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Background: Currently recommended boosted protease-inhibitor (bPI) regimens may be associated with increased risk of cardiovascular or chronic kidney diseases; in addition, boosted regimens are particularly associated with drug-drug interactions. Since both cardiovascular and renal disease, and polypharmacy, are common in ageing people with HIV, there is a need for alternative efficacious regimens. bPI-based regimens are often the treatment of choice for individuals with pre-treatment or treatment-acquired resistance but it is plausible that carefully selected HIV-positive individuals with drug resistance, who are virologically suppressed on their current bPI regimen, could maintain virological efficacy when switched to bictegravir, emtricitabine and tenofovir alafenamide (B/F/TAF) fixed dose combination (FDC)., Methods/design: A phase IV, investigator-initiated, multicentre, open label pilot, randomised two-arm study to assess the safety and efficacy of switching from bPI regimen to B/F/TAF single tablet regimen in integrase inhibitor-naïve, virologically suppressed adults with HIV-1 infection harbouring drug resistance mutations. Eligible individuals will either continue on their bPI regimen or switch to B/F/TAF FDC. After 24 weeks, all participants in the bPI arm will be switched to B/F/TAF and followed for a further 24 weeks and all participants will be followed for 48 weeks. The primary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24 using pure virologic response whilst the secondary efficacy endpoint is the proportion of participants with HIV-1 RNA < 50 copies/mL at Week 48. Other secondary outcome measures include between arm comparisons of drug resistance at virological failure, safety and tolerability and patient-reported outcome measures., Discussion: We aim to provide preliminary evidence of the efficacy of switching to B/F/TAF in patients with virological suppression on a bPI-based regimen who harbour select drug resistance mutations., Trial Registration: ISRCTN 44453201 , registered 19 June 2019 and EudraCT 2018-004732-30.

Background: Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial's secondary outcomes., Methods/design: A cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters., Discussion: We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability., Trial Registration: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974.

Background: Initiating therapy with a low CD4 cell count is associated with a substantially greater risk of disease progression and death than earlier initiation. We examined factors associated with late presentation of HIV using the new European consensus definition (CD4 cell count <350 cells/mm3) and mortality., Methods: Patients newly diagnosed with HIV infection at a UK clinic were recruited from January 1996 to May 2010. Factors associated with late presentation were assessed using logistic regression. Factors associated with mortality rates were analysed using Poisson regression., Results: Of the 1536 included in the analysis, 86% were male and 10% were aged 50 years and older. Half the cohort (49%) had a CD4 cell count below 350 cells/mm3 at presentation ("late presentation"). The frequency of late presentation was highest in those aged 50 years or older and remained unchanged over time (64.3% in 1996-1998 and 65.4% in 2008-2010). In contrast, among those aged less than 50 years, the proportion with late presentation decreased over time (57.1% in 1996-1998 and 38.5% in 2008-2010). Other factors associated with late presentation were African ethnicity and being a male heterosexual.The mortality rate was 15.47/1000 person-years (pyrs) (95%-CI: 13.00-18.41). When compared with younger adults, older individuals had a higher mortality, after adjusting for confounders (rate ratio (RR) = 2.87; 95%-CI: 1.88-4.40)., Conclusions: Older adults were more likely to present late and had a higher mortality. Initiatives to expand HIV testing in clinical and community setting should not neglect individuals aged over 50.