title: Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment: modelling study and economic analysis.
abstract: BACKGROUND
  With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial levels of transmitted drug resistance.
  
  
  METHODS
  We created a model of HIV transmission, progression, and the effects of ART, which accounted for resistance generation, transmission, and disappearance of resistance from majority virus in the absence of drug pressure. We simulated 5000 ART programmatic scenarios with different prevalence levels of detectable resistance in people starting ART in 2017 (t0) who had not previously been exposed to antiretroviral drugs. We used the model to predict cost-effectiveness of various potential changes in policy triggered by different prevalence levels of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) measured in the population starting ART.
  
  
  RESULTS
  Individual-level resistance testing before ART initiation was not generally a cost-effective option, irrespective of the cost-effectiveness threshold. At a cost-effectiveness threshold of US$500 per quality-adjusted life-year (QALY), no change in policy was cost effective (ie, no change in policy would involve paying less than $500 per QALY gained), irrespective of the prevalence of pretreatment NNRTI resistance, because of the increased cost of the policy alternatives. At thresholds of $1000 or higher, and with the prevalence of pretreatment NNRTI resistance greater than 10%, a policy to measure viral load 6 months after ART initiation became cost effective. The policy option to change the standard first-line treatment to a boosted protease inhibitor regimen became cost effective at a prevalence of NNRTI resistance higher than 15%, for cost-effectiveness thresholds greater than $2000.
  
  
  CONCLUSIONS
  Cost-effectiveness of potential policies to adopt in response to different levels of pretreatment HIV drug resistance depends on competing budgetary claims, reflected in the cost-effectiveness threshold. Results from our model will help inform WHO recommendations on monitoring of HIV drug resistance in people starting ART.
  
  
  BACKGROUND
  WHO (with funds provided by the Bill & Melinda Gates Foundation), CHAIN (European Commission).
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK. Electronic address: andrew.phillips@ucl.ac.uk.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Phillips
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cambiano
authors.affiliation: London School of Hygiene & Tropical Medicine, London, UK.
authors.forename: Alec
authors.initials: A
authors.lastname: Miners
authors.affiliation: University of York, York, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Revill
authors.affiliation: Africa Centre, KwaZulu Natal, South Africa.
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Bennett
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Elliott
authors.initials: E
authors.lastname: Raizes
authors.affiliation: Research Department of Infection and Population Health, University College London, London, UK.
authors.forename: Fumiyo
authors.initials: F
authors.lastname: Nakagawa
authors.affiliation: University Division of Infectious Diseases, Siena University Hospital, Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Vitoria
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Jhoney
authors.initials: J
authors.lastname: Barcarolo
authors.affiliation: World Health Organization, Geneva, Switzerland.
authors.forename: Joseph
authors.initials: J
authors.lastname: Perriens
authors.affiliation: Tufts University School of Medicine and Tufts Medical Center, Boston, MA, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jordan
authors.affiliation: World Health Organization, Geneva, Switzerland. Electronic address: bertagnolios@who.int.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bertagnolio