We analyzed data from 1428 users of the dapivirine vaginal ring, who participated in the MTN-020/ASPIRE phase III trial and subsequent open-label extension MTN-025/HOPE trial, to examine ...relationships between perceived ring protection, social disclosures, and self-reported ring adherence. In HOPE, 77% perceived the ring to be highly effective, and this view was associated with speaking: (a) to a greater number of people about the study, (b) with other participants, (c) to more people who were in favor of the ring, and (d) to more people whose opinions were valued. Reported adherence was not directly associated with perceived protection but was associated with disclosing to someone who was in favor of the ring. These findings suggest the importance of women’s internalized ideas about the protective benefits of the DVR in sharing information about the ring and the importance of social support on adherence.
We assessed the interference between vaginal ring use and menses among women who participated in the qualitative component of the MTN-020/ASPIRE vaginal ring trial in Malawi, South Africa, Uganda and ...Zimbabwe (N = 214). A common reason for imperfect ring adherence and premature removal of the vaginal ring cited by participants related to vaginal bleeding or menses. Whereas self-reporting via survey questions suggested that the majority (60%) of women did not mind wearing the ring while menstruating, and did not remove it (91%) during menses, in the qualitative interviews women frequently described removing the ring during menses. Their reasons included hygiene, beliefs that the ring blocked the flow of menstrual blood, fears that the ring would come out with blood or during tampon removal, and concerns around an ‘overburdened’ vagina. Examining women’s narratives and subjective experiences related to menstruation helps build a better understanding of factors affecting ring use and adherence.
Given well documented challenges faced by pregnant women living with HIV taking lifetime ART, it is critical to understand the impact of short-term ART exposure followed by treatment interruption on ...maternal health outcomes.
HIV+ breastfeeding (BF) and Formula Feeding (FF) women with CD4 counts > 350 cells/mm3, enrolled in the 1077BF/1077FF PROMISE trial were followed to assess the effect of ART during pregnancy and breastfeeding respectively. The first analysis compared ART use limited to the antepartum period (AP-only) relative to women randomized to Zidovudine. The second analysis included women with no pregnancy combination ART exposure; and compared women randomized to either ART or no ART during postpartum (PP-only). Both analyses included follow-up time beyond breastfeeding period. The primary outcome was progression to AIDS and/or death. Secondary outcomes included adverse events and HIV-related events.
3490 and 1137 HIV+ women were enrolled from 14 sites in Africa and India from April 2011 through September 2014 in cohort AP-only and PP-only, respectively. Most were Black African (96%); median age was 27 years; 97% were WHO Clinical Stage I; and most had a screening CD4 count ≥500 cells/mm3 (78%). The rate of progression to AIDS and/or death was similar and low across all comparison arms (AP comparison, HR = 1.14, 95%CI (0.44, 2.96), p-value = 0.79). In the PP-only cohort, the rate of WHO stage 2-3 events was lower for women randomized to ART(HR = 0.65, 95% CI 0.42, 1.01, p-value = 0.05).
The incidence of AIDS and/or death was low in pregnant/postpartum HIV+ women with highCD4 cell counts for all comparison arms. This provides some reassurance that there were limited consequences for short term ART interruption in this group of asymptomatic HIV+ women during up to 4 years of follow up; and underscores that even short term ART exposure postpartum may reduce the risk of WHO grade 2-3 disease progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Women in sub-Saharan Africa are a priority population for evaluation of new biomedical HIV-1 prevention strategies. Antiretroviral pre-exposure prophylaxis is a promising prevention approach; ...however, clinical trials among young women using daily or coitally-dependent products have found low adherence. Antiretroviral-containing vaginal microbicide rings, which release medication over a month or longer, may reduce these adherence challenges.
ASPIRE (A Study to Prevent Infection with a Ring for Extended Use) is a phase III, randomized, double-blind, placebo-controlled trial testing the safety and effectiveness of a vaginal ring containing the non-nucleoside reverse transcriptase inhibitor dapivirine for prevention of HIV-1 infection. We describe the baseline characteristics of African women enrolled in the ASPIRE trial.
Between August 2012 and June 2014, 5516 women were screened and 2629 HIV-1 seronegative women between 18-45 years of age were enrolled from 15 research sites in Malawi, South Africa, Uganda, and Zimbabwe. The median age was 26 years (IQR 22-31) and the majority (59%) were unmarried. Nearly 100% of participants reported having a primary sex partner in the prior three months but 43% did not know the HIV-1 status of their primary partner; 17% reported additional concurrent partners. Nearly two-thirds (64%) reported having disclosed to primary partners about planned vaginal ring use in the trial. Sexually transmitted infections were prevalent: 12% had Chlamydia trachomatis, 7% Trichomonas vaginalis, 4% Neisseria gonorrhoeae, and 1% syphilis.
