Strategies to improve adherence and continuation of shorter-term hormonal methods of contraception.

BACKGROUND: Worldwide, hormonal contraceptives are among the most popular reversible contraceptives. Despite high perfect-use effectiveness rates, typical-use effectiveness rates for shorter-term methods such as oral and injectable contraceptives are much lower. In large part, this disparity reflects difficulties in ongoing adherence to the contraceptive regimen and low continuation rates. Correct use of contraceptives to ensure effectiveness is vital to reducing unintended pregnancy. OBJECTIVES: To determine the effectiveness of strategies aiming to improve adherence to, and continuation of, shorter-term hormonal methods of contraception compared with usual family planning care. SEARCH METHODS: We searched to July 2018 in the following databases (without language restrictions): The Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 7), PubMed via MEDLINE, POPLINE, Web of Science, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing strategies aimed to facilitate adherence and continuation of shorter-term hormonal methods of contraception (such as oral contraceptives (OCs), injectable depot medroxyprogesterone acetate (DMPA or Depo-Provera), intravaginal ring, or transdermal patch) with usual family planning care in reproductive age women seeking to avoid pregnancy. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Primary outcomes were continuation or discontinuation of contraceptive method, rates of discontinuation due to adverse events (menstrual disturbances and all other adverse events), and adherence to method use as indicated by missed pills and on-time/late injections. Pregnancy was a secondary outcome. MAIN RESULTS: We included 10 RCTs involving 6242 women. Six trials provided direct in-person counseling using either multiple counseling contacts or multiple components during one visit. Four trials provided intensive reminders of appointments or next dosing, of which two provided additional educational health information as well as reminders. All trials stated 'usual care' as the comparison.The certainty of the evidence ranged from very low to moderate. Main limitations were risk of bias (associated with poor reporting of methodological detail, lack of blinding, and incomplete outcome data), inconsistency, indirectness, and imprecision.Continuation of hormonal contraceptive methodsIt is uncertain whether intensive counseling improves continuation of hormonal contraceptive methods compared with usual care (OR 1.28, 95% CI 1.07 to 1.54; 2624 participants; 6 studies; I2 = 79%; very low certainty evidence). The evidence suggested: if the chance of continuation with usual care is 39%, the chance of continuation with intensive counseling would be between 41% and 50%. The overall pooled OR suggested continuation of improvement, however, when stratified by contraceptive method type, the positive results were restricted to DMPA.It is uncertain whether reminders (+/- educational information) improve continuation of hormonal contraceptive methods compared with usual care (OR 1.33, 95% CI 1.03 to 1.73; 933 participants; 2 studies; I2 = 69%; very low certainty evidence).The evidence suggested: if the chance of continuation with usual care is 52%, the chance of continuation with reminders would be between 52% and 65%.Discontinuation due to adverse eventsThe evidence suggested that counseling may be associated with a decreased rate of discontinuation due to adverse events compared with usual care, with a lower rate of discontinuation due to menstrual disturbances (OR 0.20, 95% CI 0.11 to 0.37; 350 participants; 1 study; low certainty evidence), but may make little or no difference to all other adverse events (OR 0.73, 95% CI 0.36 to 1.47; 350 participants; 1 study; low certainty evidence). The evidence suggested: if the chance of discontinuation with usual care due to menstrual disturbances is 32%, the chance of discontinuation with intensive counseling would be between 5% and 15%; and that if the chance of discontinuation with usual care due to other adverse events is 55%, the chance of discontinuation with intensive counseling would be between 30% and 64%.Discontinuation was not reported among trials that investigated the use of reminders (+/- educational information).Adherence Adherence was not reported among trials that investigated the use of intensive counseling.Among trials that investigated reminders (+/- educational information), there was no conclusive evidence of a difference in adherence as indicated by missed pills (MD 0.80, 95% CI -1.22 to 2.82; 73 participants; 1 study; moderate certainty evidence) or by on-time injections (OR 0.84, 95% CI 0.54 to 1.29; 350 participants; 2 studies; I2 = 0%; low certainty evidence). The evidence suggested: if the chance of adherence to method use as indicated by on-time injections with usual care is 50%, the chance of adherence with method use as indicated by on-time injections with reminders would be between 35% and 56%.PregnancyThere was no conclusive evidence of a difference in rates of pregnancy between intensive counseling and usual care (OR 1.24, 95% CI 0.98 to 1.57; 1985 participants; 3 studies; I2 = 0%, very low certainty evidence). The evidence suggested: if the chance of pregnancy with usual care is 18%, the chance of pregnancy with counseling would be between 18% and 25%.Pregnancy was not reported among trials that investigated the use of reminders (+/- educational information). AUTHORS' CONCLUSIONS: Despite the importance of this topic, studies have not been published since the last review in 2013 (nine studies) with only one study added in 2019 that neither changed the results nor improved the certainty of evidence.Overall, the certainty of evidence for strategies to improve adherence and continuation of contraceptives is low. Intensive counseling and reminders (with or without educational information) may be associated with improved continuation of shorter-term hormonal contraceptive methods when compared with usual family planning care. However, this should be interpreted with caution due to the low certainty of the evidence. Included trials used a variety of shorter-term hormonal contraceptive methods which may account for the high heterogeneity. It is possible that the effectiveness of strategies for improving adherence and continuation are contingent on the contraceptive method targeted. There was limited reporting of objectively measurable outcomes (e.g. electronic monitoring device) among included studies. Future trials would benefit from standardized definitions and measurements of adherence, and consistent terminology for describing interventions and comparisons. Further research requires larger studies, follow-up of at least one year, and improved reporting of trial methodology.

