A tale of two futures: HIV and antiretroviral therapy in San Francisco

Science

Volumn 287, Issue 5453, 2000, Pages 650-654

  Blower, S M ^a   Gershengorn, H B ^a   Grant, R M ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRETROVIRUS AGENT;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ARTICLE; DRUG USE; HOMOSEXUALITY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INCIDENCE; MODEL; MORTALITY; PRIORITY JOURNAL; SEXUAL BEHAVIOR; UNITED STATES; VIRUS TRANSMISSION;

ACQUIRED IMMUNODEFICIENCY SYNDROME; ANTI-HIV AGENTS; DRUG RESISTANCE, MICROBIAL; DRUG THERAPY, COMBINATION; FORECASTING; HIV; HIV INFECTIONS; HOMOSEXUALITY; HUMANS; MODELS, BIOLOGICAL; MODELS, STATISTICAL; MONTE CARLO METHOD; PROBABILITY; RISK-TAKING; SAN FRANCISCO;

HUMAN IMMUNODEFICIENCY VIRUS;

EID: 0034723414     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.287.5453.650     Document Type: Article

References (63)

1. D. Osmond et al., Am. J. Public Health 84, 1933 (1994); J. Catania er al., in preparation.
2. D. Osmond et al., Am. J. Public Health 84, 1933 (1994); J. Catania er al., in preparation.
3. R. Stall et al., in preparation.
4. San Francisco Department of Public Health, Quarterly AIDS Surveillance Report, June 1999. Available at www.dph.sf.ca.us.
5. S. M. Hammer et al., N. Engl. J. Med. 337, 725 (1997).
6. It has been suggested that high usage of monotherapy could increase the infection rate (R. M. Anderson, S. Gupta, R. M. May, Nature 350, 356 (1991); A. D. Paltiel and E. H. Kaplan, J. AIDS 4, 795 (1991); S. Gupta, R. M. May, R. M. Anderson, Soc. Ind. Appl. Math. Rev. 35, 1 (1993); J. X. Velasco-Hernandez and Y. H. Hsieh, J. Math. Biol. 32, 233 (1994); Y. H. Hsieh and J. X. Velasco-Hernandez, Biosystems 35, 75 (1995); J. X. Velasco-Hernandez, F Brauer, C. Castillo-Chavez, Inst. Math. Appl. J. Math. Appl. Med. Biol. 13, 175 (1996)].
7. It has been suggested that high usage of monotherapy could increase the infection rate (R. M. Anderson, S. Gupta, R. M. May, Nature 350, 356 (1991); A. D. Paltiel and E. H. Kaplan, J. AIDS 4, 795 (1991); S. Gupta, R. M. May, R. M. Anderson, Soc. Ind. Appl. Math. Rev. 35, 1 (1993); J. X. Velasco-Hernandez and Y. H. Hsieh, J. Math. Biol. 32, 233 (1994); Y. H. Hsieh and J. X. Velasco-Hernandez, Biosystems 35, 75 (1995); J. X. Velasco-Hernandez, F Brauer, C. Castillo-Chavez, Inst. Math. Appl. J. Math. Appl. Med. Biol. 13, 175 (1996)].
8. It has been suggested that high usage of monotherapy could increase the infection rate (R. M. Anderson, S. Gupta, R. M. May, Nature 350, 356 (1991); A. D. Paltiel and E. H. Kaplan, J. AIDS 4, 795 (1991); S. Gupta, R. M. May, R. M. Anderson, Soc. Ind. Appl. Math. Rev. 35, 1 (1993); J. X. Velasco-Hernandez and Y. H. Hsieh, J. Math. Biol. 32, 233 (1994); Y. H. Hsieh and J. X. Velasco-Hernandez, Biosystems 35, 75 (1995); J. X. Velasco-Hernandez, F Brauer, C. Castillo-Chavez, Inst. Math. Appl. J. Math. Appl. Med. Biol. 13, 175 (1996)].
9. It has been suggested that high usage of monotherapy could increase the infection rate (R. M. Anderson, S. Gupta, R. M. May, Nature 350, 356 (1991); A. D. Paltiel and E. H. Kaplan, J. AIDS 4, 795 (1991); S. Gupta, R. M. May, R. M. Anderson, Soc. Ind. Appl. Math. Rev. 35, 1 (1993); J. X. Velasco-Hernandez and Y. H. Hsieh, J. Math. Biol. 32, 233 (1994); Y. H. Hsieh and J. X. Velasco-Hernandez, Biosystems 35, 75 (1995); J. X. Velasco-Hernandez, F Brauer, C. Castillo-Chavez, Inst. Math. Appl. J. Math. Appl. Med. Biol. 13, 175 (1996)].
