Financial Implications of Male Circumcision Scale-Up for the Prevention of HIV and Other Sexually Transmitted Infections in a Sub-Saharan African Community – Supplemental Material

Financial Implications of Male Circumcision Scale-Up for the Prevention of HIV and Other Sexually Transmitted Infections in a Sub-Saharan African Community – Supplemental Material Seema Kacker BS1, Kevin D Frick PhD2, Thomas C Quinn MD3,4, Ronald H Gray PhD5, and Aaron A R Tobian MD PhD1 Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD Methods (supplemental): Generating a Dynamic Population: Assuming the size of each annual birth cohort remained constant at “BirthCohortSize,” the portion of individuals in each of the two subpopulations (InitialPopulation or BirthCohort) would be calculated as follows: where “CurrentPopulationSize” and “BirthCohortSize” were defined by published demographic data, and “TotalYears” was the number of years over which outcomes were evaluated MC Scale-up Plans: MC scale-up plans (Strategies 2-5) incorporated a component targeting initially uncircumcised males of the initial population (catch-up MC program), and a second component targeting males of the annual birth cohorts Across all scale-up strategies, the catch-up MC program ultimately resulted in an 80% coverage rate among males 15-49 Only males between the ages 15-49 were circumcised through this catch-up program However, under Strategies and 4, 10 years of scale-up were needed to achieve this level of coverage, while under Strategies and 5, this level of coverage was achieved after only years Within the initial population, a portion of males were already circumcised at the start of the simulation We assumed that at the start of the simulation, 23.6% of men aged 15-49 were circumcised (baseline rate) Because certain subpopulations in Rakai often conduct MCs among infants, we assumed that 13.6% of individuals aged 0-14 were circumcised Each year, a portion of uncircumcised individuals aged 15-49 received a “catch-up” MC, such that at the end of the catch-up period (after years under Strategies and and after 10 years under Strategies and 4), a total of 80% of males 15-49 were circumcised While the bulk of individuals eligible to obtain a “catch-up MC” could become circumcised throughout the period of scale-up, some men were initially (at the start of the simulation) below the age of 15, but became eligible during the course of the simulation In addition, some men were only eligible for “catch-up MC” during the first few years of the scale-up, since they exceeded the 49 year old maximum age during the simulation Thus, under Strategies and 5, “catch-up MC” parameters were defined for men initially aged 11-49, and under Strategies and 4, “catch-up MC” parameters were defined for men initially aged 5-49 Only males between the ages 15-49 were circumcised through this catch-up program The portion of males becoming circumcised through the catch-up program was specified for specific age groups, as shown below in Supplemental Tables and Under Strategies and 5, individuals initially aged 15-45 would increasingly become circumcised over the period of scale-up: at the start of year 1, 23.6% of men are circumcised, but by the end of year 1, 40% of men aged 15-45 are circumcised, by the end of year 2, 50% are circumcised, by the end of year 