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)

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)

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.

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.

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.

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, 2 In 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.

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.

Universal Access to HAART(since April 1997)

Number of Newly Detected HIV Cases (every four months) in Taiwan, 1984-2002

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

Transmission in

population level

Transmission in

individual level

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

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)

HIV incidence

I(t) = R N(t) = R N(0) exp [(R–m) t] Taking natural logarithm on both sides:

N(t) = N(0) exp [(R–m) t]

ln [I(t)] = (R–m) t + ln [R N(0)]

Simple exponential model

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

dsstfsItS )()()(

The interval between infection and detection is variable. But as long as the interval distribution f(x) remains stable,

S(t): the number of newly identified HIV casesI(t): the number of new HIV infection

Incidence

Surveillance

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).

0

50

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Numb

er of

cases

HIVAIDS

0

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1984

Jan-A

pr19

85 Ja

n-Apr

1986

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n-Apr

1988

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n-Apr

1990

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n-Apr

1992

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n-Apr

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n-Apr

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pr20

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n-Apr

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Jan-A

pr

Natur

al Lo

grithm

of N

umbe

rs of

Cases

ALL new case

Introduction of HAART

Slope = 0.292 0.033(R2=0.80, P <0.0001)

Slope = 0.156 0.014(R2=0.90, P <0.0001)

Difference between two eraP = 0.005

Mortality rate m can be estimated by analyzing countrywide HIV follow-up data

Months after the Diagnosis of HIV Infection

Pro

babi

lity

of S

urvi

val

0 20 40 60 80

0.0

0.2

0.4

0.6

0.8

1.0

HAART era (n = 3,117)

Pre-HAART era (n =1,154)

m = 0.099 0.031

m = 0.046 0.019

0

1

2

3

4

5

6

7

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43

Time (4 month periods)

ln[I

(t)]

or l

n[S(

t)]

I(t)S(t)

Interval from infection to detection F (t)

Pre-HAART era HAART era

Cross-Era Effect

IncidenceSurveillance

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%)

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).

Identified HIV-infected person x % of all HIV+ patients

“Hidden” HIV patient(100 – x) %

HAART Reduced transmission by Δ%

Transmission unchanged

Average transmission rate was cut by 53% = (x%)(Δ%)

（ Δ% ≤ 100% ）

x % must be higher than 53%

No HAART

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.

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

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.

National Harm Reduction Programs

(Source of data, Taiwan CDC HIV surveillance database, 1984-2009, approved on October 6, 2010)

No Harm Reduction

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.

Thank you for your attention!

Summary of assumptions

Stable performance of HIV surveillance system

Low HIV prevalence

Stable risk behavior frequency

0

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1993 1994 1995 1996 1997 1998 1999 2000 2001 2002

Num

bers

of N

ew C

ases

SyphilisGonorrhea

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

Estimating interval distribution

F(t) = 1– exp (–0.024333 t 2.286) Transfusion-related AIDS: From infection to AIDS: Weibull distr.

(Lui KJ, et al. PNAS 1986)

If shape parameter is the same, then Weibull hazard function

Hazard ratio of AIDS vs. being detected by surveillance (AIDS

+ active screening) = AIDS ratio among newly detected cases

Median = 4.3 years

h(t) = t –1 Hazard ratio = ratio of scale parameter

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