Drug-Drug Interactions between Antiretrovirals and Hormonal Contraception: An Updated Systematic Review.

OBJECTIVE: To summarize and update information regarding drug-drug interactions (DDIs) between antiretrovirals (ARVs) and hormonal contraceptives (HCs). DESIGN: Systematic review METHODS: We searched seven databases for peer-reviewed publications from January 1, 2015, through December 31, 2023, including studies of women using ARVs and HCs concurrently with outcomes including therapeutic effectiveness or toxicity, pharmacokinetics (PK), or pharmacodynamics. We summarized findings and used checklists to assess evidence quality. RESULTS: We included 49 articles, with clinical, ARV or HC PK outcomes reported by 39, 25, and 30 articles, respectively, with some articles reporting outcomes in two or more categories. Fifteen of 18 articles assessing DDIs between efavirenz and progestin implants, emergency contraception, or combined hormonal intravaginal rings found higher pregnancy rates, luteal progesterone levels suggesting ovulation, or reduced progestin PK values. Five studies documented that CYP2B6 single nucleotide polymorphisms exacerbated this DDI. One cohort detected doubled bone density loss with concomitant depot medroxyprogesterone acetate (DMPA) and tenofovir disoproxil fumarate (TDF)-containing ART use versus TDF alone. No other studies described DDIs impacting clinical outcomes. Few adverse events were attributed to ARV-HC use with none exceeding Grade 2. Evidence quality was generally moderate, with dis-similar treatment and control groups, identifying and controlling for confounding, and minimizing attrition bias in the study design being the most frequent limitations. CONCLUSION: Most ARVs and HCs may be used safely and effectively together. TDF-DMPA DDIs warrant longer-term study on bone health and consideration of alternate combinations. For efavirenz-based ART, client counselling on relative risks, including both potential increase in pregnancy rate with concomitant efavirenz and implant use and lower pregnancy rates compared to other HCs even with concomitant efavirenz use, should continue to allow users comprehensive method choice.

A Conference Designathon to Spark Innovation: Actionable Ideas to Enhance Sexually Transmitted Disease Control.

BACKGROUND: Designathons can be used to enhance public health training and spur innovation. A designathon is a 3-stage participatory activity that includes preparation, intensive collaboration, and follow-up activities. We organized a designathon focused on developing actionable sexually transmitted disease (STD) control strategies and examined the content of ideas resulting from an STD designathon. METHODS: For this designathon, we created four groups: early career researchers, silver group (people with >10 years of experience), travelers (people from low- and middle-income countries and those who received a conference scholarship) and a community group. Each group developed its own plan to consult members, iteratively develop ideas, and aggregate insights. Each group developed STD control strategies that were presented. Cross-cutting themes across these ideas were identified. RESULTS: Designathon participants included a subset of conference participants. Cross-cutting themes from final ideas included cocreating STD interventions with end-users, using sex-positive framing, enhancing open access digital STD resources, and reducing STD stigma. Early career researchers presented a call for community ideas focusing on ending STD epidemics by increasing accessibility to STD care services among all populations. The silver group proposed digital innovations, including an AI-powered tool for testing and treatment and a social game to promote sex positivity. The traveler group conceptualized an information hub to support implementation of STD programs. Community members underscored the importance of a more human-centered approach to STD control, which reduces stigma and normalizes sex and sexual pleasure. CONCLUSION: Sex positive campaigns and open access digital resources should be considered within STD programs. Implementation research studies are needed to evaluate these ideas.

Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial.

BACKGROUND: Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods. METHODS: In this ancillary study at the East London, South Africa site of the ECHO multicentre randomized trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant. The primary outcome was free testosterone at 6 months. RESULTS: We analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p <  0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference - 22.98, p <  0.001). Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference - 50.04, p <  0.001 and than DMPA (mean percentage difference - 39.45, p <  0.001). Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001). CONCLUSIONS: This is the first randomized trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO study. ECHO TRIAL REGISTRATION: ClinicalTrials.gov , number NCT02550067 15/09/2015. Contraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method. Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users' own circulating sex hormones, both the 'female' and the 'male' sex hormones (androgens). In this study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years. We measured the participants' androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods. This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.

Use of Expedited Partner Therapy for Pregnant Women Treated for Sexually Transmitted Infections in Gaborone, Botswana.

