HIV in adults

ART is recommended for all patients with HIV, including those with acute or primary infection, regardless of CD4 count as it has been shown to reduce the risk of disease progression, decrease comorbid disease, and prevent HIV transmission.[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines  The strength of this recommendation was reinforced by the Strategic Timing of AntiRetroviral Treatment (START) study, which found that the risk of developing serious illness or death was reduced by 53% among those in the early treatment group, compared with those in the deferred treatment group.[128]Lundgren JD, Babiker AG, Gordin F, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015 Aug 27;373(9):795-807. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4569751 http://www.ncbi.nlm.nih.gov/pubmed/26192873?tool=bestpractice.com  World Health Organization (WHO) guidelines support the recommendation to initiate ART in all patients living with HIV, regardless of CD4 count.[48]World Health Organization. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. Sep 2015 [internet publication]. https://www.who.int/publications/i/item/9789241509565

ART should be started immediately (as soon as possible) after HIV diagnosis in order to increase the uptake of ART and linkage to care, decrease the time to viral suppression, reduce the risk of transmission, and improve the rate of virological suppression.[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines The WHO recommends offering rapid ART initiation to all people living with HIV following a confirmed diagnosis and clinical assessment, in patients who are willing and ready to start treatment, and where there is no clinical contraindication.[97]World Health Organization. Guidelines for managing advanced HIV disease and rapid initiation of antiretroviral therapy. Jul 2017 [internet publication]. https://iris.who.int/bitstream/handle/10665/255884/9789241550062-eng.pdf?sequence=1 Rapid ART initiation is defined as within 7 days of diagnosis, preferably on the same day as diagnosis. One Cochrane review of seven randomised controlled trials with more than 18,000 adults found that rapid initiation (within 7 days of diagnosis) of ART probably results in greater viral suppression at 12 months compared with standard initiation in low- and middle-income settings.[129]Mateo-Urdiales A, Johnson S, Smith R, et al. Rapid initiation of antiretroviral therapy for people living with HIV. Cochrane Database Syst Rev. 2019 Jun 17;(6):CD012962. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012962.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/31206168?tool=bestpractice.com [ ] For adults with HIV infection, what are the effects of rapid initiation of antiretroviral therapy (ART)?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2663/fullShow me the answer Rapid initiation of ART may be difficult to achieve in resource-limited settings.

Although ART has long-term adverse effects, these are minimal compared with complications of untreated HIV.

Treatment recommended for ALL patients in selected patient group

The choice of effective drug combinations in treatment-naive patients requires expertise, particularly in complex cases. Treatment is best individualised by a clinician who is experienced in HIV management.

A first-line ART regimen will generally consist of two nucleoside reverse transcriptase inhibitors (NRTIs) in combination with a third agent (preferably an integrase strand transfer inhibitor [INSTI], or otherwise a non-nucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]), or a two-drug regimen consisting of an INSTI plus an NRTI in select patients.[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines [130]Feng Q, Zhou A, Zou H, et al. Quadruple versus triple combination antiretroviral therapies for treatment naive people with HIV: systematic review and meta-analysis of randomised controlled trials. BMJ. 2019 Jul 8;366:l4179. https://www.bmj.com/content/366/bmj.l4179 http://www.ncbi.nlm.nih.gov/pubmed/31285198?tool=bestpractice.com [131]National Institute for Health Research. NIHR Signal: Four-drug treatment for HIV offers no benefit over standard three-drug treatment. Sep 2019 [internet publication]. https://discover.dc.nihr.ac.uk/content/signal-000814/hiv-quadruple-treatment-for-hiv-no-better-than-triple-treatment ​ Regimens recommended by the US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents are detailed here.[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines Other guidelines may recommend different regimens. 

A different regimen may be recommended for people with HIV and a history of using long-acting cabotegravir as pre-exposure prophylaxis (PrEP). INSTI genotypic resistance testing is recommended in these patients before starting ART, regardless of the amount of time since drug discontinuation. INSTI-based regimens should not be started unless genotype tests show no INSTI-resistance mutations. If treatment is started before results are obtained, the following non-INSTI regimen is recommended pending genotype results: ritonavir- or cobicistat-boosted darunavir plus tenofovir disoproxil or tenofovir alafenamide plus lamivudine or emtricitabine.[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines

Consider the potential for drug-drug interactions (including over-the-counter and complementary or alternative medicines) when prescribing or switching one or more drugs in an ART regimen. Drug-drug interactions between ART regimens and concomitant drugs are common, and may affect therapeutic responses.[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines

​University of Liverpool: HIV drug interactions Opens in new window

A specialist should be consulted for further guidance on regimens and doses. Regimens and doses may differ in children and adolescents, older people, patients with hepatic/renal impairment or other comorbidities or coinfections, and pregnant/breastfeeding women and are beyond the scope of this topic.