10. It has been suggested that high usage of monotherapy could increase the infection rate (R. M. Anderson, S. Gupta, R. M. May, Nature 350, 356 (1991); A. D. Paltiel and E. H. Kaplan, J. AIDS 4, 795 (1991); S. Gupta, R. M. May, R. M. Anderson, Soc. Ind. Appl. Math. Rev. 35, 1 (1993); J. X. Velasco-Hernandez and Y. H. Hsieh, J. Math. Biol. 32, 233 (1994); Y. H. Hsieh and J. X. Velasco-Hernandez, Biosystems 35, 75 (1995); J. X. Velasco-Hernandez, F Brauer, C. Castillo-Chavez, Inst. Math. Appl. J. Math. Appl. Med. Biol. 13, 175 (1996)].
11. It has been suggested that high usage of monotherapy could increase the infection rate (R. M. Anderson, S. Gupta, R. M. May, Nature 350, 356 (1991); A. D. Paltiel and E. H. Kaplan, J. AIDS 4, 795 (1991); S. Gupta, R. M. May, R. M. Anderson, Soc. Ind. Appl. Math. Rev. 35, 1 (1993); J. X. Velasco-Hernandez and Y. H. Hsieh, J. Math. Biol. 32, 233 (1994); Y. H. Hsieh and J. X. Velasco-Hernandez, Biosystems 35, 75 (1995); J. X. Velasco-Hernandez, F Brauer, C. Castillo-Chavez, Inst. Math. Appl. J. Math. Appl. Med. Biol. 13, 175 (1996)].
12. F. M. Hecht et al., N. Engl. J. Med. 339, 307 (1998); D. Boden et al., J. Am. Med. Assoc. 282, 1135 (1999); S. J. Little et al., J. Am. Med. Assoc. 282, 1142 (1999); S. Yerly et al., Lancet 354, 729 (1999).
13. F. M. Hecht et al., N. Engl. J. Med. 339, 307 (1998); D. Boden et al., J. Am. Med. Assoc. 282, 1135 (1999); S. J. Little et al., J. Am. Med. Assoc. 282, 1142 (1999); S. Yerly et al., Lancet 354, 729 (1999).
14. F. M. Hecht et al., N. Engl. J. Med. 339, 307 (1998); D. Boden et al., J. Am. Med. Assoc. 282, 1135 (1999); S. J. Little et al., J. Am. Med. Assoc. 282, 1142 (1999); S. Yerly et al., Lancet 354, 729 (1999).
15. F. M. Hecht et al., N. Engl. J. Med. 339, 307 (1998); D. Boden et al., J. Am. Med. Assoc. 282, 1135 (1999); S. J. Little et al., J. Am. Med. Assoc. 282, 1142 (1999); S. Yerly et al., Lancet 354, 729 (1999).
16. K. A. Page-Shafer et al., Morbid. Mortal. Wkly. Rep. 48, 45 (1999).
17. R) HIV: (equation presented)
18. R) HIV: (equation presented)
19. ART suppresses viral load in blood (4), lymph nodes [W. Cavert et al., Science 276, 960 (1997)], cerebrospinal fluid [S. Staprans et al., AIDS 13, 1051 (1999)], and semen [P. Gupta et al., J. Virol. 71, 6271 (1997); S. A. Fiscus et al., AIDS Res. Hum. Retroviruses 14 (suppl. 1), S27 (1998); J. J. Eron et al., AIDS 12, F181 (1998)].
20. ART suppresses viral load in blood (4), lymph nodes [W. Cavert et al., Science 276, 960 (1997)], cerebrospinal fluid [S. Staprans et al., AIDS 13, 1051 (1999)], and semen [P. Gupta et al., J. Virol. 71, 6271 (1997); S. A. Fiscus et al., AIDS Res. Hum. Retroviruses 14 (suppl. 1), S27 (1998); J. J. Eron et al., AIDS 12, F181 (1998)].
