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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. [ABSTRACT FROM AUTHOR]

The article offers information on the guidelines from the British HIV Association concerning the use of antiretroviral therapy for the treatment of adults with HIV-1 positive in 2015. Topics discussed include the areas of treatment and care identified by the guidelines, the factors affecting the outcomes of treatment and adverse effects, and the direct impact of the socio-economic status of an individual on adherence.

The table of contents for the October 2014 issue of "HIV Medicine" is presented.

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. [ABSTRACT FROM AUTHOR]

The article discusses the British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy (HAART) 2012. It includes guidance on initiation of ART in those previously naive to therapy; support of patients on treatment; management of patients experiencing virological failure; and recommendations in specific patient populations. They are aimed at clinical professionals directly involved with the care of adults with HIV infection and at community advocates.

The article presents treatment of HIV-1-positive adults with antiretroviral therapy guidelines, by British HIV Association (BHIVA) for the year 2012. It discusses its developmental process highlighting "Grading of Recommendations Assessment, Development and Evaluation (GRADE) system adopted by BHIVA. Offers recommendations on several conditions, including, patient involvement in decision making, Chronic infection, and Supporting patients on therapy.

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. [ABSTRACT FROM AUTHOR]

Concern has been expressed that tenofovir-containing regimens may have reduced effectiveness in the treatment of human immunodeficiency virus type 1 (HIV-1) subtype C infections because of a propensity for these viruses to develop a key tenofovir-associated resistance mutation. We evaluated whether subtype influenced rates of virological failure in a cohort of 8746 patients from the United Kingdom who received a standard tenofovir-containing first-line regimen and were followed for a median of 3.3 years. In unadjusted analyses, the rate of failure was approximately 2-fold higher among patients infected with subtype C virus as compared to those with subtype B virus (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.50-2.31; P < .001). However, the increased risk was greatly attenuated in analyses adjusting for demographic and clinical factors (adjusted HR, 1.14; 95% CI, .83-1.58; P = .41). There were no differences between subtypes C and subtypes non-B and non-C in either univariate or multivariate analysis. These observations imply there is no intrinsic effect of viral subtype on the efficacy of tenofovir-containing regimens. [ABSTRACT FROM AUTHOR]

The article presents guidelines given by the British HIV Association (BHIVA) on best clinical practice for antiretroviral therapy (ART) and management of adults living with human immunodeficiency virus (HIV). Topics discussed include involvement of people living with HIV, primary aim of ART, and considerations when managing people with spontaneous HIV viral control.

Objectives: Chemsex has been reported among men who have sex with men (MSM) living with HIV. There have been concerns about potentially harmful drug–drug interactions between chemsex drugs and antiretroviral therapy (ritonavir and cobicistat). We aimed to describe the prevalence and patterns of chemsex users in our HIV clinic population and to evaluate antiretroviral prescribing among chemsex users. Methods: We undertook a cross‐sectional study of patients attending our HIV clinic between January 2019 and December 2020. We collected data on patients who disclosed recent recreational drug use including chemsex in the previous 3 months. Results: In all, 2202/2501 (88%) patients were asked about recreational drug use and 514 (23%) disclosed recreational drug use. Eighty‐two (4%) of these disclosed recent chemsex; 73 (89%) used crystal methamphetamine, 51 (62%) used gamma‐hydroxybutyrate (GHB)/gamma‐butyrolactone (GBL), 55 (67%) reported poly‐drug use and 63 (76%) reported injecting drug use. The chemsex users were all cis‐male MSM and were significantly older (53 vs. 46 years, p < 0.0001), and more likely to have had previous syphilis (73% vs. 28%, p < 0.0001) than patients reporting non‐chemsex drug use. All chemsex users were prescribed antiretrovirals and 74 (90%) had an undetectable HIV viral load; 31 (38%) patients were taking either ritonavir (N = 12) or cobicistat (N = 19) as part of their antiretroviral regimen and this was similar to other patients attending for HIV care [31/82 (38%) vs. 768/2419 (31%), p = 0.25]. Conclusions: The prevalence of chemsex users among our HIV clinic attendants is 4%, and 38% of these were prescribed either ritonavir or cobicistat. Chemsex use should be a factor in antiretroviral therapy decision‐making to avoid potential harm. [ABSTRACT FROM AUTHOR]