Unexpected Complications Following Adult Medical Male Circumcision Using the PrePex Device.

INTRODUCTION: In this study, we describe and depict unexpected sequelae of adult medical male circumcision (MMC) using the PrePex device. MATERIALS AND METHODS: The PrePex system is an elastic compression device for adult MMC. The device is well studied, has been pre-qualified by the World Health Organization (WHO), and its use is being scaled-up in African countries targeted by WHO. We conducted a PrePex implementation study in routine service delivery among 427 men in the age range of 18-49 in western Kenya. We captured penile photographs to create a record of adverse events (AEs) and to monitor healing. Several unexpected AEs ensued, including some that have not been reported in other PrePex studies. We describe and depict those unexpected complications and resulting treatments to alert circumcision providers in the relevant areas. RESULTS: We observed 5 device displacements (1.2%); 3 cases of early sloughing of foreskin tissue (0.7%) among men with long foreskins; 2 cases of a long foreskin obstructing urine flow, as it became dry and necrotic (0.5%); and 2 cases of insufficient foreskin removal caused by invagination for which surgical completion was necessary (0.5%). All of the participants healed completely by day 42 post-circumcision or shortly thereafter. CONCLUSION: The potential for these complications should be incorporated into PrePex training programs. Integration of devices into MMC programs in medically underserved areas requires the availability of prompt surgical intervention for some sequelae, particularly displacement events.

Prospective Observational Study of the ShangRing Device for Adult Medical Male Circumcision in a Routine Clinical Setting in Malawi.

We evaluated the safety and acceptability of the ShangRing device for male circumcision during routine clinical service delivery in Namitete, Malawi. We conducted a prospective observational study enrolling 500 HIV-negative men ages 18 to 49 years at St. Gabriel's Hospital. Participants returned for two follow-up visits: the removal visit (day 7 after placement) and the healing check visit (day 42 after placement). We assessed pain, adverse events (AEs), acceptability, and healing. 500 men were screened; 498 were circumcised using the ShangRing and comprised the analysis population. Seven participants (1.4%) experienced moderate AEs related to circumcision. 93% were judged to be completely healed at or before the day 42 visit; 6% were judged to be healed later than the day 42 visit; 5 participants (1.0%) were lost to follow-up. 98% of men stated they were very satisfied with the appearance of their circumcised penis, and 99.6% would recommend ShangRing circumcision to family/friends. Adult male circumcision using the ShangRing was safe with a low AE rate at this service delivery site. Acceptability factors were also favorable. Addition of the ShangRing device could be beneficial to achieving the goals of the circumcision program in Malawi.

Monitoring microbicide gel use with real-time notification of the container's opening events: results of the CAPRISA Wisebag study.

