Search

Background To quantify the impact of the US President's Emergency Plan for AIDS Relief (PEPFAR) on the risk of HIV transmission through infected blood donations in countries supported by PEPFAR blood safety programs. Methods Data reported to the World Health Organization Global Database on Blood Safety were analyzed from 28 countries in sub-Saharan Africa (SSA), Asia, and the Caribbean during 2004-2015. We used the Goals model of Spectrum Spectrum System Software, version 5.53, to perform the modeling, assuming laboratory quality for HIV testing had 91.9% sensitivity and 97.7% specificity irrespective of testing method based on results of two external quality assurance and proficiency testing studies of transfusion screening for HIV in SSA blood centers. We calculated the number of new HIV infections from the number of transfusions and the prevalence of HIV infection acquired from blood transfusions with infected blood donations. We determined the impact of laboratory testing programs by estimating the number of new HIV infections averted since PEPFAR implementation. Results Assuming that HIV testing would not be performed in any of these countries without PEPFAR funding, the number of new HIV infections acquired from blood transfusions averted by laboratory testing increased over time in all 28 countries. The total number of HIV infections averted was estimated at 229 278 out of 20 428 373 blood transfusions during 2004-2015. Conclusion Our mathematical modeling suggests a positive impact achieved over 12 years of PEPFAR support for blood safety. Standardized HIV testing of donated blood has reduced the risk of HIV transmission through blood transfusions in SSA, Asia, and the Caribbean.

Background Women living with HIV (WLHIV) have increased risk of spontaneous preterm delivery (SPTD). We sought to identify plasma predictors of SPTD and their correlations with factors that increase the risk of SPTD, such as vitamin D deficiency and use of protease inhibitors. Design Plasma was obtained from 103 WLHIV with SPTD (≤35 weeks gestation) and 205 controls with term deliveries (TDs; ≥37 weeds) matched to cases 2:1 by race and gestational age at blood draw. TNFα, IFNγ, IL6, IL8, IL1β, IL18, IL17, granulocyte colony stimulating factor (GCSF), MCP1, IP10, sIL2Rα, sCD14, vascular endothelial factor a, monocyte colony stimulation factor, GROα, MMP9, IL10, TGFβ, sCTLA4, and eicosanoids were compared between cases adjusting for known SPTD risk factors. Results Participants had similar demographic characteristics, but cases had higher plasma HIV RNA, lower CD4 cells, and more advanced HIV disease compared with controls. High sIL2Rα was associated with increased risk of SPTD. High sCD14, GCSF, PGF2α, and 5-HEPE were marginally associated with increased risk of SPTD. Women who initiated protease inhibitors-containing antiretroviral treatment before or during the first trimester had higher levels of GCSF and 5-HEPE compared with women without such exposure before plasma collection. Vitamin D insufficiency was associated with higher inflammatory sCD14 and PGF2α, and lower anti-inflammatory 5-HEPE. Conclusions The best plasma predictor of SPTD in WLHIV was sIL2Rα, a marker of T-cell activation. Markers of monocyte activation and eicosanoids were marginally increased in WLHIV and SPTD, suggesting that they may also play a role in the pathogenesis of this disorder.

Ensuring availability of safe blood products through recruitment of voluntary, nonremunerated, blood donors (VNRDs) and prevention of transfusion-transmissible infections (TTIs), including human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis, is important for public health (1,2). During 2004–2016, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) provided approximately $468 million in financial support and technical assistance* to 14 sub-Saharan African countries† with high HIV prevalence to strengthen national blood transfusion services (NBTSs)§ and improve blood safety and availability. CDC analyzed these countries’ 2014–2016 blood safety surveillance data to update previous reports (1,2) and summarize achievements and programmatic gaps as some NBTSs begin to transition funding and technical support from PEPFAR to local ministries of health (MOHs) (2,3). Despite a 60% increase in blood supply since 2004 and steady declines in HIV prevalence (to

Cytomegalovirus (CMV) urinary shedding in pregnant women infected with human immunodeficiency virus (HIV) was evaluated to determine whether it poses an increased risk for congenital CMV infection (cCMV).A subset of mother-infant pairs enrolled in the perinatal NICHD HPTN 040 study (distinguished by no antiretroviral use before labor) was evaluated. Maternal and infant urines were tested by qualitative real-time polymerase chain reaction (RT-PCR) for CMV DNA with quantitative RT-PCR performed on positive specimens.Urine specimens were available for 260 women with 85.4% from the Americas and 14.6% from South Africa. Twenty-four women (9.2%) had detectable CMV viruria by qualitative PCR. Maternal CMV viruria was not associated with mean CD4 cell counts or HIV viral load but was associated with younger maternal age (P = .02). Overall, 10 of 260 infants (3.8%) had cCMV. Women with detectable peripartum CMV viruria were more likely to have infants with cCMV than those without: 20.8% (5/24) versus 2.1% (5/236), (P = .0001). Women with CMV viruria had significantly higher rates of HIV perinatal transmission (29.2% vs. 8.1%, P = .002). They were 5 times (adjusted odds ratio [aOR] = 5.6, 95% confidence interval [CI] 1.9-16.8) and nearly 30 times (aOR, 29.7; 95% CI, 5.4-164.2) more likely to transmit HIV and CMV to their infants, respectively. Maternal gonorrhea (aOR, 19.5; 95% CI, 2.5-151.3) and higher maternal HIV log10 viral load (OR, 2.8; 95% CI, 1.3-6.3) were also significant risk factors for cCMV.In this cohort of HIV-infected pregnant women not on antiretrovirals, urinary CMV shedding was a significant risk factor for CMV and HIV transmission to infants.NCT00099359.

The Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive (Global Plan), which was launched in 2011, set a series of ambitious targets, including a reduction of new HIV infections among children by 90% by 2015 (from a baseline year of 2009) and AIDS-related maternal mortality by 50% by 2015. To reach these targets, the Global Plan called for unprecedented investments in the prevention of mother-to-child transmission of HIV (PMTCT), innovative new approaches to service delivery, immense collective effort on the programmatic and policy fronts, and importantly, a renewed focus on data collection and use. We provide an overview of major achievements in monitoring and evaluation across Global Plan countries and highlight key challenges and innovative country-driven solutions using PMTCT program data. Specifically, we describe the following: (1) Uganda's development and use of a weekly reporting system for PMTCT using short message service technology that facilitates real-time monitoring and programmatic adjustments throughout the transition to a "treat all" approach for pregnant and breastfeeding women living with HIV (Option B+); (2) Uganda's work to eliminate parallel reporting systems while strengthening the national electronic district health information system; and (3) how routine PMTCT program data in Nigeria can be used to estimate HIV prevalence at the local level and address a critical gap in local descriptive epidemiologic data to better target limited resources. We also identify several ongoing challenges in data collection, analysis, and use, and we suggest potential solutions.

Women with HIV bear a significant burden of Human Papillomavirus (HPV) related cervical disease, and a have a higher risk of dying from cervical cancer should it occur. WLH have increased acquisition of HPV and decreased clearance, leading to persistent HPV infection: a risk for cervical cancer. The greatest burden of HIV in women occurs in sub-Saharan Africa where diagnostic and treatment services for cervical disease are limited. This paper will describe the epidemiology of HPV related cervical disease in women living with HIV (WLH) and the efforts to treat precursor lesions in HIV treatment programs supported by the President's Emergency Plan for AIDS Relief (PEPFAR.

HIV-exposed uninfected (HEU) infants are a growing population with potentially poor health outcomes. We evaluated morbidity and mortality in HEU formula-fed infants enrolled in the NICHD HPTN 040/PACTG 1043 trial.Infectious morbidity, mortality and undernutrition were evaluated within a cohort of 1000 HEU infants enrolled between April 2004 and April 2010 in Brazil (n = 766) and South Africa (n = 234) as part of the NICHD/HPTN 040 trial of 3 different antiretroviral regimens to decrease intrapartum HIV vertical transmission.Twenty-three percent of infants had at least 1 infectious serious adverse effect. Infants born to mothers with12 years of education [adjusted odds ratio (AOR), 2.6; 95% confidence interval [CI], 1.2-5.9), with maternal viral load of1,000,000 copies/mL at delivery (AOR, 9.9; 95% CI, 1.6-63.1) were more likely to have infectious serious adverse effects. At 6 months, the infant mortality rate per 1000 live births overall was 22 ± 2.6, 9.1 ± 1.8 in Brazil and 64.1 ± 3 in South Africa. Undernutrition and stunting peaked at 1 month of age with 18% having a weight-for-age Z score ≤-2, and 22% with height for Z score ≤-2. The likelihood of infant mortality was greater among infants born in South Africa compared with Brazil (AOR, 6.2; 95% CI, 2.5-15.8), high maternal viral load (AOR, 1.7; 95% CI, 1.01-2.9) and birth weight-for-age Z score ≤-2 (AOR, 5.2; 95% CI, 1.8-14.8).There were high rates of undernutrition, stunting and infectious serious adverse effect in this study's formula-fed HEU population. Suppressing maternal HIV viral load during the peripartum period may be a modifiable risk factor to decrease infant mortality.

Background Cervical cancer, almost all of which is caused by human papillomavirus, accounts for 12% of female cancers worldwide and is more common among HIV-infected women. Nine of 10 deaths from cervical cancer occur in low- and middle-income countries (LMICs). Simple screening methods and outpatient treatment of precursor lesions save lives but the benefit of these interventions among HIV-infected women is uncertain. Objective We reviewed evidence of the effects of screening with visual inspection with acetic acid (VIA), and outpatient treatment for cervical precancer among HIV-infected women in LMIC. Methods A systematic review of articles published from January 1995 through July 2013 was conducted using key terms for VIA cervical screening, cervical precancer treatment with cryotherapy or loop electrosurgical excision procedure, HIV-infected women, low-resource settings, and outcomes, including morbidity and mortality. Results Of 2159 articles screened, 14 met inclusion criteria; all considered only morbidity outcomes. No articles dealt with the long-term impact of screening/treatment on cervical cancer incidence or mortality among HIV-infected women. Articles reported on performance of VIA, prevalence of cervical dysplasia, and complications and rates of recurrent dysplasia after treatment. Conclusions Dysplasia prevalence and recurrence were higher among HIV-infected compared with HIV-uninfected women but morbidity from treatment was similar. Few data exist on long-term outcomes of VIA, cryotherapy, or loop electrosurgical excision procedure interventions among HIV-infected women in LMIC; longer-term outcomes research is needed to assess the effects of VIA or other screening modalities and outpatient treatment on prevention of cervical cancer among HIV-infected women.

BACKGROUND: The presence of antiretroviral drug-associated resistance mutations (DRMs) may be particularly problematic in human immunodeficiency virus (HIV)–infected pregnant women as it can lead to mother-to-child transmission (MTCT) of resistant HIV strains. This study evaluated the prevalence and the effect of antiretroviral DRMs in previously untreated mother-infant pairs. METHODS: A case-control design of 1:4 (1 transmitter to 4 nontransmitters) was utilized to evaluate DRMs as a predictor of HIV MTCT in specimens obtained from mother-infant pairs. ViroSeq HIV-1 genotyping was performed on mother-infant specimens to assess for clinically relevant DRMs. RESULTS: One hundred forty infants acquired HIV infection; of these, 123 mother-infant pairs (88%) had specimens successfully amplified using ViroSeq and assessed for drug resistance genotyping. Additionally, 483 of 560 (86%) women who did not transmit HIV to infants also had samples evaluated for DRMs. Sixty-three of 606 (10%) women had clinically relevant DRMs; 12 (2%) had DRMs against >1 drug class. Among 123 HIV-infected infants, 13 (11%) had clinically relevant DRMs, with 3 (2%) harboring DRMs against >1 drug class. In univariate and multivariate analyses, DRMs in mothers were not associated with increased HIV MTCT (adjusted odds ratio, 0.8 [95% confidence interval, .4–1.5]). Presence of DRMs in transmitting mothers was strongly associated with DRM presence in their infants (P < .001). CONCLUSIONS: Preexisting DRMs were common in untreated HIV-infected pregnant women, but did not increase the risk of HIV MTCT. However, if women with DRMs are not virologically suppressed, they may transmit resistant mutations, thus complicating infant management.

