Supplement. PART A: Methods. In order to estimate population-wide HIV transmission and progression rates, we

Transcription

1 Supportng document Supplement PART A: Methods 1 Epdemc Model Framework 1.1 Man Model Structure In order to estmate populaton-wde HIV transmsson and progresson rates, we developed a determnstc compartmental model, capturng transmsson through sexual contact (heterosexual and homosexual), and needle-sharng. Ths model s an extenson of a publshed HIV transmsson model [1]. Based on the current stuaton n the Chnese HIV epdemc, we subdvded our target populaton nto 7 groups: men who have sex wth men (MSM), male njectng drug users (IDU), clents of female sex workers (CSW), low-rsk men (M), female IDU (FIDU), female sex workers (FSW) and low-rsk women (W). Once nfected, ndvduals wll progress though asymptomatc, symptomatc, and AIDS stages. The flow dagram, takng the MSM group as an example, s shown n Fgure A-1. Parameters for epdemologcal factors, behavor (such as numbers of opposte/same sex partners, condom use, nfectousness of asymptomatc HIV, and needle-sharng), the mortalty rate, and the probablty of dsease transmsson were drawn from prevous publcatons (Table A-1). The defnton of all symbols can be found n Table A-4.

2 Table A-1: Key model parameters Varable Value References Demographc characterstcs Annual mortalty rate (background) Men Calculated, [2] Women Calculated, [2] IDU Calculated, [2] Annual mortalty rate (due to HIV/AIDS) Asymptomatc (CD4 > 350 cells/µl) 0.02 [3] Symptomatc (200 CD4 350 cells/µl) [3] AIDS (CD4 < 200 cells/µl) 0.22 [4, 5] Symptomatc wth ART 0.05 [3, 6] AIDS wth ART [6] Annual maturaton rate * Men Calculated, [2] Women Calculated, [2] Annual entry rate^ Men Calculated, [2] Women Calculated, [2] Intal populaton (aged years) MIDU 1,474,102 [2, 7] FIDU 982,735 [2, 7] MSM 3,600,000 [8] FSW 2,815,402 [2, 9] CSW 27,556,415 [2, 9] M 452,799,906 Calculated, [2] W 477,571,440 Calculated, [2] Intal prevalence (aged years), % MIDU 9.3 [10] FIDU 9.3 [10] MSM 5 [11] FSW 0.6 [9] CSW 0.4 [9] M [12] W [12] Sexual transmsson Transmsson probablty per partnershp Heterosexual (female to male) Asymptomatc HIV 0.01 [13-21] Symptomatc HIV 0.02 [13-21] AIDS 0.03 [13-21] Heterosexual (male to female) Asymptomatc HIV 0.03 [13-21] Symptomatc HIV 0.04 [13-21] AIDS 0.08 [13-21]

3 Table A-1 (Contnued) Varable Value References Homosexual (male to male) Asymptomatc HIV 0.04 [17, 22-24] Symptomatc HIV 0.05 [17, 22-24] AIDS 0.12 [17, 22-24] Annual same-sex partners MSM 5 [25] Condom use wth same-sex partners, % MSM 36% [25, 26] Annual opposte-sex partners MIDU 2.5 [27] FIDU 3.5 [27, 28] MSM 0.1 [29] FSW 100 [30, 31] CSW 11.2 Calculated 1 M 1.1 [32] W 1.1 [32] Condom use wth opposte-sex partners, % MIDU 35% [33] FIDU 42% [33] MSM 35% [12] FSW 60% [12, 34] CSW 50% [12] M 20% Assumed, [34] W 20% Assumed, [34] Condom effectveness 0.9 [35-37] Injectng drug use transmsson Transmsson probablty per shared njecton Asymptomatc HIV [38-40] Symptomatc HIV [38-40] AIDS [38-40] Average njectons per year 200 [1, 28, 40] Proporton of njectons that are shared, % 40 [9] HIV VCT Proporton of populaton tested n past 12 months, % Hgh-rsk groups 37% [10] Low-rsk groups 2% [10] Annual probablty of symptom-based case fndng, % HIV 10% [41] AIDS 20% [41] Reducton n partner numbers among persons dentfed as HIV-postve, % 20% [42] Reducton n partner numbers among AIDS patents, % 90% Assumed ART

