Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women.

BACKGROUND: There are gaps in uptake of, adherence to, and persistence in the use of preexposure prophylaxis for human immunodeficiency virus (HIV) prevention among cisgender women. METHODS: We conducted a phase 3, double-blind, randomized, controlled trial involving adolescent girls and young women in South Africa and Uganda. Participants were assigned in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine-tenofovir alafenamide (F/TAF), or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF; active control); all participants also received the alternate subcutaneous or oral placebo. We assessed the efficacy of lenacapavir and F/TAF by comparing the incidence of HIV infection with the estimated background incidence in the screened population and evaluated relative efficacy as compared with F/TDF. RESULTS: Among 5338 participants who were initially HIV-negative, 55 incident HIV infections were observed: 0 infections among 2134 participants in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI], 0.00 to 0.19), 39 infections among 2136 participants in the F/TAF group (2.02 per 100 person-years; 95% CI, 1.44 to 2.76), and 16 infections among 1068 participants in the F/TDF group (1.69 per 100 person-years; 95% CI, 0.96 to 2.74). Background HIV incidence in the screened population (8094 participants) was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). HIV incidence with lenacapavir was significantly lower than background HIV incidence (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.04; P<0.001) and than HIV incidence with F/TDF (incidence rate ratio, 0.00; 95% CI, 0.00 to 0.10; P<0.001). HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio, 0.84; 95% CI, 0.55 to 1.28; P = 0.21), and no evidence of a meaningful difference in HIV incidence was observed between F/TAF and F/TDF (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). Adherence to F/TAF and F/TDF was low. No safety concerns were found. Injection-site reactions were more common in the lenacapavir group (68.8%) than in the placebo injection group (F/TAF and F/TDF combined) (34.9%); 4 participants in the lenacapavir group (0.2%) discontinued the trial regimen owing to injection-site reactions. CONCLUSIONS: No participants receiving twice-yearly lenacapavir acquired HIV infection. HIV incidence with lenacapavir was significantly lower than background HIV incidence and HIV incidence with F/TDF. (Funded by Gilead Sciences; PURPOSE 1 ClinicalTrials.gov number, NCT04994509.).

Complications of high volume circumcision: glans amputation in adolescents; a case report.

BACKGROUND: The past four years has seen a rapid roll-out of male medical circumcision services in South Africa in response to clinical trials showing circumcision prevents HIV acquisition in heterosexual men. Clinics conduct substantial numbers of circumcisions per day. We report three cases of glans amputation in adolescents attending high volume clinics where modified Models of Optimising Volume and Efficiency (MOVE) are implemented. CASE PRESENTATIONS: Three cases of glans amputation in young healthy men that presented for voluntary medical male circumcision. The procedures were performed by highly experienced medical officers in two cases. All these cases shared characteristics: younger males with immature genitalia, forceps guided circumcision, and likely operator fatigue. Voluntary male medical circumcision programs should include regular monitoring and evaluation and training of operators to ensure high quality surgical techniques such as working in clean areas and taking frequent breaks. CONCLUSION: Circumcision is a relatively simple medical procedure, however regular training and quality control in high volume Male Medical Circumcision sites is essential to prevent rare catastrophic adverse events.

Voluntary medical male circumcision (VMMC) for prevention of heterosexual transmission of HIV and risk compensation in adult males in Soweto: Findings from a programmatic setting.

BACKGROUND: Clinical trials have clearly shown a reduction in HIV acquisition through voluntary medical male circumcision (VMMC). However, data assessing risk compensation under programmatic conditions is limited. METHODS: This was a prospective cohort of HIV seronegative males aged 18-40 years receiving VMMC between November 2012 and July 2014. HIV serostatus was determined pre and post VMMC. Risk compensation was defined as a decrease in condom use at last sex act and/or an increase in concurrent sexual relationships, both measured twelve months post-circumcision. RESULTS: A total of 233 males were enrolled and underwent voluntary medical male circumcision (VMMC) for prevention against HIV. There was no evidence of risk compensation post-circumcision as defined in this study. Significant increases in proportion of participants in the 18-24 years age group who knew the HIV status of their sexual partner (39% to 56%, p = 0.0019), self-reported condom use at last sex act (21% to 34%, p = 0.0106) and those reporting vaginal sexual intercourse in the past 12 months (67% to 79%, p-value = <0.0001) were found. In both 18-24 and 25-40 years age groups, there was a significant increase in perception of being at risk of contracting HIV (70% to 84%, p-value = <0.0001). CONCLUSION: No significant risk compensation was observed in this study on comparing pre-and post-circumcision behaviour. An increase in proportion of participants in the 18-24 years age group who had vaginal intercourse in the first 12 months post-circumcision as a possibility of risk compensation was minimal and negated by an increase in proportion of those reporting using a condom at the last sex act, increase in knowledge of partner's HIV status and lack of increase in alcohol post-circumcision.

PrePex circumcision surveillance: Adverse events and analgesia for device removal.