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' se fficacy 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 environ- ment, including client and health care worker behaviors and prefer- ences, 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 interven- tions. 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.

Summary Objectives To evaluate the incidence of and risk factors for hypertensive disorders in a cohort of HIV-infected pregnant women. Methods Hypertensive disorders (HD) including preeclampsia/eclampsia (PE/E) and pregnancy induced hypertension, and risk factors were evaluated in a cohort of HIV-infected pregnant women from Latin America and the Caribbean enrolled between 2002 and 2009. Only pregnant women enrolled for the first time in the study and delivered at ≥20 weeks gestation were analyzed. Results HD were diagnosed in 73 (4.8%, 95% CI: 3.8%–6.0%) of 1513 patients; 35 (47.9%) had PE/E. HD was significantly increased among women with a gestational age-adjusted body mass index (gBMI) ≥25 kg/m 2 (OR = 3.1; 95% CI: 1.9–5.0), hemoglobin (Hg) ≥11 g/dL at delivery (OR = 2.1; 95% CI: 1.2–3.6) and age ≥35 years (OR = 1.8; 95% CI: 1.1–3.2). PE/E was increased among women with a gBMI ≥25 kg/m 2 (OR = 3.0; 95% CI: 1.5–6.0) and Hg ≥11 g/dL at delivery (OR = 2.8; 95% CI: 1.2–6.5). A previous history of PE/E increased the risk of PE/E 6.7 fold (95% CI: 1.8–25.5). HAART before conception was associated with PE/E (OR = 2.3; 95% CI: 1.1–4.9). Conclusions HIV-infected women, with a previous history of PE/E, a gBMI ≥25 kg/m 2 , Hg at delivery ≥11 g/dL and in use of HAART before conception are at an increased risk of developing PE/E during pregnancy.

Other than CD4+ count, the immunologic factors that underlie the relationship of HIV/AIDS with persistent oncogenic HPV (oncHPV) and cervical cancer are not well understood. Plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) are of particular interest. pDCs have both effector and antigen presenting activity and, in HIV-positive patients, low pDC levels are associated with opportunistic infections. Tregs downregulate immune responses, and are present at high levels in HIV-positives. The current pilot study shows for the first time that low pDC and high Treg levels may be significantly associated with oncHPV persistence in both HIV-positive and HIV-negative women. Larger studies are now warranted.

OBJECTIVE To estimate the frequency of abnormal Pap and human papillomavirus (HPV) positivity among human immunodeficiency virus (HIV)-seropositive and -seronegative women who have sex with women (WSW). METHODS Pap and HPV DNA polymerase chain reaction tests were obtained every 6 months from women in a US cohort of HIV-seropositive and -seronegative women. Women who have sex with women were women reporting no male and at least 1 female sex partner for 5 years. They were frequency matched 1:5 to women reporting sex only with men (WSM) and assessed using multivariable generalized estimating equation logistic regression models. RESULTS Paps at study entry were abnormal in 12 (21%) of 49 HIV-seropositive WSW, 151 (64%) of 245 HIV-seropositive WSM, 3 (9%) of 24 HIV-seronegative WSW, and 16 (11%) of 120 HIV-seronegative WSM. Human papillomavirus was found at entry in 18 (42%) HIV-seropositive WSW, 109 (52%) HIV-seropositive WSM, 6 (27%) HIV-seronegative WSW, and 13 (13%) HIV-seronegative WSM. After controlling for HIV serostatus and CD4 count, WSW had marginally lower odds than WSM of Pap abnormality (odds ratio = 0.59, 95% confidence interval = 0.33-1.03) and of HPV (odds ratio = 0.53, 95% confidence interval = 0.32-0.89). After controlling for partner's gender, HIV seropositivity and lower CD4 count were associated with any HPV, oncogenic HPV, any abnormal Pap result, and high-grade squamous intraepithelial lesion or worse (p < .0001 for all). CONCLUSIONS Although risks for abnormal Pap and HPV are modestly lower in WSW than in WSM, both are common in HIV-seropositive women regardless of sexual preference. Both WSW and WSM should be screened similarly.

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.

Aim To describe the pharmacokinetics and safety of indinavir boosted with ritonavir (IDV/r) during the second and third trimesters of pregnancy and in the post-partum period. Methods IMPAACT P1026s is an on-going, prospective, non-blinded study of antiretroviral pharmacokinetics (PK) in HIV-infected pregnant women with a Thai cohort receiving IDV/r 400/100 mg twice daily during pregnancy through to 6–12 weeks post-partum as part of clinical care. Steady-state PK profiles were performed during the second (optional) and third trimesters and at 6–12 weeks post-partum. PK targets were the estimated 10th percentile IDV AUC (12.9 μg ml−1 h) in non-pregnant historical Thai adults and a trough concentration of 0.1 μg ml−1, the suggested minimum target. Results Twenty-six pregnant women were enrolled; thirteen entered during the second trimester. Median (range) age was 29.8 (18.9–40.8) years and weight 60.5 (50.0–85.0) kg at the third trimester PK visit. The 90% confidence limits for the geometric mean ratio of the indinavir AUC(0,12 h) and Cmax during the second trimester and post-partum (ante : post ratios) were 0.58 (0.49, 0.68) and 0.73 (0.59, 0.91), respectively; third trimester/post-partum AUC(0,12 h) and Cmax ratios were 0.60 (0.53, 0.68) and 0.63 (0.55, 0.72), respectively. IDV/r was well tolerated and 21/26 women had a HIV-1 viral load < 40 copies ml−1 at delivery. All 26 infants were confirmed HIV negative. Conclusion Indinavir exposure during the second and third trimesters was significantly reduced compared with post-partum and ∼30% of women failed to achieve a target trough concentration. Increasing the dose of IDV/r during pregnancy to 600/100 mg twice daily may be preferable to ensure adequate drug concentrations.