4 Table A-1 (Contnued) Varable Value References Proporton startng ART at CD4 cell count of 350 cells/µl 30% [10] Annual ART entry rate f CD4 cell count <350 cells/µl 0.05 [1] Reducton n sexual nfectvty due to ART, % 90% [20, 43, 44] Reducton n njecton nfectvty due to ART, % 50% [41, 45] Progresson Rates From asymptomatc to symptomatc [46] From symptomatc to AIDS Untreated [46] Treated [46] Qualty of lfe multplers HIV negatve 1 Undentfed asymptomatc HIV 0.90 [47-50] Identfed asymptomatc HIV 0.85 [41, 47-50] Undentfed symptomatc HIV 0.79 [47-50] Identfed symptomatc HIV 0.72 [47-50] Symptomatc HIV treated wth ART 0.83 [47-50] Undentfed AIDS 0.68 [47-50] Identfed AIDS 0.68 [47-50] AIDS treated wth ART 0.82 [47-50] Cost, 2010 Int.$ Annual HIV-related health care cost Untreated asymptomatc HIV 6,230 [51] Untreated symptomatc HIV 10,458 Interpolated 2 Symptomatc HIV treated wth ART 9,324 Interpolated 2 Untreated AIDS 14,108 [51] AIDS treated wth ART 12,269 Interpolated 2 Annual non-hiv related health care cost 264 [52] Annual cost of ART 4,781 [53, 54] Cost of HIV ELISA antbody test 19 [55] Cost of confrmatory western blot test 64 [55] Cost of behavor counselng 22 [56] Annual dscount rate, % 3 Annual cost of MMT per IDU 532 [57] Annual cost of NSP per IDU 192 [57] MSM = men who have sex wth men; MIDU = male njectng drug users; CSW = clents of female sex workers; M = low-rsk men; FIDU = female njectng drug users; FSW = female sex workers; W = low-rsk women (W); ART = antretrovral therapy; ELISA = enzyme-lnked mmunosorbent assay; * Entry rate s composed from the background populaton growth rate and rate of reachng adulthood; ^Maturaton rate s the sum of the background mortalty rate and the rate of agng; 1 Ths s a derved value, calculated n order to balance the total number of partnershps formed by men and women; 2 Calculated by multplyng health care costs of untreated asymptomatc HIV by the ratos of the cost of ths dsease stage wth other stages n publshed papers [1].

5 Fgure A-1: HIV transmsson compartmental model structure [1] Based on the framework of our model, we developed dfferental equatons for each rsk group. The complete model comprses 70 equatons. We coded these equatons, ntal values and parameters usng MATLAB R2010a. We ran our program for 30 years. The 10 equatons for each rsk group are: dx dt dx dt dx dt dx dt dx dt dx dt dx dt dx dt X X X ( t) X ( b ) X,1 1, j 1,1 2,2, j,1 1 1,1 j j3 X X ( t) X ( b ) X,2 1,1 2,2, j,2 2 2,2 j3 ( t) X ( t) X ( ) X ( b ) X,3, j,1, j,2 3 3, ,3 j3 j3 ( ) X ( b ) X,4 3 3, ,4 X ( ) X ( b ) X,5 3,3 5 5, ,5 (1 ) X ( )(1 ) X ( b ) X,6 4 4, , ,6 X ( ) X X ( b ) X,7 4 4, ,5 6, ,7 X ( ) X ( b ) X,8 5,5 8 8,8 8 8,8 (A-1) (A-2) (A-3) (A-4) (A-5) (A-6) (A-7) (A-8)

6 dx dt dx dt X ( )(1 ) X X ( b ) X,9 6, ,8 9,9 9 9,9 X ( ) X X ( b ) X,10 7, ,8 9, ,10 (A-9) (A-10) Where the ndex corresponds to 1: MSM, 2: MIDU, 3: CSW, 4: M, 5: FIDU, 6: FSW, and 7: W. 1.2 Target Populaton Our target populaton s adults aged years old. The rate at whch people enter the target group s composed from the background populaton growth rate and the speed of reachng adulthood. In the same way, the maturaton rate s the sum of the background mortalty rate and the rate of ageng. HIV prevalence n rsk group : Number of People lvng wth HIV n rsk group p Populaton of rsk group (A-11) Entry Rates: 15 years old populaton = ln(1 ) growth rate years old populaton (A-12) Maturaton Rates: 64 years old populaton = ln(1 ) mortalty rate years old populaton (A-13) Intal values for the populaton of each group are shown n Table A-2, calculated from populaton sze and prevalence nformaton n exstng studes [2, 7-9].

