Implementation of Adolescent-Friendly Voluntary Medical Male Circumcision Using a School Based Recruitment Program in Rural KwaZulu-Natal, South Africa

Background: Epidemiological data from South Africa demonstrate that risk of human immunodeficiency virus (HIV) infection in males increases dramatically after adolescence. Targeting adolescent HIV-negative males may be an efficient and cost-effective means of maximising the established HIV prevention benefits of voluntary medical male circumcision (VMMC) in high HIV prevalence–, low circumcision practice–settings. This study assessed the feasibility of recruiting male high school students for VMMC in such a setting in rural KwaZulu-Natal. Methods and Findings: Following community and key stakeholder consultations on the acceptability of VMMC recruitment through schools, information and awareness raising sessions were held in 42 high schools in Vulindlela. A three-phase VMMC demand-creation strategy was implemented in partnership with a local non-governmental organization, ZimnadiZonke, that involved: (i) community consultation and engagement; (ii) in-school VMMC awareness sessions and centralized HIV counselling and testing (HCT) service access; and (iii) peer recruitment and decentralized HCT service access. Transport was provided for volunteers to the Centre for the AIDS Programme of Research in South Africa (CAPRISA) clinic where the forceps-guided VMMC procedure was performed on consenting HIV-negative males. HIV infected volunteers were referred to further care either at the CAPRISA clinic or at public sector clinics. Between March 2011 and February 2013, a total of 5165 circumcisions were performed, the majority (71%) in males aged between 15 and 19 years. Demand-creation strategies were associated with an over five-fold increase in VMMC uptake from an average of 58 procedures/month in initial community engagement phases, to an average of 308 procedures/month on initiation of the peer recruitment–decentralized service phase. Post-operative adverse events were rare (1.2%), mostly minor and self-resolving. Conclusions: Optimizing a high volume, adolescent-targeted VMMC program was feasible, acceptable and safe in this setting. Adaptive demand-creation strategies are required to sustain high uptake

Factors associated with the take-up of voluntary medical male circumcision amongst learners in rural KwaZulu-Natal.

CAPRISA, 2017.Abstract available in pdf

Early resumption of sex following voluntary medical male circumcision amongst school-going males.

CAPRISA, 2016.Abstract available in pdf

Meeting the sexual and reproductive health needs of high-school students in South Africa: experiences from rural KwaZulu-Natal.

CAPRISA, 2014.Abstract available in pdf

Assessing the implementation effectiveness and safety of 1% tenofovir gel provision through family planning services in KwaZulu-Natal, South Africa: protocol for an open-label randomized controlled trial

The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial demonstrated a 39% reduction in HIV infection, with a 54% HIV reduction in women who used tenofovir gel consistently. A confirmatory trial is expected to report results in early 2015. In the interim, we have a unique window of opportunity to prepare for and devise effective strategies for the future policy and programmatic scale-up of tenofovir gel provision. One approach is to integrate tenofovir gel provision into family planning (FP) services. The CAPRISA 008 implementation trial provides an opportunity to provide post-trial access to tenofovir gel while generating empiric evidence to assess whether integrating tenofovir gel provision into routine FP services can achieve similar levels of adherence as the CAPRISA 004 trial. This is a two-arm, open-label, randomized controlled non-inferiority trial. A maximum of 700 sexually active, HIV-uninfected women aged 18 years and older who previously participated in an antiretroviral prevention study will be enrolled from an urban and rural site in KwaZulu-Natal, South Africa. The anticipated study duration is 30 months, with active accrual requiring approximately 12 months (following which an open cohort will be maintained) and follow-up continuing for approximately 18 months. At each of the two sites, eligible participants will be randomly assigned to receive tenofovir gel through either FP services (intervention arm) or through the CAPRISA research clinics (control arm). As part of the study intervention, a quality improvement approach will be used to assist the FP services to expand their current services to include tenofovir gel provision. This protocol aims to address an important implementation question on whether FP services are able to effectively incorporate tenofovir gel provision for this at-risk group of women in South Africa. Provision of tenofovir gel to the women from the CAPRISA 004 trial meets the ethical obligation for post-trial access, and helps identify a potential avenue for future scale-up of microbicides within the public health system of South Africa. This trial was registered with the South Africa Department of Health (reference: DOH-27-0812-4129) and ClinicalTrials.gov (reference: NCT01691768) on 05 July 2012

Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial

IMPORTANCE Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. OBJECTIVE To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. INTERVENTIONS Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200mg (n = 588), or placebo (n = 587). MAIN OUTCOMES AND MEASURES The primary outcomewas incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase–polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. RESULTS The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5%vs 15.2%; odds ratio, 0.43 [95%CI, 0.28-0.68]; P < .001; absolute risk difference, −6.6 [95%CI, −10.7 to −2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). CONCLUSIONS AND RELEVANCE Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Assessing the implementation effectiveness and safety of 1% tenofovir gel provision through family planning services in KwaZulu-Natal, South Africa: study protocol for an open-label randomized controlled trial.