Introduction: People living with HIV (PLHIV) have the right to exercise voluntary choices about their health, including their reproductive health. This commentary discusses the integral role that family planning (FP) plays in helping PLHIV, including those in serodiscordant relationships, achieve conception safely. The United States (US) President ’ s Emergency Plan for AIDS Relief (PEPFAR) is committed to meeting the reproductive health needs of PLHIV by improving their access to voluntary FP counselling and services, including prevention of unintended pregnancy and counselling for safer conception. Discussion: Inclusion of preconception care and counselling (PCC) as part of routine HIV services is critical to preventing unintended pregnancies and perinatal infections among PLHIV. PLHIV not desiring a current pregnancy should be provided with information and counselling on all available FP methods and then either given the method onsite or through a facilitated referral process. PLHIV, who desire children should be offered risk reduction counselling, support for HIV status disclosure and partner testing, information on safer conception options to reduce the risk of HIV transmission to the partner and the importance of adhering to antiretroviral treatment during pregnancy and breastfeeding to reduce the risk of vertical transmission to the infant. Integration of PCC, HIV and FP services at the same location is recommended to improve access to these services for PLHIV. Other considerations to be addressed include the social and structural context, the health system capacity to offer these services, and stigma and discrimination of providers. Conclusion: Evaluation of innovative service delivery models for delivering PCC services is needed, including provision in community-based settings. The US Government will continue to partner with local organizations, Ministries of Health, the private sector, civil society, multilateral and bilateral donors, and other key stakeholders to strengthen both the policy and programme environment to ensure that all PLHIV and serodiscordant couples have access to FP services, including prevention of unintended pregnancy and safer conception counselling. Keywords: Family planning; HIV; serodiscordant couples; safer pregnancy; United States Government; integration (Published: 8 March 2017) Citation: Mason J et al. Journal of the International AIDS Society 2017, 20 (Suppl 1) :21312 http://www.jiasociety.org/index.php/jias/article/view/21312 | http://dx.doi.org/10.7448/IAS.20.2.21312

Early in the 2009 pH1N1 pandemic, it was recognized that pregnant women were at high risk, with excess hospital and intensive care unit admissions and an estimated 5-fold relative risk of death. Risk was particularly associated with infection in the second and third trimesters, extending to the second week postpartum [1–6]. Similar patterns observed in previous influenza pandemics and epidemics were thought to reflect immunological and physiological changes associated with pregnancy [2]. Additionally, maternal infection with pH1N1 or seasonal influenza has been associated with preterm labor, preterm delivery, and adverse fetal/neonatal outcomes, and infection in young infants with an increased risk of severe illness and death [2, 3, 5, 7, 8]. A second group that had increased risk of hospitalization, intensive care unit admission, and death in the 2009 pH1N1 pandemic was patients with medical comorbidities, including immunocompromising conditions, which conferred an estimated 16-fold relative risk of fatality [4, 9]. Although some reports did not link human immunodeficiency virus (HIV) infection to excess pH1N1 morbidity or death [10], others demonstrated increased hospital admission rates among HIV-infected populations [11, 12]. Women who are pregnant and HIV infected lie at the intersection of 2 high-risk conditions that, in combination, may pose particular vulnerability to pH1N1 infection. This group represents a high priority for vaccination to prevent maternal morbidity and mortality, avert pregnancy complications, and provide protection to infants in the first months of life before they are eligible for vaccination. Although information is available on the immune response to pH1N1 vaccine in pregnancy [5, 7, 8], none exists for HIV-infected pregnant women. Study P1086 of the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) group was designed to evaluate safety and immunogenicity of a pH1N1 vaccination regimen in HIV-infected pregnant women.

Lactation studies are necessary evaluations of medications for reproductive-age women. We evaluated pharmacokinetics (PK), pharmacodynamics, safety, and adherence profiles associated with 7 days of 1% tenofovir (TFV) vaginal gel use during lactation. Tenofovir levels (maternal/infant serum, milk) and anti-HIV activity (milk), adverse events (AEs), and adherence were measured for 17 HIV-1-seronegative breast-feeding mother-infant pairs. Tenofovir use was well-tolerated and detected at low levels in maternal serum, milk, and infant serum but demonstrated no anti-HIV activity in milk.

Supplemental Digital Content is Available in the Text., Introduction: Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit. Methods: We developed a decision analytic model to evaluate a strategy of daily oral PrEP during pregnancy and breastfeeding in SSA. We approached the analysis from a health care system perspective across a lifetime time horizon. Model inputs were derived from existing literature and local sources. The incremental cost-effectiveness ratio (ICER) of PrEP versus no PrEP was calculated in 2015 U.S. dollars per disability-adjusted life year (DALY) averted. We evaluated the effect of uncertainty in baseline estimates through one-way and probabilistic sensitivity analyses. Results: PrEP administered to pregnant and breastfeeding women in SSA was cost-effective. In a base case of 10,000 women, the administration of PrEP averted 381 HIV infections but resulted in 779 more preterm births. PrEP was more costly per person ($450 versus $117), but resulted in fewer disability-adjusted life years (DALYs) (3.15 versus 3.49). The incremental cost-effectiveness ratio of $965/DALY averted was below the recommended regional threshold for cost-effectiveness of $6462/DALY. Probabilistic sensitivity analyses demonstrated robustness of the model. Conclusions: Providing PrEP to pregnant and breastfeeding women in SSA is likely cost-effective, although more data are needed about adherence and safety. For populations at high risk of HIV acquisition, PrEP may be considered as part of a broader combination HIV prevention strategy.

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population.

