Kavita Nanda

SAVVY vaginal gel (C31G) for prevention of HIV infection: a randomized controlled trial in Nigeria.

Background The objective of this trial was to determine the effectiveness of 1.0% C31G (SAVVY) in preventing male-to-female vaginal transmission of HIV infection among women at high risk. Methodology/Principal Findings This was a Phase 3, double-blind, randomized, placebo-controlled trial. Participants made up to 12 monthly follow-up visits for HIV testing, adverse event reporting, and study product supply. The study was conducted between September 2004 and December 2006 in Lagos and Ibadan, Nigeria, where we enrolled 2153 HIV-negative women at high risk of HIV infection. Participants were randomized 1∶1 to SAVVY or placebo. The effectiveness endpoint was incidence of HIV infection as indicated by detection of HIV antibodies in oral mucosal transudate (rapid test) or blood (ELISA), and confirmed by Western blot or PCR testing. We observed 33 seroconversions (21 in the SAVVY group, 12 in the placebo group). The Kaplan-Meier estimates of the cumulative probability of HIV infection at 12 months were 0.028 in the SAVVY group and 0.015 in the placebo group (2-sided p-value for the log-rank test of treatment effect 0.121). The point estimate of the hazard ratio was 1.7 for SAVVY versus placebo (95% confidence interval 0.9, 3.5). Because of lower-than-expected HIV incidence, we did not observe the required number of HIV infections (66) for adequate power to detect an effect of SAVVY. Follow-up frequencies of adverse events, reproductive tract adverse events, abnormal pelvic examination findings, chlamydial infections and vaginal infections were similar in the study arms. No serious adverse event was attributable to SAVVY use. Conclusions/Significance SAVVY did not reduce the incidence of HIV infection. Although the hazard ratio was higher in the SAVVY than the placebo group, we cannot conclude that there was a harmful treatment effect of SAVVY. Trial Registration ClinicalTrials.gov NCT00130078

Progestogen-only contraceptive use among breastfeeding women: a systematic review

BACKGROUND Postpartum women need effective contraception. Concerns have been raised that use of progestogen-only contraceptives (POCs) may affect breastfeeding performance and infant health outcomes. OBJECTIVES We investigated the clinical outcomes of breastfeeding duration, initiation of supplemental feeding and weaning, as well as infant outcomes including infant growth, health and development among breastfeeding women using POCs compared with breastfeeding women not using POCs. SEARCH STRATEGY We searched the PubMed database for all articles published from database inception through December 2014. SELECTION CRITERIA We included primary research studies of breastfeeding women of any age or parity who received POCs, including progestogen-only pills, injectables, implants or hormonal intrauterine devices (IUDs). The main outcomes were breastfeeding performance (as measured by initiation, continuation, frequency and exclusivity of breastfeeding) and infant health (as measured by growth, development or adverse health effects). RESULTS Forty-nine articles reporting on 47 different studies were identified that investigated the use of POCs in breastfeeding women and reported clinically relevant outcomes of infant growth, health or breastfeeding performance. Studies ranged from poor to fair methodological quality and generally failed to show negative effects of the use of POCs on breastfeeding outcomes or on infant growth or development. One randomized controlled trial (RCT) raises concerns that immediate insertion of the levonorgestrel IUD postpartum may be associated with poorer breastfeeding performance when compared with delayed insertion, although two other RCTs evaluating early etonogestrel implants compared with delayed initiation of implants or depot medroxyprogesterone acetate failed to find such an association. CONCLUSION The preponderance of evidence fails to demonstrate adverse breastfeeding outcomes or negative health outcomes in infants such as restricted growth, health problems or impaired development. Evidence newly added to this review was largely consistent with previous evidence.

Safety of hormonal and intrauterine methods of contraception for women with HIV/AIDS: a systematic review.

