Immune Activation in the Female Genital Tract: Expression Profiles of Soluble Proteins in Women at High Risk for HIV Infection

Soluble cervicovaginal biomarkers of inflammation, immune activation and risk of HIV acquisition are needed to reliably assess the safety of new biomedical prevention strategies including vaccines and microbicides. However, a fuller understanding of expression profiles in women at high risk for HIV infection is crucial to the effective use of these potential biomarkers in Phase 3 trial settings. 

We have measured 45 soluble proteins and peptides in cervicovaginal lavage samples from 100 HIV negative women at high risk for HIV infection. Women were followed over one menstrual cycle to investigate modulation by hormonal contraception, menstrual cycle phase, recent sexual exposure and intravaginal practices. 

Women using injectable DMPA had increased concentration of several soluble proteins of the innate and adaptive immune system, including IL-1α, IL-1β, IL-2, MIP-1β, IP-10, IL-8, TGF-β, HBD4, IgA, IgG1, and IgG2. Women using combined oral contraceptives had a similar signature. There were differences in concentrations among samples from post-ovulation compared to pre-ovulation, notably increased immunoglobulins. Increased prostate-specific antigen, indicative of recent sexual exposure, was correlated with increased IL-6, MCP-1, and SLPI, and decreased GM-CSF and HBD3. 

The identified signature profiles may prove critical in evaluating the potential safety and impact on risk of HIV acquisition of different biomedical intervention strategies.

Below:  Distribution of analyte concentrations in cervicovaginal lavage samples for 370 healthy visits

Full article at:   http://goo.gl/QLQAIc

By:  

Suzanna C. Francis, Kathy Baisley, Trong T. Ao, Saidi Kapiga, Richard J. Hayes

MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, United Kingdom

Suzanna C. Francis, Deborah Watson-Jones, Trong T. Ao, Kaballa Maganja, Aura Andreasen, Saidi Kapiga

Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania, United Republic of Tanzania

Yanwen Hou, Gary R. Coulton

Division of Basic Medical Sciences, St. George's Medical School, University of London, London, United Kingdom

Janneke van de Wijgert

Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom

Carolina Herrera, Robin J. Shattock

Mucosal Infection and Immunity Group, Imperial College, Department of Medicine, London, United Kingdom

Deborah Watson-Jones, Aura Andreasen

Clinical Research Department, London School of Hygiene and Tropical Medicine, London, United Kingdom

  

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Associations of Hormonal Contraceptive Use with Measures of HIV Disease Progression & Antiretroviral Therapy Effectiveness

OBJECTIVE:

To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness.

STUDY DESIGN:

A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to <350cells/mm(3), ART initiation or death. Among participants using ART at enrollment, we used linear mixed models to estimate the predicted mean CD4 change at select time points by contraceptive method.

RESULTS:

During a total of 5233months follow-up among participants not using ART with enrollment CD4 ≥350cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods.

CONCLUSION:

Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection.

IMPLICATIONS:

Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection.

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By:   Whiteman MK1, Jeng G2, Samarina A3, Akatova N3, Martirosyan M3, Kissin DM2, Curtis KM2, Marchbanks PA2, Hillis SD2, Mandel MG2, Jamieson DJ2.

• 1Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: acq5@cdc.gov.
• 2Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA.
• 3St. Petersburg AIDS Center, St. Petersburg, Russia.
• Contraception. 2016 Jan;93(1):17-24. doi: 10.1016/j.contraception.2015.07.003. Epub 2015 Jul 18.
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“Every Method Seems to Have Its Problems”- Perspectives on Side Effects of Hormonal Contraceptives in Morogoro Region, Tanzania

Family planning has been shown to be an effective intervention for promoting maternal, newborn and child health. Despite family planning's multiple benefits, women's experiences of - or concerns related to - side effects present a formidable barrier to the sustained use of contraceptives, particularly in the postpartum period. This paper presents perspectives of postpartum, rural, Tanzanian women, their partners, public opinion leaders and community and health facility providers related to side effects associated with contraceptive use.