Background. Use of antiretroviral drugs (ARVs) during pregnancy has been associated with higher risk of preterm birth. Methods. The Pediatric HIV/AIDS Cohort Study network's Surveillance Monitoring for ART Toxicities study is a US-based cohort of human immunodeficiency virus (HIV)–exposed uninfected children. We evaluated maternal ARV use during pregnancy and the risk of any type of preterm birth (ie, birth before 37 completed weeks of gestation), the risk of spontaneous preterm birth (ie, preterm birth that occurred after preterm labor or membrane rupture, without other complications), and the risk of small for gestational age (SGA; ie, a birth weight of

To evaluate the association of tenofovir disoproxil fumarate (TDF) use during pregnancy with early growth parameters in HIV-exposed, uninfected (HEU) infants.US-based prospective cohort study of HEU children to examine potential adverse effects of prenatal TDF exposure.We evaluated the association of maternal TDF use during pregnancy with small for gestational age (SGA); low birth weight (LBW,2.5 kg); weight-for-age z-scores (WAZ), length-for-age z-scores (LAZ), and head circumference-for-age (HCAZ) z-scores at newborn visit; and LAZ, HCAZ, and WAZ at age 1 year. Logistic regression models for LBW and SGA were fit, adjusting for maternal and sociodemographic factors. Adjusted linear regression models were used to evaluate LAZ, WAZ, and HCAZ by TDF exposure.Of 2029 enrolled children with maternal antiretroviral information, TDF was used by 449 (21%) HIV-infected mothers, increasing from 14% in 2003 to 43% in 2010. There was no difference between those exposed to combination regimens with vs. without TDF for SGA, LBW, and newborn LAZ and HCAZ. However, at age 1 year, infants exposed to combination regimens with TDF had significantly lower adjusted mean LAZ and HCAZ than those without TDF (LAZ: -0.17 vs. -0.03, P=0.04; HCAZ: 0.17 vs. 0.42, P=0.02).TDF use during pregnancy was not associated with increased risk for LBW or SGA. The slightly lower mean LAZ and HCAZ observed at age 1 year in TDF-exposed infants are of uncertain significance but underscore the need for additional studies of growth outcomes after TDF use during pregnancy.

OBJECTIVE To estimate the prevalence, incidence, and clearance of abnormal vaginal cytology and vaginal intraepithelial neoplasia (VAIN) in human immunodeficiency virus (HIV)-seropositive women. METHODS Pap tests were done semiannually for 335 HIV-seropositive and 75 HIV-seronegative women with prior hysterectomy in the prospective Women's Interagency HIV Study cohort. End points included abnormal Pap test results after hysterectomy and VAIN regardless of hysterectomy. RESULTS Over a median of 5.6 years of follow-up, vaginal Pap test results were abnormal at 1,076 (29%; 95% confidence interval [CI] 25-33%) of 3,700 visits among HIV-seropositive compared with 31 (4%; 95% CI 2-8%) of 763 visits among HIV-seronegative women (P

Tenofovir (TFV) 1% vaginal gel has been found to decrease sexual transmission of human immunodeficiency virus. To initiate investigations during pregnancy, 16 healthy pregnant women scheduled for cesarean delivery received a single application of TFV gel preoperatively. Maternal serum drug concentrations were determined and fetal cord blood, amniotic fluid, placental tissue, and endometrial tissue specimens were collected. The median maternal peak concentration and cord blood TFV concentrations were 4.3 and 1.9 ng/mL, respectively (∼100- and 40-fold lower than after TFV oral dosing, respectively). No adverse events were related to the use of TFV gel. These findings support ongoing and future investigations of TFV gel in pregnancy.NCT00572273. http://www.clinicaltrials.gov/ct2/show/NCT00540605?term=mtn-002rank=1.

Background—There are no previous data describing nelfinavir and lamivudine pharmacokinetics in neonates treated with weight band dosing regimens. Design—Pharmacokinetic study of nelfinavir and lamivudine pharmacokinetics in infants during the first 2 weeks of life treated with weight band dosing regimens. Methods—Intensive 12 hour pharmacokinetic profiles were performed between either days 4–7 or days 10–14 of life in 26 Brazilian infants. Results—Pharmacokinetic data were obtained from 26 infants who received median (range) per kg doses of 58.8 (48.4–79.0) mg/kg for nelfinavir and 2.0 (1.5 – 3.2) mg/kg for lamivudine. Median nelfinavir AUC0-12 was 25.5 (1.7 – 183.5) μg*hr/mL and median C12h was 1.09 (

Pregnancy is an established risk factor for the development of severe and disseminated coccidioidomycosis, particularly when infection is acquired during the later stages of gestation. Although recent studies suggest that the incidence of symptomatic coccidioidomycosis during pregnancy is decreasing and that outcome has improved, management is complicated by the observations that azole antifungal agents can be teratogenic when given to some women, particularly at high doses, early in pregnancy. This article summarizes the data on these issues and offers guidance on the management of coccidioidomycosis during pregnancy.

To determine the incidence rate of, and the relative time to pregnancy by HIV status in US women between 2002 and 2009.The Women's Interagency HIV Study (WIHS) is an ongoing, multicenter prospective cohort study of the natural and treated history of HIV infection and related outcomes among women with and without HIV.Eligible participants were 45 years of age or less; sexually active with male partner(s) or reported a pregnancy outcome within the past year; and never reported hysterectomy, tubal ligation, or oopherectomy. Poisson regression was conducted to compare pregnancy incidence rates over time by HIV status. Relative time to pregnancy was ascertained via Kaplan-Meier plots and generalized gamma survival analysis.Adjusting for age, number of male sex partners, contraception, parity, exchanging sex, and alcohol use, HIV infection was associated with a 40% reduction in the incidence rate of pregnancy [incidence rate ratio = 0.60, 95% confidence interval (CI) 0.46-0.78]. The time for HIV-infected women to become pregnant was 73% longer relative to HIV-uninfected women (relative time = 1.73, 95% CI 1.35-2.36). In addition to HIV infection, decreased parity and older age were independent predictors of lower pregnancy incidence.Despite the beneficial effects of modern antiretroviral therapy on survival and prevention of maternal-to-child transmission, our findings suggest that pregnancy incidence remains lower among HIV-infected women. Whether this lower incidence is due to behavioral differences or reduced biologic fertility remains an area worthy of further study.