Accurate estimation of the effectiveness of a microbicide for HIV prevention requires valid measurement of adherence to product use. A microbicide gel applicator container (Wisebag), fitted with cell phone technology to transmit opening events and text message reminders, was developed to monitor each opening event of the container as a proxy for gel use and adherence. Ten women were enrolled in a pilot study and followed for up to 4 months. Wisebag opening (WBO) dates and times were recorded and correlated with self-reported sex acts and gel applicator returns. During the 33 monthly follow-up visits, 47.8 % (77/161) of the recorded number of WBO events were concordant with the number of empty (used) applicators returned. The discrepancies were likely due to removal of more than one applicator during a single opening event. When the date and time of the WBO event data was assessed in relation to three different self-report adherence measures, agreement was fairly modest. The Wisebag was found to be acceptable as a storage container and the cell phone reminders generated were useful in supporting the dosing strategy. We recommend that the Wisebag be considered for larger scale and lengthier testing in microbicide trials.

Willingness to participate in future HIV prevention trials in Beira, Mozambique.

In preparation for trials of new HIV prevention methods, willingness to participate (WTP) was assessed in Beira, Mozambique. A total of 1 019 women participating in an HIV incidence study, and 97 men participating in a separate WTP survey, were interviewed. When comparing the answers to questions that were identical in the two studies, WTP was higher among women than men for all prevention methods. Among women, WTP was highest for trials evaluating daily oral pre-exposure prophylaxis (PrEP; 84.4% reporting very likely to participate), followed by vaccination (77.8%), daily vaginal gel use (67.7%), coital vaginal gel use (67.1%) and monthly vaginal ring use (47.7%). Among men, WTP was highest for trials evaluating vaccination (57.6%), followed by daily vaginal gel use for female sexual partners (52.5%), daily oral PrEP (49.5%), coital vaginal gel use for female sexual partners (46.4%) and monthly vaginal ring use for female sexual partners (39.4%). Among men, the most important motivators for trial participation were social benefits, whereas personal risks (most notably receiving injections and/or blood draws) were deterrents; this was not assessed in women. Other important lessons learnt are that male circumcision and antiretroviral drugs were not generally recognised as ways to prevent HIV, that having to use hormonal contraception during trial participation will likely reduce WTP, and that evening clinics are not likely to be popular. The barriers reported in this and other studies may be challenging but are not impossible to overcome.

Sexual behavior before and after pregnancy detection in four microbicide trials.

Vaginal microbicide gel trials for HIV prevention may require withdrawal of study product when a woman becomes pregnant. We assessed the potential impact of withdrawals in four trials by comparing self-reported sexual behavior pre- and post-pregnancy detection: (1) behavior in the month prior to positive pregnancy test versus behavior reported at the subsequent monthly visit; (2) behavior changes according to pregnancy status at the subsequent visit (continuing pregnancy versus not); (3) average sexual behaviors reported for all months prior to pregnancy detection versus all months after pregnancy was no longer detected; and (4) behavior changes among participants never testing positive for pregnancy. Pregnancy detection was associated with immediate reductions in self-reported numbers of partners and sex acts. The proportion of acts in which study gel was used following a negative pregnancy test did not return to pre-pregnancy levels. Pregnancies complicate the conduct and interpretation of vaginal microbicide trials when product must be withdrawn.

Baseline infection with a sexually transmitted disease is highly predictive of reinfection during follow-up in Malagasy sex workers.

Female sex workers who had prevalent chlamydial, gonococcal, or trichomonal infection at enrollment into a randomized trial in Madagascar were 2 to 4 times as likely to become infected during follow-up, compared to women without STIs at baseline, despite provision of condoms, safer sex counseling, and repeat STI testing and treatment.

Baseline factors associated with incident HIV and STI in four microbicide trials.

BACKGROUND: Analyzing pooled data from 4 recent microbicide trials, we aimed to determine characteristics of participants at higher risk of HIV and sexually transmitted infections (STIs), to inform targeted recruitment, preserved study power, and potentially smaller study sizes in future trials. METHODS: We evaluated the relationships between participants' characteristics and the incidence of HIV, STIs, and reproductive tract infections (RTIs). We calculated incidence rates as the number of infection events divided by the person-years of observation. We applied Cox regression models to assess the relationships between baseline demographic, reproductive and behavioral factors and incident HIV, STIs and RTIs. RESULTS: The pooled incidence rates for HIV, chlamydia, and gonorrhea were 2.1, 6.4 and 9.9 per 100 person-years, respectively. Proportions of participants with trichomoniasis, bacterial vaginosis (BV), and candidiasis were 0.06, 0.40, and 0.40, respectively. In final multivariable models, age and education were significantly (and inversely) associated with incident HIV; baseline chlamydia, baseline trichomoniasis, and younger age were associated with incident Chlamydia; and baseline gonorrhea infection, younger age, less education, nulliparous status, baseline chlamydia, and condom use for contraception were associated with incident gonorrhea. Three factors were associated with trichomoniasis: baseline trichomoniasis infection, baseline chlamydia, and baseline BV. CONCLUSIONS: Only younger age was robustly associated with multiple STI outcomes in our multivariable analyses. Although there was little evidence of associations between baseline STIs and incident HIV, they were strongly associated with incident STIs. We found no evidence that measured baseline sexual behavior factors were associated with incident HIV or STIs.

