Sustainable and cost-effective monitoring of patients on ART
Authors: Diana M Gibb, Peter Mugyenyi
Journal: The Lancet Global Health (2013)

Decision-makers in resource-limited settings, particularly in African countries hardest hit by the HIV epidemic, have to make difficult choices about the best way to spend their restricted resources on HIV care and prevention in the present economic climate. One such important policy decision is how to monitor the huge numbers of patients on antiretroviral therapy (ART) cost-effectively and sustainably. In The Lancet Global Health, Daniel Keebler and colleagues1Keebler D Revill P Braithwaite S et al.Strategies for monitoring adults on antiretroviral treatment: a combined analysis of three mathematical models.Lancet Glob Health. 2013; (published online Dec 10.)http://dx.doi.org/10.1016/S2214-109X(13)70048-2Google Scholar present an economic analysis consisting of three mathematical models to assess the costs and benefits of different strategies of clinical, CD4, and viral load monitoring for HIV-infected individuals on ART in three African countries with varying ART coverage and economies. Key strengths of this work are that independently developed and validated models have been run on the same strategies with the same costs, allowing results to be compared.1Keebler D Revill P Braithwaite S et al.Strategies for monitoring adults on antiretroviral treatment: a combined analysis of three mathematical models.Lancet Glob Health. 2013; (published online Dec 10.)http://dx.doi.org/10.1016/S2214-109X(13)70048-2Google Scholar Results show that, in most scenarios, viral load monitoring every 6 months or 12 months is not cost-effective,1Keebler D Revill P Braithwaite S et al.Strategies for monitoring adults on antiretroviral treatment: a combined analysis of three mathematical models.Lancet Glob Health. 2013; (published online Dec 10.)http://dx.doi.org/10.1016/S2214-109X(13)70048-2Google Scholar even when effects on onward transmission and resistance are included, compared with the health benefits of expanding ART coverage at the WHO 2010 CD4 threshold for ART initiation of 350 cells per μL, and even at the new proposed WHO 2013 threshold of 500 cells per μL.2WHOConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. World Health Organization, GenevaJune 2013http://www.who.int/hiv/pub/guidelines/arv2013/en/Google Scholar The authors conclude that viral load monitoring should only be considered in countries where ART rollout has been achieved with close to full coverage. The 2013 consolidated WHO guidelines2WHOConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. World Health Organization, GenevaJune 2013http://www.who.int/hiv/pub/guidelines/arv2013/en/Google Scholar make several notable recommendations, including: to move towards use of viral load monitoring, to increase the CD4 threshold for ART initiation to 500 cells per μL, and to use the Option B+ strategy for prevention of mother-to-child transmission (pMTCT) in generalised epidemics (starting ART for life in all HIV-infected pregnant women, regardless of CD4 count). The first two recommendations are aspirational and do not have supporting evidence from clinical trials.3Jourdain G Le Cœur S Ngo-Giang-Huong N et al.Switching HIV treatment in adults based on CD4 count versus viral load monitoring: a randomized, non-inferiority trial in Thailand.PLOS Med. 2013; 10: e1001494Crossref PubMed Scopus (29) Google Scholar, 4Saag MS, Westfall A, Luhanga DK, et al. A cluster randomized trial of routine vs discretionary viral load monitoring among adults starting ART: Zambia. 19th Annual Conference on Retroviruses and Opportunistic Infections. Seattle, WA, USA; March 5–8, 2012.Google Scholar, 5Sabin CA Cooper DA Collins S Schechter M Rating evidence in treatment guidelines: a case example of when to initiate combination.AIDS. 2013; 27: 1839-1846Crossref PubMed Scopus (38) Google Scholar The third is largely based on programmatic considerations. Together, they would expand the numbers of adults needing ART from 16·7 million to 25·9 million (current coverage is 10 million).6WHOWHO issues new HIV recommendations calling for earlier treatment: Earlier, safer and simpler antiretroviral therapy can push the HIV epidemic into irreversible decline.http://www.who.int/mediacentre/news/releases/2013/new_hiv_recommendations_20130630/en/index.htmlGoogle Scholar Therefore, priorities need to be set in the context of prevailing resource constraints. Appropriately framed economic studies, such as Keebler and colleagues' report,1Keebler D Revill P Braithwaite S et al.Strategies for monitoring adults on antiretroviral treatment: a combined analysis of three mathematical models.Lancet Glob Health. 2013; (published online Dec 10.)http://dx.doi.org/10.1016/S2214-109X(13)70048-2Google Scholar are valuable for decision-makers facing this task. The goals of monitoring at the individual level are to measure ART adherence (viral load), to guide the timing of switching to second-line ART to avoid severe clinical outcomes and preserve the ability to respond well to second-line ART, and to prevent onward HIV transmission7Cohen MS Chen YQ McCauley M et al.Prevention of HIV-1 infection with early antiretroviral therapy.N Engl J Med. 2011; 365: 493-505Crossref PubMed Scopus (5362) Google Scholar (including resistant virus). Clinical, viral load, and CD4 failure can be defined with different thresholds and, unsurprisingly, do not always correlate well. CD4 is a better predictor of imminent clinical progression than viral load and is best used to guide ART initiation.2WHOConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. World Health Organization, GenevaJune 2013http://www.who.int/hiv/pub/guidelines/arv2013/en/Google Scholar Viral load failure on ART occurs earliest and needs to be distinguished from temporary non-adherence; one aim of viral load monitoring is to switch earlier, well before immunological or clinical failure occur. However, this critically requires that drugs are available for second-line treatment and beyond. Clinical monitoring alone is very effective and low cost,1Keebler D Revill P Braithwaite S et al.Strategies for monitoring adults on antiretroviral treatment: a combined analysis of three mathematical models.Lancet Glob Health. 