Qualitative interviews were conducted with postpartum women (n = 34), their partners (n = 23), community leaders (n = 12) and health providers based in both facilities (n = 12) and communities (n = 19) across Morogoro Region, Tanzania. Following data collection, digitally recorded data were transcribed, translated and coded using thematic analysis.

Respondents described family planning positively due to the health and economic benefits associated with limiting and spacing births. However, side effects were consistently cited as a reason that women and their partners choose to forgo family planning altogether, discontinue methods, switch methods or use methods in an intermittent (and ineffective) manner. Respondents detailed side effects including excessive menstrual bleeding, missed menses, weight gain and fatigue. Women, their partners and community leaders also described concerns that contraceptives could induce sterility in women, or harm breastfeeding children via contamination of breast milk. Use of family planning during the postpartum period was viewed as particularly detrimental to a newborn’s health in the first months of life.

To meet Tanzania’s national target of increasing contraceptive use from 34 to 60 % by 2015, appropriate counseling and dialogue on contraceptive side effects that speaks to pressing concerns outlined by women, their partners, communities and service providers are needed.

Full article at: http://goo.gl/Oj1Ke1

By: Joy J. Chebet^1*, Shannon A. McMahon¹², Jesse A. Greenspan¹, Idda H. Mosha³, Jennifer A. Callaghan-Koru¹, Japhet Killewo⁴, Abdullah H. Baqui¹ and Peter J. Winch¹

¹Department of International Health, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, USA

²Institute of Public Health, Ruprecht-Karls-Universität, Im Neuenheimer Feld 324, Heidelberg, 69120, Germany

³Department of Behavioural Sciences, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

⁴Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania

  

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Prevalence Of & Risk Factors for Bacterial Vaginosis among Women of Reproductive Age Attending Cervical Screening in Southeastern Brazil

To determine the prevalence of and risk factors for bacterial vaginosis.

A cross-sectional study of women aged 14-54 years attending 18 primary healthcare units in Botucatu, Brazil, for cervical screening was undertaken between September 1, 2012, and January 31, 2013. Data on sociodemographics, sexual behavior, and medical history were obtained by interview. Vaginal swabs were taken to classify the vaginal flora according to the Nugent scoring system. Candida sp. hyphae and infection by Trichomonas vaginalis were also evaluated by microscopy and culture, respectively. Stepwise logistic regression analysis was performed to identify risk factors independently associated with bacterial vaginosis.

Among 1519 women included in analyses, 30.1% had bacterial vaginosis. Variables independently associated with bacterial vaginosis were a single marital status, partner infidelity, abnormal discharge in the previous year, and concurrent trichomoniasis. Current use of hormonal contraception, luteal phase of menstrual cycle, higher income, and vaginal candidiasis all had protective effects.

The prevalence of bacterial vaginosis in the study population is high. The epidemiological data provide evidence of the sexual transmissibility of bacterial vaginosis.

Purchase full article at: http://goo.gl/VUVOOM

By: Marconi C1, Duarte MT2, Silva DC3, Silva MG4.

• 1Department of Pathology, Botucatu Medical School, Univ Estadual Paulista, Botucatu, São Paulo, Brazil.
• 2Department of Nursing, Botucatu Medical School, Univ Estadual Paulista, Botucatu, São Paulo, Brazil.
• 3Department of Health of Botucatu Prefecture, Botucatu, São Paulo, Brazil.
• 4Department of Pathology, Botucatu Medical School, Univ Estadual Paulista, Botucatu, São Paulo, Brazil. Electronic address: mgsilva@fmb.unesp.br.  

