Globally, roughly 73 million abortions occur each year and the majority occur in low- and middle-income countries. 1 Post-abortion contraception is part of post-abortion care. It involves contraceptive counseling and provision to increase contraceptive prevalence and reduce unintended pregnancies and unsafe abortion. 2 Data indicate that women can begin ovulating as soon as 2 weeks post-abortion, with 75% of women restarting ovulation within 6 weeks after an abortion. Rapid return to fertility coupled with high rates of resumption of sex post-abortion indicates the need for early contraceptive counseling and access.
Purpose We describe the rationale for and design of an innovative, nested, tripartite prospective observational cohort study examining whether relative estrogen insufficiency-induced inflammation amplifies HIV-induced inflammation to cause end organ damage and worsen age-related co-morbidities affecting the neuro-hypothalamic-pituitary-adrenal axis (Brain), skeletal (Bone), and cardiovascular (Heart/vessels) organ systems (BBH Study). Methods The BBH parent study is the Multicenter AIDS Cohort/Women's Interagency HIV Study Combined Cohort Study (MWCCS) with participants drawn from the Atlanta MWCCS site. BBH will enroll a single cohort of n = 120 women living with HIV and n = 60 HIV-negative women, equally distributed by menopausal status. The innovative multipart nested study design of BBH, which draws on data collected by the parent study, efficiently leverages resources for maximum research impact and requires extensive oversight and management in addition to careful implementation. The presence of strong infrastructure minimized BBH study disruptions due to changes in the parent study and the COVID-19 pandemic. Conclusion BBH is poised to provide insight into sex and HIV associations with the neuro-hypothalamicpituitary-adrenal axis, skeletal, and cardiovascular systems despite several major, unexpected challenges.
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Brigid E O'Brien;
Paige L Williams;
Yanling Huo;
Deborah Kacanek;
Ellen G Chadwick;
Kathleen M Powis;
Katharine Correia;
Lisa Haddad;
Lisa M Yee;
Nahida Chakhtoura;
Chi Dola;
Russell B Van Dyke
BACKGROUND: Birth rates among women living with HIV (WLHIV) have increased recently, with many experiencing multiple pregnancies. Yet, viral suppression is often not sustained between pregnancies. In addition, protease inhibitors (PIs) have been associated with preterm birth, but associations between integrase strand transfer inhibitors (INSTIs) and preterm birth are less well characterized. METHODS: We studied WLHIV with ≥2 live-born infants enrolled into the Pediatric HIV/AIDS Cohort Study Surveillance Monitoring for Antiretroviral Treatment Toxicities (SMARTT) study between 2007 and 2018, comparing CD4 counts and viral loads (VLs) between 2 consecutive SMARTT pregnancies. We evaluated associations of covariates with CD4 and viral suppression and the association of PI/INSTI use during pregnancy with odds of preterm birth. RESULTS: There were 736 women who had ≥2 live-born children enrolled in SMARTT (1695 pregnancies). Median CD4 counts remained stable over repeat pregnancies. Although >80% of women achieved VL suppression during pregnancy, more than half had a detectable VL early in their subsequent pregnancy. In adjusted models including all singleton pregnancies, an increased odds of preterm birth was observed for women with first trimester PI initiation (adjusted odds ratio: 1.97; 95% confidence interval: 1.27 to 3.07) compared with those not receiving PIs during pregnancy and for first trimester INSTI initiation (adjusted odds ratio: 2.39; 95% confidence interval: 1.04 to 5.46) compared with those never using INSTIs during pregnancy. CONCLUSIONS: Most WLHIV achieved VL suppression by late pregnancy but many were viremic early in subsequent pregnancies. First trimester initiation of PIs or INSTIs was associated with a higher risk of preterm birth.
Background: Gonadal hormones can modify immune function, which may impact susceptibility to infectious diseases, including Human Immunodeficiency Virus (HIV). There is limited knowledge about how hormonal contraceptives (HC) influence the immune response during the course of use. The CHIME study aims to evaluate the effect of long-acting progestin-based hormonal contraceptives (depot medroxyprogesterone acetate, etonogestrel implant, and levonorgestrel intrauterine device) on immunologic changes in the female genital tract (FGT) and systemic compartment. Methods: CHIME is an observational cohort study where participants attend 2 visits prior to initiating the HC method of their choice, and then attend 6 visits over 12 months with biological sampling (vaginal swabs, cervicovaginal lavage, cytobrush and blood) for immunological, bacteriological, and virological analyses at each visit. Immune profiling will be evaluated by multi-color flow cytometry to determine how different T-cell subsets, in particular the CD4 T-cell subsets, change during the course of contraceptive use and whether they have different profiles in the FGT compared to the systemic compartment. The study aims are (1) to characterize the alterations in FGT and systemic immune profiles associated with three long-acting progestin-only HC and (2) to evaluate the vaginal microenvironment, determined by 16 s rRNA sequencing, as an individual-level risk factor and moderator of genital and systemic immune profile changes following exposure to three commonly used HC. Data collection started in March 2019 and is scheduled to be completed in October 2024. Discussion: The CHIME study aims to contribute to the body of research designed to evaluate the comparative impact of three long-acting progestin-only HC on innate and adaptive immune functions to understand how immunologic effects alter STI and HIV susceptibility.
