Vaginal dysbiosis has been shown to increase the risk of some adverse birth outcomes. HIV infection may be associated with shifts in the vaginal microbiome. We characterized microbial communities in ...vaginal swabs collected between 16-20 gestational weeks in the Zambian Preterm Birth Prevention Study to investigate whether HIV and its treatment alter the microbiome in pregnancy. We quantified relative abundance and diversity of bacterial taxa by whole-genome shotgun sequencing and identified community state types (CST) by hierarchical clustering. Associations between exposures-HIV serostatus (HIV+ vs HIV-) and preconceptional ART (ART+ vs ART-)-and microbiome characteristics were tested with rank-sum, and by linear and logistic regression, accounting for sampling by inverse-probability weighting. Of 261 vaginal swabs, 256 (98%) had evaluable sequences; 98 (38%) were from HIV+ participants, 55 (56%) of whom had preconceptional ART exposure. Major CSTs were dominated by: L. crispatus (CST 1; 17%), L. iners (CST 3; 32%), Gardnerella vaginalis (CST 4-I; 37%), G. vaginalis & Atopobium vaginae (CST 4-II; 5%), and other mixed anaerobes (CST 4-III; 9%). G. vaginalis was present in 95%; mean relative abundance was higher in HIV+ (0.46±0.29) compared to HIV- participants (0.35±0.33; rank-sum p = .01). Shannon diversity was higher in HIV+/ART+ (coeff 0.17; 95%CI (0.01,0.33), p = .04) and HIV+/ART- (coeff 0.37; 95%CI (0.19,0.55), p < .001) participants compared to HIV-. Anaerobe-dominant CSTs were more prevalent in HIV+/ART+ (63%, AOR 3.11; 95%CI: 1.48,6.55, p = .003) and HIV+/ART- (85%, AOR 7.59; 95%CI (2.80,20.6), p < .001) compared to HIV- (45%). Restricting the comparison to 111 women in either CST 3 (L. iners dominance) or CST 1 (L. crispatus dominance), CST 3 frequency was similar in HIV- (63%) and HIV+/ART- participants (67%, AOR 1.31; 95%CI: (0.25,6.90), p = .7), but higher in HIV+/ART+ (89%, AOR 6.44; 95%CI: (1.12,37.0), p = .04). Pregnant women in Zambia, particularly those with HIV, had diverse anaerobe-dominant vaginal microbiota.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Few longitudinal studies have measured contraceptive continuation past one year in sub‐Saharan Africa. We surveyed 674 women who had been randomized to receive the three‐month intramuscular ...contraceptive injectable (DMPA‐IM), levonorgestrel (LNG) implant, or copper intrauterine device (IUD) during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial in South Africa and Zambia and were subsequently followed for two additional years to explore method continuation, reasons for discontinuation, and access to implant and IUD removal services. We also conducted in‐depth qualitative interviews with 39 participants. We estimated cumulative discontinuation probabilities using Kaplan–Meier estimates and assessed factors associated with discontinuation using Cox‐proportional hazards models. The LNG implant continuation rate over the maximum 44‐month study period was 60 percent, while rates for the copper IUD and DMPA‐IM were 52 percent and 44 percent, respectively. Reasons for method discontinuation included side effects, particularly menstrual changes, and method stock‐outs. Most implant and IUD users who sought removal were able to access services; however, room for improvement exists. In this cohort originally randomized to receive a contraceptive method and attend regular study visits, implants and IUDs continued to be highly acceptable over an additional two years, but facilities should continue to ensure that insertions and removals are available as requested.
A Lactobacillus-deficient, anaerobe-rich vaginal microbiome has been associated with local inflammation and spontaneous preterm birth (sPTB), but few studies have assessed this association in the ...setting of HIV. We performed metagenomic sequencing and inflammatory marker assays on vaginal swabs collected in pregnancy. We grouped samples into 7 metagenomic clusters (mgClust) using the non-redundant VIRGO catalogue, and derived inflammatory scores by factor analysis. Of 221 participants, median Shannon diversity index (SDI) was highest in HIV+ with detectable viral load (1.31, IQR: 0.85-1.66; p < 0.001) and HIV+ with undetectable virus (1.17, IQR: 0.51-1.66; p = 0.01) compared to HIV- (0.74, IQR: 0.35-1.26). Inflammatory scores positively correlated with SDI (+ 0.66, 95%CI 0.28, 1.03; p = 0.001), highest among anaerobe-rich mgClust2-mgClust6. HIV was associated with predominance of anaerobe-rich mgClust5 (17% vs. 6%; p = 0.02) and mgClust6 (27% vs. 11%; p = 0.002). Relative abundance of a novel Gardnerella metagenomic subspecies > 50% predicted sPTB (RR 2.6; 95%CI: 1.1, 6.4) and was higher in HIV+ (23% vs. 10%; p = 0.001). A novel Gardnerella metagenomic subspecies more abundant in women with HIV predicted sPTB. The risk of sPTB among women with HIV may be mediated by the vaginal microbiome and inflammation, suggesting potential targets for prevention.
