. CONCLUSION: Unlike earlier periods (pre-2001) when live-birth rates were lower among HIV-positive women, rates are now similar to HIV-negative women, potentially due to improved health status and combination antiretroviral treatment. Abortion rates remain unchanged, illuminating a need to improve contraceptive services.

Use of HIV pre-exposure prophylaxis during the preconception, antepartum and postpartum periods at two United States medical centers.

BACKGROUND: Pregnancy may increase a woman's susceptibility to HIV. Maternal HIV acquisition during pregnancy and lactation is associated with increased perinatal and lactational HIV transmission. There are no published reports of preexposure prophylaxis use after the first trimester of pregnancy or during lactation. OBJECTIVE: The purpose of this study was to report the use of preexposure prophylaxis and to identify gaps in HIV prevention services for women who were at substantial risk of HIV preconception and during pregnancy and lactation at 2 United States medical centers. STUDY DESIGN: Chart review was performed on women who were identified as "at significant risk" for HIV acquisition preconception (women desiring pregnancy) and during pregnancy and lactation at 2 medical centers in San Francisco and New York from 2010-2015. Women were referred to specialty clinics for women who were living with or were at substantial risk of HIV. RESULTS: Twenty-seven women who were identified had a median age of 27 years. One-half of the women had unstable housing, 22% of the women had ongoing intimate partner violence, and 22% of the women had active substance use. Twenty-six women had a male partner living with HIV, and 1 woman had a male partner who had sex with men. Of the partners who were living with HIV, 73% (19/26) were receiving antiretroviral therapy, and 42% (11/26) had documented viral suppression. Thirty-nine percent (10/26) of partners had known detectable virus, and 19% (5/26) had unknown viral loads. Women were identified by clinicians, health educators, and health departments. Approximately one-third of the women were identified preconception (8/27); the majority of the women were identified during pregnancy (18/27) with a median gestational age of 20 weeks (interquartile range, 11-23), and 1 woman was identified in the postpartum period. None of the pregnant referrals had received safer conception counseling to reduce HIV transmission. Twenty-six percent of all women (7/27) were eligible for postexposure prophylaxis at referral, of whom 57% (4/7) were offered postexposure prophylaxis. In 30% (8/27), the last HIV exposure was not assessed and postexposure prophylaxis was not offered. The median time from identification as "at substantial risk" to consultation was 30 days (interquartile range, 2-62). Two women were lost to follow up before consultation. One woman who was identified as "at significant risk" was not referred because of multiple pregnancy complications. She remained in obstetrics care and was HIV-negative at delivery but was lost to follow up until 10 months after delivery when she was diagnosed with HIV. No other seroconversions were identified. Of referrals who presented and were offered preexposure prophylaxis, 67% women (16/24) chose to take it, which was relatively consistent whether the women were preconception (5/8), pregnant (10/15), or after delivery (1/1). Median length of time on preexposure prophylaxis was 30 weeks (interquartile range, 20-53). One-half of women (10/20) who were in care at delivery did not attend a postpartum visit. CONCLUSION: Women at 2 United States centers frequently chose to use preexposure prophylaxis for HIV prevention when it was offered preconception and during pregnancy and lactation. Further research and education are needed to close critical gaps in screening for women who are at risk of HIV for pre- and postexposure prophylaxis eligibility and gaps in care linkage before and during pregnancy and lactation. Postpartum women are particularly vulnerable to loss-to-follow-up and miss opportunities for safe and effective HIV prevention.

Incidence of cervical precancers among HIV-seropositive women.

OBJECTIVE: The objective of the study was to estimate the impact of human immunodeficiency virus (HIV) infection on the incidence of high-grade cervical intraepithelial neoplasia (CIN). STUDY DESIGN: HIV-seropositive and comparison seronegative women enrolled in a prospective US cohort study were followed up with semiannual Papanicolaou testing, with colposcopy for any abnormality. Histology results were retrieved to identify CIN3+ (CIN3, adenocarcinoma in situ, and cancer) and CIN2+ (CIN2 and CIN3+). Annual detection rates were calculated and risks compared using a Cox analysis. Median follow-up (interquartile range) was 11.0 (5.4-17.2) years for HIV-seronegative and 9.9 (2.5-16.0) for HIV-seropositive women. RESULTS: CIN3+ was diagnosed in 139 HIV-seropositive (5%) and 19 HIV-seronegative women (2%) (P<.0001), with CIN2+ in 316 (12%) and 34 (4%) (P<.0001). The annual CIN3+ detection rate was 0.6 per 100 person-years in HIV-seropositive women and 0.2 per 100 person-years in seronegative women (P<.0001). The CIN3+ detection rate fell after the first 2 years of study, from 0.9 per 100 person-years among HIV-seropositive women to 0.4 per 100 person-years during subsequent follow-up (P<.0001). CIN2+ incidence among these women fell similarly with time, from 2.5 per 100 person-years during the first 2 years after enrollment to 0.9 per 100 person-years subsequently (P<.0001). In Cox analyses controlling for age, the hazard ratio for HIV-seropositive women with CD4 counts less than 200/cmm compared with HIV-seronegative women was 8.1 (95% confidence interval, 4.8-13.8) for CIN3+ and 9.3 (95% confidence interval, 6.3-13.7) for CIN2+ (P<.0001). CONCLUSION: Although HIV-seropositive women have more CIN3+ than HIV-seronegative women, CIN3+ is uncommon and becomes even less frequent after the initiation of regular cervical screening.