PURPOSE OF REVIEW: Hormonal contraception provides women living with HIV the ability to control their fertility and avoid pregnancy-related morbidity. Due to shared metabolic pathways, there has been concern over drug-drug interactions between hormonal contraception and anti-retroviral therapy, which may affect the drugs' safety and efficacy. This article aims to provide an updated review of the most recent data around hormonal contraceptives and anti-retroviral therapy. RECENT FINDINGS: Prior data have suggested possible pharmacologic interactions between certain hormonal contraceptives and anti-retroviral therapy. The most significant interactions implicated include those between progestin-based contraceptive implants and efavirenz as well as between combined hormonal contraceptives and protease inhibitors. Most past studies, however, feature small sample sizes with few clinical outcomes reported. SUMMARY: Recent data since 2017 have largely affirmed prior studies on this topic, showing possible pharmacokinetic relationships between certain contraceptives and anti-retrovirals. Notably, while the effectiveness of progestin-based contraceptives, specifically the implant, appears reduced with efavirenz use, the overall effectiveness may remain higher than most other contraceptive methods. Larger studies are needed to provide further guidance before contraceptive-prescribing recommendations can be changed.
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Kalonde Malama;
William Kilembe;
Mubiana Inambao;
Alexandra Hoagland;
Tyronza Sharkey;
Rachel Parker;
Kristin Wall;
Amanda Tichacek;
Supriya Sarkar;
Bellington Vwalika;
Lisa Haddad;
Elwyn Chomba;
Susan Allen
Background: Zambia's total fertility rate (5 births per woman) and adult HIV prevalence (11.5%) are among the highest in the world, with heterosexual couples being the most affected group. Jointly counseling and testing couples for HIV has reduced up to 58% of new HIV infections in Zambian clinics. Married women using contraceptives in Zambia have a high (20%) unmet need for family planning and low (8.6%) uptake of cost-effective long-acting reversible contraceptives. We present an integrated counseling, testing, and family-planning program to prevent HIV and unplanned pregnancy in Zambia. Objective: The objective of this study was to integrate effective HIV prevention and family-planning services for Zambian couples. Study Design: A 3 year program (2013–2016) progressively integrated the promotion and provision of couples’ voluntary HIV counseling and testing and long-acting reversible contraceptives. The program was based in 55 urban and 215 rural government clinics across 33 districts. In the first year, a couples’ family-planning counseling training program was developed and combined with existing couples HIV counseling training materials. To avoid congestion during routine clinic hours, joint counseling services were initially provided on weekends, while nurses were trained in intrauterine device and hormonal implant insertion and removal during weekday family-planning services. Demand was created through mutual referral between weekend and weekday programs and by clinic staff, community health workers, and satisfied family-planning clients. When the bulk of integrated service training was completed, the program transitioned services to routine weekday clinic hours, ensuring access to same-day services. Performance indicators included number of staff trained, clients served, integrated service referrals, HIV infections averted, and unplanned pregnancies averted. Results: A stepwise approach trained high-performing service providers to be trainers and used high-volume clinics for practicum training of the next generation. In total, 1201 (391 urban, 810 rural) counselors were trained and served 120,535 urban and 87,676 rural couples. In urban clinics, 236 nurses inserted 65,619 long-acting reversible contraceptives, while in rural clinics, 243 nurses inserted 35,703 implants and intrauterine devices. The program prevented an estimated 12,869 urban and 8279 rural adult HIV infections, and 98,626 unintended urban pregnancies. In the final year, the proportion of clients receiving joint counseling services on weekdays rose from 11% to 89%, with many referred from within clinics including HIV testing and treatment services (32%), outpatient department (31%), family planning (16%), and infant vaccination (15%). The largest group of clients requesting long-acting reversible contraceptives (45%) did so after joint fertility goal-based counseling, confirming the high impact of this couple-focused demand creation approach. Remaining family-planning clients responded to referrals from clinic nurses (34%), satisfied implant/intrauterine device users (13%), or community health workers (8%). Conclusion: Integrated HIV and unplanned pregnancy prevention can be implemented in low-resource public sector facilities. Combination services offered to couples mutually leverage HIV prevention and unplanned pregnancy prevention. The addition of long-acting reversible contraceptives is an important complement to the method mix available in government clinics. Demand creation in the clinic and in the community must be coordinated with a growing supply of well-trained providers.