CAPRISA, 2014.Background: The Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial demonstrated a 39% reduction in HIV infection, with a 54% HIV reduction in women who used tenofovir gel consistently. A confirmatory trial is expected to report results in early 2015. In the interim, we have a unique window of opportunity to prepare for and devise effective strategies for the future policy and programmatic scale-up of tenofovir gel provision. One approach is to integrate tenofovir gel provision into family planning (FP) services. The CAPRISA 008 implementation trial provides an opportunity to provide post-trial access to tenofovir gel while generating empiric evidence to assess whether integrating tenofovir gel provision into routine FP services can achieve similar levels of adherence as the CAPRISA 004 trial. Methods/design: This is a two-arm, open-label, randomized controlled non-inferiority trial. A maximum of 700 sexually active, HIV-uninfected women aged 18 years and older who previously participated in an antiretroviral prevention study will be enrolled from an urban and rural site in KwaZulu-Natal, South Africa. The anticipated study duration is 30 months, with active accrual requiring approximately 12 months (following which an open cohort will be maintained) and follow-up continuing for approximately 18 months. At each of the two sites, eligible participants will be randomly assigned to receive tenofovir gel through either FP services (intervention arm) or through the CAPRISA research clinics (control arm). As part of the study intervention, a quality improvement approach will be used to assist the FP services to expand their current services to include tenofovir gel provision. Discussion: This protocol aims to address an important implementation question on whether FP services are able to effectively incorporate tenofovir gel provision for this at-risk group of women in South Africa. Provision of tenofovir gel to the women from the CAPRISA 004 trial meets the ethical obligation for post-trial access, and helps identify a potential avenue for future scale-up of microbicides within the public health system of South Africa. Trial registration: This trial was registered with the South Africa Department of Health (reference: DOH-27-0812-4129) and ClinicalTrials.gov (reference: NCT01691768) on 05 July 2012

Early Resumption of Sex following Voluntary Medical Male Circumcision amongst School-Going Males.

Voluntary medical male circumcision is an integral part of the South African government's response to the HIV and AIDS epidemic. Following circumcision, it is recommended that patients abstain from sexual activity for six weeks, as sex may increase the risk of female-to-male HIV transmission and prolong the healing period. This paper investigates the resumption of sexual activity during the healing period among a cohort of school-going males in the KwaZulu-Natal province of South Africa. The analysis for this paper compares two groups of sexually active school-going males: the first group reported having sex during the healing period (n = 40) and the second group (n = 98) reported no sex during the healing period (mean age: 17.7, SD: 1.7).The results show that 29% (n = 40) of young males (mean age: 17.9, SD: 1.8) who were previously sexually active, resumed sexual activity during the healing period, had on average two partners and used condoms inconsistently. In addition, those males that engage in sexual activity during the healing period were less inclined to practice safe sex in the future (AOR = 0.055, p = 0.002) than the group of males who reported no sex during the healing period. These findings suggest that a significant proportion of young males may currently and in the future, subject themselves to high levels of risk for contracting HIV post circumcision. Education, as part of a VMMC campaign, must emphasize the high risk of HIV transmission for both the males their partners during the healing period

Solid state and subcooled liquid vapour pressures of cyclic aliphatic dicarboxylic acids

Knudsen Effusion Mass Spectrometry (KEMS) has been used to measure for the first time the solid state vapour pressures of a series of aliphatic cyclic dicarboxylic acids with increasing ring size. Additionally the atmospherically important compounds; &lt;i&gt;cis&lt;/i&gt;-pinonic acid and levoglucosan were also measured. Differential Scanning Calorimetry (DSC) was used to measure melting points, enthalpies and entropies of fusion, which were used to determine sub-cooled liquid vapour pressures for the compounds. The sub-cooled liquid vapour pressure of straight chain, branched and cyclic dicarboxylic acids was compared to a selection of estimation methods