African HIV-1 seronegative women at risk of HIV -1 infection were successfully enrolled into a phase III trial of dapivirine vaginal ring for HIV-1 prevention.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Robust data summarizing the prevalence of pregnancy and neonatal outcomes in low- and middle-income countries are critically important for studies evaluating investigational products for HIV ...prevention and treatment in pregnant and breastfeeding women. In preparation for studies evaluating the safety of the dapivirine vaginal ring for HIV prevention in pregnancy, we conducted a systematic literature review and meta-analyses to summarize the prevalence of pregnancy and neonatal outcomes in Malawi, South Africa, Uganda, and Zimbabwe.
Ten individual systematic literature reviews were conducted to identify manuscripts presenting prevalence data for 12 pregnancy and neonatal outcomes pregnancy loss, stillbirth, preterm birth, low birthweight (LBW), neonatal mortality, congenital anomaly, chorioamnionitis, postpartum endometritis, postpartum hemorrhage, gestational hypertension, preeclampsia/eclampsia, and preterm premature rupture of membranes (PPROM). Studies included in the meta-analyses were published between January 1, 1998, and July 11, 2018, provided numerator and denominator data to support prevalence estimation, and included women of any HIV serostatus. Random-effects meta-analyses were conducted to estimate the pooled prevalence and 95% confidence interval (CI) for each outcome overall, by country, and by HIV status.
A total of 152 manuscripts were included across the 12 outcomes. Overall, the frequency of stillbirth (
= 75 estimates), LBW (
= 68), and preterm birth (
= 67) were the most often reported. However, fewer than 10 total manuscripts reported prevalence estimates for chorioamnionitis, endometritis, or PPROM. The outcomes with the highest pooled prevalence were preterm birth (12.7%, 95%CI 11.2-14.3), LBW (11.7%, 95%CI 10.6-12.9), and gestational hypertension (11.4%, 95%CI 7.8-15.7). Among the outcomes with the lowest pooled prevalence estimates were neonatal mortality (1.7%, 95%CI 1.4-2.1), pregnancy loss 1.9%, 95%CI 1.1-2.8, predominately studies (23/29) assessing losses occurring after the first trimester, PPROM (2.2%, 95%CI 1.5-3.2), and stillbirth (2.5%, 95%CI 2.2-2.7).
Although this review identified numerous prevalence estimates for some outcomes, data were lacking for other important pregnancy-related conditions. Additional research in pregnant populations is needed for a thorough evaluation of investigational products, including for HIV prevention and treatment, and to inform better estimates of the burden of adverse pregnancy outcomes globally.
Frequency of sex, contraceptive use and HIV infection are key determinants of fertility. Use of an effective family planning (EFP) method (injectable, oral, intra-uterine contraceptive device (IUCD), ...or Norplant) potentially eliminates women's concerns of unintended pregnancy. We report the association between EFP and frequency of sex among HIV-infected and HIV-uninfected non-pregnant African women.
Prospective fertility intentions study nested within a phase 3 randomized double-masked placebo-controlled trial (2003-2005) to treat genital tract infections in HIV-infected and HIV-uninfected non-pregnant women. Enrollment of study participants was stratified by HIV infection status. Data on demographics, family planning and sexual history were obtained at baseline and at 3, 6, 9 and 12 months. Chi square and Wilcoxon Rank-Sum tests were used to compare categorical and continuous variables, respectively. Generalized Estimating Equations method was used to estimate relative risk (RR) of frequent sex (≥ 2 acts/week) among users of different EFP methods (injectable, oral, implant or intra-uterine contraceptive device).
After adjusting for age, current health status, and fertility intentions, EFP use was significantly associated with frequent sex among HIV-infected women (RR 1.32; 95% Confidence Interval CI 1.14-1.52); this association was not statistically significant among HIV-uninfected women (RR 1.10; 95% CI 0.96-1.24). Fertility intentions among HIV-infected, and education among HIV-uninfected womenwere independent predictors of sex frequency.
These data suggest that the association between EFP use and frequency of sex among women varies by HIV infection status. Service-delivery of diverse EFP methods should be integrated within HIV counseling, testing and treatment facilities.
Registration number NCT00140764 under the clinicaltrials.gov, first Posted: September 1, 2005, last Update Posted: August 10, 2011.
Development of HIV-1 prevention methods is a global priority. In this randomized, controlled trial in sub-Saharan Africa, a vaginal ring containing the antiretroviral dapivirine was 27% effective in ...protecting against HIV-1 acquisition.
More than half of the 35 million persons currently living with human immunodeficiency virus type 1 (HIV-1) infection are women. A majority of these women reside in sub-Saharan Africa,
1
a region that has some of the highest incidences of HIV-1 infection in any population worldwide.
2
–
4
The use of antiretroviral medications as pre-exposure prophylaxis is a promising approach to the prevention of HIV-1 acquisition.
5
Several clinical trials of the antiretroviral tenofovir showed such protection against HIV-1.
2
,
6
–
8
However, in three trials involving African women, adherence to tenofovir-containing pills and vaginal gels was low, and HIV-1 protection was not shown. . . .