BACKGROUND: Partner notification and treatment for sexually transmitted infections are critical to prevent reinfection and reduce transmission. However, partner treatment rates are low globally. Expedited partner therapy (EPT), in which the patient delivers treatment directly to their partner, may result in more partners treated. We assessed partner notification and treatment outcomes among pregnant women in Gaborone, Botswana, including EPT intent, uptake, and effectiveness. METHODS: The Maduo study was a cluster-controlled trial evaluating the effect of antenatal Chlamydia trachomatis and Neisseria gonorrhoeae infection screening in pregnant women. The intervention arm received screening at first antenatal care (ANC), third-trimester, and postnatal care visits. The standard-of-care arm received screening postnatally. Participants screening positive were given options for partner treatment: contact slips, in-clinic treatment, or EPT. Self-reported partner notification and treatment outcomes were assessed at test-of-cure visit. RESULTS: Of 51 women who screened positive for C. trachomatis / N. gonorrhoeae at first ANC and returned for test of cure, 100% reported notifying their partner and 48 (94.1%) reported their partner received treatment. At third trimester 100% (n = 5), reported partners were treated. Before testing, EPT intent was lower than EPT uptake at all time points (first ANC: 17.9% vs. 80.4%; third-trimester: 57.1% vs. 71.4%; postnatal care: 0% vs. 80.0%). Partner treatment success was 100% among EPT users compared with 70% among nonusers ( P = 0.006). CONCLUSIONS: Partner notification and treatment success was high in this population. Despite low pretest intent to use EPT, uptake was high and associated with greater partner treatment success. Our findings suggest that EPT may be a successful partner treatment strategy to pursue in low- and middle-income countries.

Evaluating Chlamydia trachomatis and Neisseria gonorrhoeae screening and treatment among asymptomatic pregnant women to prevent preterm birth and low birthweight in Gaborone, Botswana: A secondary analysis from a non-randomised, cluster-controlled trial.

OBJECTIVE: To evaluate the impact of screening and treating asymptomatic pregnant women for Chlamydia (C.) trachomatis and Neisseria (N.) gonorrhoeae infections on the frequency of preterm birth or low birthweight infants in Botswana. DESIGN: Non-randomised, cluster-controlled trial. SETTING: Four antenatal care clinics in Gaborone, Botswana. POPULATION: Pregnant women aged ≥15 years, attending a first antenatal care visit, ≤27 weeks of gestation and without urogenital symptoms were eligible. METHODS: Participants in the intervention clinics received screening (GeneXpert®, Cepheid) during pregnancy and at the postnatal visit. Participants in the standard-of-care clinics received screening at the postnatal visit only. We used multivariable logistic regression and post-estimation predictive margins analysis. Post-hoc analysis was conducted among sub-samples stratified by parity. MAIN OUTCOME MEASURES: Preterm birth (<37 weeks of gestation) and low birthweight (<2500 g). RESULTS: After controlling for parity, hypertension, antenatal care visits and clinic site, the predicted prevalence of preterm birth or low birthweight was lower in the intervention arm (11%) compared with the standard-of-care arm (16%) (adjusted odds ratio [aOR] 0.59; 95% confidence interval [CI] 0.28-1.24). In post-hoc analysis, the intervention was more effective than the standard-of-care (aOR 0.20; 95% CI 0.07-0.64) among nulliparous participants. CONCLUSION: A C. trachomatis and N. gonorrhoeae infection screening and treatment intervention among asymptomatic pregnant women may have reduced preterm birth or low birthweight outcomes, but results were not statistically significant. Post-hoc analysis found that the intervention reduced adverse outcomes among nulliparous participants.

Syphilis Prevalence Among People Living With and Without HIV in Sub-Saharan Africa: A Systematic Review and Meta-Analysis.

