BHIVA guidelines on antiretroviral treatment for adults living with HIV‐1 2022
2022; Wiley; Volume: 23; Issue: S5 Linguagem: Inglês
10.1111/hiv.13446
ISSN1468-1293
AutoresLaura Waters, Alan Winston, Iain Reeves, Marta Boffito, Duncan Churchill, Ben Cromarty, David Dunn, Douglas Fink, Sarah Fidler, Caroline Foster, Julie Fox, Ravi Gupta, Andy Hilton, Saye Khoo, Clifford Leen, Nicola Mackie, Nadia Naous, Daisy Ogbonmwan, Chloe Orkin, L. B. Panton, Frank Post, Anton Pozniak, Caroline Sabin, John Walsh,
Tópico(s)HIV Research and Treatment
ResumoContents 1 Introduction7 1.1 Scope and purpose7 1.2 Methodology7 1.2.1 Guideline development process7 1.2.2 Involvement of people living with HIV8 1.2.3 GRADE8 1.2.4 Good practice points9 1.2.5 Dissemination and implementation9 1.2.6 Guideline updates and date of next review9 1.3 Treatment aims9 1.4 Resource use9 1.5 Implications for research10 1.6 References10 2 Summary of recommendations11 3 Active involvement of people living with HIV in decision-making11 4 When to start11 4.1 Established infection11 4.2 Same-day ART initiation11 4.3 Individuals presenting with AIDS or a major infection12 4.4 Treatment of primary HIV infection12 4.5 Impact of treatment on prevention of onward transmission12 4.6 Persons choosing not to commence ART12 4.7 Considerations when managing people with spontaneous HIV viral control12 4.8 Stopping therapy12 5 What to start12 5.5 What to start in the context of TDR13 5.6 What to start in the context of rapid ART initiation13 5.7 What to start in the context of very high viral load13 5.9 Switching ART in virological suppression13 5.10 Suppressed switch or maintenance14 5.11 Two-drug oral regimens: switching in virological suppression15 5.12 Two-drug injectable regimens: switching in virological suppression15 5.13 PI monotherapy16 6 Supporting individuals on therapy16 6.1 Adherence16 6.2 Pharmacology16 7 Managing virological failure17 7.2 Blips17 7.3 Low-level viraemia on ART17 7.4 Virological failure on ART17 7.5 Individuals with no or limited drug resistance17 7.6 Individuals with multi-class virological failure with or without extensive drug resistance17 7.7 Individuals with limited or no therapeutic options when a fully viral suppressive regimen cannot be constructed17 8 Specific populations18 8.1 Adolescents18 8.2 Bone disease18 8.3 Cardiovascular and metabolic disease19 8.4 Chronic kidney disease19 8.5 Chronic liver disease19 8.6 Cognitive impairment associated with HIV19 8.7 Later life and ageing with HIV20 8.8 Mental health20 8.9 Transgender people20 8.10 Women20 3 Active involvement of people living with HIV in decision-making20 3.1 References21 4 When to start22 4.1 Established infection22 4.2 Same-day ART initiation22 4.3 Individuals presenting with AIDS or a major infection24 4.4 Treatment of primary HIV infection24 4.5 Impact of treatment on prevention of onward transmission26 4.6 Persons choosing not to commence ART27 4.7 Considerations when managing people with spontaneous HIV viral control27 4.7.1 Definition of viral controllers (also known as elite controllers)28 4.7.2 Risks versus benefits of ART in viral controllers28 4.7.3 Summary29 4.8 Stopping therapy29 4.9 References30 5 What to start33 5.1 Introduction33 5.2 Regimens recommended for most people35 5.2.1 Dolutegravir versus efavirenz35 5.2.2 Dolutegravir versus bictegravir35 5.2.3 Dolutegravir/lamivudine36 5.3 Regimens recommended in certain clinical situations36 5.3.1 Doravirine36 5.3.2 Raltegravir37 5.3.3 Darunavir/ritonavir37 5.3.4 Atazanavir/ritonavir38 5.3.5 Tenofovir DF/emtricitabine compared with tenofovir AF/emtricitabine38 5.3.6 Use of abacavir in people with CVD risk factors39 5.3.7 Lamivudine versus emtricitabine in combination with tenofovir DX39 5.4 Regimens not recommended first line compared to 2015 guidelines39 5.4.1 Abacavir/lamivudine other than in combination with dolutegravir39 5.4.2. Atazanavir/ritonavir39 5.4.3 Efavirenz40 5.4.4 Rilpivirine40 5.4.5 Elvitegravir/cobicistat40 5.5 What to start in the context of TDR40 5.6 What to start in the context of rapid ART initiation41 5.7 What to start in the context of very high viral load41 5.8 What to start in people diagnosed with HIV on PrEP42 5.9 Switching ART in virological suppression42 5.10 Suppressed switch or maintenance43 5.10.1 NRTI switch44 