Randomised trial of early infant circumcision performed by clinical officers and registered nurse midwives using the Mogen clamp in Rakai, Uganda.

OBJECTIVES: To assess the safety and acceptability of early infant circumcision (EIC) provided by trained clinical officers (COs) and registered nurse midwives (RNMWs) in rural Uganda. SUBJECTS AND METHODS: We conducted a randomised trial of EIC using the Mogen clamp provided by newly trained COs and RNMWs in four health centres in rural Rakai, Uganda. The trial was registered with clinicaltrials.gov # NCT02596282. In all, 501 healthy neonates aged 1-28 days with normal birth weight and gestational age were randomised to COs (n = 256) and RNMWs (n = 245) for EIC, and were followed-up at 1, 7 and 28 days. RESULTS: In all, 701 mothers were directly invited to participate in the trial, 525 consented to circumcision (74.9%) and 23 were found ineligible on screening (4.4%). The procedure took an average of 10.5 min. Adherence to follow-up was >90% at all scheduled visits. The rates of moderate/severe adverse events were 2.4% for COs and 1.6% for RNMWs (P = 0.9). All wounds were healed by 28 days after circumcision. Maternal satisfaction with the procedure was 99.6% for infants circumcised by COs and 100% among infants circumcised by RNMWs. CONCLUSIONS: EIC was acceptable in this rural Ugandan population and can be safely performed by RNMWs who have direct contact with the mothers during pregnancy and delivery. EIC services should be made available to parents who are interested in the service.

Efficacy of knowledge and competence-based training of non-physicians in the provision of early infant male circumcision using the Mogen clamp in Rakai, Uganda.

OBJECTIVE: To assess acquisition of knowledge and competence in performing Early Infant Male Circumcision (EIMC) by non-physicians trained using a structured curriculum. SUBJECTS AND METHODS: Training in provision of EIMC using the Mogen clamp was conducted for 10 Clinical Officers (COs) and 10 Registered Nurse Midwives (RNMWs), in Rakai, Uganda. Healthy infants whose mothers consented to study participation were assigned to the trainees, each of whom performed at least 10 EIMCs. Ongoing assessment and feedback for competency were done, and safety assessed by adverse events. RESULTS: Despite similar baseline knowledge, COs acquired more didactic knowledge than RNMWs (P = 0.043). In all, 100 EIMCs were assessed for gain in competency. The greatest improvement in competency was between the first and third procedures, and all trainees achieved 80% competency and retention of skills by the seventh procedure. The median (interquartile range) time to complete a procedure was 14.5 (10-47) min for the COs, and 15 (10-50) min for the RNMWs (P = 0.180). The procedure times declined by 2.2 min for each subsequent EIMC (P = 0.005), and rates of improvement were similar for COs and RNMWs. Adverse events were comparable between providers (3.5%), of which 1% were of moderate severity. CONCLUSION: Competence-based training of non-physicians improved knowledge and competency in EIMC performed by COs and RNMWs in Uganda.

Genital Anaerobic Bacterial Overgrowth and the PrePex Male Circumcision Device, Rakai, Uganda.

The PrePex circumcision device causes ischemic necrosis of the foreskin, raising concerns of anaerobic overgrowth. We compared the subpreputial microbiome of 2 men 7 days after PrePex device placement to that of 145 uncircumcised men in Rakai, Uganda, using 16S ribosomal (rRNA) RNA gene-based quantitative polymerase chain reaction analysis and sequencing. PrePex users had higher absolute abundance of all bacteria than uncircumcised men (P = .001), largely due to increased numbers of the following anaerobes: Porphyromonas (5.2 × 10(7) 16S rRNA gene copies/swab in the PrePex group and 1.1 × 10(6) 16S rRNA gene copies/swab in uncircumcised men; P = .002), Peptoniphilus (1.0 × 10(7) and 1.8 × 10(6) 16S rRNA gene copies/swab, respectively; P < .05), Anaerococcus (1.0 × 10(7) and 1.1 × 10(6) 16S rRNA gene copies/swab, respectively; P < .001), and Campylobacter ureolyticus (1.7 × 10(5) and 1.6 × 10(7)16S rRNA gene copies/swab, respectively; P < .001). The PrePex-associated increase in anaerobes may account for unpleasant odor and a possible heightened risk of tetanus.

HIV shedding from male circumcision wounds in HIV-infected men: a prospective cohort study.