Objective:To determine from the literature whether HIV-infected women who use hormonal or intrauterine contraception are at increased risk of HIV disease progression, other adverse health outcomes, or HIV transmission to uninfected sexual partners. Design:A systematic review. Methods:We searched PubMed for articles published in peer-reviewed journals through August 2009 for evidence relevant to all hormonal and intrauterine contraceptive methods and HIV/AIDS. Results:Eight observational studies reported no increased risk of HIV disease progression with hormonal or intrauterine contraceptive use, whereas one randomized controlled trial found increased risks of declining CD4 cell count and death for hormonal contraceptive users compared with intrauterine device users. Women with HIV who used hormonal contraception had increased risks of acquiring sexually transmitted infections compared with women not using hormonal contraception, similar to the risks reported among uninfected women. One study found no association between hormonal or intrauterine contraceptive use and increased risk of HIV transmission to uninfected partners, whereas findings from nine studies examining contraceptive use and viral shedding from the genital tract were inconsistent. Conclusion:Evidence regarding the safety of hormonal and intrauterine contraceptive use among women with HIV remains limited, but generally reassuring regarding adverse health effects, disease transmission to uninfected partners, and disease progression; however, one randomized trial raised concerns about enhanced disease progression among women using hormonal contraception. Preventing unintended pregnancy among women with HIV remains a high priority in public health, both for the health of the woman as well as for the prevention of mother-to-child transmission of HIV.

Contraceptive effectiveness of a polyurethane condom and a latex condom: A randomized controlled trial

OBJECTIVE To compare the contraceptive effectivenesses of a polyurethane condom and a standard latex condom. Secondary outcomes of interest were safety, functionality, discontinuation, and acceptability. METHODS We randomized 901 couples to use either the polyurethane condom or a standard latex condom as their only form of contraception. We tested for pregnancy at enrollment and at every scheduled follow-up visit (weeks 4, 10, 16, 22, and 30). RESULTS The 6-month typical-use pregnancy probabilities were 9.0% (95% confidence interval [CI] 5.9, 12.2) for the polyurethane group and 5.4% (95% CI 2.9, 7.8) for the latex group; the hazard ratio was 1.7 (95% CI 1.1, 2.7), and we failed to reject the null hypothesis of our test of noninferiority. Females in the polyurethane group reported fewer genital irritations (hazard ratio 0.6; 95% CI 0.5, 0.8; P < .01), whereas males in both groups reported the same number of genital irritations (hazard ratio 1.0; 95% CI 0.7, 1.5; P = .94). Total clinical failures (breakage and slippage) were 8.4% for the polyurethane condom and 3.2% for the latex condom (difference 5.3%, 90% CI 2.8, 7.7). The risk of discontinuation did not differ between groups. Participants judged both condoms favorably in terms of the four primary acceptability outcomes (willingness to purchase, willingness to recommend, confidence in method, and general comfort). CONCLUSION The polyurethane condom was not shown to be as effective as the latex comparator condom for pregnancy prevention. However, the risk of pregnancy in the polyurethane group falls in the range of other barrier methods. For people with latex sensitivity or who find latex condoms unacceptable, this polyurethane condom represents one of several synthetic male condom alternatives currently available on the US market.

Effectiveness of hormonal contraception in HIV-infected women using antiretroviral therapy