5.10.2 PI switch45 5.10.3 NNRTI switch46 5.10.4 Integrase switch46 5.11 Two-drug oral regimens: switching in virological suppression47 5.11.1 Preferred options47 5.11.2 Acceptable in specific circumstances48 5.12 Two-drug injectable regimens: switching in virological suppression48 5.12.1 Service capacity49 5.13 PI monotherapy50 5.14 References51 6 Supporting individuals on therapy57 6.1 Adherence57 6.1.1 Barriers to adherence58 6.1.2 Interventions to increase adherence to treatment59 6.1.3 Should the choice of first-line ART combination be affected by risk of non-adherence?61 6.2 Pharmacology63 6.2.1 Drug interactions63 6.2.2 Stopping therapy: pharmacological considerations64 6.2.3 Switching therapy: pharmacological considerations65 6.2.4 TDM66 6.3 References67 7 Managing virological failure71 7.1 Introduction71 7.2 Blips72 7.3 Low-level viraemia on ART73 7.4 Virological failure on ART74 7.5 Individuals with no or limited drug resistance74 7.5.1 First-line treatment failure with no resistance75 7.5.2 First-line treatment failure with NNRTI resistance75 7.5.3 First-line treatment failure on a ritonavir-boosted PI-based two-NRTI regimen with or without PI resistance76 7.5.4 First-line treatment failure with first- and second-generation INSTI-based resistance77 7.6 Individuals with multi-class virological failure with or without extensive drug resistance77 7.7 Individuals with limited or no therapeutic options when a fully viral suppressive regimen cannot be constructed79 7.8 References80 8 Specific populations84 8.1 Adolescents84 8.1.1 Management of HIV, ART and sexual and reproductive health specifically for young adults and adolescents living with HIV85 8.1.2 Youth-focused HIV and sexual and reproductive health services85 8.1.3 UK Epidemiology for young adults and adolescents living with HIV85 8.1.4 Transition of clinical care from paediatric to adult services: a process for young adults and adolescents with PaHIV85 8.1.5 Cognitive and mental health impact of HIV in young adults and adolescents with PaHIV86 8.1.6 ART86 8.2 Bone disease87 8.2.1 What to start87 8.2.2 Switching treatment88 8.3 Cardiovascular and metabolic disease88 8.3.1 Cardiovascular considerations88 8.3.2 Lipid considerations89 8.3.3 Weight gain considerations89 8.4 Chronic kidney disease90 8.4.1 What to start90 8.4.2 Need to switch91 8.4.3 Dose adjustment of ART in the setting of renal impairment91 8.4.4 Assessment of renal function in the presence of agents that reduce creatinine clearance92 8.5 Chronic liver disease92 8.6 Cognitive impairment associated with HIV93 8.6.1 Introduction93 8.6.2 When to start ART93 8.6.3 What to start93 8.6.4 Simplification strategies94 8.6.5 Continuing or worsening cognitive impairment despite ART95 8.7 Later life and ageing with HIV95 8.7.1 Introduction95 8.7.2 When to start ART96 8.7.3 What to start96 8.8 Mental health97 8.9 Transgender people98 8.9.1 Accessing care98 8.9.2 Peer support99 8.9.3 ART outcomes99 8.9.4 Drug–drug interactions99 8.9.5 CVD risk99 8.9.6 Bone health99 8.9.7 Renal function99 8.10 Women100 8.10.1 Introduction100 8.10.2 What to start100 8.10.3 Women living with HIV experiencing virological failure102 8.10.4 Psychosocial issues102 8.11 References102 9 Acknowledgements114 10 List of abbreviations114 11 List of appendices115 The overall purpose of these guidelines is to provide guidance on best clinical practice for antiretroviral therapy (ART) and management of adults living with human immunodeficiency virus (HIV). The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii) support of people living with HIV on treatment; (iii) management of individuals experiencing virological failure; (iv) switch for tolerability and/or toxicity issues; and (v) recommendations for specific populations where other factors need to be taken into consideration. The guidelines are written for clinical professionals directly involved with and responsible for the care of adults living with HIV, community advocates responsible for promoting the best interests and care of adults living with HIV, and people living with HIV for whom a non-technical summary will also be available, if preferred. They should be read in conjunction with other published British HIV Association (BHIVA) guidelines. Of note, the term 'HIV' refers to HIV-1 throughout these