D Heather Watts

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Роквилл, Maryland, United States

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Publications (182)1031.18 Total impact

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    ABSTRACT: Objectives: Depot medroxyprogesterone acetate (DMPA) was associated with increased HIV transmission and accelerated disease progression in untreated women. The potential underlying mechanisms include immune-modulation. We evaluated the effect of a single DMPA injection on cell-mediated immunity (CMI), T cell activation (Tact), regulation (Treg) and inflammation in HIV-infected women on cART. Methods: Women with HIV plasma RNA ≤400 c/mL on stable cART received DMPA and had immunologic and MPA measurements at baseline, 4 weeks [peak MPA concentration (Cmax)] and 12 weeks [highest MPA area under the concentration curve (AUC)]. Results: At baseline, among 24 women with median 32 years of age and 622 CD4+ cells/µL, ≥68% had HIV, VZV, PHA and CD3/CD28 CMI measured by lymphocyte proliferation and/or IFNγ/IL2 dual-color fluorospot. CMI did not significantly change after DMPA administration except for a 1.4-fold increase in IL2/IFNγ VZV fluorospot at week 12. Tact decreased after DMPA administration, reaching statistical significance at week 12 for CD4+CD25+%. Treg behaved heterogeneously with an increase in CD8+FOXP3+% at week 4 and a decrease in CD4+IL35+% at week 12. There was a decrease in TGFβ at week 12 and no other changes in plasma biomarkers. Correlation analyses showed that high MPA Cmax and/or AUC were significantly associated with increases of IFNγ HIV ELISPOT, CD4+IL35+% and CD4+TGFβ+% Treg and decreases of plasma IL10 from baseline to weeks 4 and/or 12. Conclusions: A single dose of DMPA did not have immune-suppressive or pro-inflammatory effects in HIV-infected women on cART. Additional studies need to assess the effect of multiple doses.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2015; DOI:10.1097/QAI.0000000000000850 · 4.56 Impact Factor
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    ABSTRACT: We investigated the Th1 protective and regulatory T and B cell (Treg and Breg) responses to pH1N1 monovalent influenza vaccine (IIV1) in HIV-infected pregnant women on combination antiretroviral therapy (cART). Peripheral blood mononuclear cells (PBMCs) from 52 study participants were cryopreserved before and after vaccination and analyzed by flow cytometry. pH1N1-specific Th1, Treg, and Breg responses were measured in PBMCs after in vitro stimulation with pH1N1 and control antigen. The cohort analysis did not detect changes in pH1N1-Th1, Treg, or Breg subsets postvaccination. However, individual analyses distinguished subjects who mounted vigorous Th1 responses postvaccination from others who did not. Postvaccination, high pH1N1-Th1 correlated with high pH1N1-Treg and Breg responses, suggesting that low influenza effector responses did not result from excessive vaccine-induced immune regulation. High postvaccination pH1N1-Th1 responses correlated with baseline high PHA- and pH1N1-IFN-γ ELISpot and circulating CD4(+)CD39(+)% and CD8(+)CD39(+)% Treg, with low CD8(+) cell numbers and CD19(+)FOXP3(+)% Breg, but not with CD4(+) cell numbers or HIV viral load. These data highlight the heterogeneity of T cell responses to vaccines in HIV-infected individuals on cART. Predictors of robust Th1 responses to IIV include CD8(+) cell numbers, T cell functionality, and circulating Breg and Treg.
    AIDS research and human retroviruses 08/2015; DOI:10.1089/aid.2015.0151 · 2.33 Impact Factor
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    ABSTRACT: Intended and unintended pregnancies occur frequently among human immunodeficiency virus (HIV)-infected women. We evaluated the occurrence of repeat pregnancy and characteristics associated with this outcome among HIV-infected women in Latin America and the Caribbean who were participating in the National Institute of Child Health and Human Development (NICHD) International Site Development Initiative (NISDI). Of the 1342 HIV-infected pregnant women enrolled in NISDI, 124 (9.2%) had one or more repeat pregnancies on study. Median time between the index delivery and date of conception of the subsequent pregnancy was 1.4 years (range 0.1-5.7). Younger age (odds ratio [OR] = 1.07, 95% confidence interval [CI]: 1.04-1.11 per one year decrease in age), hospitalization during the index pregnancy or up to six months post-partum [OR = 2.0, 95% CI: 1.2-3.4], and poor index pregnancy outcome (stillbirth or spontaneous/therapeutic abortion; OR = 3.4, 95% CI: 1.4-8.4) were associated with increased occurrence of repeat pregnancy in multivariable analysis. Among women with repeat pregnancies, the proportion receiving antiretroviral treatment (vs. prophylaxis) increased from 39.4% at the time of the index pregnancy to 81.8% at the time of the repeat pregnancy (p < 0.001). These results can help identify women most likely to benefit from reproductive counseling in order to assist with healthy pregnancy planning and prevention of unintended pregnancies.