Objective. To explore the previously reported associations between cervical squamous lesions and psychologic measures of stress and depression. Methods. In a multicenter cohort study, women with HIV and HIV-seronegative women had Pap tests and completed self-report questionnaires including the Perceived Stress Scale-10 (PSS), which measures perceived stress, the Posttraumatic Stress Disorder (PTSD) Checklist-Civilian Version (PCL-C), which measures symptoms of PTSD, and the Center for Epidemiologic Studies Depression (CES-D) scale, which measures depressive symptoms. Results. Median scores were 13 (range = 0-38) for the PSS, 24 (range = 17-85) for the PCL-C, and 8 (range = 0-57) for the CES-D, indicating moderate stress and minimal depression. For PSS, compared with women in the lowest tertile of reported stress, the odds ratios (ORs) for squamous intraepithelial lesions (SIL) were 0.88 (95% confidence interval [CI] = 0.50-1.54) for women in the middle tertile and 0.96 (95% CI = 0.54-1.68) for women in the highest tertile. For PCL-C, compared with women in the lowest tertile of PTSD symptoms, ORs for SIL were 0.79 (95% CI = 0.43-1.41) for women in the middle tertile and 1.17 (95% CI = 0.68-2.01) for women in the highest tertile. Rates of SIL were similar for CES-D scores 16 or higher (compared with women with lower scores; OR = 1.41, 95% CI = 0.88-2.26) and 23 or higher (OR = 1.39, 95% CI = 0.81-2.40). In the multivariable analysis including the number of sexual partners, age, income, ethnicity, and serostatus, stress as measured by PSS and PCL-C and depressive symptoms as measured by CES-D remained unassociated with SIL. Conclusions. We found no evidence that stress and depression affect the prevalence of cervical squamous lesions.

The microbiota of the human vagina can affect the health of women, their fetuses, and newborns. Bacterial vaginosis (BV) is the most prevalent form of vaginal infection in women of reproductive age, affecting 8% to 23%, and is the most common etiology of vaginal symptoms prompting women to seek medical care. While traditional cultivation has identified numerous BV-associated bacteria involved in these processes, recent advances in molecular biology have facilitated the detection and identification of bacteria without cultivation, some of which have not previously been described or well characterized. A more complete understanding of vaginal microbial populations resulting from the adoption of molecular tools may lead to better strategies to maintain healthy vaginal microbial communities-thus enhancing women's health-and will create opportunities to explore the role of novel bacteria in reproductive tract diseases. On November 19-20, 2008, the NIH convened a workshop of experts in the field of research and clinical practice related to BV in order to discuss how these new advances should be interpreted and applied to research in progress and collaborations between relevant disciplines. This paper summarizes the presentations of this workshop and outlines general recommendations arising from the related discussions. Future studies of BV and its associated adverse outcomes should determine if specific combinations of organisms are more pathogenic than others, and causally associated with different adverse events. Moreover, determination of causality will depend not only on more precise categorization of the vaginal microbiota, but also on variations in the host environment that may be associated with changes in bacterial communities over time. In this report, we offer suggestions and recommendations that we hope will facilitate conduct of consistent approaches to collaborative efforts towards advancing our understanding of the vaginal microbiota and its impact on human health.

Objective To estimate changes in high risk women’s knowledge of cervical cancer prevention, human papillomavirus (HPV), and HPV vaccination since introduction and marketing of HPV vaccines.

Background: Some studies have detected associations between in utero antiretroviral therapy (ARV) exposure and birth defects but evidence is inconclusive. Methods: A total of 2202 human immunodeficiency virus (HIV)-exposed children enrolled in the Pediatric AIDS Clinical Trials Group 219 and 219 C protocols before 1 year of age were included. Birth defects were classified using the Metropolitan Atlanta Congenital Defects Program coding. Logistic regression models were used to evaluate associations between first trimester in utero ARV exposure and birth defects. Results: A total of 117 live-born children had birth defects for a prevalence of 5.3% (95% confidence interval [CI] : 4.4, 6.3). Prevalence did not differ by HIV infection status or overall ARV exposure; rates were 4.8% (95% CI: 3.7, 6.1) and 5.8% (95% CI: 4.2, 7.8) in children without and with first trimester ARV exposure, respectively. The defect rate was higher among children with first trimester efavirenz exposure (5/32, 15.6%) versus children without first trimester efavirenz exposure (adjusted odds ratio [aOR] = 4.31 [95% CI: 1.56, 11.86]). Protective effects of first trimester zidovudine exposure on musculoskeletal defects were detected (aOR = 0.24 [95% CI: 0.08, 0.69]), while a higher risk of heart defects was found (aOR = 2.04 [95% CI: 1.03, 4.05]). Conclusions: The prevalence of birth defects was higher in this cohort of HIV-exposed children than in other pediatric cohorts. There was no association with overall ARV exposure, but there were some associations with specific agents, including efavirenz. Additional studies are needed to rule out confounding and to evaluate newer ARV agents.

BACKGROUND Detectable HIV-1 RNA at delivery is the strongest predictor of mother-to-child transmission. The risk factors for detectable HIV, including type of regimen, are unknown. We evaluated factors, including highly active antiretroviral (HAART) regimen, associated with detectable HIV-1 RNA at delivery in the Women and Infants Transmission Study (WITS). METHODS Data from 630 HIV-1-infected women who enrolled from 1998 to 2005 and received HAART during pregnancy were analyzed. Multivariable analyses examined associations between regimens, demographic factors, and detectable HIV-1 RNA (>400 copies/milliliter) at delivery. RESULTS Overall, 32% of the women in the cohort had detectable HIV-1 RNA at delivery. Among the subset of 364 HAART-experienced women, a lower CD4 cell count at enrollment [adjusted odds ratio (AOR) = 1.20 per 100 cells/microL, confidence interval (CI) 1.04 to 1.37] and higher HIV-1 RNA at enrollment (AOR = 1.52 per log10 copies/milliliter, CI 1.32 to 1.75) were significantly associated with detectable HIV-1 RNA levels at delivery. For the 266 HAART-naive women, both lower CD4 cell count at enrollment (AOR = 1.24 per 100 cells/microL, CI 1.05 to 1.48) and higher HIV-1 RNA at enrollment (AOR = 1.35 per log10 copies/milliliter, CI 1.12 to 1.63) were associated with detectable HIV-1 RNA at delivery. In addition, age at delivery (AOR = 0.92 per 10 years older, CI 0.86 to 0.99) and maternal illicit drug use (AOR = 3.15, CI 1.34 to 7.41) were significantly associated with detectable HIV-1 RNA at delivery among HAART-naive women. Type of HAART regimen was not significant in either group. CONCLUSIONS Lack of viral suppression at delivery was common in the WITS cohort, but differences by antiretroviral regimen were not identified. Despite a transmission rate below 1% in the last 5 years of the WITS cohort, improved measures to maximize HIV-1 RNA suppression at term among high-risk women are warranted.