Background: Accurate HIV point of care testing is the cornerstone of prevention and treatment efforts globally, though false (both negative and positive) results are expected to occur. Setting: We ...assessed the spectrum of true and false positive HIV results in a large prospective study of HIV incidence in African women using three contraceptive methods tested longitudinally in Eswatini, Kenya, South Africa, and Zambia. Methods: HIV serologic testing was conducted quarterly using two parallel rapid HIV tests. When one or both tests were positive, additional confirmatory testing was conducted, including HIV enzyme immunoassay (EIA) and ribonucleic acid (RNA). Results: 7730 women contributed 48,234 visits: true positive results occurred at 412 visits (0.9%) and false positives at 96 visits (0.2%). Of 412 women with HIV seroconversion, 10 had discordant (i.e., one negative and one positive) rapid tests and 13 had undetectable HIV RNA levels. Of 62 women with false positive rapid HIV results, most had discordant rapid testing but six (9.7%) had dually-positive rapid results and four (6.5%) had false positive or indeterminate EIA results. The positive predictive value of dual positive rapid results was 98.3%. Conclusion: Although the majority of rapid test results were accurate, false positive results were expected and occurred in this population of initially HIV seronegative individuals tested repeatedly and prospectively. When HIV infection occurred, not all cases had textbook laboratory results. Our findings highlight the importance of confirmatory testing, particularly for individuals undergoing repeat testing and in settings where the point prevalence is expected to be low.
IMPORTANCE: Accurate assessment of gestational age (GA) is essential to good pregnancy care but often requires ultrasonography, which may not be available in low-resource settings. This study ...developed a deep learning artificial intelligence (AI) model to estimate GA from blind ultrasonography sweeps and incorporated it into the software of a low-cost, battery-powered device. OBJECTIVE: To evaluate GA estimation accuracy of an AI-enabled ultrasonography tool when used by novice users with no prior training in sonography. DESIGN, SETTING, AND PARTICIPANTS: This prospective diagnostic accuracy study enrolled 400 individuals with viable, single, nonanomalous, first-trimester pregnancies in Lusaka, Zambia, and Chapel Hill, North Carolina. Credentialed sonographers established the “ground truth” GA via transvaginal crown-rump length measurement. At random follow-up visits throughout gestation, including a primary evaluation window from 14 0/7 weeks’ to 27 6/7 weeks’ gestation, novice users obtained blind sweeps of the maternal abdomen using the AI-enabled device (index test) and credentialed sonographers performed fetal biometry with a high-specification machine (study standard). MAIN OUTCOMES AND MEASURES: The primary outcome was the mean absolute error (MAE) of the index test and study standard, which was calculated by comparing each method’s estimate to the previously established GA and considered equivalent if the difference fell within a prespecified margin of ±2 days. RESULTS: In the primary evaluation window, the AI-enabled device met criteria for equivalence to the study standard, with an MAE (SE) of 3.2 (0.1) days vs 3.0 (0.1) days (difference, 0.2 days 95% CI, −0.1 to 0.5). Additionally, the percentage of assessments within 7 days of the ground truth GA was comparable (90.7% for the index test vs 92.5% for the study standard). Performance was consistent in prespecified subgroups, including the Zambia and North Carolina cohorts and those with high body mass index. CONCLUSIONS AND RELEVANCE: Between 14 and 27 weeks’ gestation, novice users with no prior training in ultrasonography estimated GA as accurately with the low-cost, point-of-care AI tool as credentialed sonographers performing standard biometry on high-specification machines. These findings have immediate implications for obstetrical care in low-resource settings, advancing the World Health Organization goal of ultrasonography estimation of GA for all pregnant people. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05433519
The IPOP trial demonstrated a reduced risk of severe small for gestational age among infants born to women with HIV who received weekly intramuscular 17 alpha-hydroxyprogesterone caproate. This ...secondary analysis examined the 17P treatment effect in subgroups of maternal BMI, parity, timing of antiretroviral therapy (ART) initiation, and ART regimen. We found that 17P was more effective among nulliparous women, women who started ART before pregnancy, and those taking protease inhibitors.
Objective
Low‐cost devices have made obstetric sonography possible in settings where it was previously unfeasible, but ensuring quality and consistency at scale remains a challenge. In the present ...study, we sought to create a tool to reduce substandard fetal biometry measurement while minimizing care disruption.