21. ART suppresses viral load in blood (4), lymph nodes [W. Cavert et al., Science 276, 960 (1997)], cerebrospinal fluid [S. Staprans et al., AIDS 13, 1051 (1999)], and semen [P. Gupta et al., J. Virol. 71, 6271 (1997); S. A. Fiscus et al., AIDS Res. Hum. Retroviruses 14 (suppl. 1), S27 (1998); J. J. Eron et al., AIDS 12, F181 (1998)].
22. ART suppresses viral load in blood (4), lymph nodes [W. Cavert et al., Science 276, 960 (1997)], cerebrospinal fluid [S. Staprans et al., AIDS 13, 1051 (1999)], and semen [P. Gupta et al., J. Virol. 71, 6271 (1997); S. A. Fiscus et al., AIDS Res. Hum. Retroviruses 14 (suppl. 1), S27 (1998); J. J. Eron et al., AIDS 12, F181 (1998)].
23. ART suppresses viral load in blood (4), lymph nodes [W. Cavert et al., Science 276, 960 (1997)], cerebrospinal fluid [S. Staprans et al., AIDS 13, 1051 (1999)], and semen [P. Gupta et al., J. Virol. 71, 6271 (1997); S. A. Fiscus et al., AIDS Res. Hum. Retroviruses 14 (suppl. 1), S27 (1998); J. J. Eron et al., AIDS 12, F181 (1998)].
24. L. Zhang et al., N. Engl. J. Med. 340, 1605 (1999).
25. S. Land et al., J. Infect. Dis. 166, 1139 (1992); J. Condra et al., paper presented at the 4th International Workshop on HIV Drug Resistance, Kauai, HI (1995).
26. S. Land et al., J. Infect. Dis. 166, 1139 (1992); J. Condra et al., paper presented at the 4th International Workshop on HIV Drug Resistance, Kauai, HI (1995).
27. Models can be used as predictive tools by analyzing models with time-dependent uncertainty and sensitivity analyses based on LHS. Methodological details are given at http://itsa.ucsf.edu/∼sally and in S. M. Blower et al., Philos. Trans. R. Soc. London Ser. B 331, 171 (1991); S. M. Blower and H. Dowlatabadi, Int. Stat. Rev. 2, 229 (1994); S. M. Blower et al., Nature Med. 1, 815 (1995); M. A. Sanchez and S. M. Blower, Am. J. Epidemiol. 145, 1127 (1997); S. M. Blower, T. C. Porco, G. Darby, Nature Med. 4, 673 (1998); T. C. Porco and S. M. Blower, Theor. Pop. Biol. 54, 117 (1998); T. Lietman, T. C. Porco, S. M. Blower, Nature Med. 5, 572 (1999).
28. Models can be used as predictive tools by analyzing models with time-dependent uncertainty and sensitivity analyses based on LHS. Methodological details are given at http://itsa.ucsf.edu/∼sally and in S. M. Blower et al., Philos. Trans. R. Soc. London Ser. B 331, 171 (1991); S. M. Blower and H. Dowlatabadi, Int. Stat. Rev. 2, 229 (1994); S. M. Blower et al., Nature Med. 1, 815 (1995); M. A. Sanchez and S. M. Blower, Am. J. Epidemiol. 145, 1127 (1997); S. M. Blower, T. C. Porco, G. Darby, Nature Med. 4, 673 (1998); T. C. Porco and S. M. Blower, Theor. Pop. Biol. 54, 117 (1998); T. Lietman, T. C. Porco, S. M. Blower, Nature Med. 5, 572 (1999).
29. Models can be used as predictive tools by analyzing models with time-dependent uncertainty and sensitivity analyses based on LHS. Methodological details are given at http://itsa.ucsf.edu/∼sally and in S. M. Blower et al., Philos. Trans. R. Soc. London Ser. B 331, 171 (1991); S. M. Blower and H. Dowlatabadi, Int. Stat. Rev. 2, 229 (1994); S. M. Blower et al., Nature Med. 1, 815 (1995); M. A. Sanchez and S. M. Blower, Am. J. Epidemiol. 145, 1127 (1997); S. M. Blower, T. C. Porco, G. Darby, Nature Med. 4, 673 (1998); T. C. Porco and S. M. Blower, Theor. Pop. Biol. 54, 117 (1998); T. Lietman, T. C. Porco, S. M. Blower, Nature Med. 5, 572 (1999).