Pregnancy among sex workers participating in a condom intervention trial highlights the need for dual protection.

BACKGROUND: Little is known about pregnancy rates among sex workers (SWs) or the factors that predispose SWs to this risk. We aimed to estimate the pregnancy incidence rate among Madagascar SWs participating in an intervention trial promoting use of male and female condoms and assess the influence of various predictive factors on pregnancy risk. METHODS: SWs from two study clinics in Madagascar participated in a randomized trial to assess the effect of peer education and clinic-based counseling on use of male and female condoms and prevalence of sexually transmitted infections (STIs). Women were seen every 2 months for up to 18 months; they received structured interviews at every visit, and physical exams at baseline and every 6 months thereafter. Site staff recorded information on pregnancies during interviews; pregnancy data were then merged with trial data for this analysis. RESULTS: Of 935 SWs in the analysis population, 250 became pregnant during follow-up. The cumulative probability of pregnancy was 0.149 at 6 months and 0.227 at 12 months. Comparable proportions of nonpregnant and pregnant SWs reported using highly effective contraception at baseline (approximately 16%); these users were younger and were more consistent condom users. Method switching and discontinuation were frequent. In multivariate analysis, nonuse of effective contraceptives and any self-reported unprotected sex were associated with higher incidence of pregnancy. Approximately 51% of women delivered, 13% reported a spontaneous abortion, 13% reported an induced abortion and 23% had missing pregnancy outcomes. CONCLUSIONS: Women traditionally targeted for STI/HIV preventive interventions need more comprehensive reproductive health services. In particular, SWs could benefit from targeted family planning counseling and services.

Evaluation of SMARTube to Detect HIV Infection Before Seroconversion Using Standard Methods.

The acute phase of HIV infection carries substantial risk of transmission; identification of acute-phase infections may offer opportunities to reduce that risk. SMARTube incubation of blood specimens is designed to stimulate in vivo-primed HIV-specific lymphocytes to produce HIV antibodies in vitro. The resulting supernatant (S-plasma) can be tested to identify acute infections with commercially available HIV assays. We assessed the performance of the SMARTube to identify acute HIV infections in studies at three developing country sites. We conducted HIV incidence studies in Ho Chi Minh City, Vietnam, and Bloemfontein and Rustenburg, South Africa. We estimated HIV incidence in cross-sectional samples and measured prospective incidence in uninfected women followed for up to 12 months. We incorporated SMARTube into the HIV testing algorithm at cross-sectional screening and monthly follow-up visits. We tested 1,384 persons in Vietnam, 1,145 women in Bloemfontein, and 538 persons in Rustenburg. Cross-sectional samples from 11 participants that tested positive with SMARTube after an initial unincubated negative test result (11 of 2,472; 0.4% of all specimens) were considered "potential acute" infections. Matching samples from 3 of the 11 (27.3%) were confirmed by polymerase chain reaction (PCR) testing. In follow-up of 355, 401, and 223 uninfected women in Vietnam, Bloemfontein, and Rustenburg, respectively, 11 seroconversions occurred in Bloemfontein and Rustenburg. In four of these incident infections (36.4%), SMARTube testing had resulted in earlier detection of HIV infection than the eventual seroconversion visits. In our field studies, pretreatment with SMARTube allowed the identification of acute HIV-1 infection in some new infections, but with a positive predictive value of 27%. Larger studies are needed to evaluate SMARTube as an alternative to technically challenging and costly enzyme immunoassay and PCR testing to detect acute HIV infection.

Factors Associated With Delayed Healing in a Study of the PrePex Device for Adult Male Circumcision in Kenya.

