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Population-level Effect of Free Access to HAART on Reducing HIV Transmission in Taiwan

Population-level Effect of Free Access to HAART on Reducing HIV Transmission in Taiwan. 2013 International Conference on Global Health: HIV : Seek, test, treat, and retain. Chi-Tai Fang, MD, PhD National Taiwan University. 2013/04/17. Highly Active Antiretroviral Therapy (HAART).

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Population-level Effect of Free Access to HAART on Reducing HIV Transmission in Taiwan

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  1. Population-level Effect of Free Access to HAART on Reducing HIV Transmission in Taiwan 2013 International Conference on Global Health: HIV: Seek, test, treat, and retain Chi-Tai Fang, MD, PhD National Taiwan University 2013/04/17

  2. Highly Active Antiretroviral Therapy (HAART) • Suppress HIV RNA of treated patients • Prolonged survival • Reduced infectiousness of treated individuals • Mother-to-child transmission (RCTs) • Transmission between HIV serodiscordant couples (HTPN052 RCT)

  3. Effect of HAART in Population Level • % of HIV-infected people tested and treated • Unsafe behaviors due to therapeutic optimism • Simulation studies show a moderate increase in risky behaviors can offset the effect of a large decrease in infectiousness • The net effect needs to be evaluated by empirical study that measure its impact on HIV transmission in population level using high-quality surveillance data.

  4. Public Health Response to HIV/AIDS in Taiwan • In 1989, a highly effective countrywide surveillance system for HIV infection was established. • In 1997, soon after HAART became available, universal access to HAART was started under the National Health Insurance framework. • This provided a unique opportunity to empirically determine the effect of universal use of HAART on the evolution of HIV epidemic.

  5. Surveillance for HIV/AIDS in Taiwan • Physician report ─ Both asymptomatic HIV infection and AIDS were reportable diseases in Taiwan • Routine screening of blood donors and all enlisted servicemen (military service is mandatory for all men at 20 years of age in Taiwan) • Voluntary counseling and testing (VCT) ─ for people at higher risk, including MSM, hemophiliacs, IDUs, patients with STDs , etc. • All personal information of HIV+ patients was kept confidential.

  6. Medical Care for People living with HIV/AIDS • Before HAART era, free AZT and medical care were already provided to all identified HIV-infected citizens. • Special clinics were created where antiretroviral agents were prescribed and monitored by qualified physicians. • On April 7, 1997, universal HAART policy was implemented. • The timing of initiating HAART and the regimens were based on the United States guidelines. Initially, early intensive treatment was encouraged except for those with blood HIV-RNA levels < 5,000 copies/ml and normal CD4 cell counts.1, 2In 2002, the practice of initiating HAART in asymptomatic patients was gradually changed to the new criteria of a CD4 count <350/mcL or a blood HIV-RNA level >55,000 copies/mL, in keeping with US guidelines.3 1CDC. MMWR 1998; 47(RR-5): 1–41. 2Carpenter et al. JAMA 2000; 283: 381–90. 3DHHS guideline. May 4, 2006.

  7. HIV situation in Taiwan before 2003 • A stable HIV/AIDS surveillance system has operated since 1989, with > 29 million HIV screening tests performed, focused on groups at higher risk. • At the end of 2002, only 4,387 cases were detected. The HIV prevalence (0.019%) is low. • Before 2003, the majority of cases acquired HIV through sexual contact (96.2%), IDU (2%) play a minimal role.

  8. Number of Newly Detected HIV Cases (every four months) in Taiwan, 1984-2002 Universal Access to HAART (since April 1997)

  9. Transmission in individual level Transmission in population level 1-to-1 scenario Multiple partners • HIV serodiscordant couples • Mother-to-child transmission • Dynamic of epidemic Transmission risk = % infected Transmission rate: Must be estimated by model-fitting

  10. Dynamic of HIV Epidemic dN(t)/dt = R(t) N(t) – m(t) N(t) N(t): Number of prevalent HIV patients R(t): Transmission rate (new cases per prevalent case-year) = (probability of transmission per contact)  (contact rate)  (probability that a contacted person has not yet been infected) m(t):Mortality rate incidence mortality

  11. If HIV prevalence is low (probability that a contacted person is susceptible to HIV ～ 1) and contact rate is unchanged, then the HIV transmission rate R would be a constant. dN(t)/dt = RN(t) – mN(t) N(t) = N(0)  exp [(R–m) t] Simple exponential model HIV incidence I(t) = RN(t) = RN(0) exp [(R–m) t] Taking natural logarithm on both sides: ln [I(t)] = (R–m) t + ln [RN(0)]