Background Information is lacking on outcomes in HIV-infected Brazilian women with CD4+ T-cell counts >200 cells/mm3 who initiate HAART for the prevention of mother-to-child transmission, and discontinue after delivery. Methods Clinical event rates after postpartum HAART discontinuation were calculated for all WHO stage 2–3 events, as well as for HIV progression warranting HAART re-initiation, defined by a WHO stage 4 event and/or CD4+ T-cell decrease to ≤200 cells/mm3. Predictors of the WHO stage 2–3 events and HIV progression outcomes were evaluated with Cox's proportional hazards models. Results A total of 120 women were followed for a mean of 1.5 years after delivery. Overall, 26 women had 30 events as follows: 20 developed WHO stage 2–3 events, yielding an incidence rate of 13/100 person-years (PY; 95% CI 8–20); 10 developed HIV progression requiring HAART re-initiation (incidence ratio 6/100 PY, 95% CI 3–11). Among progressors, a single woman developed a WHO stage 4 clinical event and the remainder had CD4+ T-cell decreases. Women who had baseline CD4+ T-cell counts between 200–500 cells/mm3 had a hazard ratio for WHO stage 2–3 events of 2.5 compared to women with baseline ≥500 cells/mm3 (95% CI 1.0–6.3; P=0.05). The only significant predictor of HIV progression was baseline CD4+ T-cell count (hazard ratio 0.99, 95% CI 0.98–0.99; P=0.02). Conclusions In this observational study, a baseline CD4+ T-cell count 3 was associated with an increased risk of postpartum WHO stage 2–3 clinical events and HIV disease progression. Randomized studies are needed to further evaluate the effect of postpartum treatment discontinuation on maternal health.

Purpose Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS). Methods A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III. Results Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III. Conclusion HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified.

Background The impact of HAART on the natural history of human papillomavirus (HPV) remains uncertain following conflicting reports. Prior studies, however, did not consider patients’ adherence to their regimen, or HAART effectiveness (viral suppression).

To estimate the frequency and histologic correlates of glandular abnormalities in cervical cytology among women with the human immunodeficiency virus (HIV) and to compare findings with those of women without HIV.In a cohort study of HIV-infected and uninfected women followed between 1994 and 2007, Pap tests were obtained every 6 months. Glandular abnormalities, including atypical glandular cells (AGC), adenocarcinoma in situ (AIS), and adenocarcinoma, were identified and correlated with biopsy histology. Multivariate models to summarize data across visits used generalized estimating equations. The association of Pap and histology results was assessed using chi tests.Of 48,362 Pap tests from 3,766 women, glandular abnormalities were found in 341 (0.7%) tests from 244 (6%) women, including 93 (1.0%) of 9,564 Pap tests among HIV-seropositive women with CD4 lymphocyte counts less than 250/mm, 103 (0.8%) of 13,023 tests among those with counts 250-500/mm, 68 (0.6%) of 12,470 tests among women with counts greater than 500/mm, and 70 (0.6%) of 11,769 tests among HIV-seronegative women (P for trend=.006). Colposcopy was documented for only 148 (61%) of 244 index Pap tests in women with glandular abnormalities. After index abnormal tests, endocervical curettings were obtained from 106 (43%) women, cervical biopsies from 76 (38%), and endometrial biopsies from 19 (8%). Squamous lesions predominated among histologic findings and histology results did not differ by HIV serostatus (P=.16).Although immunosuppression increased the risk of glandular Pap test abnormalities in women with HIV, these remained uncommon. Compliance with management guidelines can improved.II.

Objective To compare serum mullerian inhibiting substance (MIS) levels between white, black, and Hispanic women to determine whether ovarian aging occurs at a different time course for women of different racial groups. Design Longitudinal study of serum MIS levels in women of different race and ethnicity over two different time points. Setting Women's Interagency HIV Study, a multicenter prospective cohort study. Patient(s) Serum samples obtained from 809 participants (122 white, 462 black, and 225 Hispanic women). Intervention(s) Comparison of serum MIS between women of different race and ethnicity at two time points (median age 37.5 years and 43.3 years). Main Outcome Measure(s) Variation in MIS by race and ethnicity over time, controlling for age, body mass index, HIV status, and smoking. Result(s) Compared with white women, average MIS values were lower among black (25.2% lower) and Hispanic (24.6% lower) women, adjusting for age, body mass index, smoking, and HIV status. Conclusion(s) There is an independent effect of race and ethnicity on the age-related decline in MIS over time.

BACKGROUND: The objective of this study was to estimate the incidence of invasive cervical cancer (ICC) in women with human immunodeficiency virus (HIV) and compare it with the incidence in HIV-uninfected women. METHODS: In a cohort study of HIV-infected and uninfected women who had Papanicolaou tests obtained every 6 months, pathology reports were retrieved for women who had biopsy results or a self-report of ICC. Histology was reviewed when reports confirmed ICC. Incidence rates were calculated and compared with those in HIV-negative women. RESULTS: After a median follow-up of 10.3 years, 3 ICCs were confirmed in HIV-seropositive women, and none were confirmed in HIV-seronegative women. The ICC incidence rate was not found to be associated significantly with HIV status (HIV-negative women [0 of 100,000 person-years] vs HIV-positive women [21.4 of 100,000 person-years]; P = .59). A calculated incidence rate ratio standardized to expected results from the Surveillance Epidemiology and End Results database that was restricted to HIV-infected Women's Interagency HIV Study participants was 1.32 (95% confidence interval, 0.27-3.85; P = 0.80). CONCLUSIONS: Among women with HIV in a prospective study that incorporated cervical cancer prevention measures, the incidence of ICC was not significantly higher than that in a comparison group of HIV-negative women. Cancer 2009. Published 2009 by the American Cancer Society.