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The Impact of Hormonal Contraception and Pregnancy on Sexually Transmitted Infections and on Cervicovaginal Microbiota in African Sex Workers

The observed association between Depo-Provera injectable use and increased HIV acquisition may be caused by hormone-induced increased susceptibility to other sexually transmitted infections (STIs) or changes in the cervicovaginal microbiota (VMB), accompanied by genital immune activation and/or mucosal remodeling.

Rwandan female sex workers (n = 800) were interviewed about contraceptive use and sexual behavior and were tested for STIs, bacterial vaginosis by Nugent score and pregnancy, at baseline. A subset of 397 HIV-negative, nonpregnant women were interviewed and tested again at regular intervals for 2 years. The VMB of a subset of 174 women was characterized by phylogenetic microarray. Outcomes of STI and VMB were compared between women with hormonal exposures (reporting oral contraceptive or injectable use, or testing positive for pregnancy) and controls (not reporting hormonal contraception and not pregnant).

Oral contraceptive use was associated with increased human papillomavirus prevalence (adjusted odds ratio [aOR], 3.10; 1.21-7.94) and Chlamydia trachomatis incidence (aOR, 6.13; 1.58-23.80), injectable use with increased herpes simplex virus-2 prevalence (aOR, 2.13; 1.26-3.59) and pregnancy with lower HIV prevalence (aOR, 0.45; 0.22-0.92) but higher candidiasis incidence (aOR, 2.14; 1.12-4.09). Hormonal status was not associated with Nugent score category or phylogenetic VMB clustering, but oral contraceptive users had lower semiquantitative vaginal abundance of Prevotella, Sneathia/Leptotrichia amnionii, and Mycoplasma species.

Oral contraceptive and injectable use were associated with several STIs but not with VMB composition. The increased herpes simplex virus-2 prevalence among injectable users might explain the potentially higher HIV risk in these women, but more research is needed to confirm these results and elucidate biological mechanisms.

Via: http://goo.gl/cXVFQC  Purchase full article at: http://goo.gl/QI3X5c

By: Borgdorff H1, Verwijs MC, Wit FW, Tsivtsivadze E, Ndayisaba GF, Verhelst R, Schuren FH, van de Wijgert JH.

• 1From the *Amsterdam Institute for Global Health and Development and Department of Global Health, Academic Medical Center, Amsterdam, the Netherlands; †Institute of Infection and Global Health, University of Liverpool, Liverpool, UK; ‡TNO Microbiology & Systems Biology, Zeist, the Netherlands; §Rinda Ubuzima, Kigali, Rwanda; and ¶International Center for Reproductive Health, Ghent University, Ghent, Belgium. 

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Sexually Transmitted Infections in Pediatric Renal Transplant Recipients: Time to Take Notice!

We sought to assess the prevalence of STIs, contraception use, and unintentional pregnancy in our pediatric renal transplant recipients. We performed a retrospective chart review. 
Forty-nine of 65 patients in our program are currently in the high-risk age window of 13 yr or older (34 men, 15 women; mean age 17 yr old, range 13-23 yr old). 

• There was a disproportionate difference in sexual behavior among the men and women, 
• Such that while only 15% of the men reported being sexually active, 
• 53% of the women were sexually active. 
• Among high-risk age-group women, 40% were on hormonal contraception. 
• This increased to 75% in sexually active women. 
• There were no cases of unintentional pregnancy. 
• 30% of sexually active recipients had at least one STI. 
• This was higher among sexually active women (37.5%) compared to men (20%). 
• STIs identified included gonococcal and chlamydial urethritis/cervicitis, Trichomonas vaginitis, HSV-2 genital sores, pelvic inflammatory disease, and HIV. 

In conclusion, STIs are a realistic public health concern in our pediatric renal transplant recipients. Consensus guidelines on STI screening and reproductive health counseling are needed to address this understudied problem.

Via: http://goo.gl/RCLnQJ  Purchase full article at: http://goo.gl/4SoHa1

By: Ashoor I1, Aviles D1, Pasternak R2, Vehaskari VM1.