Methods
We developed a deep learning artificial intelligence (AI) model to estimate gestational age (GA) in the second and third trimester from fly‐to cineloops—brief videos acquired during routine ultrasound biometry—and evaluated its performance in comparison to expert sonographer measurement. We then introduced random error into fetal biometry measurements and analyzed the ability of the AI model to flag grossly inaccurate measurements such as those that might be obtained by a novice.
Results
The mean absolute error (MAE) of our model (±standard error) was 3.87 ± 0.07 days, compared to 4.80 ± 0.10 days for expert biometry (difference −0.92 days; 95% CI: −1.10 to −0.76). Based on simulated novice biometry with average absolute error of 7.5%, our model reliably detected cases where novice biometry differed from expert biometry by 10 days or more, with an area under the receiver operating characteristics curve of 0.93 (95% CI: 0.92, 0.95), sensitivity of 81.0% (95% CI: 77.9, 83.8), and specificity of 89.9% (95% CI: 88.1, 91.5). These results held across a range of sensitivity analyses, including where the model was provided suboptimal truncated fly‐to cineloops.
Conclusions
Our AI model estimated GA more accurately than expert biometry. Because fly‐to cineloop videos can be obtained without any change to sonographer workflow, the model represents a no‐cost guardrail that could be incorporated into both low‐cost and commercial ultrasound devices to prevent reporting of most gross GA estimation errors.
Synopsis
Our model predicts gestational age (GA) more accurately from routinely available fly‐to cineloops than expert sonographer acquired biometry and can act as a guardrail to prevent gross GA estimation errors.
Current guidelines recommend starting antiretroviral therapy (ART) as soon as possible after HIV diagnosis to reduce morbidity, mortality and onward HIV transmission. We examined factors influencing ...ART initiation by women who seroconverted during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. ECHO, conducted between 2015 and 2018, enrolled HIV-negative, sexually active women, aged 16-35 years, from four African countries. Follow-up was 12-18 months, with quarterly HIV testing. Women with incident HIV infection received extensive counselling by trial staff and referral to local facilities for HIV care. Of 304 women with ≥90 days follow-up time since HIV diagnosis, 186(61.2%) initiated ART within 90 days, 69(22.7%) initiated after 90 days, and 49(16.1%) had not initiated by the end of the study. There were no statistically significant differences in characteristics among women who initiated ART ≤90 days versus those who did not. Frequent reasons for delayed or non-initiation of ART included not feeling ready to start ART and being newly diagnosed. In a large clinical trial, ART initiation was modest within 90 days of HIV diagnosis and grew to 84% with longer observation. Despite extensive counselling on the importance of early ART initiation, personal barriers delayed some women from starting ART.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Objective
To compare the performance of mid upper arm circumference (MUAC) and body mass index (BMI) for prediction of small for gestational age (SGA) in Zambia.
Methods
This is a secondary analysis ...of an ongoing clinical cohort that included women with a single gestation and MUAC measured before 24 weeks of pregnancy. We assessed relationships between maternal MUAC and birth weight centile using regression. The performance of MUAC and BMI to predict SGA was compared using receiver operating characteristic curves and the effect of maternal HIV was investigated in sub‐group analyses.
Results
Of 1117 participants, 847 (75%) were HIV‐negative (HIV−) and 270 (24%) were HIV‐positive (HIV+). Seventy‐four (7%) delivered severe SGA infants (<3rd centile), of whom 56 (76%) were HIV− and 18 (24%) were HIV+ (odds ratio OR 1.01, 95% confidence interval CI 0.58–1.75). MUAC was associated with higher birth weight centile (+1.2 centile points, 95% CI 0.7–1.6; P < 0.001); this relationship was stronger among HIV+ women (+1.7 centile points, 95% CI 0.8–2.6; P < 0.001) than HIV− women (+0.9 centile points, 95% CI 0.4–1.4; P = 0.001). The discriminatory power was similar, albeit poor (area under the curve AUC < 0.7), between MUAC and BMI for the prediction of SGA. In stratified analysis, MUAC and BMI showed excellent discrimination predicting severe SGA among HIV+ (AUC 0.83 and 0.81, respectively) but not among HIV− women (AUC 0.64 and 0.63, respectively).
Conclusion
Maternal HIV infection increased the discrimination of both early pregnancy MUAC and BMI for prediction of severe SGA in Zambia.
Clinical Trial Number
ClinicalTrials.gov (NCT02738892).
Synopsis
Maternal mid‐upper arm circumference measured early in pregnancy is associated with small for gestational age with predictive performance similar to body mass index.
PDF