guidelines. BHIVA fully revised and updated the Association's guideline development manual in 2021 [1]. Full details of the guideline development process, including conflict of interest policy, are outlined in the manual. BHIVA has adopted the modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for the assessment, evaluation and grading of evidence and development of recommendations (see below and Appendix 1) [2,3]. The scope, purpose and guideline topics were agreed by the writing group. Questions concerning each guideline topic were drafted and a systematic literature search was undertaken. Details of the search questions and strategy (including the definitions of populations, interventions, comparisons and outcomes) are outlined in Appendix 2. BHIVA guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy were last published in 2015 [4] with a subsequent interim update in 2016 to include tenofovir alafenamide (AF), and interim statements in 2019 and 2022, to cover two-drug regimens and long-acting cabotegravir/rilpivirine respectively. For the 2022 guidelines Medline, Embase and the Cochrane library were searched between January 2014 (August 2014 for Virological failure/Transmitted drug resistance) and March 2021. Abstracts from selected conferences were searched between January 2017 and March 2021. For the narrative, authors could add publications of major importance at their discretion. For further details see Appendix 2. For each topic and healthcare question, evidence was identified and evaluated by writing group members with expertise in the field. Using the modified GRADE system, writing group members were responsible for assessing and grading the quality of evidence for predefined outcomes across studies and developing and grading the strength of recommendations. An important aspect of evaluating evidence is an understanding of the design and analysis of clinical trials, including the use of surrogate marker data. Decisions regarding the clinical importance of difference in outcomes were made by the writing group. For a number of questions, GRADE evidence profile and summary of findings tables were constructed, using predefined and rated treatment outcomes (Appendix 3), to help achieve consensus for key recommendations and aid transparency of the process. Before final approval by the writing group, the guidelines were published online for public consultation and external peer reviews were commissioned. BHIVA views the involvement of people living with HIV and community representatives in the guideline development process as essential. The writing group included two representatives appointed through the UK Community Advisory Board (UK-CAB) who were involved in all aspects of the guideline development process. Community groups were invited to participate in the draft guideline consultation process and have reviewed and commented on the guidelines. A community question and answer session was held on 11 August 2022 with members of the UK-CAB. The GRADE Working Group [5] has developed an approach to grading evidence that moves away from initial reliance on study design to consider the overall quality of evidence across outcomes. BHIVA has adopted the modified GRADE system for its guideline development. The advantages of the modified GRADE system are (i) the grading system provides an informative, transparent summary for clinicians, people living with HIV and policy makers by combining an explicit evaluation of the strength of the recommendation with a judgement of the quality of the evidence for each recommendation, and (ii) the two-level grading system of recommendations has the merit of simplicity and provides clear direction to clinicians, people living with HIV and policy makers. The strength of a recommendation is determined not only by the quality of evidence for defined outcomes but also by the balance between desirable and undesirable effects of a treatment or intervention, differences in values and preferences and, where appropriate, resource use. Each recommendation concerns a defined target population and is actionable. In addition to graded recommendations, the BHIVA writing group has also included good practice points (GPPs), which are recommendations based on the clinical judgement and experience of the writing group. GPPs emphasise