7 Table A-2: Intal values for the populatons of rsk groups X1 X2 X3 X4 X5 X6 X7 X8 X9 X10 MIDU 935, ,103 43,184 25,362 25,910 13,695 1,522 17,274 9,130 1,014 FIDU 623, ,402 28,789 16,908 17,274 9,130 1,014 11,516 6, MSM 2,394,000 1,026,000 56,700 33,300 34,020 17,982 1,998 22,680 11,988 1,332 FSW 1,958, ,553 5,321 3,125 3,193 1, ,128 1, CSW 19,212,333 8,233,857 34,721 20,392 20,833 11,012 1,224 13,888 7, Low-rsk Man 443,632,972 9,053,734 55,468 1,132 33, , Low-rsk Woman 467,903,006 9,549,041 58,503 1,194 35, , Transmsson Forces Susceptble ndvduals can become nfected n three ways: heterosexual contact, homosexual contact, and needle-sharng among IDUs. Table A-3 shows the detals of potental modes of nfecton between any two rsk groups. We consder heterosexual transmsson to be possble for MSM as well Common transmsson formula The probablty that men are not nfected by HIV-postve women n rsk group, and compartment j, though one heterosexual contact, NM j, (=5~7, j=3~10) s: N M N M X n (1 u ) X n (1 r )(1 u ) CT CT F F O O O O,3 a,4 1 a 1 ; N M 1,3 f, m,4 f, m X n (1 u ) X n (1 r )(1 u ) CT CT F F O O O O,5 S,6 1 S 1 ; N M 1,5 f, m,6 f, m O O O O X n (1 r )(1 u ) (1 ),7 1 X n u S,8 AIDS N M 1 (1 r ) ; N M 1,7 f, m 2,8 f, m CT CT F F O O O O X n (1 r ')(1 u ) (1 ')(1 ),9 1 X n r u, AIDS AIDS N M ; N M 1 (1 r ),9 f, m,10 f, m 2 CT CT F F where CT F s the total heterosexual contacts among women:

8 O O O O O O CT ( ) (1 ) ( ) (1 )(1 ) ( ) (1 ')(1 ) F X n u, j X n r u, j 1 X n r u, j 1 5,6,7 j1,2,3,5,8 j4,6,7 j9,10 The probablty that MSM are not nfected by HIV-postve MSM n compartment j though one homosexual contact, N MSM j (j=3~10) s: N MSM N MSM X n (1 u ) X n (1 r )(1 u ) CT CT MSM MSM S S S S 1,3 1 1 a 1, a 1 ; N MSM 1 3 m, m 4 m, m X n (1 u ) X n (1 r )(1 u ) CT CT MSM F S S S S 1,5 1 1 S 1, S 1 ; N MSM 1 5 m, m 6 m, m S S S S X n (1 r )(1 u ) (1 ) 1, X n u S 1,8 1 1 AIDS N MSM 1 (1 r ) ; N MSM 1 7 m, m 2 8 m, m CT CT MSM MSM S S S S X n (1 r ')(1 u ) (1 ')(1 ) 1, X n r u AIDS 1, AIDS N MSM 1 ; N MSM 1 (1 r ) 9 m, m 10 m, m 2 CT CT MSM MSM where CT MSM s the total number of homosexual contacts. CT ( X ) n (1 u ) ( X ) n (1 r )(1 u ) ( X ) n (1 r ')(1 u ) S S S S S S MSM 1, j 1 1 1, j , j j1,2,3,5,8 j4,6,7 j9,10 The probablty that IDU are not nfected by HIV postve IDU n rsk group, and compartment j, through one needle-sharng contact, N IDU j, (=2 or 5, j=3~10) s: X d S,3 X d S a,4 X d S a,5 S N IDU 1 ; N IDU 1 ; N IDU 1,3,4,5 CT CT CT IDU IDU IDU X d S,6 X d S,7 X d S S S,8 S N IDU 1 ; N IDU 1 (1 r ') ; N IDU 1,6,7 2,8 CT CT CT IDU IDU IDU X d S,9 X d S,10 1 S S N IDU ; N IDU 1 (1 r '),9,10 2 CT CT IDU IDU Where CT IDU s the total number of needle-sharng contacts n IDUs: CT ( X ) d s ( X ) d s, j 1, 2,3, 4,..10 IDU 2, j 2 2 5, j 5 5 j j

9 NF j, (=1~4, j=3~10) s the probablty that women are not nfected by N F N F HIV-postve men n rsk group, and compartment j, though one heterosexual contact. X n (1 u ) X n (1 r )(1 u ) CT CT M M O O O O,3 a,4 1 a 1 ; N F 1,3 m, f,4 m, f X n (1 u ) X n (1 r )(1 u ) CT CT M M O O O O,5 S,6 1 S 1 ; N F 1,5 m, f,6 m, f O O O O X n (1 r )(1 u ) (1 ),7 1 X n u S,8 AIDS N F 1 (1 r ) ; N F 1,7 m, f 2,8 m, f CT CT M M O O O O X n (1 r ')(1 u ) (1 ')(1 ),9 1 X n r u, AIDS AIDS N F ; N F 1 (1 r ),9 m, f,10 m, f 2 CT CT M M Where CT M s the total number of heterosexual contacts for men. O O O O O O CT ( ) (1 ) ( ) (1 )(1 ) ( ) (1 ')(1 ) M X n u, j X n r u X n r u, j 1, j 1 1,2,3,4 j1,2,3,5,8 j4,6,7 j9,10 Agan corresponds to 1: MSM, 2: MIDU, 3: CSW, 4: M, 5: FIDU, 6: FSW, and 7: W; and j corresponds to the 10 compartments reflectng HIV progresson ( 1: undentfed unnfected, 2: Identfed unnfected, 3:undentfed asymptomatc, 4: Identfed asymptomatc, 5: undentfed symptomatc, 6: Identfed symptomatc, 7: Identfed symptomatc wth ART, 8: undentfed AIDS, 9: Identfed AIDS, 10: Identfed AIDS wth ART).