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Lisa Haddad;
Kristin Wall;
Katherine Tote;
William Kilembe;
Bellington Vwailika;
Tyronza Sharkey;
Ilene Brill;
Elwyn Chomba;
Amanda Tichacek;
Susan Allen
OBJECTIVE:To examine the relationship between hormonal contraception and vaginal infections with bacterial vaginosis, vaginal candidiasis, or trichomoniasis.METHODS:Couples who were human immunodeficiency virus (HIV) serodiscordant in Zambia were enrolled in a longitudinal cohort study. From 1994 to 2002, both partners were seen quarterly and received physical exams including genital examinations. Separate rates for three outcome infections of interest (bacterial vaginosis, vaginal candidiasis, and trichomoniasis) were calculated. Bivariate associations between baseline and time-varying covariates and outcome infections of interest were evaluated using unadjusted Anderson-Gill survival models. Adjusted hazard ratios (aHRs) were generated using multivariable Anderson-Gill survival models that included demographic and clinical factors associated with both hormonal contraceptive use and each infection of interest.RESULTS:There were 1,558 cases of bacterial vaginosis, 1,529 cases of vaginal candidiasis, and 574 cases of trichomoniasis over 2,143 person-years of observation. Depot medroxyprogesterone acetate (DMPA) users had significantly lower rates of trichomoniasis and bacterial vaginosis. In adjusted models, DMPA was protective for bacterial vaginosis (aHR=0.72; 95% CI 0.54-0.95), candidiasis (aHR 0.75, 95% CI 0.57-1.00) and trichomoniasis (aHR=0.43, 95% CI 0.25-0.74). Oral contraceptive pills were protective for candidiasis (aHR=0.79, 95% CI 0.65-0.97).CONCLUSION:We confirm that DMPA use was associated with reduced rates of the three most common causes of vaginitis, and oral contraceptive pill use was associated with reduced rates of candidiasis among women in couples who were HIV discordant.
To improve women’s access to pre-exposure prophylaxis (PrEP) in family planning (FP) clinics, we examined readiness to provide PrEP, and barriers and facilitators at the clinic level to integrate PrEP services into Title X-funded FP clinics across the Southern US. Title X-funded FP clinics across DHHS regions III (Mid-Atlantic), IV (Southeast), and VI (Southwest), comprising the Southern US. From February to June, 2018, we conducted a web-based, geographically targeted survey of medical staff, providers and administrators of Title X-funded FP clinics in DHHS regions III (Mid-Atlantic), IV (Southeast), and VI (Southwest). Survey items were developed using the Consolidated Framework for Implementation Research to assess constructs relevant to PrEP implementation. One-fifth of 283 unique Title X clinics across the South provided PrEP. Readiness for PrEP implementation was positively associated with a climate supportive of HIV prevention, leadership engagement, and availability of resources, and negatively associated with providers holding negative attitudes about PrEP’s suitability for FP. The Title X FP network is a vital source of sexual health care for millions of individuals across the US. Clinic-level barriers to providing PrEP must be addressed to expand onsite PrEP delivery in Title X FP clinics in the Southern US.
The importance of fetal placental macrophages (Hofbauer cell [HCs]) is underscored by their appearance 18 d postconception and maintenance through term; however, how human HCs evolve during healthy pregnancy and how microenvironment and ontogeny impact phenotype and function remain unknown. In this study, we comprehensively classify human HCs ex vivo, interrogate phenotypic plasticity, and characterize antiviral immune responses through gestation. Activated HCs were abundant in early pregnancy and decreased by term; molecular signatures emphasize inflammatory phenotypes early in gestation. Frequency of HCs with regulatory phenotypes remained high through term. Furthermore, term HCs exhibited blunted responses to stimulation, indicating reduced plasticity. IFN-l1 is a key placental IFN that appeared less protective than IFN-a, suggesting a potential weakness in antiviral immunity. Ligand-specific responses were temporally regulated: we noted an absence of inflammatory mediators and reduced antiviral gene transcription following RIG-I activation at term despite all HCs producing inflammatory mediators following IFN-g plus LPS stimulation. Collectively, we demonstrate sequential, evolving immunity as part of the natural history of HCs through gestation.
BACKGROUND: Some human immunodeficiency virus (HIV) serodiscordant couples are faced with the dual challenge of preventing HIV transmission to the uninfected partner and avoiding unintended pregnancy. Therefore, we hypothesized that serodiscordance is associated with dual method use at last sex. METHODS: We analyzed data from a cross-sectional survey of HIV-infected men and women attending 2 ante-retroviral therapy clinics in Lilongwe, Malawi. We used Fisher exact test and Wilcoxon rank sum to assess for associations between serodiscordance, covariates, and dual method use. Multivariable logistic regression was used to estimate the adjusted odds ratio (aOR) and 95% confidence intervals (CI) of dual method use at last sex, comparing serodiscordant to seroconcordant relationships. Separate analyses were conducted for men and women. RESULTS: We surveyed 253 HIV-infected men, of which 44 (17.4%) were in a known serodiscordant relationship and 63 (24.9%) were using dual methods at last sex. Likewise, among 302 HIV-infected women surveyed, 57 (18.9%) were in a known serodiscordant relationship, and 80 (26.5%) were using dual method at last sex. Serodiscordance was not significantly associated with dual method use at last sex for among HIV-infected men (aOR, 0.62; 95% CI, 0.27-1.44) or women (aOR, 1.21; 95% CI, 0.59-2.47). CONCLUSION: Dual method use was low among all HIV-infected individuals, irrespective of their partner's HIV status. Given these findings, we recommend greater efforts to encourage HIV providers to counsel their patients about the importance of dual method use to prevent both unintended pregnancy and sexually transmitted infections.