30. Models can be used as predictive tools by analyzing models with time-dependent uncertainty and sensitivity analyses based on LHS. Methodological details are given at http://itsa.ucsf.edu/∼sally and in S. M. Blower et al., Philos. Trans. R. Soc. London Ser. B 331, 171 (1991); S. M. Blower and H. Dowlatabadi, Int. Stat. Rev. 2, 229 (1994); S. M. Blower et al., Nature Med. 1, 815 (1995); M. A. Sanchez and S. M. Blower, Am. J. Epidemiol. 145, 1127 (1997); S. M. Blower, T. C. Porco, G. Darby, Nature Med. 4, 673 (1998); T. C. Porco and S. M. Blower, Theor. Pop. Biol. 54, 117 (1998); T. Lietman, T. C. Porco, S. M. Blower, Nature Med. 5, 572 (1999).
31. Models can be used as predictive tools by analyzing models with time-dependent uncertainty and sensitivity analyses based on LHS. Methodological details are given at http://itsa.ucsf.edu/∼sally and in S. M. Blower et al., Philos. Trans. R. Soc. London Ser. B 331, 171 (1991); S. M. Blower and H. Dowlatabadi, Int. Stat. Rev. 2, 229 (1994); S. M. Blower et al., Nature Med. 1, 815 (1995); M. A. Sanchez and S. M. Blower, Am. J. Epidemiol. 145, 1127 (1997); S. M. Blower, T. C. Porco, G. Darby, Nature Med. 4, 673 (1998); T. C. Porco and S. M. Blower, Theor. Pop. Biol. 54, 117 (1998); T. Lietman, T. C. Porco, S. M. Blower, Nature Med. 5, 572 (1999).
32. Models can be used as predictive tools by analyzing models with time-dependent uncertainty and sensitivity analyses based on LHS. Methodological details are given at http://itsa.ucsf.edu/∼sally and in S. M. Blower et al., Philos. Trans. R. Soc. London Ser. B 331, 171 (1991); S. M. Blower and H. Dowlatabadi, Int. Stat. Rev. 2, 229 (1994); S. M. Blower et al., Nature Med. 1, 815 (1995); M. A. Sanchez and S. M. Blower, Am. J. Epidemiol. 145, 1127 (1997); S. M. Blower, T. C. Porco, G. Darby, Nature Med. 4, 673 (1998); T. C. Porco and S. M. Blower, Theor. Pop. Biol. 54, 117 (1998); T. Lietman, T. C. Porco, S. M. Blower, Nature Med. 5, 572 (1999).
33. Models can be used as predictive tools by analyzing models with time-dependent uncertainty and sensitivity analyses based on LHS. Methodological details are given at http://itsa.ucsf.edu/∼sally and in S. M. Blower et al., Philos. Trans. R. Soc. London Ser. B 331, 171 (1991); S. M. Blower and H. Dowlatabadi, Int. Stat. Rev. 2, 229 (1994); S. M. Blower et al., Nature Med. 1, 815 (1995); M. A. Sanchez and S. M. Blower, Am. J. Epidemiol. 145, 1127 (1997); S. M. Blower, T. C. Porco, G. Darby, Nature Med. 4, 673 (1998); T. C. Porco and S. M. Blower, Theor. Pop. Biol. 54, 117 (1998); T. Lietman, T. C. Porco, S. M. Blower, Nature Med. 5, 572 (1999).
34. Models can be used as predictive tools by analyzing models with time-dependent uncertainty and sensitivity analyses based on LHS. Methodological details are given at http://itsa.ucsf.edu/∼sally and in S. M. Blower et al., Philos. Trans. R. Soc. London Ser. B 331, 171 (1991); S. M. Blower and H. Dowlatabadi, Int. Stat. Rev. 2, 229 (1994); S. M. Blower et al., Nature Med. 1, 815 (1995); M. A. Sanchez and S. M. Blower, Am. J. Epidemiol. 145, 1127 (1997); S. M. Blower, T. C. Porco, G. Darby, Nature Med. 4, 673 (1998); T. C. Porco and S. M. Blower, Theor. Pop. Biol. 54, 117 (1998); T. Lietman, T. C. Porco, S. M. Blower, Nature Med. 5, 572 (1999).
35. For each uncertainty analysis, LHS was used to randomly sample (without replacement) the pdf for each uncertain parameter 1000 times. This procedure produced 1000 different parameter sets, which were then used to numerically simulate the model and generate 1000 different predictions for each analysis.