10 Table A-3: Modes of HIV transmsson between rsk groups Male MSM Male IDU Male CSW Male Other Female IDU Female FSW Female Other Male MSM Homosexual Heterosexual Heterosexual Heterosexual Male IDU Needle-sharng Heterosexual Heterosexual Heterosexual Needle-sharng Male CSW Heterosexual Heterosexual Heterosexual Male Other Heterosexual Heterosexual Heterosexual Female IDU Heterosexual Heterosexual Heterosexual Heterosexual Needle-sharng Needle-sharng Female FSW Heterosexual Heterosexual Heterosexual Heterosexual Female Other Heterosexual Heterosexual Heterosexual Heterosexual Transmsson rates for each group Transmsson forces j3 () t, quoted n equatons (A-1) to (A-10), for the seven, j rsk groups are: ( t) 1 N M 1 N MSM n1 O (1 u1 O ) n1 S (1 u1 S ) 1, j, j j j3 5,6,7 j3 j3 O O (1 ) ( t) 1 N M 1 N IDU n2 u2 d2s2 2, j, j, j j3 5,6,7 j3 2,5 j3 O O n3 (1 u3 ) ( t) 3, 1 j N M, j j3 5,6,7 j3 O O n4 (1 u4 ) ( t) 4, 1 j N M, j j3 5,6,7 j3 O O (1 ) ( t) 1 N F 1 N IDU n5 u5 d5s5 5, j, j, j j3 1,2,3,4 j3 2,5 j3 O O n6 (1 u6 ) ( t) 6, 1 j N F, j j3 1,2,3,4 j3 O O n7 (1 u7 ) ( t) 7, 1 j N F, j j3 1,2,3,4 j3 (A-14) (A-15) (A-16) (A-17) (A-18) (A-19) (A-20) 1.4 Interventon types We compared four dfferent nterventon types aganst a control stuaton that was defned to match the current stuaton n Chna. The control stuaton (the base

11 case ) and the four nterventon types are defned as follows: 1) The Base Case: all parameters and assumptons match the current stuaton n Chna. Assume current testng rates of 37% for hgh-rsk groups and 2% for low-rsk groups, wth an ART utlzaton rate of 30%, and wthout MMT and NSP. 2) Expanded Voluntary Counselng and Testng (VCT) Only: ths case assumes that testng s expanded to a larger proporton of the populaton, wth no change n ART treatment provson or harm reducton programs. VCT was modeled as beng offered at dfferent rates to hgh- and low-rsk groups. Four sub-strateges are ncluded under ths strategy, defned by the testng rates for low- and hgh-rsk groups: one tme low-rsk and annual hgh-rsk VCT; low-rsk every three years and annual hgh-rsk VCT; everyone screened every three years; and everyone screened annually. 3) Expanded ART Treatment Only: n ths case, utlzaton of ART treatment s mproved, wth no expanson of the VCT or harm reducton programs. As ART treatment s expanded, more and more people enter treatment once ther CD4 count s less than 350 cells / l. 4) Harm Reducton Program: ths strategy ncluded methadone mantenance treatment (MMT) and needle/syrnge programs (NSP). In ths paper, a harm

12 Coverage reducton program s consdered to be a combnaton of NSP and MMT. IDUs covered by harm reducton programs are n ether NSP or MMT, whch means that those who drop out of MMT wll nject drugs wthout a hgh needle-sharng rsk. The VCT rate and ART utlzaton rate remaned the same as the base case. We dd not expect the coverage of access to NSP or MMT to reach 100% mmedately upon mplementaton, so we assumed that coverage would ncrease gradually to 5% at year 5, 50% at year 15, and would reach 95% at year 25, n the pattern shown n Fgure A-2. Twelve month retenton n MMT s assumed to be 50% [58, 59]. NSP or MMT Coverage Year Fgure A-2: The Coverage of NSP or MMT over 30 Years 5) Combnaton Strateges: combnaton strateges of any two of Expanded VCT, ART Treatment and Harm Reducton Program, or a combnaton strategy of all three. 2 Model Outputs In order to capture the HIV epdemologcal trend we calculated prevalence,