The Effects of Viral Load Burden on Pregnancy Loss among HIV-Infected Women in the United States.

BACKGROUND: To evaluate the effects of HIV viral load, measured cross-sectionally and cumulatively, on the risk of miscarriage or stillbirth (pregnancy loss) among HIV-infected women enrolled in the Women's Interagency HIV Study between 1994 and 2013. METHODS: We assessed three exposures: most recent viral load measure before the pregnancy ended, log10 copy-years viremia from initiation of antiretroviral therapy (ART) to conception, and log10 copy-years viremia in the two years before conception. RESULTS: The risk of pregnancy loss for those with log10 viral load >4.00 before pregnancy ended was 1.59 (95% confidence interval (CI): 0.99, 2.56) times as high as the risk for women whose log10 viral load was ≤1.60. There was not a meaningful impact of log10 copy-years viremia since ART or log10 copy-years viremia in the two years before conception on pregnancy loss (adjusted risk ratios (aRRs): 0.80 (95% CI: 0.69, 0.92) and 1.00 (95% CI: 0.90, 1.11), resp.). CONCLUSIONS: Cumulative viral load burden does not appear to be an informative measure for pregnancy loss risk, but the extent of HIV replication during pregnancy, as represented by plasma HIV RNA viral load, predicted loss versus live birth in this ethnically diverse cohort of HIV-infected US women.

Long-term cumulative incidence of cervical intraepithelial neoplasia grade 3 or worse after abnormal cytology: impact of HIV infection.

To estimate the long term cumulative risk for cervical intraepithelial neoplasia grade 3 or worse after an abnormal cervical Pap test and to assess the effect of HIV infection on that risk. Participants in the Women's Interagency HIV Study were followed semiannually for up to 10 years. Pap tests were categorized according to the 1991 Bethesda system. Colposcopy was prescribed within 6 months of any abnormality. Risk for biopsy-confirmed CIN3 or worse after abnormal cytology and at least 12 months follow-up was assessed using Kaplan-Meier curves and compared using log-rank tests. Risk for CIN2 or worse was also assessed, since CIN2 is the threshold for treatment. After a median of 3 years of observation, 1,947 (85%) women subsequently presented for colposcopy (1,571 [81%] HIV seropositive, 376 [19%] seronegative). CIN2 or worse was found in 329 (21%) of HIV seropositive and 42 (11%) seronegative women. CIN3 or worse was found in 141 (9%) of seropositive and 22 (6%) seronegative women. In multivariable analysis, after controlling for cytology grade HIV seropositive women had an increased risk for CIN2 or worse (H.R. 1.66, 95% C.I 1.15, 2.45) but higher risk for CIN3 or worse did not reach significance (H.R. 1.33, 95% C.I. 0.79, 2.34). HIV seropositive women with abnormal Paps face a marginally increased and long-term risk for cervical disease compared to HIV seronegative women, but most women with ASCUS and LSIL Pap results do not develop CIN2 or worse despite years of observation.

Accuracy of colposcopy in HIV seropositive and seronegative women with abnormal Pap tests.

