The Impact of the 2013 WHO Antiretroviral Therapy Guidelines on the Feasibility of HIV Population Prevention Trials

Background: Several cluster-randomized HIV prevention trials aim to demonstrate the population-level preventive impact of antiretroviral therapy (ART). 2013 World Health Organization (WHO) guidelines raising the ART initiation threshold to CD4 <500/µL could attenuate these trials’ effect size by increasing ART usage in control clusters. Methods: We used a computational model to simulate strategies from a hypothetical cluster-randomized HIV prevention trial. The primary model outcome was the relative reduction in 24-month HIV incidence between control (ART offered with CD4 below threshold) and intervention (ART offered to all) strategies. We assessed this incidence reduction using the revised (CD4 <500/µL) and prior (CD4 <350/µL) control ART initiation thresholds. Additionally, we evaluated changes to trial characteristics that could bolster the incidence reduction. Results: With a control ART initiation threshold of CD4 <350/µL, 24-month HIV incidence under control and intervention strategies was 2.46/100 person-years (PY) and 1.96/100 PY, a 21% reduction. Raising the threshold to CD4 <500/µL decreased the incidence reduction by more than one-third, to 12%. Using this higher threshold, moving to a 36-month horizon (vs 24-month), yearly control-strategy HIV screening (vs bian-nual), and intervention-strategy screening every 2 months (vs biannual), resulted in a 31% incidence reduction that was similar to effect size projections for ongoing trials. Alternate assumptions regarding cross-cluster contamination had the greatest influence on the incidence reduction. Conclusions: Implementing the 2013 WHO HIV treatment threshold could substantially diminish the incidence reduction in HIV population prevention trials. Alternative HIV testing frequencies and trial horizons can bolster this incidence reduction, but they could be logistically and ethically challenging. The feasibility of HIV population prevention trials should be reassessed as the implementation of treatment guidelines evolves.     

Using two on-going HIV studies to obtain clinical data from before, during and after pregnancy for HIV-positive women

ABSTRACT: BACKGROUND: The UK Collaborative HIV Cohort (UK CHIC) is an observational study that collates data on HIV-positive adults accessing HIV clinical care at (currently) 13 large clinics in the UK but does not collect pregnancy specific data. The National Study of HIV in Pregnancy and Childhood (NSHPC) collates data on HIV-positive women receiving antenatal care from every maternity unit in the UK and Ireland. Both studies collate pseudonymised data and neither dataset contains unique patient identifiers. A methodology was developed to find and match records for women reported to both studies thereby obtaining clinical and treatment data on pregnant HIV-positive women not available from either dataset alone. RESULTS: Women in UK CHIC receiving HIV-clinical care in 1996-2009, were found in the NSHPC dataset by initially 'linking' records with identical date-of-birth, linked records were then accepted as a genuine 'match', if they had further matching fields including CD4 test date. In total, 2063 women were found in both datasets, representing 23.1% of HIV-positive women with a pregnancy in the UK (n=8932). Clinical data was available in UK CHIC following most pregnancies (92.0%, 2471/2685 pregnancies starting before 2009). There was bias towards matching women with repeat pregnancies (35.9% (741/2063) of women found in both datasets had a repeat pregnancy compared to 21.9% (1502/6869) of women in NSHPC only) and matching women diagnosed before their first reported pregnancy (54.8% (1131/2063) compared to 47.7% (3278/6869), respectively). CONCLUSIONS: Through the use of demographic data and clinical dates, records from two independent studies were successfully matched, providing data not available from either study alone.     

Prevention of mother-to-child transmission of HIV infection: Ukraine experience to date

BACKGROUND: Despite the availability of effective interventions for the prevention of mother-to-child transmission (PMTCT), questions remain regarding implementation of programmes in settings with limited resources. This article sets out to describe the first 2 years of the implementation of the national PMTCT programme in Ukraine. METHODS: National data sources and data from a cohort of pregnant HIV-infected women delivering in 13 centres in Ukraine since 2000 were analysed. RESULTS: Interventions for prevention of MTCT have been implemented as a national programme within Ukraine's well developed infrastructure for maternal and child health. Implementation of an 'opt-out' model of counselling and HIV testing in antenatal clinics resulted in a 97% uptake of women who agreed to be HIV tested. In 2002, approximately 91% of HIV-positive pregnant women received ARV prophylaxis (mainly single-dose nevirapine or short-course zidovudine) for PMTCT. The MTCT rate has decreased from 30% in 2000 to 10% in 2002. The need to scale-up prevention interventions in pregnant women with risky behaviour and late access to medical services was identified in a review of the national programme in 2003. CONCLUSIONS: Further implementation of a comprehensive approach for the prevention of HIV infection in infants, including more extensive ART regimen, as recommended by WHO, would help Ukraine to achieve the strategic goal of virtual elimination of HIV infection in infants by 2010.     