BACKGROUND: Syphilis is a curable sexually transmitted infection that, untreated, is associated with significant morbidity and mortality. In people living with HIV (PLWH), syphilis carries greater risks of disease progression. We estimated syphilis prevalence among PLWH in the general population in sub-Saharan Africa and compared the prevalence among PLWH and without HIV. METHODS: We searched for studies published January 1, 2011, to March 28, 2022, reporting syphilis prevalence among PLWH in sub-Saharan Africa (PROSPERO No. CRD42020167328). We excluded studies in high-risk subpopulations. We estimated pooled syphilis prevalence among PLWH using random-effects modeling and compared the prevalence with people without HIV when included in the same study. We examined influences of region, study setting, and test type in subgroup analyses. RESULTS: We identified 926 studies; 53 were included in the meta-analysis. Pooled syphilis prevalence among PLWH was 7.3% (95% confidence interval [CI], 6.3%-8.5%). Prevalence differed by region: 3.1% (95% CI, 2.2%-4.0%) in Southern, 5.5% (95% CI, 2.3%-9.3%) in West/Central, and 10.5% (95% CI, 8.0%-13.1%) in Eastern Africa. Prevalence also differed by study setting: 13.8% (95% CI, 5.7%-23.0%) in sexual and reproductive health/sexually transmitted infection care, 8.7% (95% CI, 5.0%-12.8%) in HIV care, 7.1% (95% CI, 5.8%-8.5%) in antenatal care, and 3.8% (95% CI, 2.0%-5.8%) in household/community-based settings. Syphilis prevalence was higher among PLWH than without HIV (relative risk, 3.5; 95% CI, 2.8-4.5). CONCLUSIONS: Syphilis is highly prevalent among PLWH in sub-Saharan Africa and is more common among PLWH than without HIV. Integration of syphilis screening and management into HIV care may reduce complications of HIV-syphilis coinfection among PLWH in sub-Saharan Africa.

Incidence and Predictors of Pregnancy in Women Enrolled in Large Multinational HIV Treatment Trials of the AIDS Clinical Trials Group.

OBJECTIVES: Women are under-represented in clinical trials and must often commit to using contraception to enroll. We sought to determine the incidence and predictors of pregnancy in women participating in HIV treatment trials. DESIGN: Individual participant data meta-analysis. METHODS: We included data from multicountry HIV treatment trials conducted during the period 2005-2019 by the AIDS Clinical Trials Group that included females with HIV who were of reproductive potential, did not intend to become pregnant, and agreed to use effective contraception during study treatment. We extracted data from all female participants of age 18-55 years, including occurrence and dates of pregnancy on-study; however, only a few incident pregnancy predictor variables were available for analysis. RESULTS: One thousand six hundred twenty-six women from 4 trials were included. Over a median of 28 months (6461 person-years) of follow-up, 143 (9%) women became pregnant, for an overall incidence of 2.2 pregnancies/100 person-years (range 0.5-3/100 person-years, by study). In multivariable analysis including baseline age, type of regimen, and country as predictor variables, younger age remained the strongest predictor of incident pregnancy ( P < 0.0001 adjusted for country and antiretroviral treatment regimen). CD4 and HIV-1 RNA were not associated with pregnancy incidence. CONCLUSIONS: Pregnancy incidence was 2.2/100 person-years in female participants of HIV treatment trials. Rather than leading to exclusion of young women from trials, this finding should prompt appropriate adaptations in study design and analysis for earlier generation of pregnancy safety information for drugs.

Case series and literature review of chlamydial ophthalmia neonatorum in Botswana.

BACKGROUND: We describe 12 cases of chlamydial ophthalmia neonatorum and the current scientific evidence on its prevention and treatment. The data presented were obtained from the "Maduo" study, a prospective observational study of the relationship between curable sexually transmitted infections and adverse neonatal outcomes at four antenatal clinics in Gaborone, Botswana. METHODS: Infants of mothers with perinatal chlamydia infection were evaluated for chlamydial ophthalmia neonatorum based on clinical presentation of conjunctivitis or positive test via GeneXpert CT/NG assay. Data on 29 infants born to mothers with postnatal C. trachomatis infection were analysed. RESULTS: 12 infants were diagnosed with chlamydial ophthalmia neonatorum. Eight of those cases were confirmed with the GeneXpert CT/NG assay while four were identified as probable cases based on clinical history and presentation. Overall, nine infants presented with signs of conjunctivitis, while three who had a positive diagnostic test result had asymptomatic infection. All but one infant had received ocular 1% tetracycline prophylaxis at birth, and four infants had signs suggestive of chlamydial pneumonia at presentation. Two out of five symptomatic cases whose mothers reported completion of their treatment course with erythromycin had lingering symptoms. CONCLUSIONS: Our findings affirm that the current prophylaxis and treatment modalities for chlamydial ophthalmia neonatorum are inadequate. To the extent feasible in low- and middle-income countries, we recommend implementation of routine C. trachomatis screening and treatment in pregnant women.

Prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infection and associated factors among asymptomatic pregnant women in Botswana.