BACKGROUND: The PrePex medical male circumcision (MMC) device is relatively easy to place and remove with some training. PrePex has been evaluated in several countries to assess feasibility and acceptability. However, several studies have reported pain associated with removal. OBJECTIVE: To assess safety of PrePex and whether analgesia administered prior to removal reduces pain experienced by participants. METHODS: A multi-site non-randomized, prospective cohort study in which adult (18-45 years old) males requesting PrePex device male circumcision, were enrolled in six South African clinics from July 2014 to March 2015. Participants were routinely provided with analgesia shortly after the surveillance commenced following a protocol review. Analgesia regimen for device removal depended on medication availability at clinics. RESULTS: Of 1023 enrolled participants who had PrePex placed, 98% (1004) had the device removed at a study clinic. Their median age was 25 (IQR: 21-30) years. HIV sero-positivity was 3.6% (37/1023). Nurses placed and removed half of all devices. Adverse events were experienced by 2.4% (25/1023) of participants; 15 required surgical intervention: device displacement (5/14), early removals (3/14), self-removals (5/14) and insufficient skin removed (2/14). Majority (792: 79%) of participants received analgesia. Most received either paracetamol-codeine (33%), lidocaine (29%) or EMLA and Oral Combination (28%). A lower proportion of participants who received any analgesia (except for lidocaine) prior to PrePex removal experienced severe pain compared to those who received no analgesia (16.6% vs. 29%: p = 0.0001). CONCLUSION: Reported adverse events during this PrePex active surveillance were similar to previous reports and to those of surgical circumcision. Pain medication provided prior to removal is effective at decreasing severe pain during PrePex device removal.

A Cross Sectional Study of the Prevalence of Preputial and Penile Scrotal Abnormalities among Clients Undergoing Voluntary Medical Male Circumcision in Soweto, South Africa.

OBJECTIVE: Medical device use is currently approved for males without preputial or major penile scrotal abnormalities for voluntary medical male circumcision (VMMC). We determined the prevalence of preputial abnormalities at a busy VMMC centre in Soweto, South Africa. METHODS: This was a cross-sectional record review at a high-volume VMMC centre in South Africa. We collated pre-circumcision demographic and genital examination findings from clients 8 years and older who had undergone VMMC from 01 May 2013 to 30 April 2014. Logistic regression was used to determine factors associated with preputial abnormalities. FINDINGS: During the review period, 6861 circumcisions were conducted and 37.1% (n = 2543) were 8-13 year olds. Median age was 15 years (IQR: 12-23 years). Fifteen percent (n = 1030) had preputial abnormalities or major penile scrotal abnormalities. Age-specific prevalence of preputial or major genital abnormalities were 27.3%, 10.6% and 6.0% in 8-13, 14-18 and > 18 year olds respectively. The odds of preputial or major penile scrotal abnormality were higher in younger clients aged 8-13 years (OR = 5.9; 95% CI = 4.8-7.1) and 14-18 years (OR = 1.9; 95% CI = 1.5-2.4) compared to older clients above18 years and in those testing for HIV outside our clinic network (OR = 1.9; 95% CI = 1.4-2.7). CONCLUSION: The high prevalence of preputial and penile scrotal abnormalities observed suggests a need for VMMC sites to provide for both open surgical and devices methods in the provision of VMMC services. This is especially so among young male subjects presenting themselves for VMMC services at the various sites being developed in sub Saharan African countries.

Piloting PrePex for Adult and Adolescent Male Circumcision in South Africa--Pain Is an Issue.

BACKGROUND: The World Health Organisation and the Joint United Nations Programme on HIV/AIDS have recommended the scale-up of Medical Male Circumcision (MMC) in countries with high HIV and low MMC prevalence. PrePex device circumcision is proposed as an alternate method for scaling up MMC. OBJECTIVE: Evaluate safety and feasibility of PrePex in South Africa. DESIGN: A multisite prospective cohort PrePex study in adults and adolescents at three MMC clinics. Participants were followed-up 8 times, up to 56 days after PrePex placement. RESULTS: In total, 398 PrePex circumcisions were performed (315 adults and 83 adolescents) their median ages were 26 (IQR: 22-30) and 16 years (IQR: 15-17), respectively. The median time for device placement across both groups was 6 minutes (IQR: 5-9) with the leading PrePex sizes being B (30%) and C (35%) for adults (18-45 years), and A (31%) and B (38%) for adolescents (14-17 years). Additional sizes (size 12-20) were rarely used, even in the younger age group. Pain of device application was minimal but that of removal was severe. However, described pain abated rapidly and almost no pain was reported 1 hour after removal. The Adverse Events rate were experienced by 2.7% (11/398) of all participants, three of which were serious (2 displacements and 1 self-removal requiring prompt surgery). None of the Adverse Events required hospitalization. The majority of participants returned to work within a day of device placement. CONCLUSION: Our study shows that PrePex is a safe MMC method, for males 14 years and above. PrePex circumcision had a similar adverse event rate to that reported for surgical MMC, but device removal caused high levels of pain, which subsided rapidly.