OBJECTIVE: The aim of this study is to compare colposcopic findings and the accuracy of colposcopic impression in HIV seropositive and seronegative women with abnormal Pap tests. METHODS: HIV seropositive and seronegative women in a national cohort study had Pap tests collected every six months, with colposcopy for any abnormal result. Prospectively collected colposcopy and histology findings were analyzed retrospectively using Pearson Chi-square, t-test and Wilcoxon two-sample tests, logistic regression models, and Kappa coefficients. RESULTS: After adjusting for age and Pap result, 1618 eligible HIV seropositive women were more likely than 406 seronegative women to have inadequate colposcopic examinations, abnormal colposcopic findings, and large cervical lesions. However, among those with abnormal colposcopy, colposcopic characteristics and lesion size and number did not differ by HIV serostatus. Agreement between colposcopists' impressions and highest grade biopsy diagnoses was fair (kappa coefficient 0.35, 95% C.I. 0.31, 0.38). Agreement did not differ by HIV serostatus and did not improve with multiple biopsies (weighted kappa coefficient 0.35, 95% C.I. 0.32, 0.39) or after including all histology results over two years following colposcopy. CONCLUSION: Although HIV seropositive women with abnormal cytology are more likely to have colposcopic abnormality, the performance of colposcopy appears to be similar to that in HIV seronegative women. Biopsy is required to confirm colposcopic impression.

Complex decisions in managing HIV infection during pregnancy.

Both the World Health Organization and the United States Department of Health and Human Services have recently substantially revised perinatal HIV treatment guidelines based on emerging data, much of it from the developing world. Management of HIV infection in pregnancy and delivery is complicated by concerns for maternal and fetal drug toxicity, acquisition of antiretroviral resistance, prior therapy, co-infections with other viruses, as well as incident opportunistic infections. Intrapartum and peripartum obstetric management, including the role of Caesarean section, continue to evolve in the setting of maternal HIV infection. Finally, new data have expanded the role of antiviral therapy in allowing safer infant feeding choices for HIV-infected mothers in resource-limited settings.

Influence of adherent and effective antiretroviral therapy use on human papillomavirus infection and squamous intraepithelial lesions in human immunodeficiency virus-positive women.

BACKGROUND: The impact of highly active antiretroviral therapy (HAART) on the natural history of human papillomavirus (HPV) remains uncertain following conflicting reports. Prior studies, however, did not consider patients' adherence to their regimens or HAART effectiveness (viral suppression). METHODS: Human immunodeficiency virus (HIV)-positive women (N = 286) who initiated HAART during follow-up in a prospective cohort were assessed semiannually for HPV infection (by polymerase chain reaction) and squamous intraepithelial lesions (SILs). Adherence was defined as use of HAART as prescribed > or = 95% of the time, and effective HAART was defined as suppression of HIV replication. The prevalence, incident detection, and clearance of HPV infection and/or SILs before versus after HAART initiation were compared (using women as their own comparison group). RESULTS: HAART initiation among adherent women was associated with a significant reduction in prevalence (odds ratio, 0.60 [95% confidence interval {CI}, 0.44-0.81]; P = .001), incident detection of oncogenic HPV infection (hazard ratio [HR], 0.49 [95% CI, 0.30-0.82]; P = .006), and decreased prevalence and more rapid clearance of oncogenic HPV-positive SILs (HR, 2.35 [95% CI, 1.07-5.18]; P = .03). Effects were smaller among nonadherent women. The associations of HPV infection and/or SILs with HAART effectiveness were fairly similar to those with HAART adherence. CONCLUSION: Effective and adherent HAART use is associated with a significantly reduced burden of HPV infection and SILs; this may help explain why rates of cervical cancer have not increased during the HAART era, despite greater longevity.

Characteristics and Outcomes of 241 Births to Women With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection at Five New York City Medical Centers.

OBJECTIVE: To describe the characteristics and birth outcomes of women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as community spread in New York City was detected in March 2020. METHODS: We performed a prospective cohort study of pregnant women with laboratory-confirmed SARS-CoV-2 infection who gave birth from March 13 to April 12, 2020, identified at five New York City medical centers. Demographic and clinical data from delivery hospitalization records were collected, and follow-up was completed on April 20, 2020. RESULTS: Among this cohort (241 women), using evolving criteria for testing, 61.4% of women were asymptomatic for coronavirus disease 2019 (COVID-19) at the time of admission. Throughout the delivery hospitalization, 26.5% of women met World Health Organization criteria for mild COVID-19, 26.1% for severe, and 5% for critical. Cesarean birth was the mode of delivery for 52.4% of women with severe and 91.7% with critical COVID-19. The singleton preterm birth rate was 14.6%. Admission to the intensive care unit was reported for 17 women (7.1%), and nine (3.7%) were intubated during their delivery hospitalization. There were no maternal deaths. Body mass index (BMI) 30 or higher was associated with COVID-19 severity (P=.001). Nearly all newborns tested negative for SARS-CoV-2 infection immediately after birth (97.5%). CONCLUSION: During the first month of the SARS-CoV-2 outbreak in New York City and with evolving testing criteria, most women with laboratory-confirmed infection admitted for delivery did not have symptoms of COVID-19. Almost one third of women who were asymptomatic on admission became symptomatic during their delivery hospitalization. Obesity was associated with COVID-19 severity. Disease severity was associated with higher rates of cesarean and preterm birth.