• 1Nephrology, Children's Hospital of New Orleans, New Orleans, LA, USA.
• 2Adolescent Medicine, Children's Hospital of New Orleans, New Orleans, LA, USA. 

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Hormonal Contraception, Pregnancy, Breastfeeding & Risk of HIV Disease Progression among Zambian Women

Some studies suggest hormonal contraception, pregnancy, and/or breastfeeding may influence rates of HIV disease progression.

From 1994-2012, HIV discordant couples recruited at couples' voluntary HIV counseling and testing centers in Lusaka were followed 3-monthly. Multivariate survival analyses explored associations between time-varying contraception, pregnancy, and breastfeeding and two outcomes among HIV-positive women: 1) time-to-death and 2) time-to-antiretroviral treatment (ART) initiation.

Among 1,656 female seropositive, male seronegative couples followed for 3,359 person years (PY), 224 women died. After 2003, 290 women initiated ART. In a multivariate model of time-to-death, hormonal implant and injectable were significantly protective relative to non-hormonal method use while OCP use was not controlling for baseline HIV disease stage, time-varying pregnancy, time-varying breastfeeding, and year of enrollment. In a multivariate model of time-to-ART initiation, implant was protective while OCP and injectable were not relative to non-hormonal method use controlling for variables above, woman's age, and literacy. Pregnancy was not significantly associated with death or ART initiation while breastfeeding was protective for death and ART initiation.

Hormonal implants and injectables significantly predicted lower mortality; implants were protective for ART initiation. OCPs and pregnancy were not associated with death or ART initiation, while breastfeeding was protective for both. 

Findings from this 18-year cohort study suggest 1) HIV-positive women desiring pregnancy can be counseled to do so and breastfeed, and 2) all effective contraceptive methods including injectables and implants should be promoted to prevent unintended pregnancy.

Via: http://ht.ly/SxVbk Purchase full article at:  http://ht.ly/SxVdj 

By: Wall KM1, Kilembe W, Haddad L, Vwalika B, Lakhi S, Htee Khu N, Brill I, Chomba E, Mulenga J, Tichacek A, Allen S.

• 1aRwanda Zambia HIV Research Group, Department of Pathology & Laboratory Medicine, School of Medicine and Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA bDepartment of Epidemiology, Rollins School of Public Health, Laney Graduate School, Emory University, Atlanta, Georgia, USA cDepartment of Gynecology and Obstetrics, Emory University, School of Medicine, Atlanta, Georgia, USA dDepartments of Gynecology and Obstetrics (BV) and Internal Medicine (SL), School of Medicine, University of Zambia, Lusaka, Zambia eDepartment of Epidemiology, Ryals School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA fMinistry of Community Development, Mother and Child Health, Lusaka, Zambia.
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Use of Injectable Hormonal Contraception & Women's Risk of Herpes Simplex Virus Type 2 Acquisition: A Prospective Study of Couples in Rakai, Uganda

HIV-negative and HSV2-negative women aged 15-49 years whose HIV-negative male partners were concurrently enrolled in a randomised trial of male circumcision in Rakai, Uganda. We excluded women if either they or their male partners HIV seroconverted. The primary outcome was HSV2 seroconversion, assessed annually. The male circumcision trial was registered with ClinicalTrials.gov, number NCT00425984.

:

We noted HSV2 seroconversions in 70 (10%) women. Incidence was 13·5 per 100 person-years in women consistently using depo-medroxyprogesterone acetate (DMPA) (nine incident infections per 66·5 person-years), 4·3 per 100 person-years in pregnant women who were not using hormonal contraception (18 incident infections per 423·5 person-years), and 6·6 per 100 person-years in women who were neither pregnant nor using hormonal contraception (35 incident infections per 529·5 person-years). Women consistently using DMPA had an adjusted hazard ratio for HSV2 seroconversion of 2·26 (95% CI 1·09-4·69; p=0·029) compared with women who were neither pregnant nor using hormonal contraception. Of 132 women with HSV2-seropositive partners, seroconversion was 36·4 per 100 person-years in consistent DMPA users (four incident infections per 11 person-years) and 10·7 per 100 person-years in women who were neither pregnant nor using hormonal contraception (11 incident infections per 103 person-years; adjusted hazard ratio 6·23, 95% CI 1·49-26·3; p=0·012).