Objective:The objective of this study is to assess whether antiretroviral therapy (ART) may diminish the effectiveness of hormonal contraceptive methods. Methods:Using data from 5153 HIV-infected women followed prospectively for 1–3 years in three HIV prevention studies in Africa, we compared incident pregnancy rates by contraceptive method (implant, injectable, oral or none) and ART use. Multivariable Cox regression models were used to determine adjusted hazard ratios (aHRs) and test interactions between each method and ART use. Results:During follow-up, 9% of women ever used implants, 40% used injectables and 14% used oral contraceptives; 31% of women ever used ART, mostly nevirapine (75% of ART users) or efavirenz-based (15%). Among women not using contraception, pregnancy rates were 13.2 and 22.5 per 100 women-years for those on and not on ART, respectively. Implants greatly reduced the incidence of pregnancy among both women on ART [aHR 0.06, 95% confidence interval (95% CI) 0.01–0.45] and not on ART (aHR 0.05, 95% CI 0.02–0.11). Injectables (aHR 0.18 on ART and aHR 0.20 not on ART) and oral contraceptives (aHR 0.37 on ART and aHR 0.36 not on ART) also reduced pregnancy risk, though by lesser degrees. ART use did not significantly diminish contraceptive effectiveness, although all methods showed nonstatistically significant reduced effectiveness when concurrently using efavirenz. Conclusion:Hormonal contraceptive methods are highly effective in reducing pregnancy risk in HIV-infected women, including those concurrently using ART. Studies of potential interactions between ART and contraceptives should evaluate real-world effectiveness of contraceptive methods; in this study, implants were the most effective method to prevent pregnancy, even during ART use.

Safety of quinacrine contraceptive pellets: results from 10-year follow-up in Vietnam.

BACKGROUND This study was conducted to evaluate long-term safety of quinacrine pellets for nonsurgical sterilization among women in Vietnam. STUDY DESIGN Observational cohort study of 2735 women who had quinacrine insertions between 1989 and 1993 compared to 1623 women who received an intrauterine device (IUD). RESULTS Cumulative follow-up times for the quinacrine and IUD cohorts were 28,697 and 17,382 person-years, respectively, and losses to follow-up were 6% and 7%, respectively. Quinacrine users had a higher incidence of ectopic pregnancy compared to IUD users (risk ratio, 2.2; 95% confidence interval, 1.06-4.54); the risks of cancer, hysterectomy, pelvic/gynecologic surgery and death were similar in the two groups. Two quinacrine insertions appeared to lower the risk of ectopic pregnancy to that of surgical tubal occlusion. CONCLUSIONS Use of quinacrine in this cohort appeared to have minimal health risks. Other research, including preclinical studies, needs to be considered in an overall evaluation of whether the combination of safety and efficacy provide a basis for quinacrines approval by appropriate regulatory agencies.

Randomized crossover trial comparing the eZ·on™ plastic condom and a latex condom

This randomized crossover trial compared the breakage and slippage rates, safety, and acceptability of the recently developed polyurethane bi-directional eZ.on condom with a marketed latex condom. Three hundred sixty couples were asked to use 4 eZ.on condoms and 4 latex condoms. Like several other non-latex condoms tested to date, the eZ.on condom had a higher clinical breakage rate than its latex comparator, while the slippage rates were similar. The clinical breakage rate for the eZ.on condom was 5.6%, compared with 0.9% for the latex condom (difference = 4.76%, with upper 95% confidence bound on the difference = 6.26%). Thus, based on an a priori definition of a 2% clinically acceptable difference, the study failed to conclude equivalence relative to clinical breakage. The complete slippage rate for eZ.on was 1.6%; compared to 0.7% for latex (difference = 0.87%, with upper 95% confidence bound = 1.55%). Thus, based on an a priori definition of a 2% difference we concluded equivalence relative to complete slippage. The safety profile of the eZ.on condom was good and similar to the latex condom. The eZ.on was also found to be easier to don and remove than the latex condom. Although no overall preference existed for either condom, nearly 30%women and men strongly preferred the eZ.on condom to the latex condom. The eZ.on condom may be an acceptable alternative for couples unable or unwilling to use latex condoms.