13 ncdence, and cumulatve ncdence. For economc outcomes, we calculated QALYs. 2.1 Epdemologcal Outcomes The key epdemologcal outcomes of the model are: The number of susceptble ndvduals n rsk-group, S X ( t) X ( t),1,2 (A-21) The number of PLWHA n rsk-group, 10 j=3 I X ( t);, j (A-22) HIV prevalence n rsk-group, 10 P X ( t) X ( t), j, j j=3 j (A-23) New nfectons n rsk-group, NI ( ), ( ) ( ),1,2 ; t X t X t j j3 (A-24) Cumulatve new nfectons n rsk-group, t CI ( ), ( ) ( ) t X t X t j,1,2 dt 0 j3 (A-25) 2.2 Economc Outcomes We measured economc outcomes as QALYs, whch were n turn based on cost calculatons for the dfferent nterventon types. These are calculated n equatons (A-26) to (A-32). 30 rt QALYs n rsk-group : Q e q X ( t) dt (A-26) Total QALYs: TQ Q Cost of ART n rsk-group : 0 j j, j 30 rt ART j, j 0 j C e c X ( t) dt (A-27) (A-28)

14 Cost of VCT n rsk-group : 30 rt C screen e c X ( t) 1,1 c ( ) X ( t) dt neg pos j j, j 0 j3,5,8 (A-29) Cost for NSP: 30 rt C ( ( ) ( )) ( ) NSP e cnsp X t X t Cover t dt 2, j 5, j 0 j (A-30) 30 rt Cost for MMT: C ( ( ) ( )) ( ) MMT e cmmt X t X t Cover t dt 2, j 5, j 0 j Health care cost n rsk-group : 30 rt HC j, j 0 j C e c X ( t) dt (A-31) (A-32) We calculated QALYs over the 30 year lfe of the project, wth an annual dscount rate of 3%.

15 Table A-4: Summary and Descrpton of Model Varables Varables/Symbols Defnton Demographc characterstcs X j, Number of people n rsk group wth status j b j Annual background mortalty rate j, Annual mortalty rate due to HIV/AIDS Annual maturaton rate Annual entry rate Sexual transmsson Z f, m Z mf, Z mm, S n1 Annual transmsson probablty per partnershp from female to male, where z= asymptomatc HIV, symptomatc HIV, and AIDS Annual transmsson probablty per partnershp from male to female, where z= asymptomatc HIV, symptomatc HIV, and AIDS Annual transmsson probablty per partnershp from male to male, where z= asymptomatc HIV, symptomatc HIV, and AIDS Annual same-sex partners of MSM S u1 Condom use wth same-sex partners, percent O n Annual opposte-sex partners n rsk group O u Condom use wth opposte-sex partners n rsk group Condom effectveness Injecton drug use transmsson Z Transmsson probablty per shared njecton, where z= asymptomatc HIV, symptomatc HIV, and AIDS d Average njectons per year, =2 or 5,(count) s Fracton of njectons that are shared, =2 or 5, percent Voluntary Counselng and Testng j Fracton of populaton tested n past 12 months for rsk group wth status j, percent

16 1/ j r 1 r 1 2 Average duraton (years) that unnfected ndvduals reman dentfed after testng n rsk group Annual probablty of symptom-based case fndng n rsk group wth status j, percent Reducton n sexual behavor among persons dentfed as HIV-postve, percent Reducton n sexual behavor among people wth AIDS, percent ART Treatment j Fracton startng ART at CD4 cell count of 350 n rsk group wth status j j Annual ART entry rate f CD4 cell count <350 of rsk group wth status j r 2 Reducton n sexual nfectvty due to ART, percent r 2 Reducton n njecton nfectvty due to ART, percent Cost-effectveness q j Qualty-of-lfe adjustment of ndvduals n rsk group wth status j c j cj c neg c pos c NSP c MMT Cover() t R Annual ART cost per person Annual health care cost per ndvdual n rsk group wth status j VCT cost per HIV-negatve person, ncludng cost of counselng, ELISA test VCT cost per HIV-postve person, ncludng cost of counselng, ELISA test and Western blot test Annual cost per IDU of NSP program, ncludng Human Resource (HR), captal, and needle costs. Annual cost per IDU of MMT program, ncludng HR, captal, and methadone costs. Coverage of NSP or MMT at tme t Dscount rate Others j j3 () t, j HIV dsease progresson rate for ndvduals n rsk group wth status j Transmsson forces for each rsk groups