    AIDS Care 08/2015; 27(10):1-9. DOI:10.1080/09540121.2015.1050987 · 1.60 Impact Factor
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    ABSTRACT: Background: Sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) can lead to adverse pregnancy and neonatal outcomes. The prevalence of STIs and its association with HIV mother-to-child transmission (MTCT) were evaluated in a substudy analysis from a randomized, multicenter clinical trial. Methodology: Urine samples from HIV-infected pregnant women collected at the time of labor and delivery were tested using polymerase chain reaction testing for the detection of CT and NG (Xpert CT/NG; Cepheid, Sunnyvale, CA). Infant HIV infection was determined by HIV DNA polymerase chain reaction at 3 months. Results: Of the 1373 urine specimens, 249 (18.1%) were positive for CT and 63 (4.6%) for NG; 35 (2.5%) had both CT and NG detected. Among 117 cases of HIV MTCT (8.5% transmission), the lowest transmission rate occurred among infants born to CT- and NG-uninfected mothers (8.1%) as compared with those infected with only CT (10.7%) and both CT and NG (14.3%; P = 0.04). Infants born to CT-infected mothers had almost a 1.5-fold increased risk for HIV acquisition (odds ratio, 1.47; 95% confidence interval, 0.9-2.3; P = 0.09). Conclusions: This cohort of HIV-infected pregnant women is at high risk for infection with CT and NG. Analysis suggests that STIs may predispose to an increased HIV MTCT risk in this high-risk cohort of HIV-infected women.
    Sex Transm Dis 08/2015; 42(10):1. DOI:10.1097/OLQ.0000000000000340 · 2.84 Impact Factor
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    ABSTRACT: Tenofovir disoproxil fumarate (TDF) is increasingly used in the highly active antiretroviral therapy (HAART) regimens of pregnant women, but limited data exist on the pregnancy pharmacokinetics of chronically dosed TDF. This study described tenofovir pharmacokinetics during pregnancy and postpartum. International Maternal Pediatric and Adolescent AIDS Clinical Trials (IMPAACT) P1026s is a prospective, nonblinded pharmacokinetic study of HIV-infected pregnant women that included a cohort receiving 300 mg TDF once daily. Steady-state 24-hour pharmacokinetic profiles were measured at the second and third trimesters, postpartum, and in maternal and umbilical cord samples collected at delivery. Tenofovir was measured by liquid chromatography-mass spectrometry (LC-MS). The target area under the concentration versus time curve from time 0 to 24 h post dose (AUC) was ≥ 1.99 μg h/mL (nonpregnant historical control 10th percentile). The median tenofovir AUC was decreased during the second (1.9 μg h/mL) and third (2.4 μg h/mL; P = 0.005) trimesters versus postpartum (3.0 μg h/mL). Tenofovir AUC exceeded the target for two of four women (50%) in the second trimester, 27 of 37 women [73%; 95% confidence interval (CI) 56%, 86%] in the third trimester, and 27 of 32 women (84%; 95% CI 67%, 95%) postpartum (P > 0.05). Median second/third-trimester troughs were lower (39/54 ng/mL) than postpartum (61 ng/mL). Median third-trimester weight was greater for subjects below the target AUC versus those above the target (97.9 versus 74.2 kg, respectively; P = 0.006). The median ratio of cord blood to maternal concentrations was 0.88. No infants were HIV infected. This study found lower tenofovir AUC and troughs during pregnancy. Transplacental passage with chronic TDF use during pregnancy was high. Standard TDF doses appear to be appropriate for most HIV-infected pregnant women but therapeutic drug monitoring with dose adjustment should be considered in pregnant women with high weight (> 90 kg) or inadequate HIV RNA response. © 2015 British HIV Association.