OBJECTIVES: To explore factors associated with healing requiring more than 6 weeks after placement of the PrePex device for adult medical male circumcision. METHODS: We enrolled 427 men ages 18-49 years in an observational study of PrePex at 1 urban and 2 peripheral clinics in western Kenya. Participants were scheduled for device removal at day 7 and a follow-up visit at day 42 (allowable range, 40-44) at which the provider recorded wound status, with complete healing defined as a dry wound without any scab, later confirmed by site investigator review of digital penile photographs. We performed univariate and multivariate logistic regression to explore associations between selected demographic, surgical, and follow-up factors and delayed healing (not healed by day 42 visit). RESULTS: Of the 427 men, 341 completing a day 42 visit with physical examination and recorded healing status were included. Fifty-four percent of included men were healed by day 42 visit. Factors associated with delayed healing in univariate analysis and remaining significant in the multivariate analysis were as follows: age 25 years or older [odds ratio (OR): 1.8; 95% confidence interval (CI): 1.4 to 2.4], an adverse event by day 44 (OR: 1.4; 95% CI: 1.03 to 2.0), and severe pain during device removal (protective association: OR: 0.7; 95% CI: 0.5 to 0.99). CONCLUSIONS: Older age (25+ years), occurrence of an adverse event, and lesser self-reported pain at device removal were associated with delayed wound healing. If confirmed by larger surveillance studies, these results should be incorporated into the counseling given to male circumcision clients.

Randomized Controlled Trial of the ShangRing for Adult Medical Male Circumcision: Safety, Effectiveness, and Acceptability of Using 7 Versus 14 Device Sizes.

OBJECTIVES: To assess the safety, effectiveness, and acceptability of providing a reduced number of ShangRing sizes for adult voluntary medical male circumcision (VMMC) within routine service delivery in Lusaka, Zambia. METHODS: We conducted a randomized controlled trial and enrolled 500 HIV-negative men aged 18-49 years at 3 clinics. Participants were randomized to 1 of 2 study arms (Standard Sizing arm vs Modified Sizing arm) in a 1:1 ratio. All 14 adult ShangRing sizes (40-26 mm inner diameter, each varying by 1 mm) were available in the Standard Sizing arm; the Modified Sizing arm used every other size (40, 38, 36, 34, 32, 30, 28 mm inner diameter). Each participant was scheduled for 2 follow-up visits: the removal visit (day 7 after placement) and the healing check visit (day 42 after placement), when they were evaluated for adverse events (AEs), pain, and healing. RESULTS: Four hundred and ninety-six men comprised the analysis population, with 255 in the Standard Sizing arm and 241 in the Modified Sizing arm. Three men experienced a moderate or severe AEs (0.6%), including 2 in the Standard Sizing arm (0.8%) and 1 in the Modified Sizing arm (0.4%). 73.2% of participants were completely healed at the scheduled day 42 healing check visit, with similar percentages across study arms. Virtually all (99.6%) men, regardless of study arm, stated that they were very satisfied or satisfied with the appearance of their circumcised penis, and 98.6% stated that they would recommend ShangRing circumcision to family/friends. CONCLUSIONS: The moderate/severe AE rate was low and similar in the 2 study arms, suggesting that provision of one-half the number of adult device sizes is sufficient for safe service delivery. Effectiveness, time to healing, and acceptability were similar in the study arms. The simplicity of the ShangRing technique, and its relative speed, could facilitate VMMC program goals. In addition, sufficiency of fewer device sizes would simplify logistics and inventory.

Surgical Outcomes of Newly Trained ShangRing Circumcision Providers.

BACKGROUND: Devices can potentially accelerate scale-up of voluntary medical male circumcision in sub-Saharan Africa. Studies have demonstrated advantages of the ShangRing device over conventional circumcision. With the need to train providers rapidly for scale-up, concerns arise about the transferability of techniques and the expertise of new trainees. METHODS: We compared outcomes of ShangRing circumcisions conducted in Kenya by experienced providers (experience with more than 100 ShangRing circumcisions) and newly trained providers (trained in Kenya by the experienced providers before the study began). During training, trainees performed at least 7 ShangRing circumcisions and 3 removals. Newly trained providers received intermittent clinical mentoring initially during the study but otherwise conducted circumcisions on their own. RESULTS: Four hundred six and 115 ShangRing procedures were performed by the new trainees and the experienced providers, respectively. The mean duration of circumcisions was 6.2 minutes for both trained and experienced provider groups (P = 0.45), whereas the mean pain score (on an 11-point scale) was 2.5 and 3.2, respectively (P = 0.65). There was no difference in the proportion of participants healed by the day 42 visit (P = 0.13) nor in the incidence of moderate and severe adverse events observed (P = 0.16). Participants in both groups were equally satisfied with final wound cosmesis. DISCUSSION: Results demonstrate that the ShangRing circumcision technique is easy to learn and master. Newly trained providers can safely conduct ShangRing circumcisions in routine service settings. The ShangRing can facilitate rapid rollout of voluntary medical male circumcision for HIV prevention in sub-Saharan Africa.