an area of important clinical practice for which there is no significant research evidence, nor is there likely to be any. They address an aspect of treatment and care that is regarded as such sound clinical practice that healthcare professionals are unlikely to question it and where the alternative is deemed unacceptable. It must be noted that GPPs are not an alternative to evidence-based recommendations. The guidelines will be fully updated and revised in 2027. However, the writing group will continue to meet regularly to consider new information from high-quality studies and publish amendments and addendums to the current recommendations before the full revision date where this is thought to be clinically important to ensure continued best clinical practice. The primary aim of ART is to achieve viral suppression (to less than 50 copies/mL), thus reducing HIV-associated mortality and morbidity, with a low level of drug toxicity. Treatment should improve the physical and psychological well-being of people living with HIV. The effectiveness and tolerability of ART has improved significantly over time. The overwhelming majority of people attending HIV services in the UK and receiving ART experience long-term virological suppression and good treatment outcomes [6], which compare very favourably with other high-income countries. Of note, in 2020 around 99% of those diagnosed with HIV in the UK had initiated ART, with 97% of those on ART having a suppressed viral load [6]. A UK analysis of individuals commencing ART between 2000 and 2010 demonstrated that life expectancy in men and women with an undetectable viral load and CD4 count greater than 350 cells/mm3 is the same as, or slightly better than, that of the general population (of note, a small group of people who acquired HIV vertically or through injection drug use were excluded from these analyses) [7]. Decreasing late diagnosis (and consequently starting ART earlier), maintaining individuals in care, reducing long-term drug toxicity and optimal management of comorbidities are crucial to ensure optimal outcomes for all people living with HIV. A further benefit of ART is the reduction in HIV transmission. There is no risk of sexual transmission in the context of suppressive ART [8-10]. The use of ART to prevent vertical transmission is universally accepted and best practice is addressed in the BHIVA guidelines for the management of HIV in pregnancy and postpartum [11]. ART is extremely cost-effective and is one of the most cost-effective medical interventions for long-term conditions [12-15]. There has been a steady decline in annual diagnoses of HIV since 2005 and the number of people living with HIV in the UK by the end of 2020 was estimated to be 106,890 (95% credible interval 105,460–109,510), of whom 5% were undiagnosed [6]. Data on total ART spend are scant. It was estimated that the annual population treatment and care costs rose from £104 million in 1997 to £483 million in 2006, with a projected annual cost of £721 million in 2013 [16]. However, data for England showed an antiretroviral (ARV) spend of £413.7 million in 2016/2017, a more than 3.5% saving compared to the previous year, despite higher numbers on treatment [17]. This was driven by routine switching of branded to generic drugs, targeted value schemes and a relative reduction in the price of some branded products following the availability of generic drugs. Since then, costs in England have continued to decline further, to a predicted £270 million for 2022/2023 [18], and it is likely that relative cost reductions have been similar in other UK nations. Balancing cost efficiency against the preferences of people living with HIV will continue to be a challenge and a continued collaborative approach between commissioners, healthcare professionals and people living with HIV is required. In the UK, higher annual treatment and care costs have been associated with late diagnosis and initiation of ART at lower CD4 cell counts [19,20]. In addition to earlier diagnosis and initiation of ART, reducing inpatient episodes, decreasing drug toxicity, preventing HIV-associated comorbidities, streamlined monitoring and innovations in models of care are likely to have a beneficial effect on costs. However, the cost of ARV drugs remains the major