    HIV Medicine 05/2015; 16(8). DOI:10.1111/hiv.12252 · 3.99 Impact Factor
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    ABSTRACT: Several observational studies have reported that HIV-1 acquisition seems to be higher in women who use depot medroxyprogesterone acetate (DMPA) than in those who do not use hormonal contraception. We aimed to assess whether two injectable progestin-only contraceptives, DMPA and norethisterone enanthate (NET-EN), confer different risks of HIV-1 acquisition. We included data from South African women who used injectable contraception while participating in the VOICE study, a multisite, randomised, placebo-controlled trial that investigated the safety and efficacy of three formulations of tenofovir for prevention of HIV-1 infection in women between Sept 9, 2009, and Aug 13, 2012. Women were assessed monthly for contraceptive use and incident infection. We estimated the difference in incident HIV-1 infection between DMPA and NET-EN users by Cox proportional hazards regression analyses in this prospective cohort. The VOICE trial is registered with ClinicalTrials.gov, NCT00705679. 3141 South African women using injectable contraception were included in the present analysis: 1788 (56·9%) solely used DMPA, 1097 (34·9%) solely used NET-EN, and 256 (8·2%) used both injectable types at different times during follow-up. During 2733·7 person-years of follow-up, 207 incident HIV-1 infections occurred (incidence 7·57 per 100 person-years, 95% CI 6·61-8·68). Risk of HIV-1 acquisition was higher among DMPA users (incidence 8·62 per 100 person-years, 95% CI 7·35-10·11) than among NET-EN users (5·67 per 100 person-years, 4·35-7·38; hazard ratio 1·53, 95% CI 1·12-2·08; p=0·007). This association persisted when adjusted for potential confounding variables (adjusted hazard ratio [aHR] 1·41, 95% CI 1·06-1·89; p=0·02). Among women seropositive for herpes simplex virus type 2 (HSV-2) at enrolment, the aHR was 2·02 (95% CI 1·26-3·24) compared with 1·09 (0·78-1·52) for HSV-2-seronegative women (pinteraction=0·07). Although moderate associations in observational analyses should be interpreted with caution, these findings suggest that NET-EN might be an alternative injectable drug with a lower HIV risk than DMPA in high HIV-1 incidence settings where NET-EN is available. National Institutes of Health, Mary Meyer Scholars Fund, and the Ruth Freeman Memorial Fund.
    The Lancet HIV 05/2015; 2(7). DOI:10.1016/S2352-3018(15)00058-2
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    ABSTRACT: HIV infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA, n=32), the levonorgestrel releasing intrauterine device (LNG-IUD, n=27), oral contraceptive pills (n=32), or who did not use hormonal contraception (n=33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases in the magnitude of T cell subset CCR5 expression were observed with DMPA and LNG-IUD (p<0.01 for all comparisons). LNG-IUD and, to a lesser extent, DMPA use was associated with increased peripheral T cell CCR5 expression. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    The Journal of Infectious Diseases 04/2015; DOI:10.1093/infdis/jiv233 · 6.00 Impact Factor
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    ABSTRACT: Influenza infections have high frequency and morbidity in HIV-infected pregnant women, underscoring the importance of vaccine-conferred protection. To identify the factors that determine vaccine immunogenicity in this group, we characterized the relationship of B- and T-cell responses to pandemic H1N1 (pH1N1) vaccine with HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1 (sH1N1) antibodies were measured in 119 HIV-infected pregnant women after two double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1- and sH1N1-interferon γ (IFNγ) and granzyme B (GrB) T-cell FluoroSpot, and flow cytometric characterization of B- and T-cell subsets were performed in 57 subjects. pH1N1-antibodies increased after vaccination, but less than previously described in healthy adults. pH1N1-IgG memory B cells (Bmem) increased, IFNγ-effector T-cells (Teff) decreased, and IgA Bmem and GrB Teff did not change. pH1N1-antibodies and Teff were significantly correlated with each other and with sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody responses to the vaccine significantly increased with high proportions of CD4+, low CD8+ and low CD8+HLADR+CD38+ activated (Tact) cells. pH1N1-IgG Bmem responses increased with high proportions of CD19+CD27+CD21- activated B cells (Bact), high CD8+CD39+ regulatory T cells (Treg), and low CD19+CD27-CD21- exhausted B cells (Bexhaust). IFNγ-Teff responses increased with low HIV plasma RNA, CD8+HLADR+CD38+ Tact, CD4+FoxP3+ Treg and CD19+IL10+ Breg. In conclusion, pre-existing antibody and Teff responses to sH1N1 were associated with increased responses to pH1N1 vaccination in HIV-infected pregnant women suggesting an important role for heterosubtypic immunologic memory. High CD4+% T cells were associated with increased, whereas high HIV replication, Tact and Bexhaust were associated with decreased vaccine immunogenicity. High Treg increased antibody responses but decreased Teff responses to the vaccine. The proportions of immature and transitional B cells did not affect the responses to vaccine. Increased Bact were associated with high Bmem responses to the vaccine.