BACKGROUND: A randomized trial of voluntary medical male circumcision (MC) of HIV-infected men reported increased HIV transmission to female partners among men who resumed sexual intercourse prior to wound healing. We conducted a prospective observational study to assess penile HIV shedding after MC. METHODS AND FINDINGS: HIV shedding was evaluated among 223 HIV-infected men (183 self-reported not receiving antiretroviral therapy [ART], 11 self-reported receiving ART and had a detectable plasma viral load [VL], and 29 self-reported receiving ART and had an undetectable plasma VL [<400 copies/ml]) in Rakai, Uganda, between June 2009 and April 2012. Preoperative and weekly penile lavages collected for 6 wk and then at 12 wk were tested for HIV shedding and VL using a real-time quantitative PCR assay. Unadjusted prevalence risk ratios (PRRs) and adjusted PRRs (adjPRRs) of HIV shedding were estimated using modified Poisson regression with robust variance. HIV shedding was detected in 9.3% (17/183) of men not on ART prior to surgery and 39.3% (72/183) of these men during the entire study. Relative to baseline, the proportion shedding was significantly increased after MC at 1 wk (PRR = 1.87, 95% CI = 1.12-3.14, p = 0.012), 2 wk (PRR = 3.16, 95% CI = 1.94-5.13, p < 0.001), and 3 wk (PRR = 1.98, 95% CI = 1.19-3.28, p = 0.008) after MC. However, compared to baseline, HIV shedding was decreased by 6 wk after MC (PRR = 0.27, 95% CI = 0.09-0.83, p = 0.023) and remained suppressed at 12 wk after MC (PRR = 0.19, 95% CI = 0.06-0.64, p = 0.008). Detectable HIV shedding from MC wounds occurred in more study visits among men with an HIV plasma VL > 50,000 copies/ml than among those with an HIV plasma VL < 400 copies/ml (adjPRR = 10.3, 95% CI = 4.25-24.90, p < 0.001). Detectable HIV shedding was less common in visits from men with healed MC wounds compared to visits from men without healed wounds (adjPRR = 0.12, 95% CI = 0.07-0.23, p < 0.001) and in visits from men on ART with undetectable plasma VL compared to men not on ART (PRR = 0.15, 95% CI = 0.05-0.43, p = 0.001). Among men with detectable penile HIV shedding, the median log10 HIV copies/milliliter of lavage fluid was significantly lower in men with ART-induced undetectable plasma VL (1.93, interquartile range [IQR] = 1.83-2.14) than in men not on ART (2.63, IQR = 2.28-3.22, p < 0.001). Limitations of this observational study include significant differences in baseline covariates, lack of confirmed receipt of ART for individuals who reported ART use, and lack of information on potential ART initiation during follow-up for those who were not on ART at enrollment. CONCLUSION: Penile HIV shedding is significantly reduced after healing of MC wounds. Lower plasma VL is associated with decreased frequency and quantity of HIV shedding from MC wounds. Starting ART prior to MC should be considered to reduce male-to-female HIV transmission risk. Research is needed to assess the time on ART required to decrease shedding, and the acceptability and feasibility of initiating ART at the time of MC.

Effects of medical male circumcision (MC) on plasma HIV viral load in HIV+ HAART naïve men; Rakai, Uganda.

BACKGROUND: Medical male circumcision (MC) of HIV-infected men may increase plasma HIV viral load and place female partners at risk of infection. We assessed the effect of MC on plasma HIV viral load in HIV-infected men in Rakai, Uganda. METHODS: 195 consenting HIV-positive, HAART naïve men aged 12 and above provided blood for plasma HIV viral load testing before surgery and weekly for six weeks and at 2 and 3 months post surgery. Data were also collected on baseline social demographic characteristics and CD4 counts. Change in log10 plasma viral load between baseline and follow-up visits was estimated using paired t tests and multivariate generalized estimating equation (GEE). RESULTS: Of the 195 men, 129 had a CD4 count ≧ 350 and 66 had CD4 <350 cells/mm3. Men with CD4 counts <350 had higher baseline mean log10 plasma viral load than those with CD4 counts ≧ 350 cells/mm3 (4.715 vs 4.217 cps/mL, respectively, p = 0.0005). Compared to baseline, there was no statistically significant increase in post-MC HIV plasma viral loads irrespective of CD4. Multivariate analysis showed that higher baseline log10 plasma viral load was significantly associated with reduction in mean log10 plasma viral load following MC (coef.  = -0.134, p<0.001). CONCLUSION: We observed no increase in plasma HIV viral load following MC in HIV-infected, HAART naïve men.