17 PART B: Calbraton Analyss We calbrated our model aganst the number of PLWHA, annual deaths due to HIV/AIDS, and annual new nfectons n Chna usng fgures publshed n the UNAIDS Global Report on HIV/AIDS. We ran the model for 30 years usng the ntal populaton and HIV prevalence of Chna n 2002, usng base case parameters. Fgure B-1 compares the number of people lvng wth HIV/AIDS, annual death due to HIV/AIDS and new nfectons estmated by our model wth the publshed values from the UNAIDS Global Report on HIV/AIDS [33, 60, 61]. All of the predctons of these ndcators based on our model are wthn the range of the values publshed by UNAIDS. Number of People Lvng wth HIV/AIDS Number of Death Due to HIV/AIDS Estmates UNAIDS Global Report Estmates UNAIDS Global Report year year Number of Newly Infecton Estmates UNAIDS Global Report year Fgure B-1: The number of PLWHA, annual deaths and new nfectons under the model estmates and publshed UNAIDS data

18 Part C: Senstvty Analyss 1 Method Multvarate Senstvty Analyss We used Latn Hypercube samplng to randomly generate one thousand sets of values of key parameters. Latn Hypercube Samplng draws random values wthout replacement from across the range of the dstrbuton for each parameter of nterest, and provdes an effcent way to conduct multvarate senstvty analyss [62]. Because dstrbutons for many of the parameters are dffcult to quantfy, and values outsde of certan ranges were mpossble, trangular dstrbutons were used for all parameters, wth the peak of the dstrbuton centered at the pont estmate used n the prmary model. The parameters that we vared and the range wthn whch the trangular dstrbuton was sampled are shown n Table C-1. We ran the model a thousand tmes wth these sets of parameters and calbrated each run aganst the number of people lvng wth HIV/AIDS, reported by UNAIDS. Model ft was tested usng the Modelng effcency statstc, EF (Equaton C-1), whch s conceptually smlar n meanng to the R-squared statstc from lnear regresson, and ndcates better ft for larger values of EF. We kept the 200 runs wth the largest EF values, and calculated the epdemologcal trends for the base case, percentage of HIV nfectons prevented

19 over 30 years and ncremental cost-effectveness ratos (ICERs) relatve to the base case for ten selected nterventons usng these 200 sets of parameters. Table C-1: Ranges of Key Parameters for Senstvty Analyss Varables Value Range Annual same-sex partners of MSM Condom use wth same-sex partners of MSM 36% 20-50% Annual opposte-sex partners MIDU FIDU MSM FSW CSW Low-rsk men Low-rsk women Condom use wth opposte-sex partners MIDU 35% 20-50% FIDU 42% 21-63% MSM 35% 20-50% FSW 60% 30-90% CSW 50% 25-75% Low-rsk men 20% 10-30% Low-rsk women 20% 10-30% Average njectons per year

20 Proporton of njectons that are shared 40% 20-60% Cost, 2010 nt.$ Annual cost of ART 4, Cost of HIV ELISA antbody test Cost of confrmatory western blot test Cost of behavor counselng Annual cost of MMT per IDU Annual cost of NSP per IDU The formula for the EF score for comparng a set of values from a model to a set of observed values s: (C-1) Where s the observed value, s the mean of the observed values, and represents the estmated value from the model. EF s very smlar n structure to the R-squared statstc from lnear regresson, and has an upper bound of one. Because the modeled values are not derved from an ordnary least squares model-fttng process, the EF has no lower bound (unlke the R-squared, whch has a mnmum value of 0) and the EF score s thus not fully analogous wth the R-squared statstc [63]. Scenaro-based Senstvty Analyss I also tested the robustness of my prmary fndngs to my assumptons about the

21 effectveness of the dfferent nterventons usng scenaro-based senstvty analyss. In the model, I assumed that HIV-postve ndvduals would reduce ther sexual partners by 20% after dentfcaton, and that the sexual transmsson nfectvty of nfected persons would decrease by 90% after treatment wth ART. I also assumed one-year retenton n MMT was 50%. In addton to the multvarate senstvty analyss of the behavor and costs parameters, I also conducted scenaro-based senstvty analyss of the number of HIV nfectons prevented and cost-effectveness aganst varatons n these assumptons about VCT, ART and MMT effectveness. 2 Results 2.1 Senstvty analyss on the epdemologcal trends We explored trends n new HIV nfectons and the total number of PLWHA amongst the seven rsk groups durng the next three decades for the base case Prevalence n each rsk group Fgure C-1 shows the prevalence amongst the man rsk groups for the base case, under the best 200 scenaros. The prmary model s plotted n red n each chart.

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23 Fgure C-3: Senstvty Analyss for Prevalence by Rsk Groups under the Base Case. For the base case, the HIV prevalence amongst CSW, FSW and low-rsk groups appears to be robust under the senstvty analyss, whle the values n MSM and IDU are relatvely senstve to the parameters of numbers of same sex partners and annual njectons, resultng n wde senstvty ranges The number of PLWHA Fgure C-2 shows the total number of people lvng wth HIV/AIDS under the best 200 scenaros for the base case. The prmary model s plotted n red. Fgure C-4: Senstvty Analyss for PLWHA under the Base Case.