Contraceptive effectiveness of two insertions of quinacrine : results from 10-year follow-up in Vietnam

BACKGROUND This study was conducted to evaluate the long-term effectiveness of two insertions of quinacrine pellets for nonsurgical sterilization among women in northern Vietnam. STUDY DESIGN Observational cohort study of 1335 women who received two quinacrine insertions between 1989 and 1993. RESULTS About 90% of the study population participated in the last round of interviews. Cumulative follow-up time for this cohort was 14,294 person-years. The 1-, 5- and 10-year cumulative pregnancy probabilities for quinacrine were 3.3% (95% CI, 2.4-4.3), 10.0% (95% CI, 8.4-11.6) and 12.1% (95% CI, 10.4-13.9), respectively. Pregnancy estimates with quinacrine in this cohort were higher than that reported from US-based research on surgical tubal sterilization and higher than results of quinacrine sterilization in Chile. Quinacrine effectiveness was better among older women. CONCLUSION The effectiveness of quinacrine in Vietnam was lower than other forms of sterilization. Factors such as inconsistent training and use of various insertion techniques may have contributed to the relatively high failure rate.

Quinacrine sterilization and gynecologic cancers: a case-control study in northern Vietnam.

Background: Over 100,000 women worldwide have been sterilized by insertion of quinacrine into the uterus to induce tubal scarring. Concern has been expressed about possible carcinogenicity, and specifically the risk of uterine cancer. Methods: From 2001 through 2006, we conducted a population-based, case–control study of gynecologic cancers in 12 provinces in northern Vietnam, where relatively large numbers of women had received quinacrine. Cases of incident cervical, ovarian, and uterine cancer were identified at provincial hospitals or at referral hospitals in Hanoi. For each case, 3 age- and residence-matched controls were randomly selected from the population registries of the cases home community. Results: The prevalence of quinacrine exposure was 1.2% among cases and 1.1% among controls. For cervical cancer, analysis of 606 cases (9 exposed) and their 1774 matched controls (18 exposed) produced an odds ratio of 1.44 (95% confidence interval = 0.59–3.48) (adjusted for several covariates including human papillomavirus risk score). For ovarian cancer, based on 262 cases (3 exposed) and 755 controls (8 exposed) and adjusted for age and number of years of ovulation, the odds ratio was 1.26 (0.21–5.45). For uterine cancer, none of the cases—including 23 cases of leiomyosarcoma—was exposed to quinacrine. The 95% confidence interval, based on 161 cases (none exposed) and 470 controls (7 exposed) and adjusted only for age, was 0–1.85. Conclusion: We found no evidence of a relationship between quinacrine sterilization and gynecologic cancer.

Nevirapine-based antiretroviral therapy does not reduce oral contraceptive effectiveness.

Objective:To evaluate the effect of nevirapine-containing antiretroviral therapy (ART) on combined oral contraceptive (COC) effectiveness. Design:Nonrandomized prospective clinical trial. Methods:We enrolled HIV-infected women aged 18–35 years in South Africa and Uganda who had regular menses, were sexually active, and had no medical contraindications to COC use. We enrolled 196 women taking nevirapine-containing ART and 206 women not yet eligible for ART as a control group. We treated all participants with low-dose COCs. Our main outcomes were ovulation and pregnancy rates. We estimated ovulation in the first two cycles using weekly serum progesterone and tested for pregnancy monthly for 24 weeks. Results:The median age of participants was 29 and their median CD4+ cell count was 486. In the ART group, 43 of 168 (26%) ovulated in cycle 1, 30 of 163 (18%) in cycle 2, and 18 of 163 (11%) in both cycles. In the non-ART group, 26 of 168 (16%) ovulated in cycle 1, 31 of 165 (19%) in cycle 2, and 20 of 165 (12%) in both cycles. We found no significant difference in ovulation rates between groups: unadjusted odds ratio 1.36 (95% confidence interval 0.85–2.18). Pregnancy rates also did not differ: 10.0 per 100-women-years in the ART group and 10.1 per 100-women-years in the non-ART group. Self-reported COC adherence, condom use, vaginal bleeding, and adverse events were similar. Five serious adverse events were reported, all in the non-ART group. Conclusion:ART use did not affect risk of ovulation or pregnancy in women taking COCs, suggesting that nevirapine-containing ART does not interfere with COC contraceptive effectiveness.