Squamous cervical lesions in women with human immunodeficiency virus: long-term follow-up.

OBJECTIVE: To estimate the frequency of and trends in abnormal Pap test results in women with human immunodeficiency virus (HIV) and HIV-uninfected women. METHODS: In a cohort study of HIV-infected and uninfected women, Pap tests were obtained every 6 months. Results of atypical squamous cells of undetermined significance (ASC-US) or worse were considered abnormal. RESULTS: Over a median of 8.4 years, 23,843 Pap tests were obtained from 1,931 HIV-positive women with 6,828 Pap tests from 533 HIV-negative women (13 women seroconverted during the study). Among women with HIV, Pap test results were ASC-US in 4,462 (19%), low-grade squamous intraepithelial lesion (LSIL) in 3,199 (13%), high-grade squamous intraepithelial lesion (HSIL) in 267 (1%), and cancer in 11 (0.05%). The incidence of abnormal Pap test results was 179 in 1,000 person-years for HIV-positive and 75 in 1,000 person-years for HIV-negative women (incidence rate ratio 2.4, 95% confidence interval 2.0-2.8). The incidence of HSIL or cancer was 4.4 in 1,000 person-years for HIV-positive and 1.3 in 1,000 person-years for HIV-negative women (incidence rate ratio 3.4, 95% confidence interval 1.2-9.5). CONCLUSION: Among women with HIV in a cervical cancer prevention program, Pap test abnormalities are common, but high-grade abnormalities are infrequent. LEVEL OF EVIDENCE: II.

Low Birth Weight in Human Immunodeficiency Virus-Exposed Uninfected Infants in Bronx, New York.

BACKGROUND: Prevention of mother-to-child transmission of human immunodeficiency virus (HIV) with antiretroviral therapy (ART) has been highly successful. However, HIV-exposed uninfected (HIV-EU) infants might be at increased risk for low birth weight and/or preterm birth. We compared the birth weights and gestational ages of HIV-EU infants to those of HIV-unexposed control infants in Bronx, New York, an epicenter of the HIV epidemic in the United States. METHODS: This study was performed with a retrospective cohort of HIV-EU infants born at Montefiore Medical Center between 2008 and 2012 and HIV-unexposed control infants. Each HIV-EU infant was matched according to year of birth with 5 HIV-unexposed controls from the New York City Department of Health and Mental Hygiene birth certificate database. We used regression models to assess the association between HIV exposure and birth weight while controlling for potential confounders. A secondary analysis was performed to determine the association of maternal protease inhibitor-based ART use and birth weight among HIV-EU infants. RESULTS: We included 155 HIV-EU infants born between 2008 and 2012 (51% female, 61% black, 32% Hispanic) and 775 HIV-unexposed infants. The mean (± standard deviation) unadjusted birth weights were 2971 ± 616 g (HIV-EU infants) and 3163 ± 644 g (HIV-unexposed infants) (P < .01). Multivariable regression revealed significantly lower birth weight for the HIV-EU infants (difference, -101.5 g [95% confidence interval, -181.4 to -21.6]). We found no difference in mean birth weight or gestational age with maternal protease inhibitor-based ART use when compared to the use of other regimens. CONCLUSIONS: We found significantly lower birth weight among HIV-EU infants. Long-term prospective studies are necessary to determine the implications of this finding on infant growth and development.

Prolonged Amenorrhea and Resumption of Menses in Women with HIV.