24 At year 30, the number of PLWHA would be 1.50 mllon, wth a senstvty range of mllon. 2.2 Senstvty analyss on the cost-effectveness New HIV nfectons prevented The senstvty ranges of percentage of HIV nfectons averted over 30 years for all the nterventon types are shown n Table C-2. Expanded VCT Only (low-rsk once and hgh-rsk annually) would prevent % of the total new HIV nfectons, whle the Harm Reducton Program strategy would prevent % of the total new nfectons. Under a combnaton strategy of Expanded VCT (low-rsk once and hgh-rsk annually), ART and Harm Reducton Programs, % of the total new nfectons over 30 years would be averted.

25 Expanded VCT Only Table C-2: Percentage of HIV nfectons prevented over 30 years. Strategy VCT (low-rsk once, hgh-rsk annually) Percentage of HIV nfectons prevented over 30 years, % Value Range VCT (low-rsk every 3 years, hgh-rsk annually) VCT (every 3 years) VCT (annually) Expanded ART Only ART (50% utlzaton) Harm Reducton Program Only Combnaton Strateges harm reducton, expanded ART and VCT (low-rsk once, hgh-rsk annually) harm reducton, expanded ART and VCT (low-rsk every 3 years, hgh-rsk annually) harm reducton, expanded ART and VCT (everyone every 3 years) harm reducton, expanded ART and VCT (everyone annually) Incremental cost-effectveness ratos Fgure C-3 shows the ncremental costs and QALYs of the dfferent nterventons relatve to the base case, charted on the cost-effectveness plane.

26 Fgure C-5: Senstvty Analyss for ICER of Selected Interventons Relatve to the Base Case. Because all sets of values for all nterventons le entrely n one quadrant, t s

27 possble to calculate meanngful senstvty ranges for the ICER (Table C-3). Expanded VCT Only Table C-3: ICER of Selected Interventons Relatve to the Base Case. Strategy VCT (low-rsk once, hgh-rsk annually) Incremental Cost-effectveness Rato, 2010 nt.$/qaly Value Range 5,810 2,730-10,430 VCT (low-rsk every 3 years, hgh-rsk annually) VCT (every 3 years) VCT (annually) Expanded ART Only ART (50% utlzaton) Harm Reducton Program Only Combnaton Strateges harm reducton, expanded ART and VCT (low-rsk once, hgh-rsk annually) harm reducton, expanded ART and VCT (low-rsk every 3 years, hgh-rsk annually) harm reducton, expanded ART and VCT (everyone every 3 years) harm reducton, expanded ART and VCT (everyone annually) 27,110 14,970-44,620 41,670 24,770-67,630 56,440 32,440-92,410 4,840 3,960-5,980 5,090 1,120-15,380 5,130 2,970-6,180 9,310 4,930-11,460 9,860 5,080-12,410 16,490 8,410-20,960 All selected strateges reman cost-effectve relatve to the base case under all ranges of senstvty values. Note that the Harm Reducton Program shows a wde range of possble values for the ICER, possbly because t focuses on IDU, whose prevalence and ncdence trends are hghly senstve to a sngle value (number of njectons).

28 2.3 Modelng effcency Modelng effcency of the best 200 fts by key parameters s shown n Fgure C-4 for the base case. The modelng effcency statstc scores are greater than 0.7, whch could be nterpreted as evdence of good fts. Fgure C-6: Modelng Effcency EF by Key Parameters. 2.4 Scenaro-based senstvty analyss Screenng and counselng effectveness Compared to the base case, 6.6% of future new HIV nfectons are avoded wth the Expanded VCT Only strategy (low-rsk once and hgh-rsk annually). Under

29 the extreme assumpton of no reducton n sex partners after screenng and counselng (screenng effectveness s 0), 0.20 mllon nfectons, 4.7% of the total (Fgure C-5), are stll prevented by ths strategy, at a cost of 7,208 nt.$ per QALY ganed. Ths beneft can be attrbuted to more nfected ndvduals beng dentfed and referred to ART treatment under the expanded VCT program. If screenng and counselng reduce the number of sex partners of PLWHA by 50%, 8.0% of new nfectons could be prevented by mplementng expanded one tme low-rsk and annual hgh-rsk VCT (Fgure C-5). Ths can be attrbuted not only to mproved dentfcaton of PLWHAs and referral to ART, but also to a reducton n sex partners after screenng and counselng. Wth the combnaton strategy of Expanded VCT (one tme low-rsk and annual hgh-rsk) and Expanded ART (50% utlzaton), the ICERs range from 4,891 to 5,289 nt.$ per QALY ganed ART effectveness ART treatment has a preventatve effect on the HIV epdemc through a reducton n blood plasma vral load n nfected ndvduals, whch reduces ther nfectvty. ART treatment also sgnfcantly reduces morbdty and mortalty among PLWHAs. Fgure C-6 presents the results of senstvty analyss of varous assumptons about ART s effectveness n reducng sexual transmsson nfectvty. If there s no reducton n nfectvty due to ART treatment, an addtonal 0.08 mllon new HIV nfectons, 1.9% of the total, would occur over 30 years (Fgure