  12. Time lag between HIV Incidence and Surveillance Data • Real time survey ─ Not possible due to • Long asymptomatic period • People may hesitate to come out for testing • Time lag between infection and detection • Variable among different patients

  13. The interval between infection and detection is variable. But as long as the interval distribution f(x) remains stable, Surveillance Incidence S(t):the number of newly identified HIV cases I(t): the number of new HIV infection

  14. By applying the theorem of the derivative of a convolution integral, we can further prove the following principle : If HIV incidence I(s) follows a simple exponential model, then HIV surveillance data S(t) will also follows a simple exponential model of the same exponential parameter ln [S(t)] = (R–m) t + ln [(R–m) C(0)] The slope of logarithm transformed surveillance curve is an unbiased estimate of (R–m).

  15. Introduction of HAART Slope = 0.156  0.014 (R2=0.90, P <0.0001) Slope = 0.292  0.033 (R2=0.80, P <0.0001) Difference between two era P = 0.005

  16. Mortality rate m can be estimated by analyzing countrywide HIV follow-up data m = 0.046  0.019 m = 0.099  0.031

  17. Cross-Era Effect Surveillance Incidence Interval from infection to detection F (t) Pre-HAART era HAART era

  18. Final results 0.391 new cases per prevalent case per year (pre-HAART era, January 1990 ─ March 1997) 0.184 new cases per prevalent case per year (HAART era, May 1997 ─ December 2002) Universal HAART cut the average transmission rate by: (0.391–0.184)/0.391 = 53% (95% CI, 31%–65%)

  19. Trend of syphilis incidence among HIV-positive patients in Taiwan Among the 1,152 HIV-positive patients treated and followed-up at TMVDC, the incidence of syphilis: • 60 episodes/11,048 person-months in pre-HAART era (January 1, 1990–March 31, 1997) • 158 episodes/32,023 person-months in HAART era (April 7, 1997–December 31, 2002) • no significant difference in the incidence between two periods (P = .53), with an incidence ratio of 0.91 (95% CI: 0.67–1.22).

  20. Identified HIV-infected person x % of all HIV+ patients （ Δ% ≤ 100%） HAART Reduced transmission by Δ% “Hidden” HIV patient (100 – x)% Average transmission rate was cut by 53% = (x%)(Δ%) No HAART Transmission unchanged x % must be higher than 53%

  21. Implications for Global HIV Control Policy • Universal HAART reduces HIV transmission rate by 53% in population level. • Providing universal access to HAART treatment is an effective HIV prevention strategy.

  22. World Health Organization. Guidance on ethics and equitable access to HIV treatment and care. Geneva, 2004: p13.

  23. Limitation of HAART in HIV prevention • Universal HAART is not a substitute for safe sex and harm reduction • HAART can only be given to HIV-infected people that are detected and ART-indicated, who constitute just a small proportion of the entire IDU population at risk. • The long-time absence of harm reduction program in Taiwan finally led to an HIV outbreak among its IDUs, first noticed since 2003.

  24. National Harm Reduction Programs No Harm Reduction (Source of data,Taiwan CDC HIV surveillance database, 1984-2009, approved on October 6, 2010)

  25. The Lesson of IDUT-HIV Outbreak • The universal access to HAART provide the ethical basis for the extensive HIV screening, which has a pivotal role in delivering IDUs-targeted education and harm reduction service. • Even a large IDUT-HIV epidemic can be successfully reversed and controlled by scaling-up and sustaining an integrated harm reduction program in the context of universal access to HAART.

  26. Thank you for your attention!

  27. Summary of assumptions • Stable performance of HIV surveillance system • Low HIV prevalence • Stable risk behavior frequency

  28. Trend of countrywide cases of syphilis and gonorrhea in Taiwan, 1993─2002

  29. Estimating interval distribution Transfusion-related AIDS: From infection to AIDS: Weibull distr. F(t) = 1– exp (–0.024333 t 2.286) Median = 4.3 years (Lui KJ, et al. PNAS 1986) If shape parameter is the same, then Weibull hazard function h(t) = t –1 Hazard ratio = ratio of scale parameter Hazard ratio of AIDS vs. being detected by surveillance (AIDS + active screening) = AIDS ratio among newly detected cases

  30. Distribution of interval from infection to detection in Taiwan The proportion of AIDS among newly identified cases remained stable before 2001 (0.25  0.05) Interval distribution: F(t) = 1– exp (– 0.0982 t 2.286) Median = 2.35 years • The proportion decreased to 0.16  0.01 in years 2001 and • 2002. The improvement of performance of surveillance • will cause an underestimation of HAART effect

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