Table 1.

Studies estimating the cost‐effectiveness of viral load (VL) monitoring

First author	Location	Year studied	Key features modelled	Authors’ conclusion on cost‐effectiveness+	Factors that make VL testing more cost‐effective	Incremental cost‐effectiveness ratio (ICER)
Kahn 21	Tororo, Uganda	2001 to 2002	Randomized trial	Definite no	VL testing was not effective in this RCT (no evidence of health benefit)	Clinical + CD4 + VL monitoring vs. Clinical + CD4 monitoring: $5181 per DALY averted
Schneider 31	Thailand	2001 to 2009	Heterogeneity in VL Virologic failure Effect of VL on differentiation of care	^Qualified yes	Lower cost of ART	Annual monitoring after single screen at six months vs. Supplying only first‐line ART for ten years (with ART costs): $68,084 per QALY Annual monitoring after single screen at six months vs. Supplying only first‐line ART for ten years (without ART costs): $7224 per QALY
Bishai 22	Sub‐Saharan Africa	2004 (Cost data)	Heterogeneity in VL Virologic failure	^Qualified yes	Second line treatment would have to be available Cost of VL testing would have to be reduced to $14 per test to have same median ICER as CD4 testing compared to clinical monitoring	VL vs. CD4 monitoring (second line unavailable): $16,139 per QALY VL vs. CD4 monitoring (second line available): $14,670 per QALY
Vijayaraghavan 32	South Africa	2005	Heterogeneity in VL Virologic failure Variation switching to second line in first line failures	Definite yes	Treating patients with VLs >100,000 copies/ml to reduce HIV transmission by “highly efficient transmitters”	Use of VL testing every six months vs. WHO guidelines: $7860 per QALY Increased VL testing frequency (every three months) vs. WHO guidelines: $41,286 per QALY
Pham 30	Vietnam	2005 to 2013	Resistance Virologic failure	^Qualified yes	VL testing every two years and individuals with VL >1000 copies/ml and detectable HIV drug resistance placed on second line ART Lower cost of second line ART Low cost POC‐VL and resistance tests	WHO recommendations for VL monitoring (six months after treatment initiation and every 12 months thereafter) vs. Status quo (no VL monitoring): $5243 per DALY averted
Kimmel 27	Côte d'Ivoire	2006	Heterogeneity in VL Resistance	^Qualified yes	HIV RNA test <$90 Decrease in second line efficacy due to time spent on failing first line ART is greater than 1% per month Cost of second line ART <$300	VL monitoring (test cost = $50 to $87) vs. Cotrimoxazole prophylaxis for opportunistic infections: $1990 to 2920 per YLS
Boyer 20	Cameroon	2006 to 2010	Clinical Trial	Qualified no	Lower priced generic in‐house assay Use VL assay for patients with CD4 <200 cells/μl	Clinical monitoring vs. VL + CD4 + clinical monitoring (Abbot RealTime HIV‐1 assay): $4768 per LYS Clinical monitoring vs. VL + CD4 + clinical monitoring (Generic assay): $3339 per LYS
Bendavid 24	Cape Town area	2007	Heterogeneity in VL Virologic failure	^Qualified yes	Lower price of VL testing Possibly reduced HIV transmission (not modelled) Fewer accumulated resistance mutations (not modelled) Higher rate of virologic failure	VL monitoring + CD4 vs. CD4: $5414 per LYG Every three months vs. every six months: $100,000 per LYG
Phillips 34	Lower to middle income countries	2008	Heterogeneity in VL Virologic failure Resistance Variation in switching to second line in first line failures	Qualified no	Lower cost of second line ART	VL >500 copies/ml vs. Switch after WHO stage four event: $1500 per LYG VL >10,000 copies/ml vs. Switch after WHO stage four event: $4011 per LYG
Scott Braithwaite 16	Sub‐Saharan Africa	2008 (Cost data)	Virologic failure Heterogeneity in VL	Qualified no	ICER for VL testing better when first and second line costs are equal Use routine virological testing when ART is already initiated at 500 cells/μl and coverage targets have been met Low cost VL testing Six monthly VL testing, switching threshold at 1000 copies/ml is the only strategy on the efficient frontier	VL monitoring (10,000 copies/ml to 1000 copies/ml threshold) vs. Starting ART at CD4 count 200 cells/μl: $4723 to $25,370 per QALY
Estill 5	LMIC (Cost data can be updated for specific setting)	2010	Variation in switching to second line in first line failures Resistance Effect of VL on differentiated care Virologic failure Heterogeneity in VL	Qualified no	Routine VL monitoring cost‐effectiveness depends on cost of second line ART POC VL cost‐effectiveness improved if first and second line ART prices are close Targeted VL monitoring is cost‐efficient only if second line costs are much higher than first line, and routine VL monitoring does not prevent failure	VL monitoring vs. Clinical monitoring: $951 to $5813 per DALY averted POC‐VL (every six to twenty‐four months) vs. CD4 monitoring (irregular every six months, every six to twenty‐four months): $426 to $33,515 per DALY averted Lab‐VL (every six to twenty‐four months) vs. CD4 monitoring (irregular every six months, every six to twenty‐four months): $984 to $8862 per DALY averted