Objective. Obstetric fistula (OF) is a morbid condition caused by prolonged obstructed labor. Women with OF experience profound injury and have high rates of infertility and poor obstetric outcomes. ...We examined endovaginal ultrasound parameters in women with and without OF. Design/Setting/Sample/Methods. This cross-sectional study enrolled women evaluated at the Fistula Care Centre in Lilongwe, Malawi. Eligibility criteria included age 18–45, prior pregnancy, and a uterus on ultrasound. Participants underwent endovaginal ultrasound with measurement of cervical dimensions. Comparisons were done using t-tests and Fisher's exact test. Among women with OF, linear regression was used to assess whether fistula stage was associated with cervical length. Results. We enrolled 98 cases and 12 controls. Women with OF had shorter cervical lengths (18.8 mm versus 27.3 mm, p < 0.01), as well as shorter anterior (7.0 mm versus 9.3 mm, p < 0.01) and posterior (9.5 mm versus 11.0 mm, p < 0.04) cervical stroma, compared to controls. Conclusion. Women with OF have shorter cervical lengths and anterior and posterior cervical stroma, when compared to women without OF. This may offer a partial explanation for subfertility and poor obstetric outcomes in OF patients. Additional studies to clarify the role of ultrasound in OF patients and prediction of future fertility are warranted.
BACKGROUND:No randomized trial has directly compared the efficacy of prolonged infant antiretroviral prophylaxis versus maternal antiretroviral therapy (mART) for prevention of mother-to-child ...transmission throughout the breastfeeding period.
SETTING:Fourteen sites in Sub-Saharan Africa and India.
METHODS:A randomized, open-label strategy trial was conducted in HIV-1–infected women with CD4 counts ≥350 cells/mm (or ≥country-specific ART threshold if higher) and their breastfeeding HIV-1–uninfected newborns. Randomization at 6–14 days postpartum was to mART or infant nevirapine (iNVP) prophylaxis continued until 18 months after delivery or breastfeeding cessation, infant HIV-1 infection, or toxicity, whichever occurred first. The primary efficacy outcome was confirmed infant HIV-1 infection. Efficacy analyses included all randomized mother–infant pairs except those with infant HIV-1 infection at entry.
RESULTS:Between June 2011 and October 2014, 2431 mother–infant pairs were enrolled; 97% of women were World Health Organization Clinical Stage I, median screening CD4 count 686 cells/mm. Median infant gestational age/birth weight was 39 weeks/2.9 kilograms. Seven of 1219 (0.57%) and 7 of 1211 (0.58%) analyzed infants in the mART and iNVP arms, respectively, were HIV-infected (hazard ratio 1.0, 96% repeated confidence interval 0.3–3.1); infant HIV-free survival was high (97.1%, mART and 97.7%, iNVP, at 24 months). There were no significant differences between arms in median time to breastfeeding cessation (16 months) or incidence of severe, life-threatening, or fatal adverse events for mothers or infants (14 and 42 per 100 person-years, respectively).
CONCLUSIONS:Both mART and iNVP prophylaxis strategies were safe and associated with very low breastfeeding HIV-1 transmission and high infant HIV-1–free survival at 24 months.
Abstract
Background
Globally, the number of infected women of childbearing age living with human immunodeficiency virus (HIV) and conceiving on antiretroviral therapy (ART) is increasing. Evidence of ...ART safety at conception and during pregnancy and adverse pregnancy outcomes remains conflicting. The Promoting Maternal and Infant Survival Everywhere (PROMISE) 1077 breastfeeding (BF) and formula feeding (FF) international multisite trials provide an opportunity to examine the impact of ART at conception on pregnancy outcomes with subsequent pregnancies.
Methods
The PROMISE 1077BF/1077FF trials were designed to address key questions in the management of HIV-infected women who did not meet clinical guidelines for ART treatment during the time of the trials. After the period of risk of mother-to-child transmission was over, women were randomized to either continue or discontinue ART. We compared subsequent pregnancy outcomes of nonbreastfeeding women randomized to continue ART following delivery, or breastfeeding women randomized to continue ART following breastfeeding cessation who conceived while on ART to women randomized to discontinue ART, who restarted ART after pregnancy was diagnosed.
Results
Pregnancy outcomes of 939 subsequent pregnancies of 826 mothers were recorded. The intention-to-treat analyses showed increased incidence of low birth weight (<2500 g) for women who conceived while on ART (relative risk, 2.65 95% confidence interval {CI}, 1.20–5.81), and also a higher risk of spontaneous abortion, stillbirth, or neonatal death (hazard ratio, 1.40 95% CI, .99–1.98) compared to women who restarted ART after they were found to be pregnant during trial follow-up.
Conclusions
We found an increased risk for adverse pregnancy outcomes in women conceiving on ART, emphasizing the need for improved obstetric and neonatal care for this group.
Clinical Trials Registration
NCT01061151.
Globally more women living with HIV conceive on antiretroviral therapy (ART). This study reports an increased risk of low birth weight, spontaneous abortion, stillbirth, and neonatal death for women conceiving on ART compared to those not on ART at conception.
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