Men's Understanding of and Experiences During the Postcircumcision Abstinence Period: Results From a Field Study of ShangRing Circumcision During Routine Clinical Services in Kenya and Zambia.

BACKGROUND: Men's understanding of counseling messages after voluntary medical male circumcision (VMMC) plays an important role in whether they follow them. Data on triggers for early resumption of sex may be useful as scale-up of VMMC for HIV prevention continues in sub-Saharan Africa. METHODS: Data on understanding of post-VMMC abstinence recommendations, resumption of sex, condom use, and triggers for resuming sex were collected from participants during a follow-up interview 35-42 days after ShangRing circumcision in Kenya and Zambia. RESULTS: Of 1149 men who had ShangRing circumcision, 1096 (95.4%) completed follow-up. Nearly all (99.2%) reported being counseled to abstain from sex post-VMMC; among those, most (92.2%) recalled the recommended abstinence period was 6 weeks. Most men (94.1%) reported that the counselor gave reasons for post-VMMC abstinence and recalled appropriate reasons. Few (13.4%) men reported resuming sex at 35-42 days' follow-up. Among those, 54.8% reported never using a condom post-VMMC. Younger participants (odds ratio 0.3, 95% confidence interval: 0.2 to 0.5, P < 0.0001) and those reporting at least some condom use at baseline (odds ratio 0.5, 95% confidence interval: 0.3 to 0.7, P = 0.0003) were less likely to report resuming sex. Among men who reported some condom use, most (71.5%) said condoms were much easier or easier to use after circumcision. Men reported various reasons for early resumption of sex, primarily strong sexual desire (76.4%). CONCLUSIONS: Most men reported awareness of and adherence to the counseling recommendations for post-VMMC abstinence. A minority reported early resumption of sex, and, among those, condom use was low. Results could be used to improve post-VMMC counseling.

Randomized assignment to copper IUD or depot-medroxyprogesterone acetate: feasibility of enrollment, continuation and disease ascertainment.

OBJECTIVES: We conducted a feasibility study to enroll and follow family planning acceptors who were randomly assigned to use an intrauterine device (IUD) or injectable depot-medroxyprogesterone acetate (DMPA). METHODS: Centers in Brazil, Guatemala, Egypt and Vietnam aimed to enroll 100 participants per site. Enrolled women were randomly assigned to have inserted a TCu 380A IUD, or to receive injections of 150 mg of DMPA every 3 months, and scheduled for up to 12 months of follow-up. We tested for cervical infection at first and final visits, and examined for signs of pelvic inflammatory disease (PID) at each visit. RESULTS: The sites screened 555 women and enrolled 368. Two women (0.5%) had three discomfort signs of PID during follow-up. The prevalence of gonorrhea at each woman's final follow-up visit was 0.5%, and the prevalence of chlamydia at final visit was 5.4%. Sixty-eight percent of women either completed 12 months of observation with their assigned method or were still using their method at the end of the study. CONCLUSION: A larger, definitive clinical trial appears feasible. The majority of women we approached agreed to participate; nearly 400 women were enrolled; two thirds continued to use their assigned method until study closeout; and the STI risk was moderate.

Longer-Term Follow-Up of Kenyan Men Circumcised Using the ShangRing Device.