BACKGROUND: Chlamydia trachomatis (C. trachomatis) and Neisseria gonorrhoeae (N. gonorrhoeae) are curable sexually transmitted infections (STIs) that cause adverse pregnancy and neonatal outcomes. Most countries, including Botswana, do not offer C. trachomatis or N. gonorrhoeae screening during antenatal care (ANC) and instead use a syndromic approach for management of STIs. METHODS: The Maduo Study is a prospective, cluster-controlled trial in Botswana evaluating the impact of diagnostic screening for antenatal C. trachomatis and N. gonorrhoeae infections to prevent adverse neonatal outcomes. Using baseline data from the Maduo Study (March 2021-March 2022), we determined the prevalence of C. trachomatis and N. gonorrhoeae infection among asymptomatic pregnant women in Botswana and correlates of infection using multivariable logistic regression. RESULTS: Of 251 women who underwent C. trachomatis and N. gonorrhoeae screening at first ANC visit, 55 (21.9%, 95%CI 17.0-27.5) tested positive for C. trachomatis, 1 (0.4%, 95%CI 0-2.2) for N. gonorrhoeae; and 2 (0.8%, 95%CI 0-2.8) for dual C. trachomatis and N. gonorrhoeae infection. Older age was associated with lower odds (aOR 0.93; 95%CI 0.88-0.98; p = 0.011) while any alcohol use during pregnancy was associated with higher odds (aOR = 3.53; 95%CI 1.22-10.16; p = 0.020) of testing positive for C. trachomatis or N. gonorrhoeae. CONCLUSIONS: A high frequency of C. trachomatis infections was detected among asymptomatic pregnant women in Botswana indicating that many antenatal STIs are missed by the syndromic management approach. Our results highlight the need for diagnostic C. trachomatis screening during ANC in Botswana and other low- and middle-income countries that rely solely on the syndromic approach for management of STIs.

Measuring the impact of COVID-19 social distancing measures on sexual health behaviours and access to HIV and sexual and reproductive health services for people living with HIV in Botswana.

Introduction: Uninterrupted access to HIV and sexual and reproductive health (SRH) services is essential, particularly in high HIV prevalence settings, to prevent unintended pregnancy and vertical HIV transmission. Understanding the challenges that COVID-19 and associated social distancing measures (SDMs) posed on health service access is imperative for future planning. Methods: This cross-sectional study was conducted in Botswana between January-February 2021. A web-based questionnaire was disseminated on social media as part of the International Sexual Health and REproductive Health (I-SHARE) Survey. Respondents answered questions on SRH, before and during COVID-19 SDMs. Subgroup analysis and comparison of descriptive data was performed for people living with HIV (PLWH). Results: Of 409 participants, 65 were PLWH (80% female, 20% male). During SDMs, PLWH found it more difficult to access condoms and treatment for HIV and STIs; attend HIV appointments; and maintain adherence to antiretroviral therapy. Compared to HIV-negative women, a higher proportion of women living with HIV used condoms as their primary method of contraception (54% vs. 48%), and had lower use of long-acting reversible contraception (8% vs. 14%) and dual contraception (8% vs. 16%). Discussion: Mirroring global trends, COVID-19 disrupted HIV and SRH service access in Botswana. However, in high HIV-prevalence settings, disruption may more severely impact population health with disproportionate effects on women. Integration of HIV and SRH services could build health system capacity and resilience, reduce missed opportunities for delivering SRH services to PLWH and limit the consequences of future restrictions that may cause health system disruption.

High Cure Rate Among Pregnant Women in a Chlamydia trachomatis and Neisseria gonorrhoeae Testing and Treatment Intervention Study in Gaborone, Botswana.

Between March 2021 and March 2022, 251 pregnant women were tested for Chlamydia trachomatis and Neisseria gonorrhoeae infection in Botswana. Fifty-eight (23%) tested positive for at least 1 infection, and 57 (98%) were treated. No participants tested positive at test of cure. In some settings, cost of test of cure may outweigh the benefits.

Incident HIV acquisition among pregnant women in Botswana: findings from the Tsepamo birth outcomes surveillance study.

