Trypanosoma cruzi screening in people living with HIV in the UK.

People living with HIV (PLWH) are at higher risk of reactivation of Chagas disease, a neglected tropical disease, caused by Trypanosoma cruzi. There are no data from UK HIV clinics on the prevalence of T. cruzi. We implemented T. cruzi screening at our clinic as part of routine care for PLWH with epidemiological risk factors. Among 86 patients screened, none had positive serology: one seropositive patient was identified due to increased clinician awareness. Implementing T. cruzi screening as part of routine clinical care was feasible, though labour intensive and identified at-risk individuals.

Lessons Learned From the Implementation of a School-Based Sexual Health Education Program for Adolescent Girls in Cape Town, South Africa.

Comprehensive sexual education (CSE) is an important approach for health promotion dissemination in schools, particularly when delivered in participatory ways that are sport based, peer or near-peer led, and include concepts of gender and power dynamics. Sufficient attendance at CSE sessions is critical to ensure content exposure and build potential for impact. This article details implementation lessons from the delivery of an after-school, near-peer-led CSE program called SKILLZ during a cluster randomized controlled trial among 40 secondary schools in Cape Town, South Africa. SKILLZ is an evidence-based program previously implemented in similar contexts. Attendance in this study was suboptimal (less than 50%) despite qualitative indications of high acceptability and extensive efforts to adapt implementation and boost attendance. Qualitative and quantitative data gathered during anonymous surveys, in-depth interviews, and focus group discussions with participants with high and low attendance records, near-peer coaches, and school staff from both cohorts indicated that poor attendance could be attributed to several factors. Program adaptations, such as delivering difficult-to-access health services before participants attended the SKILLZ program rather than after, may have reduced the incentive for young people to attend the program. Practical barriers to attendance were identified, including security concerns, competing priorities, and unfamiliarity with after-school programming culture in this setting. Community engagement and acceptability of sexual education programs for adolescents alone may be insufficient to ensure program uptake and engagement.

Retrospective analysis of the biopharmaceutics characteristics of solid oral Modified-Release drug products in approved US FDA NDAs designated as Extended-Release or Delayed-Release formulations.

BACKGROUND: Modified Release (MR) orally administered drugs products [Extended-Release (ER) and Delayed-Release (DR)] differ from Immediate-Release (IR) drug products in their drug release site and/or rate to offer therapeutic advantages. It is important to understand the biopharmaceutics factors that determine how a drug works in the gastrointestinal tract and the various pharmacokinetic properties that determine a drug's rate of absorption and release in the human body. To better understand the biopharmaceutics characteristics of ER and DR drug products, this study retrospectively analyzed submissions approved by the US Food and Drug Administration (FDA), from 2001 to 2021, and their corresponding review documents. This review work is expected to enhance the readers' understanding regarding the biopharmaceutics properties that supported approval of these products' ER claims, as per 21 CFR 320.25(f), and DR claims. METHODS: A comprehensive search was conducted using the FDA's internal New Drug Application (NDA) database for ER and DR oral drug products approved between 2001 and 2021. The search yielded 87 ER applications (23 ER capsules and 64 ER tablets) and 21 DR applications (10 DR capsules, 11 DR tablets) for which electronic records were accessible. These products were analyzed for overall drug product design, dosing frequency compared to the reference (if applicable), degree of fluctuation, dissolution method, and alcohol dose-dumping. RESULTS: Out of 87 total applications for ER drug products that were assessed, 62% of the ER tablets contained a polymer matrix formulation, and hypromellose (HPMC) was used in 50% of these products. 52% of the ER capsules consisted of polymer beads while about half of the DR drug products contained a non-bead formulation with a combination of polymers. The majority of ER drug products were found to have a reduction in dosing frequency and a decrease in the degree of fluctuation when compared to the IR reference product. The 13 ER drug products that exhibited an increase in degree of fluctuation exhibited general and pharmacodynamic benefits, such as reduced dosing frequency and reduced pill burden. The majority of DR formulations were developed to prevent drug degradation in the stomach, followed by to decrease potential stomach irritation, and lastly for localized release in the colon. The majority of ER drug products had 1:1 ratios of dissolution duration compared to dosing frequency (i.e., the majority of ER drug products had a dissolution duration of 24 h and were dosed every 24 h while those with a dissolution duration of 12 h were dosed every 12 h). The majority of ER applications had single-stage dissolution methods while most DR drug products used biphasic dissolution methods. All of the DR dissolution methods incorporated an acid stage of 2 h and a buffer stage with various timeframes. 53% the DR drug products had a ratio of dissolution duration to dosing frequency of 1:4 (e.g. a dissolution duration of 2 h to a dosing frequency of 8 h) or 1:8 (e.g. a dissolution duration of 2 h to a dosing frequency of 16 h). Of the ER tablets and DR drug products, 72% exhibited no alcohol dose-dumping under in vitro testing conditions. ER capsules, however, did not yield similar results-most of which exhibited alcohol induced dose-dumping. Alcohol dose dumping was mitigated by either in vivo studies or warnings on the drug product label. CONCLUSION: The results of this study help the reader understand the design, characteristics, and pharmacological advantages of the ER and DR drug products for patient benefit; as well as the regulations governing the FDA's assessment of ER claims.