    PLoS ONE 04/2015; 10(4):e0122431. DOI:10.1371/journal.pone.0122431 · 3.23 Impact Factor
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    ABSTRACT: We conducted an open-label, steady-state pharmacokinetic (PK) study of drug-drug interactions between DMPA and twice daily lopinavir plus low dose ritonavir (LPV/r) among 24 HIV-infected women, and compared results to those of HIV-infected women receiving DMPA while on no antiretroviral therapy or nucleosides only (N=14, control arm of ACTG 5093). The objectives of the study were to address the effect of LPV/r on DMPA and to address the effect of DMPA on LPV/r therapy. PK parameters were estimated using non-compartmental analysis, with between-group comparisons of medroxyprogesterone acetate (MPA) PK and within-subject comparisons of lopinavir (LPV) and ritonavir (RTV) PK before and 4 weeks after DMPA dosing. Plasma progesterone concentrations were measured every two weeks after DMPA dosing through week 12. Although MPA area under the concentration-time curve and Cmax were statistically significantly increased in study women on LPV/r compared to historical controls, these increases were not considered clinically significant. There were no changes in LPV and RTV drug exposure after DMPA. DMPA was well tolerated and suppression of ovulation was maintained. (Clinical Trials.gov number, NCT 01296152). Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 01/2015; 59(4). DOI:10.1128/AAC.04701-14 · 4.48 Impact Factor
  • Marc Bulterys · Robert J Berry · D Heather Watts ·

    AIDS (London, England) 11/2014; 28(18):2777-2780. DOI:10.1097/QAD.0000000000000500 · 5.55 Impact Factor
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    ABSTRACT: Importance Most studies examining the association of prenatal antiretroviral (ARV) exposures with congenital anomalies (CAs) in children born to human immunodeficiency virus (HIV)–infected women have been reassuring, but some evidence suggests an increased risk with specific ARV agents.Objective To evaluate the association of in utero ARV exposures with CAs in HIV-exposed uninfected children.Design, Setting, and Participants Prospective cohort study design. The Pediatric HIV/AIDS Cohort Study’s Surveillance Monitoring of ART Toxicities (SMARTT) Study was performed at 22 US medical centers among 2580 HIV-exposed uninfected children enrolled in the SMARTT Study between March 23, 2007, and June 18, 2012.Exposures First-trimester exposure to any ARV and to specific ARV medications.Main Outcomes and Measures The primary end point was a CA based on physician review of infant physical examinations according to the Antiretroviral Pregnancy Registry modification of the Metropolitan Atlanta Congenital Defects Program. Rates of CAs were estimated overall and by birth year. Logistic regression models were used to evaluate the association of CAs with first-trimester ARV exposures, adjusting for demographic and maternal characteristics.Results Congenital anomalies occurred in 175 of 2580 children, yielding a prevalence of 6.78% (95% CI, 5.85%-7.82%); 242 major CAs were confirmed, including 72 musculoskeletal and 55 cardiovascular CAs. The prevalence of CAs increased significantly among successive birth cohorts (3.8% for children born before 2002 and up to 8.3% for those born 2008-2010). In adjusted models, no association of first-trimester exposures with CAs was found for any ARV, for combination ARV regimens, or for any drug class. No individual ARV in the reverse transcriptase inhibitor drug classes was associated with an increased risk of CAs. Among protease inhibitors, higher odds of CAs were observed for atazanavir sulfate (adjusted odds ratio [aOR], 1.95; 95% CI, 1.24-3.05) and for ritonavir used as a booster (aOR, 1.56; 95% CI, 1.11-2.20). With first-trimester atazanavir exposure, risks were highest for skin (aOR, 5.23) and musculoskeletal (aOR, 2.55) CAs.Conclusions and Relevance Few individual ARVs and no drug classes were associated with an increased risk of CAs in HIV-exposed infants after adjustment for calendar year and maternal characteristics. While the overall risk remained low, a relative increase was observed in successive years and with atazanavir exposure. Given the low absolute CA risk, the benefits of recommended ARV therapy use during pregnancy still outweigh such risks, although further studies are warranted.