INTRODUCTION: In Botswana, where almost all pregnant women known to have HIV receive antiretroviral therapy, a large proportion of vertical HIV transmission may occur among women with incident undiagnosed HIV infection during pregnancy. Botswana guidelines recommend repeat HIV testing every 3 months in pregnancy, with at least one test in the third trimester. We evaluated the rate of repeat HIV testing, calculated HIV incidence during pregnancy and estimated missed seroconversions. METHODS: In the Botswana Tsepamo Study, we abstracted HIV test dates and results from obstetric records of all women who delivered at maternity wards in 18 communities between 7th May 2017 and 20th August 2021. We defined seroconversion as an initial negative/indeterminate HIV test in pregnancy followed by a positive test during pregnancy/at delivery. The incidence rate (IR) of seroconversion was calculated among women with > = 2 known test dates. Missed seroconversions were estimated among women without a test in the third trimester by applying the IR to the time after the last HIV test until delivery. RESULTS: Among 103,529 women delivering in the study period testing negative at the first test and with known conception and HIV test dates, 29,085 (28%) were tested in one trimester of pregnancy, 73,156 (71%) were tested in ≥ 2 trimesters of pregnancy and 9628 (9%) had a test in all trimesters. A total of 78,162 (75%) women had a third-trimester test. There were 223 seroconversions (2.58/1000 pregnancies, 0.26%) among those with ≥ 2 known HIV test dates, yielding an IR of 0.69/100 person-years. Among 25,289 women who did not have a test in the third trimester, we estimate approximately 58 seroconversions may have been missed during pregnancy due to a lack of repeat testing. Factors associated with seroconversion during pregnancy included younger age, less education and not being married. CONCLUSIONS: More than two-thirds of women had repeat HIV testing in pregnancy and HIV incidence was low. However, an estimated 21% of seroconversions in pregnancy were likely missed due to a lack of re-testing. To reach the goal of zero new paediatric HIV infections, Botswana will need to intensify repeat HIV testing in the third trimester of pregnancy.

Intimate Partner Violence During COVID-19 Restrictions: A Study of 30 Countries From the I-SHARE Consortium.

Intimate partner violence (IPV) causes substantial physical and psychological trauma. Restrictions introduced in response to the COVID-19 pandemic, including lockdowns and movement restrictions, may exacerbate IPV risk and reduce access to IPV support services. This cross-sectional study examines IPV during COVID-19 restrictions in 30 countries from the International Sexual HeAlth and REproductive Health (I-SHARE) study conducted from July 20th, 2020, to February, 15th, 2021. IPV was a primary outcome measure adapted from a World Health Organization multicountry survey. Mixed-effects modeling was used to determine IPV correlates among participants stratified by cohabitation status. The sample included 23,067 participants from 30 countries. A total of 1,070/15,336 (7.0%) participants stated that they experienced IPV during COVID-19 restrictions. A total of 1,486/15,336 (9.2%) participants stated that they had experienced either physical or sexual partner violence before the restrictions, which then decreased to 1,070 (7.0%) after the restrictions. In general, identifying as a sexual minority and experiencing greater economic vulnerability were associated with higher odds of experiencing IPV during COVID-19 restrictions, which were accentuated among participants who were living with their partners. Greater stringency of COVID-19 restrictions and living in urban or semi-urban areas were associated with lower odds of experiencing IPV in some settings. The I-SHARE data suggest a substantial burden of IPV during COVID-19 restrictions. However, the restrictions were correlated with reduced IPV in some settings. There is a need for investing in specific support systems for survivors of IPV during the implementation of restrictions designed to contain infectious disease outbreaks.

The prevalence of gestational syphilis in Malawi between 2014 and 2022: spatiotemporal modeling of population-level factors.

Background: Mother-to-child transmission of syphilis remains high especially in the WHO AFRO region with a prevalence of 1.62%, resulting in a congenital syphilis rate of 1,119 per 100,000 live births. Elimination efforts can be supported by an understanding of the spatial and temporal changes in disease over time, which can identify priority areas for targeted interventions aimed at reducing transmission. Methods: We collated routine surveillance data from health facilities and covariate data from demographic and health surveys conducted in Malawi between 2014 and 2022. We fitted a Bayesian hierarchical mixed model with spatial and temporally structured random effects to model the district-level monthly counts of maternal syphilis notifications as a function of individual- and district-level predictors. We then generated district-level spatiotemporally explicit risk profiles to estimate the effect of individual- and district-level covariates on maternal syphilis notifications and to identify hotspot areas. Results: Overall, the national prevalence of maternal syphilis increased from 0.28% (95% CI: 0.27-0.29%) in 2014 to peaking in 2021 at 1.92% (95% CI: 1.89-1.96%). Between 2020 and 2022, there was a decline in prevalence, with the most significant decline seen in Zomba District (1.40, 95% CI: 1.12-1.66%). In regression models, a one percentage point increase in district-level antenatal HIV prevalence was associated with increased maternal syphilis (prevalence ratio [PR]: 1.15, 95% credible interval [CrI]: 1.10-1.21). There was also an increased prevalence of maternal syphilis associated with an increased district-level mean number of sex partners (PR: 1.05, 95% CrI: 0.80-1.37). The number of districts with a high prevalence of maternal syphilis also increased between 2014 and 2022, especially in the southern region, where most had a high probability (approaching 100%) of having high maternal syphilis (defined as relative risk >1 compared to the standard population of women aged 15-49 years) in 2022. Conclusion: Maternal syphilis prevalence in Malawi shows an increasing upward trend, with an estimated six times relative increase between 2014 and 2022 (0.28% to 1.73%) and strong associations with higher district-level HIV prevalence. Controlling syphilis depends on reaching vulnerable populations at the sub-national level, which may be disproportionately affected. Our findings support the move to integrate the elimination of mother-to-child transmission (EMTCT) of syphilis programs with existing prevention of mother-to-child transmission (PMTCT) of HIV programs.