Objectives: To describe the impact that the COVID‐19 pandemic has had on HIV testing in Brighton and Hove, United Kingdom. Methods: All HIV tests performed in Brighton and Hove from January 2016 to June 2021 were extracted, de‐duplicated and anonymized. Analysis was performed to compare the monthly numbers of tests and diagnoses before and during the pandemic across different services. Results: The number of patients having tests for HIV in sexual health services (SHS) decreased by 64% in April 2020, followed by a recovery to baseline levels by the start of 2021. Similarly, the monthly number of diagnoses decreased drastically after April 2020, with almost half of diagnoses made by SHS in 2020 occurring in the three pre‐pandemic months of the year. 'Self‐sampling', used more by women and younger patients, has contributed significantly to the recovery. The number of patients tested in secondary care was seemingly unaffected by the pandemic. However, testing numbers were reduced in specialist services, whereas in the emergency department (ED) testing increased four‐fold (most notably in the elderly) without finding any cases. General practice saw decreases in both the number of HIV tests performed and the number of new diagnoses made, which had not returned to baseline by June 2021. Discussion: The COVID‐19 pandemic has had a large impact on the number of HIV tests performed in Brighton and Hove with sizeable decreases in the number of patients tested likely leading to 'missed' diagnoses. By June 2021 testing had still not returned to normal across the city. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. Methods: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV‐1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. Results: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71–0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73–1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80–1.19) amongst those on tenofovir‐containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54–0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64–1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34–1.11). Conclusions: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir. [ABSTRACT FROM AUTHOR]

HIV is a global pandemic. However, anti-retroviral therapy has transformed the prognosis and, providing compliance is good, a normal life expectancy can be anticipated. This has led to increasing numbers of people with chronic prevalent, treated infection living to older ages. Musculoskeletal pain is commonly reported by HIV patients and, with resumption of near-normal immune function, HIV-infected patients develop inflammatory rheumatic diseases that require assessment and management in rheumatology clinics. Moreover, it is becoming apparent that avascular necrosis and osteoporosis are common comorbidities of HIV. This review will contextualize the prevalence of musculoskeletal symptoms in HIV, informed by data from a UK-based clinic, and will discuss the management of active inflammatory rheumatic diseases among HIV-infected patients taking anti-retroviral therapy, highlighting known drug interactions. [ABSTRACT FROM AUTHOR]

Objectives: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis.Patients and methods: We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs.Results: Subtype B patients ( n  =   3410) were mostly MSM (78%) and those with subtype C ( n  =   810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55-2.62, P  <   0.001).Conclusions: Patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. The exact clinical implications of this finding need to be further elucidated. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir.Methods: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large European databases. HIV-1 subtype B-infected patients were used as the derivation dataset and HIV-1 non-B-infected patients were used as the validation dataset. The adjusted association of each mutation with week 8 HIV RNA change from baseline was analysed by linear regression. A prediction model was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0).Results: TCEs were selected from 681 subtype B-infected and 199 non-B-infected adults. Accompanying drugs were NRTIs in 87%, NNRTIs in 27% and raltegravir or maraviroc or enfuvirtide in 53%. The prediction model included weighted protease mutations, HIV RNA, CD4 and activity of accompanying drugs. The model's association with week 8 HIV RNA change in the subtype B (derivation) set was R(2) = 0.47 [average squared error (ASE) = 0.67, P < 10(-6)]; in the non-B (validation) set, ASE was 0.91. Accuracy investigated by means of area under the receiver operating characteristic curves with a binary response (above the threshold value of HIV RNA reduction) showed that our final model outperformed models with existing interpretation systems in both training and validation sets.Conclusions: A model with a new darunavir-weighted mutation score outperformed existing GISs in both B and non-B subtypes in predicting virological response to darunavir. [ABSTRACT FROM AUTHOR]

The article presents the guidelines of the British HIV Association (BHA) for HIV-associated malignancies in 2014. Topics discussed include the diagnosis, prognosis, and management of malignancies such as systemic AIDS-related non-Hodgkin lymphoma (ARL), cervical intraepithelial neoplasia (CIN) and cervical cancer, and non-small cell lung cancer.