Safety of medical male circumcision in human immunodeficiency virus-infected men in Rakai, Uganda.

OBJECTIVE: To assess the safety of medical male circumcision (MMC) among human immunodeficiency virus (HIV)-infected men with CD4 levels <350 cells/mm(3), CD4 counts ≥ 350 cells/mm(3), and HIV-negative men. METHODS: Two hundred forty-two HIV-infected men and a sample of 262 HIV-negative consenting men aged 12 years or older who requested free MMC were enrolled in a prospective study. Blood for HIV testing and a CD4 count were collected before surgery. During weekly follow-up over 6 weeks, data were collected on wound healing and adverse events (AEs) by examination, and resumption of sex and condom use ascertained by interview. Surgery-related AEs were characterized by type, severity, management, and resolution. Chi-square and Fisher's exact tests were used to test for differences in AE proportions. RESULTS: Overall, only 2 of the 453 men experienced moderate AEs, a rate of 0.44 per 100 surgeries. No AE occurred among HIV-negative men, whereas the AE rate among HIV-infected men with CD4 counts ≥ 350 cells/mm(3) was 0.79 per 100 surgeries, and among men with CD4 counts <350 cells/mm(3) the rate was 1.19 per 100 surgeries (P = .214). AE rates were comparable for all characteristics (P >.05). CONCLUSION: HIV-positive men can be safely included in MMC roll out programs without necessitating presurgery CD4 counts determination.

Male circumcision wound healing in human immunodeficiency virus (HIV)-negative and HIV-positive men in Rakai, Uganda.

OBJECTIVE: To assess completed wound healing after medical male circumcision (MMC) among human immunodeficiency virus (HIV)-negative and HIV-positive men with cluster of differentiation 4 (CD4) counts of <350 and ≥350 cells/mm(3) , as minimal data are available on the safety of MMC among HIV-positive men with low CD4 counts. PATIENTS AND METHODS: In all, 262 HIV-negative and 177 HIV-positive consenting males aged ≥12 years accepted MMC using the dorsal slit procedure and were enrolled in the study. Socio-demographic and behavioural data and blood for HIV testing and CD4 counts were collected at baseline. Participants were followed weekly to collect information on resumption of sex, condom use and both self-reported and clinically assessed wound healing. The proportions healed among HIV-positive men were compared with HIV-negative men. Time to complete wound healing was assessed by Kaplan-Meier survival analysis. RESULTS: There were no statistically significant differences in the proportion of men healed by HIV status. At 4 weeks, the proportions healed were 85.9% in HIV-negative men, 77.4% in HIV-positive men with a CD4 count of ≥350 cells/mm(3) and 87.1% in HIV-positive men with a CD4 count of <350 cells/mm(3) . The median time to healing was 4 weeks and did not vary by HIV or CD4 status. All men had certified complete wound healing at 6 weeks after MMC. In all, 1.4% of HIV-positive men with a CD4 count of <350 cells/mm(3) resumed sex before healing, compared with 8.5% among HIV-positive men with a CD4 count of ≥350 cells/mm(3) (P = 0.052) and 7.8% (P = 0.081) among HIV-negative men. CONCLUSION: Inclusion of HIV-positive men with low CD4 counts in MMC services is not deleterious to postoperative wound healing.

The acceptability and safety of the Shang Ring for adult male circumcision in Rakai, Uganda.

OBJECTIVES: Medical male circumcision (MMC) is recommended for HIV prevention in men. We assessed the acceptability and safety of the Shang Ring device compared with those of the dorsal slit method. METHODS: HIV-negative, uncircumcised men aged 18 years or older who requested free MMC services in rural Rakai, Uganda, were informed about the Shang Ring and dorsal slit procedures and offered a free choice of procedure. Men were followed at 7 days postoperatively to assess adverse events related to surgery and to remove the Shang Ring. Wound healing was assessed at 4 weeks postoperatively. RESULTS: Six hundred twenty-one men were enrolled, of whom 508 (81.8%) chose the Shang Ring and 113 the dorsal slit. The Shang Ring was provided to 504 men, among whom there were 4 failures of Ring placement (0.8%) that required surgical hemostasis and wound closure. Five hundred men received the Shang Ring and postoperative surgery-related moderate adverse events were 1.0%, compared with 0.8% among dorsal slit recipients. Complete wound healing at 4 weeks was 84% with the Ring and 100% with the dorsal slit (P < 0001). Resumption of intercourse before 4 weeks was 7.0% with the Ring and 15.0% with the dorsal slit (P = 0.01.) The mean time for surgery was 6.1 minutes with the Ring and 17.7 minutes with the dorsal slit. The mean time for Ring removal was 2.2 minutes. CONCLUSIONS: The Shang Ring is highly acceptable and safe in this setting, and could improve the efficiency of MMC services. However, back-up surgical services are needed in cases of Ring placement failures.