Pain management for medical abortion before 14 weeks' gestation: A systematic review.

INTRODUCTION: Abortion is common worldwide and increasingly abortions are performed at less than 14 weeks' gestation using medical methods, specifically using a combination of mifepristone and misoprostol. Medical abortion is known to be a painful process, but the optimal method of pain management is unclear. We sought to identify and compare pain management regimens for medical abortion before 14 weeks' gestation. STUDY DESIGN: We conducted our search in August 2019 and included randomized controlled trials (RCT) and observational studies of any pain relief intervention (pharmacological and non-pharmacological) for mifepristone-misoprostol combination medical abortion of pregnancies less than 14 weeks' gestation. RESULTS: We included four RCTs and one observational study. Due to the heterogeneity of study designs, interventions and outcome reporting, meta-analysis was not possible. Only one study found evidence of an effect between interventions on pain score: a prophylactic dose of ibuprofen 1600mg likely reduces the pain score when compared to a dose of paracetamol 2000mg (MD 2.26/10 [CI 3-1.52 lower]). For other interventions (pregabalin 300mg vs placebo; ibuprofen 800mg vs placebo; therapeutic vs prophylactic administration of ibuprofen 800mg; ambulation vs non-ambulation during treatment) there appeared to be little to no difference with comparator. CONCLUSIONS: The findings of this review provide some support for the use of ibuprofen as a single dose given with misoprostol prophylactically, or in response to pain as needed. The optimal dosing of ibuprofen is unclear, but a single dose of ibuprofen 1600mg was shown to be effective and it was less certain whether 800mg was effective.

Effects of Depot Medroxyprogesterone Acetate Intramuscular Injection, Copper Intrauterine Device and Levonorgestrel Implant Contraception on Estradiol Levels: An Ancillary Study of the ECHO Randomized Trial.

Introduction: Hormonal contraception affects endogenous sex steroid levels. Robust evidence from randomized trials of the relative effects of different contraceptive methods is scarce. We compared the effects of three contraceptive methods on serum estradiol levels using data from women (18-35 years) requesting contraception in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial. Methods: Women were randomly allocated to the depot medroxyprogesterone acetate intramuscular (DMPA-IM) injection, copper intrauterine device (IUD) or levonorgestrel (LNG) implant. In this sub-study, stored baseline and 6-month serum samples were analyzed in 401 participants from East London, South Africa (DMPA-IM: 131, IUD: 135 and LNG: 135). Results: Baseline median (interquartile range, IQR) estradiol levels were similar between the three groups [DMPA-IM 229 (152-455), IUD 235 (168-426) and LNG 216 (153-419 pmol/L)]. At 6-months, median estradiol in the IUD group was unchanged (298 (163-467) pmol/L), whilst levels in the DMPA-IM and implant groups were significantly reduced from baseline. The median estradiol level in the DMPA-IM group [139 (97-193) pmol/L] was significantly lower than in both IUD (p < 0.0001) and implant (p = 0.005) groups; and level in the implant group [156 (112-250) pmol/L] was significantly lower than in the IUD group (p = 0.004). Conclusions: At 6-months (DMPA-IM nadir), median estradiol with DMPA-IM was 53% lower and with the LNG implant, 48% lower than with the IUD. The greater reduction in estradiol levels with the DMPA-IM injection compared to the LNG implant and IUD has implications for the relative psychological, sexual as well as physiological side-effects of these contraceptive methods. ECHO Study Registration: ClinicalTrials.gov, identifier: NCT02550067.