Patients must be ready to adhere to treatment, and their readiness should be established through counselling. Fixed-dose combination tablets that combine two or three classes of drugs in one tablet (or two drugs from the same class) are available, and can assist in improving compliance with ART regimens.

ClinicalInfo.Hiv.gov: guidelines for the use of antiretroviral agents in adults and adolescents with HIV Opens in new window

US FDA: HIV treatment information for adults Opens in new window

Treatment recommended for ALL patients in selected patient group

Counselling: risk reduction counselling in HIV-positive people has been shown to be effective in reducing further transmission of HIV. More than one session of counselling may be needed. Referral should be made to appropriate counsellor/support groups for ongoing counselling sessions.[17]Pope M, Hause AT. Transmission, acute HIV-1 infection and the quest to prevent infection. Nat Med. 2003 Jul;9(7):847-52. http://www.ncbi.nlm.nih.gov/pubmed/12835704?tool=bestpractice.com [115]The Voluntary HIV Counseling and Testing Efficacy Study Group. Efficacy of voluntary HIV-1 counselling and testing in individuals and couples in Kenya, Tanzania and Trinidad: a randomised trial. Lancet. 2000 Jul 8;356(9224):103-12. http://www.ncbi.nlm.nih.gov/pubmed/10963246?tool=bestpractice.com ​​​ Counselling before initiating antiretroviral therapy (ART) should focus on preparing the patient to commit to long-term ART. Adherence to ART should be regularly assessed at every clinic visit.[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines One Cochrane review found that simple ART adherence measures (e.g., self-reporting measures, tablet counts, electronic monitoring, pharmacy records) did not help identify patients who might not be taking their ART and who had higher viral loads. No one modality consistently offered a sufficiently high sensitivity to detect viral non‐suppression across groupings of similar measures.[116]Smith R, Villanueva G, Probyn K, et al. Accuracy of measures for antiretroviral adherence in people living with HIV. Cochrane Database Syst Rev. 2022 Jul 25;7(7):CD013080. https://www.doi.org/10.1002/14651858.CD013080.pub2 http://www.ncbi.nlm.nih.gov/pubmed/35871531?tool=bestpractice.com ​

Prophylaxis of opportunistic infections (OIs): primary prophylaxis against OIs including tuberculosis, Pneumocystis jirovecii, Mycobacterium avium complex, toxoplasmosis, and malaria (if required) is recommended. Pre-emptive treatment for cryptococcal infection should be considered in certain patients. Early identification and management of OIs is extremely important. See HIV-related opportunistic infections.

Other infections: patients with concomitant hepatitis B or C virus infection should be treated according to the latest guidance.

Comorbidities: routine primary prevention for chronic diseases of ageing is recommended based on age and risk (e.g., risk assessment, screening, and testing for age-appropriate conditions such as cardiovascular disease, liver disease, diabetes, cancers, and bone disease). Assessment of diet, physical activity, smoking status, alcohol use, and substance use should be included.