To estimate the frequency of and trends in abnormal Pap test results in women with human immunodeficiency virus (HIV) and HIV-uninfected women.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.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).Among women with HIV in a cervical cancer prevention program, Pap test abnormalities are common, but high-grade abnormalities are infrequent.II.

Background: The optimal neonatal antiretroviral (ARV) regimen for prevention of HIV mother-to-child transmission (MTCT) is unknown for infants born to mothers who receive no ARVs during pregnancy. Methods: As part of a protocol comparing the efficacy of 3 neonatal ARV regimens in preventing HIV-1 MTCT in neonates bom to mothers who receive no prenatal treatment with ARVs, we devised a 3-dose nevirapine (NVP) regimen with the goal of maintaining the NVP plasma concentration >100 ng/mL (10 times the in vitro median inhibitory concentration of 10 ng/mL) during the first 2 weeks of life. NVP concentrations were measured in 14 newborns participating in a pharmacokinetics substudy during the second week of life and in single samples from 30 more newborns on day 10 to 14. Results: The median NVP elimination half-life was 30.2 hours (range: 17.8 to 50.3 hours). The NVP concentration remained greater than the target of 100 ng/mL in all samples collected through day 10 of life. By day 14, more than half of the newborns in the pharmacokinetic substudy had NVP levels < 100 ng/mL, although only 1 neonate had no detectable NVP. Conclusion: Although this regimen failed to meet our 100-ng/mL target, it did maintain detectable NVP concentrations in nearly all newborns through the end of the second week of life and is to be used in the parent efficacy protocol.

Background Concomitant use of antiretroviral (ARV) and hormonal contraceptives may change the metabolism of each and the resulting safety profiles. We evaluated the safety and tolerability of depot medroxyprogesterone acetate (DMPA) among women on ARV. Study Design HIV-infected women on selected ARV regimens or no ARV were administered DMPA 150 mg intramuscularly and evaluated for 12 weeks for adverse events, changes in CD4+ count and HIV RNA levels, and ovulation. Results Seventy evaluable subjects were included, 16 on nucleoside only or no ARV, 21 on nelfinavir-containing regimens, 17 on efavirenz-containing regimens and 16 on nevirapine-containing regimens. Nine Grade 3 or 4 adverse events occurred in seven subjects; none were judged related to DMPA. The most common findings possibly related to DMPA were abnormal vaginal bleeding (nine, 12.7%), headache (three, 4.2%), abdominal pain, mood changes, insomnia, anorexia and fatigue, each occurring in two (2.9%) subjects. No significant changes in CD4+ count or HIV RNA levels occurred with DMPA. No evidence of ovulation was detected, and no pregnancies occurred. Conclusions The clinical profile associated with DMPA administration in HIV-infected women, most on ARV, appears similar to that seen in HIV-uninfected women. DMPA prevented ovulation and did not affect CD4+ counts or HIV RNA levels. In concert with previously published DMPA/ARV interaction data, these data suggest that DMPA can be used safely by HIV-infected women on the ARV studied.

Objective. Animal data suggest that cocaine has an immunosuppressive effect, but no human studies have been conducted to assess the relation of cocaine use with human papillomavirus (HPV) infection, the viral cause of cervical cancer. Since both cocaine use and HPV infection are common among HIV-positive women, we sought to determine whether use of cocaine and/or crack influences the natural history of HPV among women with or at high risk of HIV.Methods. Women enrolled in the Women's Interagency HIV Study (2278 HIV-seropositive and 826 high-risk seronegative women) were examined every six months for up to 9.5 years with Pap smear, collection of cervicovaginal lavage (CVL) samples, and detailed questionnaires regarding health and behavior, including use of crack and cocaine (crack/cocaine). CVLs were tested for HPV DNA by PCR, with genotyping for over forty HPV types.Results. In multivariate logistic regression models, censoring women treated for cervical neoplasia, crack/cocaine use within the last six months was associated with prevalent detection of oncogenic HPV DNA (odds ratio [OR] = 1.30 (1.09–1.55)), and with oncogenic HPV-positive squamous intraepithelial lesions (SIL) (OR = 1.70 (1.27–2.27)), following adjustment for age, race, HIV-serostatus, and CD4+ T-cell count, the number of sexual partners in the past six months, and smoking. In multivariate Cox models crack/cocaine use was also associated with a trend that approached significance in regard to incident detection of oncogenic HPV-positive SIL (HR = 1.51, 95% CI 0.99–2.30), and while the rate of oncogenic HPV clearance was not related to cocaine use, the clearance of any SIL was significantly lower in those with versus those without recent crack/cocaine use (HR = 0.57, 95% CI 0.34–0.97).Conclusions. Cocaine use is associated with an increased risk of detection of both prevalent and incident oncogenic HPV infection, as well as an increased risk of HPV-positive SIL over time.

High serum levels of insulin-like growth factor-I (IGF-I) are reported to be a risk factor for several common cancers, and recent cross-sectional data suggest a possible additional association of IGF-I with cervical neoplasia. To prospectively assess whether circulating IGF-I levels influence the natural history of oncogenic human papillomavirus (HPV), the viral cause of cervical cancer, we conducted a pilot investigation of 137 women who underwent semiannual type-specific HPV DNA PCR testing and cervical cytology. Total IGF-I and IGF binding protein-3 (IGFBP-3), the most abundant IGFBP in circulation, were measured using baseline serum specimens. Having a high IGF-I/IGFBP-3 ratio was associated with increased persistence of oncogenic HPV infection [that is, a lower rate of clearance; adjusted hazard ratio (AHR), 0.14; 95% confidence interval (95% CI), 0.04-0.57], whereas IGFBP-3 was inversely associated with both the incident detection of oncogenic HPV (AHR, 0.35; 95% CI, 0.13-0.93) and the incidence of oncogenic HPV-positive cervical neoplasia (that is, squamous intraepithelial lesions at risk of progression; AHR, 0.07; 95% CI, 0.01-0.66). These prospective data provide initial evidence that the IGF axis may influence the natural history of oncogenic HPV. (Cancer Epidemiol Biomarkers Prev 2008;17(1):245–8)