36. 1(t) = [1 - Q(t)] × 100, where Q(t) = the cumulative number of HIV infections at time t when using ART divided by the cumulative number of HIV infections at time t in the absence of ART and behavior change.
37. u = 12 years, c = 1.7 new risky sex partners per year, π = 2133 gay men per year, and 1/μ = 30 years.
38. We assumed that r = 0.10; this value reflects the current optimal performance of ART in clinical trials where only 10% of the cases on ART develop resistance per year (4).
39. u.
40. R. L. Iman, J. C. Helton, J. E. Campbell, J. Qual. Technol. 13, 174 (1981); J. Qual. Technol. 13, 232 (1981).
41. R. L. Iman, J. C. Helton, J. E. Campbell, J. Qual. Technol. 13, 174 (1981); J. Qual. Technol. 13, 232 (1981).
42. L. Pollack and J. Catania (UCSF), personal communication; data for the study reported in (Z) were collected from November 1996 through February 1998.
43. U + q + μ].
44. R we used a pdf with a triangular distribution (min = 0.02, max = 0.5, peak at 0.1).
45. E. M. Connor et al., N. Engl. J. Med. 331, 1173 (1994); M. Musicco et al., Arch. Intern. Med. 154, 1971 (1994).
46. E. M. Connor et al., N. Engl. J. Med. 331, 1173 (1994); M. Musicco et al., Arch. Intern. Med. 154, 1971 (1994).
47. U.
48. Data from 3 years of observations in San Francisco suggest that viremia remains partially suppressed after virologic failure, possibly due to residual drug activity or decreased replication capacity of drug-resistant viruses (8).
49. T from a pdf that ranged from 18 to 36 years.
50. U (25).
51. U (25).
52. U (25).
53. U (25).
54. T from a uniform pdf (range 0.0 to 1.0). We modeled uncertainty in the average time before reversion (1/q) by using LHS to sample 1000 values from a triangular pdf (min = 2 weeks, max = 6 months, peak at 6 weeks) (11).
55. T.
56. These data are available on Science Online at www. sciencemag.org/feature/data/1044287.shl.
57. Over the 10-year time period the value of the PRCC for effectiveness and the parameter r (which specifies the rate at which drug resistant strains emerge) remained between zero and -0.2.
58. S. M. Blower, P. M. Small, P. Hopewell, Science 273, 497 (1996); S. M. Blower and J. L. Gerberding, J. Mol. Med. 76, 624 (1998); T. C. Porco and S. M. Blower, Interfaces 28, 167 (1998); S. M. Blower, K. Koelle, T. Lietman, Nature Med. 5, 358 (1999).
59. S. M. Blower, P. M. Small, P. Hopewell, Science 273, 497 (1996); S. M. Blower and J. L. Gerberding, J. Mol. Med. 76, 624 (1998); T. C. Porco and S. M. Blower, Interfaces 28, 167 (1998); S. M. Blower, K. Koelle, T. Lietman, Nature Med. 5, 358 (1999).
60. S. M. Blower, P. M. Small, P. Hopewell, Science 273, 497 (1996); S. M. Blower and J. L. Gerberding, J. Mol. Med. 76, 624 (1998); T. C. Porco and S. M. Blower, Interfaces 28, 167 (1998); S. M. Blower, K. Koelle, T. Lietman, Nature Med. 5, 358 (1999).
61. S. M. Blower, P. M. Small, P. Hopewell, Science 273, 497 (1996); S. M. Blower and J. L. Gerberding, J. Mol. Med. 76, 624 (1998); T. C. Porco and S. M. Blower, Interfaces 28, 167 (1998); S. M. Blower, K. Koelle, T. Lietman, Nature Med. 5, 358 (1999).
62. J. X. Velasco-Hernandez, H. B. Gershengorn, S. M. Blower, in preparation.
63. Supported by NIH-National Institute of Allergy and Infectious Diseases (NIAID) grants AI41935 and AI42923 (S.M.B.) and by NIH-NIAID grants P30-MH59037 and RR-0165 and UCSF-AIDS Clinical Research Center (R.M.G). We are grateful to the following for their insights: J. Catania, T. Coates, S. Deeks, H. Gaff, J. Gerberding, M. Haddad, M. Katz, M. McCune, W. McFarland, J. Mills, L. Pollack, R. Stall, K. Swanson, P. Volberding, and E. Ziv. We also thank D. Freimer, J. Freimer, and N. Freimer for their support throughout this work.