Use of a mixture of lignocaine and bupivacaine vs lignocaine alone for male circumcision under local anaesthesia in Rakai, Uganda.

OBJECTIVE: To assess self-reported pain control during and after surgery with a mixture of lignocaine and bupivacaine compared with lignocaine alone among male circumcision (MC) service recipients in Rakai, Uganda. PATIENTS AND METHODS: The two formulations of local anaesthesia for MC were used alternatively at weekly intervals in 360 patients; 179 received lignocaine alone and 181 received the lignocaine and bupivacaine mixture (LBmix). The proportions of men reporting pain during or after surgery, and the need for additional anaesthesia during surgery were determined for the LBmix vs lignocaine using Poisson adjusted rate ratios (RRs). Characteristics including age, weight, surgeon (medical officer vs clinical officer), surgical method and duration of surgery were compared between the arms using two-sample t-tests and chi-square tests. RESULTS: Patient and provider characteristics were comparable between the two anaesthetic groups. A higher proportion of patients reported pain during surgery in the lignocaine group (adjusted RR 11.6, 95% confidence interval [CI] 3.5-37.9, P < 0.001), required additional anaesthesia (adjusted RR 4.8, 95% CI 1.4-17.1, P = 0.015), and were more likely to report pain during the immediate postoperative period (adjusted RR 3.4, 95% CI 2.3-5.0, P < 0.001). These differences were particularly marked among patients with MC times longer than the median (adjusted RR 13.4, 95% CI 3.1-57.0, P < 0.001). CONCLUSION: The LBmix significantly reduced pain associated with MC and the need for additional anaesthesia during MC.

Designing and usage of a low-cost penile model for male medical circumcision skills training in Rakai, Uganda.

OBJECTIVE: To describe the designing and usage of a locally made low-cost penile model used for male medical circumcision (MMC) skills training. MATERIAL AND METHODS: The Rakai MMC training team has experienced a number of challenges during conduct of MMC skills training, one of which was the lack of a model to use for MMC skills training. To address this challenge, the Rakai MMC skills training team has designed and developed a low-cost penile model for use in MMC skills training. RESULTS: The model has been successfully used to demonstrate external penile anatomy, to describe the biological mechanisms through which male circumcision (MC) prevents HIV acquisition, and for demonstration and practice of the MMC procedures. CONCLUSIONS: With an initial cost of only $10 and a recurrent cost of $5, this is a cost-efficient and useful penile model that provides a simulation of normal penile anatomy for use in MC training in resource-limited settings. It has also been used as a visual aid in preoperative education of patients before receiving male circumcision. The model can be improved and scaled up to develop cheaper commercial penile models.

The number of procedures required to achieve optimal competency with male circumcision: findings from a randomized trial in Rakai, Uganda.

OBJECTIVE: To assess the number of procedures required to achieve optimal competency (time required for surgery with minimal adverse events) in Rakai, Uganda, and thus facilitate the development of guidelines for training providers, as male circumcision reduces the acquisition of human immunodeficiency virus (HIV) in men and is recommended for HIV prevention. PATIENTS AND METHODS: In a randomized trial, 3011 men were circumcised, using the sleeve method, by six physicians who had completed training, which included 15-20 supervised procedures. The duration of surgery from local anaesthesia to wound closure, moderate or severe surgery-related adverse events (AEs), and wound healing were assessed in relation to the number of procedures done by each physician. RESULTS: The median age of the patients was 24 years. The number of procedures per surgeon was 20-981. The mean time required to complete surgery was approximately 40 min for the first 100 procedures and declined to 25 min for the subsequent 100 circumcisions. After controlling for the number of procedures there was no significant difference in duration of the surgery by patient HIV status or age. The rate of moderate and severe AEs was 8.8% (10/114) for the first 19 unsupervised procedures after training, 4.0% for the next 20-99 (13/328) and 2.0% for the last 100 (P for trend, 0.003). All AEs resolved with management. CONCLUSION: The completion of more than 100 circumcisions was required before newly trained physicians achieved the optimum duration of surgery. AEs were higher immediately after training and additional supervision is needed for at least the first 20 procedures after completing training.