Micronutrient supplementation: there is limited evidence of consistent clinically important benefits with micronutrient supplementation; however, most practitioners add a multivitamin and mineral combination supplement containing vitamins A, B6, B12, C, D, E, and folate, with calcium, magnesium, iron, zinc, and selenium.[119]Visser ME, Durao S, Sinclair D, et al. Micronutrient supplementation in adults with HIV infection. Cochrane Database Syst Rev. 2017 May 18;(5):CD003650. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003650.pub4/full http://www.ncbi.nlm.nih.gov/pubmed/28518221?tool=bestpractice.com [120]Teixeira NDSCCA, Pereira BM, Oliveira IKF, et al. Effect of vitamin D3 supplementation on HIV-infected adults: a systematic review. Nutr Hosp. 2019 Oct 17;36(5):1205-12. https://www.doi.org/10.20960/nh.02647 http://www.ncbi.nlm.nih.gov/pubmed/31526009?tool=bestpractice.com [ ] What are the effects of multiple micronutrient supplementation for adolescents and adults with HIV infection?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2643/fullShow me the answer [ ] How do nutritional interventions affect outcomes in adults with HIV?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.560/fullShow me the answer [ ] For adults with HIV infection receiving multivitamin supplementation, how does a high dose compare with a standard dose?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2642/fullShow me the answer​​ There is some evidence that selenium supplementation can delay CD4 cell decline in patients with HIV; however, there is no quantifiable evidence that it reduces viral load.[121]Muzembo BA, Ngatu NR, Januka K, et al. Selenium supplementation in HIV-infected individuals: A systematic review of randomized controlled trials. Clin Nutr ESPEN. 2019 Dec;34:1-7. https://www.doi.org/10.1016/j.clnesp.2019.09.005 http://www.ncbi.nlm.nih.gov/pubmed/31677697?tool=bestpractice.com [122]Pourmoradian S, Rezazadeh L, Tutunchi H, et al. Selenium and zinc supplementation in HIV-infected patients. Int J Vitam Nutr Res. 2024 Apr;94(2):153-9. https://econtent.hogrefe.com/doi/epdf/10.1024/0300-9831/a000778 http://www.ncbi.nlm.nih.gov/pubmed/36728996?tool=bestpractice.com ​​

Vaccinations: recommended vaccinations include COVID-19, hepatitis A, hepatitis B, human papillomavirus (HPV), influenza, meningococcal, pneumococcal, tetanus/diphtheria/pertussis, and herpes zoster. Additional vaccines may be recommended depending on the patient’s age, risk factors for a specific disease, and previous vaccination history. Other vaccines may be recommended in travellers depending on the risk of acquiring a given disease in the area of travel. Live vaccines are generally contraindicated.[124]US Department of Health and Human Services. HIV and immunizations. Dec 2023 [internet publication]. https://hivinfo.nih.gov/understanding-hiv/fact-sheets/hiv-and-immunizations Consult current local immunisation schedules for more information. 

Once virological suppression is achieved, regimen switching (within or between a class of drugs) or optimising ART may be considered in some patients, provided there is no evidence of viral resistance to the drugs in the new regimen. A regimen may be switched, for example, to simplify regimens, enhance tolerability, decrease toxicity, prevent drug interactions, and reduce costs. The aim is to maintain viral suppression without jeopardising future treatment options. The patient’s ART history should be reviewed, and any past instances of treatment failure and drug resistance should be taken into account when selecting a new regimen. Two- or three-drug regimens may be used.[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines A specialist should be consulted before switching regimens. HIV RNA (viral load), CD4 counts, adherence, and adverse effects should be monitored to optimise and evaluate the efficacy of ART.

Supportive care (e.g., counselling, vaccinations, micronutrient supplementation, prophylaxis of opportunistic infections) should continue throughout treatment.

Additional treatment recommended for SOME patients in selected patient group

Once antiretroviral therapy (ART) has been started, virological suppression has been achieved, and opportunistic infections have been addressed, statin therapy may be considered in certain patients as people living with HIV are at a greater risk of atherosclerotic cardiovascular disease (ASCVD).[127]Feinstein MJ, Achenbach CJ, Stone NJ, et al. A systematic review of the usefulness of statin therapy in HIV-infected patients. Am J Cardiol. 2015 Jun 15;115(12):1760-6. http://www.ncbi.nlm.nih.gov/pubmed/25907504?tool=bestpractice.com  

The US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents with HIV recommends statin therapy for primary prophylaxis in people with HIV who have low to intermediate (<20%) 10-year ASCVD risk estimates. Initiate at least moderate-intensity statin therapy in patients aged 40-75 years with a 10-year ASCVD risk estimate of 5% to <20%. Initiate at least moderate-intensity statin therapy in patients aged 40-75 years with a 10-year ASCVD risk estimate of <5%, taking into account the presence or absence of HIV-related factors that can increase ASCVD risk, (the absolute benefit is modest in these patients). Data are insufficient to recommend either for or against statin therapy in patients aged <40 years with HIV; lifestyle recommendations are recommended in the general population, with statin therapy considered in select populations only. Treat patients aged 40-75 years with a 10-year ASCVD risk estimate of ≥20% as per the general population based on evidence-based guidelines (i.e., high-intensity statin therapy).[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines

The Infectious Diseases Society of America (IDSA) recommends statin therapy for primary prevention in people with HIV aged 40-75 years, regardless of lipid levels and ASCVD risk. The recommendation is strongest for those with a 10-year ASCVD risk estimate of ≥5%. Evidence is insufficient to recommend either for or against statin therapy for people with HIV who are <40 years of age.[91]Horberg M, Thompson M, Agwu AL, et al. Primary care guidance for providers who care for persons with human immunodeficiency virus: 2024 update by HIVMA/IDSA. Clin Infect Dis. 2024 Oct 6:ciae479. https://www.idsociety.org/practice-guideline/primary-care-management-of-people-with-hiv/#Abstract

The British HIV Association (BHIVA) recommends offering statin therapy to all HIV-positive people over the age of 40 years to reduce their risk of cardiovascular disease, regardless of their estimated ASCVD risk or lipid profile. Patients with an estimated 10-year ASCVD risk ≥5% should be prioritised for primary prophylaxis with a statin.[126]British HIV Association. ​BHIVA rapid guidance on the use of statins for primary prevention of cardiovascular disease in people living with HIV. Mar 2024 [internet publication]. https://bhiva.org/rapid-guidance/bhiva-rapid-guidance-on-the-use-of-statins-for-primary-prevention-of-cardiovascular-disease  

The REPRIEVE study, a large randomised controlled trial undertaken in people living with HIV, demonstrated a significant reduction in major cardiovascular events in participants at low to moderate risk of cardiovascular disease who were receiving pitavastatin (a moderate-intensity statin) compared to those receiving placebo (35% reduction in major cardiovascular events after a median follow-up of 5.1 years).[125]Grinspoon SK, Fitch KV, Zanni MV, et al. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med. 2023 Aug 24;389(8):687-99. https://pmc.ncbi.nlm.nih.gov/articles/PMC10564556 http://www.ncbi.nlm.nih.gov/pubmed/37486775?tool=bestpractice.com  

Drug-drug interactions between statins and ART should be considered before starting treatment as dose adjustments may be required.

Statins are associated with muscle-related adverse effects including myalgia, myopathy, and rhabdomyolysis. Increased serum transaminases and hepatotoxicity have also been reported.

Virological failure is defined as the inability to achieve or maintain suppression of viral replication to an HIV RNA level <200 copies/mL.[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines

Patients with virological failure should be referred back to an HIV-experienced clinician or infectious diseases consultant for further drug-resistance testing, adherence assessment, and optimisation of their treatment regimens based on drug resistance patterns.[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines ​​

Immunological failure is the failure to achieve and maintain an adequate CD4 response despite virological suppression.[139]Lederman MM, Calabrese L, Funderburg NT, et al. Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J Infect Dis. 2011 Oct 15;204(8):1217-26. http://jid.oxfordjournals.org/content/204/8/1217.long http://www.ncbi.nlm.nih.gov/pubmed/21917895?tool=bestpractice.com These patients should also be referred to their specialist for assessment of current drugs, untreated coinfections, and serious medical conditions.

First-line INSTI-based regimens were associated with a lower risk of virological failure compared with PI-based regimens in one study. However, both INSTI- and PI-based regimens were associated with a higher risk of virological failure compared with NNRTI-based regimens, potentially due to channelling bias whereby non-adherent patients may have been more likely to be initiated on INSTI- or PI-based ART first line.[140]El Bouzidi K, Jose S, Phillips AN, et al. First-line HIV treatment outcomes following the introduction of integrase inhibitors in UK guidelines. AIDS. 2020 Oct 1;34(12):1823-31. https://www.doi.org/10.1097/QAD.0000000000002603 http://www.ncbi.nlm.nih.gov/pubmed/32516283?tool=bestpractice.com

Assessing and managing a patient who is experiencing ART failure can be complex. Drugs with a novel mechanism of action that the patient has not received before may be considered (e.g., cabotegravir and rilpivirine, ibalizumab, lenacapavir, fostemsavir, maraviroc).[78]US Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Sep 2024 [internet publication]. https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/whats-new-guidelines Detailed information on the management of treatment-experienced patients is beyond the scope of this topic, and treatment-experienced patients should be managed by a specialist.