Disease progression in children with vertically-acquired HIV infection in sub-Saharan Africa: reviewing the need for HIV treatment

Approximately 700,000 children become newly infected with HIV annually, mainly through mother-to-child transmission (MTCT), making paediatric HIV a leading cause of morbidity and mortality worldwide. The substantial interest in preventing MTCT (PMTCT) has generated information on rates of transmission and associated factors, but there is a lack of information on disease progression and mortality in vertically-infected children, especially from resource-poor settings. Peer-review journals with titles or abstracts containing reference to the review's themes were selected using widely available search engines. We review relevant literature on mortality in children born to HIV infected mothers; morbidity and mortality associated with paediatric HIV infections; eligibility to and efficacy of antiretroviral therapy (ART). Child mortality is independently associated with maternal HIV status and maternal death, with paediatric infection resulting in approximately 4 fold increase in mortality by age 2 years. Morbidities seen in infected children were similar to those seen in uninfected children, although the rates and recurrences of illness were greater. There is some evidence that progression to AIDS may be more rapid in resource poor settings, although data on this are very limited. PMTCT and paediatric ART have been shown to be highly successful in resource-limited settings, but are not universally applied. Further efforts to increase coverage of both PMTCT and paediatric ART could substantially reduce the numbers of children becoming infected and improve survival of those infected. Additionally, improvements in health infrastructures could improve care provision, not only through improved detection and monitoring but also through treatment of co-morbidities and nutritional support.     

The health and well-being of LGBTQ serving and ex-serving personnel: a narrative review

Abstract

The relaxation of discriminatory policies against lesbian, gay, bisexual, transgender, and queer (LGBTQ) service personnel has led to increased diversity among military populations. Given this increase, it is important to assess sexual and gender minority groups’ health and well-being in the context of military service. This narrative review assessed these outcomes in LGBTQ military personnel. The electronic databases OVID Medline, PsycInfo, and Embase were searched for papers published between January 2000 and July 2018. Thirty papers were included. In line with life course model, studies aligned with four themes: (1) mental health and well-being; (2) stigma and healthcare utilization; (3) sexual trauma; and (4) physical health. These themes highlighted that LGBTQ military personnel and veterans have poorer mental health and well-being; report more stigma and barriers to mental healthcare, which reduces uptake of accessed healthcare services; experience more sexual trauma; and have poorer physical health than heterosexual military personnel and veterans. However, there are substantial gaps in the current evidence for this population. Future research should aim to address limitations of the literature, and to ensure that data on LGBTQ personnel and veterans is collected as standard.     

The impact of the anastomotic configuration on low anterior resection syndrome 3 years after total mesorectal excision for rectal cancer: a national cohort study

Aim

After low anterior resection, the bowel can be anastomosed in different ways. It is not clear which configuration is optimal from a functional and complication point of view. The primary aim was to investigate the impact of the anastomotic configuration on bowel function evaluated by the low anterior resection syndrome (LARS) score. Secondarily, the impact on postoperative complications was evaluated.

Method

All patients who had undergone low anterior resection from 2015 to 2017 were identified in the Swedish Colorectal Cancer Registry. Three years after surgery, patients were sent an extensive questionnaire and were analysed based on anastomotic configuration (‘J-pouch/side-to-end anastomosis’ or ‘straight anastomosis’). Inverse probability weighting by propensity score was used to adjust for confounding factors.

Results

Among 892 patients, 574 (64%) responded, of whom 494 patients were analysed. After weighting, the anastomotic configuration had no significant impact on the LARS score (J-pouch/side-to-end OR 1.05, 95% confidence interval [CI] 0.82–1.34). The J-pouch/side-to-end anastomosis was significantly associated with overall postoperative complications (OR 1.43, 95% CI 1.06–1.95). No significant difference was seen regarding surgical complications (OR 1.14, 95% CI 0.78–1.66).

Conclusion

This is the first study investigating the impact of the anastomotic configuration on long-term bowel function, evaluated by the LARS score, in an unselected national cohort. Our results suggested no benefit for J-pouch/side-to-end anastomosis on long-term bowel function and postoperative complication rates. The anastomotic strategy may be based upon the anatomical conditions of the patient and surgical preference.     

COVID-19 in lung transplant recipients: an overview of the Swedish national experience

Although it is known that solid organ transplant recipients fare worse after COVID-19 infection, data on the impact of COVID-19 on clinical outcomes and allograft function in lung transplant (LTx) recipients are limited and based mainly on reports with short follow-up. In this nationwide study, all LTx recipients with COVID-19 diagnosed from 1 February 2020 to 30 April 2021 were included. The patients were followed until 1 August 2021 or death. We analysed demographics, clinical features, therapeutic management and outcomes, including lung function. Forty-seven patients were identified: median age was 59 (10–78) years, 53.1% were male, and median follow-up was 194 (23–509) days. COVID-19 was asymptomatic or mild at presentation in 48.9%. Nine patients (19.1%) were vaccinated pre-COVID infection. Two patients (4.3%) died within 28 days of testing positive, and the overall survival rate was 85.1%. The patients with asymptomatic or mild symptoms had a higher median % expected forced expiratory volume during the first second than the patients with worse symptoms (P = 0.004). LTx recipients develop the entire spectrum of COVID-19, and in addition to previously acknowledged risk factors, lower pre-COVID lung function was associated with more severe disease presentation.