factor contributing to treatment and care costs [21]. With the increasing availability of generic drugs, commissioners and the NHS must continuously review the value and relative benefit of different drugs. The writing group recognises that price of drugs is an important ethical consideration in ART choice within a resource-constrained health economy which is free at the point of access. In addition to drug acquisition costs there are costs associated with, for example, multidisciplinary team meetings, switching ART, comorbidities and management of drug–drug interactions. There are limited cost-effectiveness data in the UK comparing different ART options, and each nation undertakes separate drug procurement processes (securing different prices); for this reason, we did not include cost-effectiveness as an outcome in ART comparisons. In the setting of similar virological efficacy, determining the acceptable threshold at which differences in the risk of toxicity, tolerability and convenience outweigh differences in resource use and cost will be important. These thresholds may differ among both clinicians and people living with HIV. In developing the recommendations in these guidelines, we have considered differences in critical treatment outcomes between different drug regimens in determining recommended treatment regimens. Regimens no longer recommended for first-line therapy still have a role in terms of switching in virologically suppressed people and/or maintenance treatment in people already established on ART. We recognise that commissioning arrangements and local drug costs will influence ART choice where outcomes, across a range of clinical measures, are similar between individual drugs in the treatment of defined populations. We support prescribing algorithms based on cost where preferred options are recommended by BHIVA. However, we believe that optimal treatment outcomes and quality of care should be the primary drivers of prescribing decisions, with cost a secondary consideration where more than one treatment option is considered clinically appropriate. In reviewing quality of evidence for guidelines, areas of treatment and care will be identified where there is an absence of evidence or limited confidence in the size of effect to influence choice of treatments or determine treatment and management strategies. For this reason, it is not the intention of these guidelines to stifle clinical research but rather to help promote continued research with the aim to further improve clinical care and treatment outcomes. BHIVA is highly committed to the development and provision of HIV clinical trials to further improve ART options, and access to and participation in a clinical trial should be offered to people living with HIV where appropriate, considering the need to offer trials to women and racial minority groups. BHIVA strongly supports broader representation of under-studied populations in clinical trials with better inclusion of women, pregnant or breastfeeding people, people of non-white ethnicity, transgender people and children. 1. British HIV Association. British HIV Association (BHIVA) Guideline Development Manual. 2021. Available at: https://www.bhiva.org/file/jgCacHqmuxZFL/GuidelineDevelopmentManual.pdf (accessed July 2022). 2. Guyatt GH, Oxman AD, Kunz R et al. Going from evidence to recommendations. BMJ 2008; 336: 1049–1051. 3. GRADE Working Group. Publications about the GRADE approach. Available at: https://www.gradepro.org/resources (accessed April 2022). 4. Churchill D, Waters L, Ahmed N et al. British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2015. HIV Med 2016; 17 Suppl 4: s2–s104. 5. GRADE Working Group. GRADE. Available at: https://www.gradeworkinggroup.org/ (accessed April 2022). 6. UK Health Security Agency. HIV testing, PrEP, new HIV diagnoses, and care outcomes for people accessing HIV services: 2022 report. Available at: https://www.gov.uk/government/statistics/hiv-annual-data-tables/hiv-testing-prep-new-hiv-diagnoses-and-care-outcomes-for-people-accessing-hiv-services-2022-report (accessed October 2022). 7. May MT, Gompels M, Delpech V et al.; UK Collaborative HIV Cohort (UK CHIC) Study. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS 2014; 28: 1193–1202. 