30 C-6), because nfected persons wth ART are expected to lve much longer than those wthout ART and subsequently have a longer perod of exposure to the susceptble populaton. If nstead of 90% effectveness (n the base case), ART treatment reduces to 50% effectveness, over 30 years, 0.18 mllon new nfectons, 4.6% of the total wll be prevented, at a cost of 6,681 nt.$ per QALY ganed, under the Expanded ART (50% utlzaton) strategy. Wth a decrease n ART effectveness from 90% to 0%, the costs for the Expanded ART strategy (50% Utlzaton) ncrease from 4,840 nt.$ to 11,619 nt.$ per QALY ganed. Wth the extreme assumpton that ART has no effect n reducng sexual nfectvty, nfectons wll ncrease by 1.9%, because people on ART are lvng longer and then have longer perods of exposure to susceptble ndvduals. Furthermore, the cost of the jont strategy of one tme low-rsk and annual hgh-rsk VCT and 50% ART utlzaton vares from 4,958 nt.$ to 9,691 nt.$ per QALY ganed wth dfferent ART effectveness.

31 Screenng Effectveness (Reducton n Sexual Partners), % ART Effectveness (Reducton n Sexual Infectvty), % Screenng and ART ART Screenng (1-tme low-rsk, hgh-rsk annually) Screenng and ART ART 0 0 Screenng (1-tme low-rsk, hgh-rsk annually) HIV Infectons Prevented, % Fgure C-5: Percentage of HIV Infectons Prevented wth Varous Screenng and Counselng Effectveness HIV Infectons Prevented, % Fgure C-6: Percentage of HIV Infectons Prevented wth Varous ART Effectveness HIV nfectousness Includng acute HIV nfecton n HIV epdemc model s mportant, although nterventons amed at affectng the mmedate post-nfecton stage are dffcult to mplement, especally amongst margnalzed populatons such as IDU and n countres that do not yet have mature test-and-treat strateges (such as Chna). Because of ths, and n order to avod excessve complexty, we chose to focus the compartmental structure of the model on treatment and testng rather than drectly attemptng to model nterventons amed at the acute post-nfecton phase. However, because the effect of ncludng acute nfecton n ths study can be approxmated by ncreasng the nfectousness of HIV durng the asymptomatc stage, we ncluded the nfectousness of HIV durng the asymptomatc stage n our

32 Infectousness of Asymptomatc HIV (percent of the man model) scenaro-based senstvty analyss. In our man model, the jont strategy of one tme low-rsk and annual hgh-rsk VCT, ART and harm reducton wll prevent 1.2 mllon nfectons, 35.4% of the total over the next 30 years, at a cost of 5,080 nt.$ per QALY ganed. If the nfectousness of HIV durng the asymptomatc stage ncreases to 200% of the man model, 25.5% of the total nfectons wll stll be prevented (Fgure C-7). If the nfectousness of HIV durng the asymptomatc stage vares from 70% to 200% of the man model, the combned strategy of ART and VCT (one tme low-rsk and annual hgh-rsk) wll range n cost from 4,290 nt.$ to 5,640 nt.$ per QALY ganed, and wll prevent % of the total nfectons over the next three decades. 200% 190% ART, VCT and harm reducton Harm reducton ART 160% 130% 100% 70% HIV Infectons Prevented, % Fgure C-7: Effect of varyng nfectousness of asymptomatc HIV on percentage of HIV nfectons prevented. 3 Summary

33 We conducted senstvty analyss of both epdemologcal trends and cost-effectveness for a wde range of parameters. The overall senstvty range of the number of PLWHA s concentrated around the estmate from the prmary model. However, the prevalence amongst MSM and IDU for the base case are relatvely senstve to the parameters of numbers of same sex partners and annual njectons, havng wde senstvty ranges. Thrdly, under a combnaton strategy of Expanded VCT (low-rsk once and hgh-rsk annually), ART and Harm Reducton Programs, 35.3% ( %) of the total new nfectons over 30 years would be averted. Fnally, all selected strateges reman cost-effectve relatve to the base case under all ranges of senstvty values.

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