School-based healthcare services in Cape Town, South Africa: When there's a will, there's a way.

South African secondary schools do not deliver school-based healthcare services despite high rates of human immunodeficiency virus (HIV) infection, sexually transmitted infections, and unplanned pregnancies among adolescents, ongoing sub-optimal uptake of healthcare services from public healthcare facilities by adolescents, and national policy support for such services. A pilot school health nursing programme (SHNP) was offered to 44 secondary schools in a single health sub-district within the Western Cape, South Africa. The programme included fortnightly nurse visits that offered a standard package of healthcare services, including sexual and reproductive health services tailored according to school preference.Of the 44 schools, 42 gave permission for the SHNP to operate, with the majority of schools selecting the full comprehensive package of services. Programme implementation was truncated such that delivery only occurred over two school terms (20 weeks); however, 344 students attended the service. The majority of service users were female with a median age of 16 years, and over a half attended the service for sexual and reproductive health services.Contribution: A key challenge to school-based health service delivery arose from inadequate stakeholder support and differential views of adolescent healthcare needs among government officials, parents, guardians, school staff and governing bodies. These findings motivate for ongoing multi-level stakeholder engagement around the reality of adolescent healthcare needs and further opportunities to deliver school health services for longer time periods such that their feasibility, acceptability, and potential to impact healthcare outcomes can be assessed in this setting.

Preferences for oral PrEP dosing among adolescent boys and young men in three sub-Saharan African countries.

BACKGROUND: HIV remains a leading contributor to the disease burden in sub-Saharan Africa, with adolescents and young people disproportionately affected. Optimising pre-exposure prophylaxis (PrEP) uptake has predominantly focused on women and adult men who have sex with men. We explore adolescent boys and young men's PrEP uptake preferences in South Africa, Uganda, and Zimbabwe. METHODS: A cross-sectional sequential exploratory mixed-methods study amongst males aged 13-24 years was conducted between April and September 2019 as part of the CHAPS trial. Group discussions (GDs) and In-Depth Interviews (IDIs) focused on motivations and hindrances for HIV testing, PrEP preference, and reasons for the uptake of PrEP. A thematic approach was used to analyse the qualitative data. A quantitative survey following the qualitative work covered questions on demographics, HIV risk and PrEP preferences (on-demand vs. daily). For quantitative analysis, we fitted logistic regression models to determine factors associated with on-demand vs daily PrEP preference. RESULTS: Overall, 647 adolescent boys and young men (median age 20, IQR: 17-22) were enrolled. Of these, 422 (65.22%) preferred on-demand PrEP (South Africa 45.45%, Uganda 76.80%, Zimbabwe 70.35%; p<0.001). Factors independently associated with on-demand PrEP included country (South Africa, adjusted odds ratio (aOR) = 0.19 [95%CI:0.1-0.3] compared to Uganda) and advanced planning of sex [>24 hours in advance aOR = 1.4 (0.9-2.3) compared to <2 hours]. Qualitatively, participants commonly believed they were not at risk of HIV acquisition most of the time and thought that on-demand PrEP would be suitable as they tend to plan sexual activity in advance. CONCLUSION: Preference for on-demand PrEP is high in young males. The qualitative data support a preference for on-demand PrEP in those who plan sex in advance. HIV intervention programs should offer both on-demand and daily PrEP to engage more adolescent boys and young men in HIV prevention practices.

Effective prolonged suppression of HIV-1 viral load using tenofovir alafenamide, emtricitabine and efavirenz in an adult with BMI >59 kg/m2.