8. Rodger AJ, Cambiano V, Bruun T et al.; PARTNER Study Group. Sexual activity without condoms and risk of HIV transmission in serodifferent couples when the HIV-positive partner is using suppressive antiretroviral therapy. JAMA 2016; 316: 171–181. 9. Rodger AJ, Cambiano V, Bruun T et al.; PARTNER Study Group. Risk of HIV transmission through condomless sex in serodifferent gay couples with the HIV-positive partner taking suppressive antiretroviral therapy (PARTNER): final results of a multicentre, prospective, observational study. Lancet 2019; 393: 2428–2438. 10. Bavinton BR, Pinto AN, Phanuphak N et al.; Opposites Attract Study Group. Viral suppression and HIV transmission in serodiscordant male couples: an international, prospective, observational, cohort study. Lancet HIV 2018; 5: e438–e447. 11. Gilleece Y, Tariq S, Bamford A et al. British HIV Association guidelines for the management of HIV in pregnancy and postpartum 2018. HIV Med 2019; 20 Suppl 3: s2–s85. 12. Sendi PP, Bucher HC, Harr T et al. Cost effectiveness of highly active antiretroviral therapy in HIV-infected patients. Swiss HIV Cohort Study. AIDS 1999; 13: 1115–1122. 13. Miners AH, Sabin CA, Trueman P et al. Assessing the cost-effectiveness of HAART for adults with HIV in England. HIV Med 2001; 2: 52–58. 14. Freedberg KA, Losina E, Weinstein MC et al. The cost effectiveness of combination antiretroviral therapy for HIV disease. N Engl J Med 2001; 344: 824–831. 15. Yazdanpanah Y. Costs associated with combination antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother 2004; 53: 558–561. 16. Mandalia S, Mandalia R, Lo G et al. Rising population cost for treating people living with HIV in the UK, 1997–2013. PLoS One 2010; 5: e15677. 17. Waters L, Aubrey P, Harper J et al. Was the pain worth the gain? Antiretroviral savings from the 'Improving value' project and generics use in England. Clin Med (Lond) 2019; 19 Suppl 2: 76. doi:10.7861/clinmedicine.19-2-s76. 18. NHS England. National procurement for HIV and preventative treatments. Available at: https://www.find-tender.service.gov.uk/Notice/006329-2022 (accessed April 2022). 19. Beck EJ, Mandalia S, Sangha R et al. The cost-effectiveness of early access to HIV services and starting cART in the UK 1996-2008. PLoS One 2011; 6: e27830. 20. Beck EJ, Mandalia S, Lo G et al. Cost-effectiveness of early treatment with first-line NNRTI-based HAART regimens in the UK, 1996–2006. PLoS One 2011; 6: e20200. 21. Beck EJ, Mandalia S, Yfantopoulos P et al. The efficiency of the EmERGE pathway of care for people living with HIV in England. AIDS Care 2022: 1-10. doi: 10.1080/09540121.2022.2040723. Recommendations for choice of first-line ART are summarised in Table 5.1. Where clinically appropriate, lamivudine and emtricitabine can be considered interchangeable (see Section 5.3.7 Lamivudine versus emtricitabine in combination with tenofovir DX). No baseline lamivudine resistance Baseline viral load 200 cells/mm3 No active hepatitis B infection and if at risk of hepatitis B, hepatitis B virus immune Baseline viral load less than 100,000 copies/mL Bone/renal caveats for tenofovir DX Where a woman living with HIV is pregnant, or planning to conceive, the BHIVA pregnancy guidelines should be followed [3]. All regimens recommended for first-line ART are also recommended for suppressed switch or maintenance. In addition, the following regimens are also acceptable (see Table 5.2). Acceptable for switch or to continue where clinically appropriate Where feasible, lamivudine and emtricitabine are considered interchangeable Where resistance necessitates a PI; improvements in renal/bone biomarkers for tenofovir AF over tenofovir DF are most evident in the context of boosted ART. Atazanavir and tenofovir DX are both associated with renal toxicity No other oral two-drug regimens are recommended as switch strategies. • Along with the general recommendation to offer ART to all persons with HIV, we recommend that symptomatic HIV-associated cognitive disorders is considered a further indication to commence ART (Grade 1C). Rationale People living with HIV should be given the opportunity to consider and contribute to decisions about their treatment and the Medicines and Healthcare products Regulatory Agency now asks applicants to include evidence for patient involvement activities when submitting applications