Consistent DMPA use might increase risk of HSV2 seroconversion; however, study power was low. These findings should be assessed in larger populations with more frequent follow-up than in this study, and other contraceptive methods should also be assessed. Access to a wide range of highly effective contraceptive methods is needed for women, particularly in sub-Saharan Africa.

Read more at: http://ht.ly/S4THW

By: Grabowski MK1, Gray RH2, Makumbi F3, Kagaayi J3, Redd AD4, Kigozi G3, Reynolds SJ5, Nalugoda F3, Lutalo T3, Wawer MJ2, Serwadda D6, Quinn TC7,Tobian AA8.

• 1Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
• 2Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; Rakai Health Sciences Program, Entebbe, Uganda.
• 3Rakai Health Sciences Program, Entebbe, Uganda.
• 4Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA.
• 5Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Rakai Health Sciences Program, Entebbe, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA.
• 6Rakai Health Sciences Program, Entebbe, Uganda; School of Public Health, Makerere University, Kampala, Uganda.
• 7Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, MD, USA.
• 8Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Rakai Health Sciences Program, Entebbe, Uganda. 

Fear of Becoming Pregnant among Female Healthcare Students in Spain

Below:  Probability of fear of becoming pregnant among female university healthcare students in a Spanish region. 2005–2009 data

The inconsistent use of hormonal contraceptive methods can result, during the first year of use, in one in twelve women still having an undesired pregnancy. This may lead to women experiencing fear of becoming pregnant (FBP). We have only found one study examining the proportion of FBP among women who used hormonal contraceptives. To gather further scientific evidence we undertook an observational, cross-sectional study involving 472 women at a Spanish university in 2005–2009. The inclusion criteria were having had vaginal intercourse with a man in the previous three months and usual use for contraception of a male condom or hormonal contraceptives, or no method of contraception. The outcome was FBP. The secondary variables were contraceptive method used (oral contraceptives; condom; none), desire to increase the frequency of sexual relations, frequency of sexual intercourse with the partner, the sexual partner not always able to ejaculate, desire to increase the partner’s time before orgasm, age and being in a stable relationship. A multivariate logistic regression model was used to determine the associated factors. Of the 472 women, 171 experienced FBP (36.2%). Factors significantly associated (p < 0.05) with this FBP were method of contraception (condom and none), desire to increase the partner’s ability to delay orgasm and higher frequency of sexual intercourse with the partner. There was a high proportion of FBP, depending on the use of efficient contraceptive methods. A possible solution to this problem may reside in educational programmes. Qualitative studies would be useful to design these programmes.

Read more at: http://ht.ly/RRI2I 

By: Navarro-Cremades F1, Palazón-Bru A1, Arroyo-Sebastián Mdel Á2, Gómez-Pérez L3, Sepehri A1, Martínez-Pérez S4, Marhuenda-Amorós D3, Rizo-Baeza MM5, Gil-Guillén VF1.

• 1Department of Clinical Medicine, Miguel Hernández University , San Juan de Alicante, Alicante , Spain.
• 2Health Centre of San Juan de Alicante, Conselleria de Sanitat , San Juan de Alicante, Alicante , Spain.
• 3Department of Pathology and Surgery, Miguel Hernandez University , San Juan de Alicante, Alicante , Spain.
• 4Department of Histology and Anatomy, Miguel Hernandez University , San Juan de Alicante, Alicante , Spain.
• 5Department of Nursing, University of Alicante , San Vicente del Raspeig, Alicante , Spain.