Limited information is available regarding the efficacy of antiretrovirals in people with HIV-1 and high or very high Body Mass Index (BMI). This is especially the case for the alafenamide salt of tenofovir as clinical trials have only enrolled patients with BMI ≤30 kg/m2. Lower concentrations of some antiretrovirals are expected in patients with BMI >30 kg/m2 due to potential changes in clearance and distribution of medication. This report describes an individual taking tenofovir alafenamide, emtricitabine and efavirenz in whom HIV-1 viral load was consistently undetectable (<50 copies/ml) over a 2.5 year period. During this period the patient's BMI ranged between 59.8 and 68.1 kg/m2. Further data is required to support the efficacy of antiretrovirals in individuals with high and very high BMI.

Escherichia coli DNA repair helicase Lhr is also a uracil-DNA glycosylase.

DNA glycosylases protect genetic fidelity during DNA replication by removing potentially mutagenic chemically damaged DNA bases. Bacterial Lhr proteins are well-characterized DNA repair helicases that are fused to additional 600-700 amino acids of unknown function, but with structural homology to SecB chaperones and AlkZ DNA glycosylases. Here, we identify that Escherichia coli Lhr is a uracil-DNA glycosylase (UDG) that depends on an active site aspartic acid residue. We show that the Lhr DNA helicase activity is functionally independent of the UDG activity, but that the helicase domains are required for fully active UDG activity. Consistent with UDG activity, deletion of lhr from the E. coli chromosome sensitized cells to oxidative stress that triggers cytosine deamination to uracil. The ability of Lhr to translocate single-stranded DNA and remove uracil bases suggests a surveillance role to seek and remove potentially mutagenic base changes during replication stress.

A qualitative study to explore daily versus on-demand oral pre-exposure prophylaxis (PrEP) in young people from South Africa, Uganda and Zimbabwe.

BACKGROUND: Adolescents in sub-Saharan Africa (SSA) remain vulnerable to HIV infection. While pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV transmission as a daily or on-demand regimen, tailored approaches are necessary. The Combined HIV Adolescent PrEP and Prevention Study (CHAPS) is a mixed-methods research program investigating the acceptability and feasibility of implementing daily and on-demand PrEP among young people in SSA. It also aims to determine an on-demand dosing schedule for insertive sex. For this paper, we explored preferences for daily versus on-demand PrEP amongst adolescents as part of CHAPS. METHODS: Purposive sampling was used to recruit participants from Soweto and Cape Town (South Africa), Wakiso district (Uganda) and Chitungwiza (Zimbabwe). At the time of the study in 2018/2019, Uganda had not rolled out PrEP to the general population; in Zimbabwe, PrEP for young people was only available at selected sites with one located within the study recruitment area. In South Africa, PrEP was made available to selected high-risk groups. We conducted 60 in-depth interviews and 24 group discussions amongst young people aged 13-24 without HIV in South Africa, Uganda, and Zimbabwe. All in-depth interviews and group discussions were audio-recorded, transcribed verbatim and translated to English. Data were analysed using framework analysis. The main themes were centered around preferences for daily and on-demand PrEP. RESULTS: Reasons for on-demand preferences included stigma, pill fatigue, adherence and side effects. Reasons for daily PrEP preferences included factors related to sexual risk behaviour, continuous protection against incidents of unintentional exposure, and the increased efficacy of a daily dose. Participants at all sites preferring daily PrEP identified the same reasons, with more males than females citing inadvertent blood contact or perceived increased efficacy. Similarly, participants at all sites preferring on-demand PrEP gave the same reasons for their preferences for on-demand PrEP; the exception was South Africans who did not mention the hope of having fewer side effects by not taking daily PrEP. Additionally, more males than females cited intermittent sex as a reason for opting for on-demand PrEP. CONCLUSIONS: Our study is the first known to explore and describe youth preferences for daily versus on-demand PrEP. While the choice is clear-cut, the reasons cited in the different options provide invaluable insights into their decisions, and the actual and perceived facilitators and barriers to access to PrEP. Further education is needed amongst young people, not only about PrEP but also in other areas of comprehensive sexuality education. Exploring all options of HIV prevention is crucial to provide a tailored, one-size-does-not-fit-all approach to adolescent care in SSA to reduce and, the continued and increasing risk of this preventable infection.