Hamers 26	South Africa	2011	Virological failure	Definite yes	Reduced accumulation of drug‐resistance mutations, reduced incidence of opportunistic infections and mortality, increased economic productivity, reduced HIV transmission	VL‐only every six months vs. Symptom‐based approach: $3183 per LYG VL‐only every 12 months vs. Symptom‐based approach: $5319 per LYG
Estill 25	LMIC (Cost data can be updated for specific setting)	2012	Heterogeneity in VL Virologic failure	^Qualified yes	Include reductions in HIV transmission with suppression Lower cost of second line ART and VL Risk of virological failure with monitoring strategy (reduced by VL monitoring compared to clinical/CD4 monitoring) Use POC‐VL test level of detection criteria of 1000 copies/ml to reduce unnecessary switches to second line ART	More accurate detection of treatment failure and faster, more appropriate switching to second line: $4010 to $9230 per QALY vs. clinical monitoring and $5960 to $25,540 vs. CD4 monitoring Taking transmission into account + More accurate detection of treatment failure and faster, more appropriate switching to second line: $2450 to $5830 per QALY vs. clinical monitoring and $2230 to $10,380 vs. CD4 monitoring Risk of virologic failure twice as high with clinical or CD4 compared to VL monitoring + Taking transmission into account + More accurate detection of treatment failure and faster, more appropriate switching to second line: $960 to $2500 per QALY vs. clinical monitoring and cost saving $2460 per QALY vs. CD4 monitoring
Keebler 15	Zambia	2012	Presents results from three different models Heterogeneity in VL Resistance – HIV Synthesis model (Phillips), Braithwaite and colleagues Variation in switching to second line in first line failures Virological failure	Qualified no	VL monitoring after high ART coverage is achieved Lower second line ART cost Lower test costs Targeted VL strategy	VL every 12 months vs. VL every 36 months: Braithwaite (20 years): $6018.83 per DALY averted HIV Synthesis (15 years): $3413.8 per DALY averted Estill (five years): $3760 per DALY averted
Negoescu 28	Uganda	2013	Virologic failure Effect of VL on differentiated care	^Qualified yes	Client centered and tailored to country GDP: Adjusting VL monitoring intervals of HIV patients on ART according to individual patient characteristics, disease dynamics, behavior, and GDP. Implementation in high resource settings	Adaptive VL optimized to 1× GDP threshold vs. monitoring every 24 months: $491 per QALY Adaptive VL optimized to 3× GDP threshold vs. adaptive VL optimized to 1× GDP threshold: $1311 per QALY
Ouattarra 29	Côte d'Ivoire	2013 to 2017	Virologic failure Effect of VL on differentiated care Heterogeneity in VL	Definite yes	Adaptive VL ICER <1× GDP if second line ART and VL costs decreased to $156 and $13 Sensitive to initial CD4 count of cohort Lower HIV transmission rate due to monitoring (not modelled)	Adaptive VL vs. VL confirmation: $4100/YLS (2013 USD)
Phillips 35	Zimbabwe	2015 to 2025	Paper was primarily focused on whether use of drug resistance testing was likely to be cost effective as part of ART monitoring strategy. Variation in switching to second line in first line failures Virologic failure Resistance Heterogeneity in VL	Qualified no	Most effective strategy for DALYs averted was VL monitoring without confirmation	VL monitoring with no confirmation vs. no monitoring, no second line: $2113 per DALY averted
Phillips 23	Zimbabwe	2015 to 2035	Variation in switching to second line in first line failures Virologic failure Resistance Heterogeneity in VL Effect of VL on differentiated care	^Qualified yes	With $22 viral‐load test cost, annual savings of $30 needed to make program cost‐effective. Reducing visits from every one to three months to every six months or every nine to twelve months should enable these savings. Reduction in non‐ART program costs Use VL monitoring less frequently than every 12 months (caveat: health risks with such infrequent VL monitoring not well understood)	DBS VL monitoring every 12 months vs. No monitoring: $326 per DALY averted ((if used to differentiate care and reduce clinic visit costs)

^Qualified yes – the authors’ overall conclusion was that viral load monitoring was cost effective, but that this was conditional on the existence of certain conditions, +The author's conclusions on cost effectiveness depend on the choice of cost effectiveness threshold – the appropriate threshold is now recognised as being lower than had previously been supposed, particularly when using the 1× or 3× GDP criteria. ART, antiretroviral therapy; DALY, disability‐adjusted life years; GDP, gross domestic product; LYG, years of life gained; LYS, life years saved; QALY, quality‐adjusted life years; VL, viral load; YLG, years of life gained; WHO, World Health Organization; LMIC, low‐ and middle‐income countries.