OBJECTIVES: To ascertain clinical sequelae, client satisfaction and sexual behavior 2+ years after male circumcision using the ShangRing device. METHODS: We enrolled 199 men from the Kenya sites (Homa Bay district) participating in a 2012 study of the ShangRing device used in routine male circumcision services (N = 552). We enrolled men who had had the ShangRing placed successfully, and over-sampled men who had had an adverse event and/or were HIV-positive during the field study. In the present study, each participant was examined and interviewed by a study clinician, and penile photographs were taken to document longer-term cosmetic results and any abnormal findings. RESULTS: 194 men were included in the analysis. The mean and median times between circumcision and the longer-term follow-up visit in this study were 31.8 and 32 months, respectively. Four men (2.1%) had signs/symptoms of a sexually transmitted infection (STI). Virtually all (99.5%) of the men were very satisfied with the appearance of their circumcised penis, and all would recommend a ShangRing circumcision to friends or family members. The most prevalent reported advantage of the circumcision was the ease of bathing and enhanced cleanliness of the penis (75.8%). 94.3% of the men did not cite a single negative feature of their circumcision. 87.5% of men reported more sexual pleasure post-MC, the most common reason being more prolonged intercourse. The majority of men (52.6%) reported one sexual partner post-MC, but more than a quarter of the men (28.1%) reported an increased number of partners post-MC. Less than half of the men (44.3%) reported using condoms half of the time or more, but the great majority of condom users stated that condom use was much easier post-MC, and 76.9% of users said they used condoms more after circumcision than before. CONCLUSIONS: This study supports the safety and acceptability of ShangRing male circumcision during 2-3 years of follow-up. It should allay worries that the ShangRing procedure could lead to delayed complications later than the observation period of most clinical studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT01567436.

Effectiveness, safety and acceptability of Sino-implant (II) during the first year of use: results from Kenya and Pakistan.

BACKGROUND: Sino-implant (II) is a two-rod subcutaneous contraceptive implant used up to 4 years, containing 150 mg of levonorgestrel. We conducted two observational studies of Sino-implant (II) to evaluate its performance in routine service delivery settings. METHODS: We enrolled 1326 women age 18-44 who had Sino-implant (II) inserted at clinics in Pakistan and Kenya. Women were followed-up using either an active or passive follow-up scheme in each study. Study outcomes were: one-year cumulative pregnancy and discontinuation rates; rates of insertion and removal complications; adverse event and side effect rates; reasons for discontinuation; and implant acceptability and satisfaction with clinic services. RESULTS: A total of 754 women returned for at least one follow-up visit. The overall Pearl pregnancy rate was 0.4 per 100 woman-years [95% confidence interval (CI) 0.1, 0.9] resulting from 1 confirmed post-insertion pregnancy in Kenya and 4 in Pakistan. Country-specific Pearl rates were 0.2 (95% CI 0.0, 0.9) in Kenya and 0.6 (95% CI 0.2, 1.6) in Pakistan. The total cumulative 12-month probability of removal was 7.6% (95% CI 6.1, 9.1), with country-specific removal probabilities of 3.7% in Kenya (95% CI 2.1, 5.3) and 10.8% in Pakistan (95% CI 8.5, 13.2). Four serious adverse events occurred in Kenya and none occurred in Pakistan; one SAE (an ectopic pregnancy) was possibly related to Sino-implant (II). Most women in both countries said they would recommend the implant to others. CONCLUSION: The results from these studies reveal high effectiveness and favorable safety and acceptability during the first year of use of Sino-implant. IMPLICATION: The favorable Sino-implant (II) findings from Kenya and Pakistan provide further evidence from disparate regions that Sino-implant (II) is safe, effective and acceptable during routine service delivery.

HIV prevalence and incidence in a cohort of women at higher risk for HIV acquisition in Chókwè, southern Mozambique.

BACKGROUND: Reliable HIV incidence estimates for Mozambique are limited. We conducted a prospective HIV incidence study as part of a clinical research site development initiative in Chókwè district, Gaza Province, southern Mozambique. METHODS: Between June 2010 and October 2012, we recruited women at sites where women at higher risk of HIV infection would likely be found. We enrolled and tested 1,429 sexually active women in the screening phase and 479 uninfected women in the prospective phase. Participants were scheduled for 12+ months follow-up, when they underwent face-to-face interviews, HIV counseling and testing, and pregnancy testing. We observed a total of 373.1 woman-years (WY) of follow-up, with mean (median) of 9.4 (9.7) women-months per participant. RESULTS: The prevalence of HIV was 29.4% (95% confidence interval [CI]: 27.0-31.8%). In multivariable logistic regression analysis, factors that remained significantly associated with prevalent HIV were: older age (OR: 0.6; 95% CI: 0.4-0.7), lower educational level (OR: 0.4; 95% CI: 0.3-0.7), and using hormonal contraception (OR: 0.6; 95% CI: 0.4-0.7) or condoms (OR: 0.5; 95% CI: 0.3-0.7). We observed an HIV incidence rate of 4.6 per 100 WY (95% CI: 2.7, 7.3). The HIV incidence was 4.8 per 100 WY (95% CI: 2.5, 8.3) in women aged 18-24 years, 4.5 per 100 WY (95% CI: 1.2, 11.4) in women aged 25-29 years and 3.2 per 100 WY (95% CI: 0.1, 18.0) in the 30-35 years stratum. None of the demographic factors or time-varying behavioral factors examined was significantly associated with incident HIV infection in bivariable analysis at p ≤ 0.10. CONCLUSIONS: We found a high HIV incidence among sexually active young women in Chókwè, Mozambique. HIV prevention programs should be strengthened in the area, with more comprehensive reproductive health services, regular HIV testing, condom promotion, and messaging about multiple sexual partners.

