www.thelancet.com/infection Vol 15 February 2015 241 Personal View The future role of CD4 cell count for monitoring antiretroviral therapy Nathan Ford, Graeme Meintjes, Anton Pozniak, Helen Bygrave, Andrew Hill, Trevor Peter, Mary-Ann Davies, Beatriz Grinsztejn, Alexandra Calmy, N Kumarasamy, Praphan Phanuphak, Pierre deBeaudrap, Marco Vitoria, Meg Doherty, Wendy Stevens, George K Siberry For more than two decades, CD4 cell count measurements have been central to understanding HIV disease progression, making important clinical decisions, and monitoring the response to antiretroviral therapy (ART). In well resourced settings, the monitoring of patients on ART has been supported by routine virological monitoring. Viral load monitoring was recommended by WHO in 2013 guidelines as the preferred way to monitor people on ART, and efforts are underway to scale up access in resource-limited settings. Recent studies suggest that in situations where viral load is available and patients are virologically suppressed, long-term CD4 monitoring adds little value and stopping CD4 monitoring will have major cost savings. CD4 cell counts will continue to play an important part in initial decisions around ART initiation and clinical management, particularly for patients presenting late to care, and for treatment monitoring where viral load monitoring is restricted. However, in settings where both CD4 cell counts and viral load testing are routinely available, countries should consider reducing the frequency of CD4 cell counts or not doing routine CD4 monitoring for patients who are stable on ART. Introduction For more than two decades CD4 cell count measurements have been central to understanding HIV disease progression and making important clinical management decisions. Measurements of CD4 cell count are an important predictor of disease progression 1–5 and death 6–8 in people living with HIV and have been the main means to assess eligibility for initiation of antiretroviral therapy (ART), use of prophylaxis for opportunistic infections, and monitoring the response to treatment. 8–10 In well resourced settings, monitoring of patients on ART has been supported by routine virological monitoring. 11 Viral load (plasma HIV RNA) monitoring also predicts HIV-related mortality, accurately detects virological failure usually before immunological or clinical deterioration, and signals the need for more intensive adherence support and resistance geno- typing. 12,13 Recognising these benefits, WHO recom- mends measurement of HIV viral load as the preferred approach to treatment monitoring, 14 and concerted efforts are supporting scale-up of viral load capability in resource-limited settings. 15 As access to viral load becomes increasingly available, the role of CD4 monitoring in virologically suppressed patients is increasingly being questioned. Several studies have recently suggested that CD4 cell count monitoring has little added value in situations where viral load is available and patients are virologically suppressed. 16–18 In September, 2013, WHO held an expert consultation on the future role of CD4 testing for ART monitoring. We summarise the evidence and experience shared and the conclusions reached at this consultation. Current policies for ART monitoring During the past decade, WHO guidelines for ART in countries with low and middle incomes have evolved towards recommending that countries phase in viral load for monitoring of treatment. The value of viral load was recognised by WHO guidelines in 2003, although access at the time was restricted by the complexity and cost of available assays. 19 Since then, improvements in technology and access have led to increased use of viral load monitoring. WHO guidelines released in June, 2013, recommend that countries use HIV viral load as the preferred approach to ART monitoring. 20,21 Guidelines for ART monitoring vary between countries. Several resource-limited settings, including Mozambique, Swaziland, and Zimbabwe rely on routine CD4 monitoring, with viral load used only in a targeted way to confirm virological failure in patients with immunological or clinical failure. Other countries, including Cameroon and Côte d’Ivoire, provide both CD4 cell counts and viral load measurement routinely, albeit with different frequencies. Malawi and South Africa rely on viral load for long-term monitoring. In South Africa, discontinuation of routine CD4 cell count is now recommended after 1 year for patients stable on ART, although CD4 cell counts are done when needed for decisions regarding the stopping of prophylaxis for some AIDS-associated opportunistic infections. 22 Monitoring strategies can also differ between public and private sectors: in India for example, targeted use of viral load is provided in the public sector, whereas routine viral load monitoring is offered in the private sector. The frequency of CD4 cell counts and viral load tests for ART monitoring also varies substantially between countries (table). Prospects to increase access to viral load monitoring Although viral load measurement is recommended by WHO as the preferred approach to treatment monitoring and is included in guidelines of most countries with high HIV burden, access is restricted. Several middle-income countries—notably Botswana, Brazil, South Africa, and Thailand—were early adopters of HIV viral load Lancet Infect Dis 2015; 15: 241–47 Published Online November 19, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)70896-5 Department of HIV/AIDS, World Health Organization, Geneva, Switzerland (N Ford PhD, M Vitoria MD, M Doherty PhD); Clinical Infectious Diseases Research Initiative, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa (G Meintjes PhD); Chelsea and Westminster Hospital, London, UK (A Pozniak MD); Southern Africa Medical Unit, Médecins Sans Frontières, Cape Town, South Africa (H Bygrave MBChB); Department of Pharmacology and Therapeutics, Liverpool University, UK (A Hill PhD); Clinton Health Access Initiative, Boston, MA, USA (T Peter PhD); Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa (M-A Davies MD, N Ford); Fundação Oswaldo Cruz, Ministry of Health, Brazil (B Grinsztejn MD); HIV/AIDS Unit, Infectious Disease Service, Geneva University Hospital, Geneva, Switzerland (Prof A Calmy PhD); YRG Centre for AIDS Research and Education, Chennai, India (N Kumarasamy MD); Thai Red Cross AIDS Research Centre, Bangkok, Thailand (Prof P Phanuphak MD); Institut de Recherche pour le Développement (IRD), Montpellier, France (P deBeaudrap PhD); Department of Molecular Medicine and Haematology, University of the Witwatersrand and National health Laboratory Services, Johannesburg, South Africa (Prof W Stevens PhD); and Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD, Rockville, USA (G Siberry MD)