    JAMA Pediatrics 11/2014; 169(1). DOI:10.1001/jamapediatrics.2014.1889 · 5.73 Impact Factor
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    ABSTRACT: : In resource-limited countries, interventions to prevent mother-to-child HIV transmission (PMTCT) have not yet realized their full potential health impact, illustrating the common gap between the scientific proof of an intervention's efficacy and effectiveness and its successful implementation at scale into routine health services. For PMTCT, this gap results, in part, from inadequate adaptation of PMTCT interventions to the realities of the implementation environment, including client and health care worker behaviors and preferences, health care policies and systems, and infrastructure and resource constraints. Elimination of mother-to-child HIV transmission can only be achieved through understanding of key implementation barriers and successful adaptation of scientifically proven interventions to the local environment. Central to such efforts is implementation science (IS), which aims to investigate and address major bottlenecks that impede effective implementation and to test new approaches to identifying, understanding, and overcoming barriers to the adoption, adaptation, integration, scale-up, and sustainability of evidence-based interventions. Advancing IS will require deliberate and strategic efforts to facilitate collaboration, communication, and relationship-building among researchers, implementers, and policy-makers. To speed the translation of effective PMTCT interventions into practice and advance IS more broadly, the US National Institutes of Health, in collaboration with the President's Emergency Plan for AIDS Relief launched the National Institutes of Health/President's Emergency Plan for AIDS Relief PMTCT IS Alliance, comprised of IS researchers, PMTCT program implementers, and policy-makers as an innovative platform for interaction and coordination.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2014; 67 Suppl 2:S163-S167. DOI:10.1097/QAI.0000000000000323 · 4.56 Impact Factor
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    AIDS Research and Human Retroviruses 10/2014; 30 Suppl 1(S1):A267-8. DOI:10.1089/aid.2014.5601.abstract · 2.33 Impact Factor
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    ABSTRACT: Objective: To estimate the effects of infection by HIV on the type-specific cumulative detection of cervicovaginal infection by human papillomavirus (HPV). Design: Retrospective assessment of prospectively collected data in a multicenter US cohort. Methods: HIV-seropositive and at-risk seronegative participants in the Women's Interagency HIV Study were followed semiannually for up to 11 years. HPV typing was determined from cervicovaginal lavage specimens by PCR; types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68 were considered carcinogenic. Results: Among the 3438 women enrolled (2543 HIV-seropositive, 895 seronegative), the cumulative detection of any HPV infection rose among HIV-seropositive women from 53% at baseline to 92% at 8 years, and among seronegative women from 22 to 66% (P< 0.0001 for HIV-seropositive vs. seronegative women). The 8-year cumulative detection of carcinogenic and noncarcinogenic HPV was 67 and 89% among HIV-seropositive, and 36 and 56% among seronegative women (P = 0.001 for both carcinogenic and noncarcinogenic HPV). The 8-year cumulative detection of HPV16 and HPV18 was 15.2 and 15.0% in HIV-seropositive, and 6.7 and 6.1% in HIV-seronegative women (P< 0.0001 for both). In multivariable regression analyses, lower CD4(+) cell count, age under 30 years, and smoking, but not number of lifetime sexual partners, were significant correlates of cumulative HPV detection. Conclusion: More than 90% of the HIV-seropositive women have HPV detected during a long follow-up. The rates are lower among at-risk HIV-seronegative women, though most also develop HPV infections. (c) 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
    AIDS (London, England) 09/2014; 28(17). DOI:10.1097/QAD.0000000000000455 · 5.55 Impact Factor
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    ABSTRACT: Objective: We evaluated the pharmacokinetics (PK) of raltegravir in HIV-infected women during pregnancy and postpartum. Methods: International Maternal Pediatric Adolescent AIDS Clinical Trials 1026s is an ongoing prospective study of antiretroviral PK during pregnancy (NCT00042289). Women receiving 400 mg raltegravir twice daily in combination antiretroviral therapy had intensive steady-state 12-hour PK profiles performed during pregnancy and at 6- to 12-week postpartum. Targets were trough concentration above 0.035 μg/mL, the estimated 10th percentile in nonpregnant historical controls. Results: Median raltegravir area under the curve was 6.6 μg·h/mL for second trimester (n = 16), 5.4 μg·h/mL for third trimester (n = 41), and 11.6 μg·h/mL postpartum (n = 38) (P = 0.03 postpartum vs second trimester, P = 0.001 pp vs third trimester). Trough concentrations were above the target in 69%, 80%, and 79% of second trimester, third trimester, and postpartum subjects, respectively, with wide variability (<0.010-0.917 μg/mL), and no significant difference between third trimester and postpartum trough concentrations was detected. The median ratio of cord blood/maternal raltegravir concentrations was 1.5. HIV RNA levels were <400 copies per milliliter in 92% of women at delivery. Adverse events included elevated liver transaminases in 1 woman and vomiting in 1. All infants with known status are HIV uninfected. Conclusions: Median raltegravir area under the curve was reduced by approximately 50% during pregnancy; trough concentrations were frequently below target both during late pregnancy and postpartum. Raltegravir readily crossed the placenta. High rates of viral suppression at delivery and the lack of a clear relationship between raltegravir concentration and virologic effect in nonpregnant adults suggest that despite the decreased exposure during pregnancy, a higher dose is not necessary.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2014; 67(4). DOI:10.1097/QAI.0000000000000318 · 4.56 Impact Factor
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    ABSTRACT: 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.