Safety, effectiveness and acceptability of the PrePex device for adult male circumcision in Kenya.

OBJECTIVE: To assess the safety, effectiveness and acceptability of the PrePex device for adult medical male circumcision (MMC) in routine service delivery in Kenya. METHODS: We enrolled 427 men ages 18-49 at one fixed and two outreach clinics. Procedures were performed by trained clinical officers and nurses. The first 50 enrollees were scheduled for six follow-up visits, and remaining men were followed at Days 7 and 42. We recorded adverse events (AEs) and time to complete healing, and interviewed men about acceptability and pain. RESULTS: Placement and removal procedures each averaged between 3 and 4 minutes. Self-reported pain was minimal during placement but was fleetingly intense during removal. The rate of moderate/severe AEs was 5.9% overall (95% confidence interval [CI] 3.8%-8.5%), all of which resolved without sequelae. AEs included 5 device displacements, 2 spontaneous foreskin detachments, and 9 cases of insufficient foreskin removal. Surgical completion of MMC was required for 9 men (2.1%). Among the closely monitored first 50 participants, the probability of complete healing by Day 42 was 0.44 (95% CI 0.30-0.58), and 0.90 by Day 56. A large majority of men was favorable about their MMC procedure and would recommend PrePex to friends and family. CONCLUSIONS: The PrePex device was effective for MMC in Kenya, and well-accepted. The AE rate was higher than reported for surgical procedures there, or in previous PrePex studies. Healing time is longer than following surgical circumcision. Provider experience and clearer counseling on post-placement and post-removal care should lead to lower AE rates. TRIAL REGISTRATION: ClinicalTrials.gov NCT01711411.

Pregnancy incidence and correlates in a clinical trial preparedness study, North West Province South Africa.

INTRODUCTION: Women in HIV prevention trials often must typically agree to avoid pregnancy. Regardless, some become pregnant. Screening tools predicting pregnancy risk could maximize trial safety and efficiency. OBJECTIVES: We assessed incidence and correlates of pregnancy among women at high HIV risk. METHODS: We enrolled sexually-active, HIV-negative women into an observational cohort (2008-2011). At enrollment demographic, contraceptive, reproductive, pregnancy intention and behavioural data were collected. Women reported if one or both partners wanted or intended for the couple to become pregnant. We measured gender role beliefs using a locally validated eight-point index. We tested HIV and pregnancy, and inquired about sexually transmitted infection symptoms (STIs) at enrollment and monthly. HIV testing included behavioural counselling and condom provision, but did not specifically counsel women to avoid pregnancy. Cox proportional hazard modelling evaluated the associations with pregnancy. The multivariate model included the following variables "Recent pregnancy attempts", "Gender Roles Beliefs", "Self-reported STIs" and "Age". RESULTS: We screened 1068 women and excluded (24.6%, 263/1068) who did not report risk behaviour. Non-pregnant, non-sterilized women aged 18-35 (median = 21 years) enrolled (n = 438). Most women reported one partner (74.7%) and a prior live birth (84.6%). Median follow-up time was 6 months (range 0.7-15.5). Pregnancy incidence was 25.1 per 100 women-years (n = 57 pregnancies). Conservative beliefs on gender roles (Adjusted Hazard Ratio (aHR) 1.8; 95% confidence interval [CI] 1.1-2.9), recent pregnancy attempts (aHR 1.9; 95% CI 1.1-3.4) and baseline self-reported STI (aHR 2.5; 95% CI 1.4-4.4) were associated with increased incident pregnancy. Report of no pregnancy intention was associated with lowered pregnancy risk (aHR 0.3; 95% CI 0.1-0.7). CONCLUSIONS: We identified new and confirmed existing factors that can facilitate screening for pregnancy risk.