OBJECTIVE: To compare etiologies of prolonged amenorrhea in a cohort of HIV-infected women with a cohort of similar uninfected at-risk women. MATERIALS AND METHODS: Women from the Women's Interagency HIV Study were seen every 6 months, and completed surveys including questions about their menstruation. Those who reported no vaginal bleeding for at least 1 year ("prolonged amenorrhea") with subsequent resumption of bleeding were compared with women in whom bleeding had stopped permanently ("menopause"). Characteristics associated with reversible prolonged amenorrhea were ascertained. RESULTS: Of 828 women with prolonged amenorrhea, 37.6% had reversible amenorrhea and 62.4% never resumed menses. HIV-seropositive women with prolonged amenorrhea were significantly younger at cessation of menses than HIV-negative women (p < 0.0001). Of those with reversible prolonged amenorrhea, approximately half were taking medications associated with amenorrhea, including 95 (30.6%) hormonal contraception, 80 (25.7%) opiates/stimulants, 16 (5.1%) psychotropic medications, and 6 (1.9%) chemotherapy. HIV-seropositive women were less likely to have medications as a cause of amenorrhea than seronegative women (p = 0.02). In multivariable analysis, women with reversible prolonged amenorrhea of unknown etiology were younger (p < 0.0001), more often obese (p = 0.03), and less educated (p = 0.01) than those with permanent amenorrhea. Among HIV-seropositive women, markers of severe immunosuppression were not associated with prolonged amenorrhea. CONCLUSION: Women with HIV infection have unexplained prolonged amenorrhea more often than at-risk seronegative women. This is especially common among obese, less-educated women. Prolonged amenorrhea in the HIV-seropositive women should be evaluated and not be presumed to be to the result of menopause.

Smoking, HIV, and risk of pregnancy loss.

OBJECTIVE: Cigarette smoking during pregnancy increases risks of poor pregnancy outcomes including miscarriage and stillbirth (pregnancy loss), but the effect of smoking on pregnancy loss among HIV-infected women has not been explored. Here, investigated the impact of smoking on risk of pregnancy loss among HIV-positive and HIV-negative women, and estimated the potential impact of realistic smoking cessation interventions on risk of pregnancy loss among HIV-positive women. DESIGN: We analyzed pregnancy outcomes in HIV-positive and HIV-negative participants in the Women's Interagency HIV Study between 1994 and 2014. METHODS: We estimated effects of current smoking at or immediately before pregnancy on pregnancy loss; we controlled for confounding using regression approaches, and estimated potential impact of realistic smoking cessation interventions using a semiparametric g-formula approach. RESULTS: Analysis examined 1033 pregnancies among 659 women. The effect of smoking on pregnancy loss differed dramatically by HIV status: adjusted for confounding, the risk difference comparing current smokers to current nonsmokers was 19.2% (95% confidence limit 10.9-27.5%) in HIV-positive women and 9.7% (95% confidence limit 0.0-19.4%) in HIV-negative women. These results were robust to sensitivity analyses. We estimated that we would need to offer a realistic smoking cessation intervention to 36 women to prevent one pregnancy loss. CONCLUSION: Smoking is a highly prevalent exposure with important consequences for pregnancy in HIV-positive pregnant women in the United States, even in the presence of potent highly active antiretroviral therapy. This evidence supports greater efforts to promote smoking cessation interventions among HIV-positive women, especially those who desire to become pregnant.

Return on Investment From Expenditures Incurred to Eliminate Mother-To-Child Transmission Among HIV-Infected Women in New York State: 1998-2013.

BACKGROUND: Eliminating mother-to-child transmission (MTCT) of HIV has been one of New York State's public health priorities, and the goal has been virtually accomplished by meeting criteria established by the Centers for Disease Control and Prevention. METHODS: We use a return on investment (ROI) approach, from the perspective of the state, to compare expenditures incurred to prevent MTCT of HIV in NYS during the period 1998-2013 to benefits realized, as expressed as HIV treatment costs saved from averting an estimated number of HIV infections among newborns. Extrapolating from the 11.5% incidence rate of HIV-infected newborns in 1997, we projected the number of cases of MTCT of HIV that were averted over the 16-year period. A published estimate of lifetime HIV treatment costs was used to estimate HIV treatment costs saved from the averted infections; expenditures for clinical protocols and other services directly associated with preventing MTCT of HIV were also estimated. The ROI was then calculated by dividing program benefits by the expenditures incurred to achieve these benefits. RESULTS: We estimate that 898 cases of MTCT of HIV were averted between 1998 and 2013, resulting in a savings of $321.03 million in HIV treatment costs. Expenditures to achieve these benefits totaled $81.07 million, yielding an ROI of $3.96. CONCLUSIONS: Aside from the human suffering from MTCT of HIV that is averted, expenditures for treatment protocols and interventions to prevent MTCT of HIV are relatively inexpensive and can result in almost 4 times their value in HIV treatment cost savings realized.

Changes in knowledge of cervical cancer following introduction of human papillomavirus vaccine among women at high risk for cervical cancer.