    International Journal of Cancer 04/2014; 134(8). DOI:10.1002/ijc.28523 · 5.09 Impact Factor
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    Lynne M Mofenson · D Heather Watts ·
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    ABSTRACT: Lynne Mofenson and Heather Watts discuss the context and implications of the study by J. Sibuide and colleagues, which provides a detailed analysis of birth defects in infants with in utero antiretroviral drug exposure in the French Perinatal Cohort. Please see later in the article for the Editors' Summary
    PLoS Medicine 04/2014; 11(4):e1001636. DOI:10.1371/journal.pmed.1001636 · 14.43 Impact Factor
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    ABSTRACT: Plasma HIV RNA levels have been associated with risk of human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive women. However, little is known regarding local genital tract HIV RNA levels and their relation with cervical HPV and neoplasia. In an HIV-seropositive women's cohort with semi-annual follow-up, we conducted a nested case-control study of genital tract HIV RNA levels and their relation with incident high-grade squamous intraepithelial lesions sub-classified as severe (severe HSIL), as provided for under the Bethesda 2001 classification system. Specifically, 66 incident severe HSIL were matched to 130 controls by age, CD4+ count, HAART use, and other factors. We also studied HPV prevalence, incident detection, and persistence in a random sample of 250 subjects. Risk of severe HSIL was associated with genital tract HIV RNA levels (odds ratio comparing HIV RNA ≥ the median among women with detectable levels versus undetectable [ORVL] 2.96; 95% CI:0.99-8.84; Ptrend=0.03). However, this association became non-significant (Ptrend=0.51) following adjustment for plasma HIV RNA levels. There was also no association between genital tract HIV RNA levels and the prevalence of any HPV or oncogenic HPV. However, the incident detection of any HPV (Ptrend=0.02) and persistence of oncogenic HPV (Ptrend=0.04) were associated with genital tract HIV RNA levels, after controlling plasma HIV RNA levels. These prospective data suggest that genital tract HIV RNA levels are not a significant independent risk factor for cervical pre-cancer in HIV-seropositive women, but leave open the possibility that they may modestly influence HPV infection, an early stage of cervical tumoriogenesis.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 04/2014; 66(3). DOI:10.1097/QAI.0000000000000157 · 4.56 Impact Factor

Publication Stats

6k Citations
1,031.18 Total Impact Points


  • 2003-2015
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Роквилл, Maryland, United States
  • 2013
    • University of Pittsburgh
      • Department of Obstetrics, Gynecology and Reproductive Sciences
      Pittsburgh, PA, United States
  • 2000-2012
    • National Institute of Child Health and Human Development
      베서스다, Maryland, United States
    • Institute of Human Virology
      Maryland City, Maryland, United States
    • University of Maryland, Baltimore
      • Institute of Human Virology
      Baltimore, Maryland, United States
  • 2008-2011
    • University of California, San Francisco
      San Francisco, California, United States
  • 2010
    • George Washington University
      Washington, Washington, D.C., United States
  • 2001-2010
    • National Institutes of Health
      Maryland, United States
  • 2004-2009
    • University of Illinois Springfield
      Спрингфилд, Florida, United States
  • 1987-2006
    • University of Washington Seattle
      • Department of Obstetrics and Gynecology
      Seattle, Washington, United States
  • 1997
    • Memorial Hospital, TN
      Chattanooga, Tennessee, United States
    • Duke University Medical Center
      • Department of Obstetrics and Gynecology
      Durham, North Carolina, United States