3, etc By the end of year 5, 80% of men initially aged 15-45 are circumcised (Supplemental Table 1) Under these two strategies, men initially aged 11 would begin year with an MC rate of 13.6% This rate would persist (no “catch-up MCs”) until year (at which point these individuals reached age 15), and then the rate would keep pace with the 15-45 year old group Men initially aged 46 would undergo “catch-up MCs” at the same rate as the 15-45 year old group until reaching the age of 50 (year 5) Men initially 47-49 would undergo a similar process, undergoing catch-up MCs at the same rate of the 15-45 year old group until exceeding the appropriate age range for MC Supplemental Table 1: MC Rates Among Initial Population (Catch-up MCs Under Strategies and 5) Initial Age 11 12 13 14 15-45 46 47 48 49 Initial MC Rate: Start of Year (%) 13.6 13.6 13.6 13.6 23.6 23.6 23.6 23.6 23.6 MC Rate: End of Year (%) 23.6 23.6 23.6 23.6 40 40 40 40 40 MC Rate: End of Year (%) 23.6 23.6 23.6 50 50 50 50 50 40 MC Rate: End of Year (%) 23.6 23.6 60 60 60 60 60 50 40 MC Rate: End of Year (%) 23.6 70 70 70 70 70 60 50 40 MC Rate: End of Year (%) 80 80 80 80 80 70 60 50 40 A similar process was defined for Strategies and (Supplemental Table 2) Males initially aged 15-40 increasingly received catch-up MCs so that at the start of year 1, the MC rate was at 23.6%, but by the end of year 10, the MC rate reached 80% Individuals who were initially aged 6-14 were only included in the MC catch-up program once they reached age 15 Individuals initially aged 41-49 were included only while they were aged 49 or below Supplemental Table 2: MC Rates Among Initial Population (Catch-up MCs Under Strategies and 4) Initial Age 10 11 12 13 14 15-40 41 42 43 44 45 46 47 48 49 MC Rate: Start of Year (%) 13.6 13.6 13.6 13.6 13.6 13.6 13.6 13.6 13.6 23.6 23.6 23.6 23.6 23.6 23.6 23.6 23.6 23.6 23.6 MC Rate: End of Year (%) 23.6 23.6 23.6 23.6 23.6 23.6 23.6 23.6 23.6 35 35 35 35 35 35 35 35 35 35 MC Rate: End of Year (%) 23.6 23.6 23.6 23.6 23.6 23.6 23.6 23.6 40 40 40 40 40 40 40 40 40 40 35 MC Rate: End of Year (%) 23.6 23.6 23.6 23.6 23.6 23.6 23.6 45 45 45 45 45 45 45 45 45 45 40 35 MC Rate: End of Year (%) 23.6 23.6 23.6 23.6 23.6 23.6 50 50 50 50 50 50 50 50 50 50 45 40 35 MC Rate: End of Year (%) 23.6 23.6 23.6 23.6 23.6 55 55 55 55 55 55 55 55 55 55 50 45 40 35 MC Rate: End of Year (%) 23.6 23.6 23.6 23.6 60 60 60 60 60 60 60 60 60 60 55 50 45 40 35 MC Rate: End of Year (%) 23.6 23.6 23.6 65 65 65 65 65 65 65 65 65 65 60 55 50 45 40 35 MC Rate: End of Year (%) 23.6 23.6 70 70 70 70 70 70 70 70 70 70 65 60 55 50 45 40 35 MC Rate: End of Year (%) 23.6 75 75 75 75 75 75 75 75 75 75 70 65 60 55 50 45 40 35 MC Rate: End of Year 10 (%) 80 80 80 80 80 80 80 80 80 80 75 70 65 60 55 50 45 40 35 Infection Rates Specific to MC Protection Status: Because published incidence and prevalence reflect an average population, including some individuals already experiencing MC protective benefits, incidence and prevalence rates specific to MCprotection status were derived: , where and “pMC” was the prior MC rate, “(Rate|MC)” indicated incidence(or prevalence) among those with MC protection and “MC_Effect” was defined as the incidence rate ratio(IRR) of MC for the infection For BV and trichomoniasis, however, the MC_Effect parameter was defined by a