2013; (published online Dec 10.)http://dx.doi.org/10.1016/S2214-109X(13)70048-2Google Scholar, 8Mugyenyi P Walker AS Hakim J et al.Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.Lancet. 2010; 375: 123-131Summary Full Text Full Text PDF PubMed Scopus (259) Google Scholar but it will not perfectly predict CD4 or viral load failure, and switching might also occur unnecessarily—ie, with undetectable viral load.9van Oosterhout JJ Brown L Weigel R et al.Diagnosis of antiretroviral therapy failure in Malawi: poor performance of clinical and immunological WHO criteria.Trop Med Int Health. 2009; 14: 856-861Crossref PubMed Scopus (86) Google Scholar This is the principle behind targeted monitoring, whereby CD4 or viral load, or both, are used to prevent switching in case of poor specificity of clinical failure diagnosis.10Gilks CF Walker AS Munderi P et al.A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria.PloS ONE. 2013; 8: e57580Crossref PubMed Scopus (14) Google Scholar The WHO 2013 guidelines aspire to bring together treatment and prevention in both its earlier ART initiation and viral load monitoring guidance, and also to decrease the gap between well resourced and resource-poor settings. Although this goal is laudable, the importance of equity must be highlighted, since prioritising viral load monitoring over ART rollout would be likely to lead to more unequal health outcomes, as discussed in Keebler and colleagues' report.1Keebler D Revill P Braithwaite S et al.Strategies for monitoring adults on antiretroviral treatment: a combined analysis of three mathematical models.Lancet Glob Health. 2013; (published online Dec 10.)http://dx.doi.org/10.1016/S2214-109X(13)70048-2Google Scholar The scarcity in capacity for laboratory monitoring must not be a barrier to providing ART to those in most need, nor to switching clinically failing sick patients, as endorsed by WHO.2WHOConsolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Recommendations for a public health approach. World Health Organization, GenevaJune 2013http://www.who.int/hiv/pub/guidelines/arv2013/en/Google Scholar The Option B+ pMTCT strategy will require that ART availability is expanded and rolled out to low-level health facilities in which pMTCT programmes are already operating in many African countries. This availability will be a good thing for patients who will not be required to travel so far to obtain drugs, and will hopefully reduce loss to follow-up.11Jani IV Sitoe NE Alfai ER et al.Effect of point-of-care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: an observational cohort study.Lancet. 2011; 378: 1572-1579Summary Full Text Full Text PDF PubMed Scopus (227) Google Scholar However, Option B+ will very probably increase costs and make the WHO 2013 monitoring recommendation even more challenging, since most health facilities in Africa are missing many basic commodities, let alone the capacity to manage viral load monitoring. Of 58 health facilities surveyed across Malawi, Uganda, and Zimbabwe in 2012, only two of those providing ART provided viral load monitoring (both tertiary facilities). This number compared with CD4 testing in about a third of mainly secondary and tertiary facilities, with a further half sending samples off-site for CD4 testing.12Abongomera G, Namata H, Nkhata M, et al. Lablite: baseline mapping survey of 9 decentralised ART service provision in Malawi, Uganda and Zimbabwe. XIX International AIDS 10 Conference. Washington DC, USA, July 22–27. Abstr LBPE572012.Google Scholar CD4 monitoring, especially with simpler machines (eg, Alere Pima CD4) and point-of-care tests that are currently being field tested in Africa, will undoubtedly save some lives by ensuring earlier switching than that with clinical monitoring alone.8Mugyenyi P Walker AS Hakim J et al.Routine versus clinically driven laboratory monitoring of HIV antiretroviral therapy in Africa (DART): a randomised non-inferiority trial.Lancet. 2010; 375: 123-131Summary Full Text Full Text PDF PubMed Scopus (259) Google Scholar Viral load remains mostly unaffordable and point-of-care tests are not likely to become available in the near future. Since CD4 also identifies individuals most in need of immediate ART and other prophylaxis, caution should be applied before recommending doing away with it. As suggested by Keebler and colleagues,1Keebler D Revill P Braithwaite S et al.Strategies for monitoring adults on antiretroviral treatment: a combined analysis of three mathematical models.Lancet Glob Health. 2013; (published online Dec 10.)http://dx.doi.org/10.1016/S2214-109X(13)70048-2Google Scholar the continued implementation of CD4 monitoring is more likely to be cost-effective in many settings than would be a rapid transition to viral load monitoring, although this must also be assessed against other competing priorities. In conclusion, the authors and WHO should be congratulated for this work. Although not included in the main WHO 2013 guidelines document, it provides important guidance for policy-makers in resource-limited countries as they choose between competing priorities, and decide how to apply the new guidelines in their own settings. We declare that we have no conflicts of interest. Cost-effectiveness of different strategies to monitor adults on antiretroviral treatment: a combined analysis of three mathematical modelsThe priority for HIV programmes should be to expand antiretroviral therapy coverage, firstly at CD4 cell count lower than 350 cells per μL, and then at a CD4 cell count lower than 500 cells per μL, using lower-cost clinical or CD4 monitoring. At current costs, viral load monitoring should be considered only after high antiretroviral therapy coverage has been achieved. Point-of-care technologies and other factors reducing costs might make viral load monitoring more affordable in future. Full-Text PDF Open Access