PURPOSE: To describe changes in knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination among women at high risk for cervical cancer in the first five years after introduction of HPV vaccination. METHODS: In 2007, 2008-9, and 2011, women in a multicenter U.S. cohort study completed 44-item self-report questionnaires assessing knowledge of cervical cancer prevention, HPV, and HPV vaccination. Results across time were assessed for individuals, and three study enrollment cohorts were compared. Knowledge scores were correlated with demographic variables, measures of education and attention, and medical factors. Associations were assessed in multivariable models. RESULTS: In all, 974 women completed three serial questionnaires; most were minority, low income, and current or former smokers. The group included 652 (67%) HIV infected and 322 (33%) uninfected. Summary knowledge scores (possible range 0-24) increased from 2007 (12.8, S.D. 5.8) to 2008-9 (13.9, S.D. 5.3, P < 0.001) and to 2011 (14.3, S.D 5.2, P < 0.0001 vs 2007 and <0.04 vs 2008-9). Higher knowledge scores at first and follow-up administration of questionnaires, higher income, and higher education level were associated with improved knowledge score at third administration. Women not previously surveyed had scores similar to those of the longitudinal group at baseline. CONCLUSION: Substantial gaps in understanding of HPV and cervical cancer prevention exist despite years of health education. While more effective educational interventions may help, optimal cancer prevention may require opt-out vaccination programs that do not require nuanced understanding.

Combination antiretroviral treatment for women previously treated only in pregnancy: week 24 results of AIDS clinical trials group protocol a5227.

BACKGROUND: Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of mother-to-child transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and coformulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). METHODS: Nonpregnant women with plasma HIV-1 RNA of ≥500 copies per milliliter, previously cART exposed for pMTCT only, were eligible if they were off ART for ≥24 weeks before entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA <400 copies/mL) at 24 weeks. RESULTS: Fifty-four women were enrolled between October 2007 and December 2009; 52 of 54 completed 24 weeks of follow-up. Median baseline CD4 T-cell count was 265/mm and baseline plasma HIV-1 RNA was 4.6 log10 copies per milliliter. Median prior cART duration was 14 weeks, and median time elapsed from the last pMTCT dose to entry was 22 months. Virologic response at 24 weeks was observed in 42 of 52 women or 81% (exact 95% confidence interval: 68% to 90%). There were no differences in response by country, by number, or class of prior pMTCT exposures. Although confirmed virologic failure occurred in 8 women, no virologic failures were observed in women reporting perfect early adherence. CONCLUSIONS: In this first prospective clinical trial studying combination antiretroviral retreatment in women with a history of pregnancy-limited cART, the observed virologic response to TDF/FTC and EFV at 24 weeks was 81%. Virologic failures occurred and correlated with self-reported nonadherence.

Negative predictive value of pap testing: implications for screening intervals for women with human immunodeficiency virus.

OBJECTIVE: To estimate the accuracy of Pap testing for women who are human immunodeficiency virus (HIV)-seropositive, with a focus on negative predictive value. METHODS: Participants in the Women's Interagency HIV Study were monitored with conventional Pap tests every 6 months. After excluding those with abnormal Pap test results before study, cervical disease, or hysterectomy, women with negative enrollment Pap test results were monitored for development of precancer within 15 or 39 months, defined as a Pap test result read as high-grade squamous intraepithelial lesion, atypical glandular cells favor neoplasia, or adenocarcinoma in situ, or a cervical biopsy read as cervical intraepithelial neoplasia 2 or worse. Correlations between one or more consecutive negative Pap test results and subsequent precancer were assessed using Cox proportional hazards models. RESULTS: Among 942 HIV-infected women with negative baseline Pap test results, eight (1%) developed precancer within 15 months and 40 (4%) within 39 months. After three consecutive negative Pap test results, precancer was rare, with no cases within 15 months and 10 of 539 (2%) within 39 months. No women developed precancer or cancer within 39 months after 10 consecutive negative Pap test results. Risks for precancer within 15 months after negative Pap test result included current smoking (adjusted hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.2-2.0 compared with nonsmokers), younger age (adjusted HR 1.5, 95% CI 1.1-2.1 for women aged younger than 31 years compared with older than 45 years), and lower CD4 count (adjusted HR 11.8, 95% CI 1.3-2.3 for CD4 200-500/microliter, adjusted HR 2.2, 95% CI 1.6-2.9 for CD4 less than 200/microliter, compared with CD4 more than 500/microliter). CONCLUSION: Annual Pap testing appears safe for women infected with HIV; for those with serial negative tests, longer intervals are appropriate. LEVEL OF EVIDENCE: II.