prevalence risk ratio (PRR) because an IRR was unavailable from trial data s29 Age-Specific Input Parameters (Details from Table 2): HIV Incidence (Among Men): Age Annual Incidence 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 75 0.00558 0.00558 0.00558 0.00558 0.00558 0.0135 0.0135 0.0135 0.0135 0.0135 0.01583 0.01583 0.01583 0.01583 0.01583 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 0.01011 HIV Prevalence (Among Men): Age 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 75 Prevalence Rate 0.003 0.003 0.024 0.024 0.059 0.059 0.081 0.081 0.092 0.092 0.093 0.093 0.069 0.069 0.069 0.069 0.058 0.058 Penile Cancer Incidence (Among Men): Age Annual Incidence 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 0.000002 0.000002 0.000004 0.000004 0.000002 0.000002 0.000003 0.000003 0.000003 0.000003 0.000024 0.000024 0.000026 0.000026 0.000018 0.000018 0.000069 0.000069 0.000159 0.000159 0.000278 0.000278 100 Cervical Cancer Incidence (Among Women): Age Annual Incidence 14 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75 100 0.000001 0.000001 0.000001 0.000016 0.000016 0.000108 0.000108 0.000329 0.000329 0.000613 0.000613 0.00086 0.00086 0.001479 0.001479 0.001174 0.001174 0.001543 0.001543 0.001657 0.001657 0.000973 0.000973 0.000785 0.000785 0.000785 Age-Specific Mortality Rates (Among Men): Age 10 11 12 Mortality Rate 0.0145 0.0145 0.0145 0.0145 0.00344 0.00344 0.00344 0.00344 0.00344 0.00255 0.00255 0.00255 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 0.00255 0.00255 0.00332 0.00332 0.00332 0.00332 0.00332 0.00607 0.00607 0.00607 0.00607 0.00607 0.00835 0.00835 0.00835 0.00835 0.00835 0.01158 0.01158 0.01158 0.01158 0.01158 0.01582 0.01582 0.01582 0.01582 0.01582 0.02048 0.02048 0.02048 0.02048 0.02048 0.02524 0.02524 0.02524 0.02524 0.02524 0.02905 0.02905 0.02905 0.02905 0.02905 0.03494 0.03494 0.03494 0.03494 0.03494 0.04313 0.04313 0.04313 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 0.04313 0.04313 0.05676 0.05676 0.05676 0.05676 0.05676 0.08139 0.08139 0.08139 0.08139 0.08139 0.11713 0.11713 0.11713 0.11713 0.11713 0.17098 0.17098 0.17098 0.17098 0.17098 0.24359 0.24359 0.24359 0.24359 0.24359 0.3384 0.3384 0.3384 0.3384 0.3384 0.4581 0.4581 0.4581 0.4581 0.4581 0.6043 Age-Specific Mortality Rates (Among Women): Age 10 Mortality Rate 0.01246 0.01246 0.00222 0.00222 0.00167 14 15 19 20 24 25 29 30 34 35 39 40 44 45 49 50 54 55 59 60 64 65 69 70 74 75 79 80 84 85 89 90 94 95 99 100 0.00167 0.0017 0.0017 0.00349 0.00349 0.00576 0.00576 0.0078 0.0078 0.01104 0.01104 0.01262 0.01262 0.01321 0.01321 0.01351 0.01351 0.01642 0.01642 0.02189 0.02189 0.0343 0.0343 0.05567 0.05567 0.08953 0.08953 0.13904 0.13904 0.20897 0.20897 0.30338 0.30338 0.42497 0.42497 0.57439 Supplemental Table Change in Infection Prevalence Associated with MC Scale-Up Strategies (Base-Case Analysis) Time Period years Male MC-Related Infections HIV: Cases (%) Penile Cancer - HR-HPV: Cases (%) GUD: Cases (%) Female MC-Related Infections Cervical Cancer - HR-HPV: Cases (%) GUD: Cases (%) Trichomonas: Cases (%) BV: Cases (%) 25 years Male MC-Related Infections HIV: Cases (%) Penile Cancer - HR-HPV: Cases (%) GUD: Cases (%) Female MC-Related Infections Cervical Cancer - HR-HPV: Cases (%) GUD: Cases (%) Trichomonas: Cases (%) BV: Cases (%) MC Scale-up Strategies Adolescent/Adult Only (15-49) Include Infants (0-1,15-49) 2: Gradual 3: Rapid 4: Gradual 5: Rapid -146 (-1.14) (66.67) -3097 (-4.4) -483 (-3.88) (66.67) -5484 (-8.07) -146 (-1.14) (66.67) -3160 (-4.49) -483 (-3.88) (66.67) -5781 (-8.54) -1496 (-1.1) -2814 (-2.38) -1207 (-6.36) -4 (-0.83) -3124 (-2.32) -5362 (-4.64) -2158 (-11.97) -1594 (-1.17) -3364 (-2.86) -1207 (-6.36) -4 (-0.83) -3495 (-2.61) -7657 (-6.76) -2158 (-11.97) -10170 (-13.92) -17 (-70.00) -23964 (-6.26) -12244 (-17.25) -17 (-70.00) -30461 (-8.09) -12784 (-18.15) -19 (-88.89) -40102 (-10.94) -15082 (-22.13) -17 (-70.00) -49135 (-13.74) -215 (-11.51) -3665 (-0.70) -17149 (-3.64) -25847 (-19.86) -239 (-12.95) -4929 (-0.94) -21216 (-4.55) -28521 (-22.37) -220 (-11.79) -7508 (-1.44) -34824 (-7.69) -26184 (-20.17) -246 (-13.39) -9486 (-1.83) -43151 (-9.7) -29668 (-23.48) Supplemental Table 4: Distribution of MC-Reduced Infection Costs Attributable to each MC-Related Infection - Base-Case Analysis Male MC-Reduced Infections Female MC-Reduced Infections b c HIV HR-HPV GUD Total HR-HPV GUD Trich BV years Portion of Total Infection Costs (%) 1: Baseline MC 46.40 0.01 9.44 55.85 10.85 17.72 13.24 2.34 2: Gradual (Adolescent/Adult Only) 46.41 0.04 9.22 55.67 11.03 17.86 13.19 2.25 3: Rapid (Adolescent/Adult Only) 45.90 0.04 9.17 55.11 11.26 18.16 13.28 2.20 4: Gradual (Including Infants) 46.45 0.04 9.22 55.71 11.04 17.86 13.14 2.25 5: Rapid (Including Infants) 46.05 0.04 9.17 55.26 11.30 18.17 13.07 2.20 a Portion of Total Infection Cost Change (%) 2: Gradual (Adolescent/Adult Only) 45.89 -1.38 20.76 65.28 1.29 10.08 16.10 7.25 3: Rapid (Adolescent/Adult Only) 56.89 -0.56 14.97 71.30 2.34 8.57 12.51 5.28 4: Gradual (Including Infants) 44.12 -1.32 20.33 63.13 1.24 10.27 18.38 6.97 5: Rapid (Including Infants) 53.26 -0.52 14.72 67.45 2.19 8.90 16.52 4.95 25 years Portion of Total Infection Costs (%) 1: Baseline MC 79.95 0.03 4.15 84.14 3.91 5.79 4.65 1.51 2: Gradual (Adolescent/Adult Only) 78.68 0.02 4.39 83.09 4.01 6.44 5.03 1.43 3: Rapid (Adolescent/Adult Only) 78.34 0.02 4.43 82.79 4.07 6.59 5.11 1.44 4: Gradual (Including Infants) 78.62 0.02 4.34 82.98 4.09 6.52 4.95 1.46 5: Rapid (Including Infants) 78.26 0.02 4.37 82.65 4.18 6.70 5.01 1.47 a Portion of Total Infection Cost Change (%) 2: Gradual (Adolescent/Adult Only) 90.36 0.10 2.25 92.71 3.09 0.46 1.57 2.16 3: Rapid (Adolescent/Adult Only) 90.51 0.09 2.35 92.95 2.88 0.52 1.63 2.02 4: Gradual (Including Infants) 89.11 0.10 2.89 92.09 2.67 0.78 2.58 1.87 5: Rapid (Including Infants) 89.10 0.07 3.00 92.17 2.47 0.85 2.74 1.76 a Total Infection Cost Change calculated in comparison to the Baseline strategy b HR-HPV among males included only cases resulting in penile cancer c HR-HPV among females included only cases resulting in cervical cancer Total 44.15 44.33 44.89 44.29 44.74 34.72 28.70 36.87 32.55 15.86 16.91 17.21 17.02 17.35 7.29 7.05 7.91 7.83 Supplemental References (See Table in Main Manuscript): s1 s2 s3 s4 s5 s6 s7 s8 s9 s10 s11 s12 s13 s14 s15 s16 s17 s18 s19 s20 s21 Ministry of Health (MOH) Uganda and ORC Macro Uganda HIV/AIDS Sero-behavioral Survey 2004-2005 Calverton, Maryland, USA: Ministry of Health and ORC Macro2006 (USAID) The Potential Cost and Impact of Expanding Male Circumcision in Uganda 2009 Binagwaho A, Pegurri E, Muita J, Bertozzi 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