for selected new medicines [2]. Studies show that trust in providers improves linkage to and retention in care and ART adherence [3-5], that patient–provider relationship quality is associated with HIV-related and psychosocial outcomes [6] and that trust transfers from offline to online health services [7]. Having a consistent healthcare provider has been associated with better rates of viral suppression [8]. Clinicians should establish what level of involvement the individual living with HIV would like and carry out an informed clinical and psychosocial assessment to choose the best treatment options. The individual should be able to access and understand relevant information relative to different languages and literacy levels in line with BHIVA standards [9]. If there is a question about an individual's capacity to make an informed decision, this should be assessed in line with General Medical Council guidance [10]. Good care requires good communication with the GP and any clinicians involved in management of comorbid conditions. People living with HIV should be offered copies of any correspondence about them. Disclosure of their HIV status to the GP by people living with HIV should be considered best practice and the benefits of sharing HIV status with GPs and the potential risks of not doing so (such as drug–drug interactions) should be explained. However an individual's decision not to share their status with their GP should be respected but revisited regularly. A systematic review of 20 randomised controlled trials showed that peer support with routine medical care was superior to routine clinic follow-up, yielding better retention in care, ART adherence and viral suppression [12]. Benefits for other outcomes such as mental health and quality of life were 'promising' but too uncertain to draw firm conclusions. We recommend following the EACS guidance on assessing the readiness of people living with HIV to start and maintain ART [1]. 1. European AIDS Clinical Society. EACS Readiness to Start/Maintain ART. Available at: https://eacs.sanfordguide.com/art/readiness-to-start-maintain-art (accessed July 2022). 2. Medicines and Healthcare products Regulatory Agency. MHRA pilots patient involvement in new applications. Available at: https://www.gov.uk/government/news/mhra-pilots-patient-involvement-in-new-applications (accessed April 2022). 3. Michel KG, Ocampo JMF, Spence AB et al. High provider trust associates with high HIV antiretroviral adherence among women living with HIV in a metropolitan Washington, DC cohort. AIDS Patient Care STDS 2022; 36: 17–25. 4. Graham JL, Shahani L, Grimes RM et al. The influence of trust in physicians and trust in the healthcare system on linkage, retention, and adherence to HIV care. AIDS Patient Care STDS 2015; 29: 661–667. 5. Mitchell BD, Utterback L, Hibbeler P et al. Patient-identified markers of quality care: improving HIV service delivery for older African Americans. J Racial Ethn Health Disparities 2022: 1–12. doi: 10.1007/s40615-022-01237-2. 6. Zhang C, McMahon J, Leblanc N et al. Association of medical mistrust and poor communication with HIV-related health outcomes and psychosocial wellbeing among heterosexual men living with HIV. AIDS Patient Care STDS 2020; 34: 27–37. 7. van Velsen L, Flierman I, Tabak M. The formation of patient trust and its transference to online health services: the case of a Dutch online patient portal for rehabilitation care. BMC Med Inform Decis Mak 2021; 21: 188. 8. Wang Z, Lin HC. Having a consistent HIV health care provider and HIV-related clinical outcomes. Am J Manag Care 2020; 26: 288–294. 9. British HIV Association. British HIV Association standards of care for people living with HIV 2018. Available at: https://www.bhiva.org/standards-of-care-2018 (accessed July 2022). 10. General Medical Council. Decision making and consent. 2020. Available at: https://www.gmc-uk.org/-/media/documents/gmc-guidance-for-doctors---decision-making-and-consent-english_pdf-84191055.pdf (accessed April 2022). 11. Horne R, Chapman SC, Parham R et al. Understanding patients' adherence-related beliefs about medicines prescribed for long-term conditions: a meta-analytic review of the Necessity-Concerns Framework. PLoS One 2013; 8: e80633. 12. Berg RC, Page S, Øgård-Repål A. The effectiv
Referência(s)