World AIDS Day 2008Where Are We With Prevention?

Kees Rietmeijer, MD, PhD

STD Control ProgramDenver Public Health Department

Department of Community and Behavioral HealthColorado School of Pubic Health

University of Colorado Denver

New York Times December 1, 2008

Global estimates for adults and children, 2007

• People living with HIV 33 million [30 – 36 million]

• New HIV infections in 2007 2.7 million [2.2 – 3.2 million]

• Deaths due to AIDS in 2007 2.0 million [1.8 – 2.3 million]

Total: 33 million (30 – 36 million)

Western & Central Europe

730 000730 000[580 000 – 1.0 million][580 000 – 1.0 million]

Middle East & North Africa380 000380 000

[280 000 – 510 000][280 000 – 510 000]

Sub-Saharan Africa22.0 million22.0 million

[20.5 – 23.6 million][20.5 – 23.6 million]

Eastern Europe & Central Asia

1.5 million 1.5 million [1.1 – 1.9 million][1.1 – 1.9 million]

South & South-East Asia4.2 million4.2 million

[3.5 – 5.3 million][3.5 – 5.3 million]

Oceania74 00074 000

[66 000 – 93 000][66 000 – 93 000]

North America1.2 million

[760 000 – 2.0 million]

Latin America1.7 million1.7 million

[1.5 – 2.1 million][1.5 – 2.1 million]

East Asia740 000740 000

[480 000 – 1.1 million][480 000 – 1.1 million]Caribbean230 000

[210 000 – 270 000]

Adults and children estimated to be living with HIV, 2007

Recent Developments in “Biomedical” Interventions for

HIV Prevention

• Vaccines

• Circumcision

• Treatment of sexually transmitted infections (STI) as HIV Prevention

• HIV Treatment as HIV Prevention

Vaccines

• Fact: Many viral and bacterial infections result in immunologic protection

• Fact: Many viral and bacterial infections can be prevented through immunization

• Question: Can/will an effective HIV vaccine ever be available?

• Answer: Perhaps, but it doesn’t look good…

Efficacy of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomized,

placebo-controlled, test-of-concept trial.

• 3000 HIV-1-seronegative participants randomly assigned to receive three injections of MRKAd5 HIV-1 gag/pol/nef vaccine (n=1494) or placebo (n=1506) and followed every six months

• 24 (3%) of 741 vaccine recipients became HIV-1 infected versus 21 (3%) of 762 placebo recipients (hazard ratio [HR] 1.2 [95% CI 0.6-2.2]).

• The HR of HIV-1 infection between vaccine and placebo recipients was higher in Ad5 seropositive men (HR 2.3 [95% CI 1.2-4.3]) and uncircumcised men (3.8 [1.5-9.3]), but was not increased in Ad5 seronegative (1.0 [0.5-1.9]) or circumcised (1.0 [0.6-1.7]) men.

Buchbinder et al. Lancet 2008, November 12 Epub Ahead of Print

Circumcision

• Fact: Circumcision status is shown to be protective for HIV acquisition among men in HIV prevalence studies

• Question: Can circumcision prevent HIV acquisition prospectively?

• Answer: Yes

STI Treatment for HIV Prevention• Fact: STI act as co-factor for the acquisition and

transmission of HIV• Question: Does STI treatment reduce HIV

transmission?• Answer: Yes

– Mwanza trial: Expanding STI diagnostic and treatment services resulted in 40% reduction of HIV incidence• Grosskurth et al. Lancet 1995;346:530-6.

• Answer: No– Rakai study: Mass STI treatment did not result in reduced

HIV incidence • Wawer et al. Lancet 1999:353:525-35

HSV Suppressive Treatment for HIV Prevention

• Fact: Chronic genital HSV infection is an important co-factor in HIV acquisition and transmission

• Question: Can chronic suppressive HSV treatment reduce HIV acquisition?

• Answer: No– Tanzania: no effect of acyclovir 400 mg bid among HSV-2

sero-positive, HIV-negative women after 1.5 years• Watson-Jones et al. N Engl J Med 2008;358:1560-71

• Answer: No– Africa/Peru/USA: no effect of acyclovir 400 mg bid among

HSV-2 sero-positive, HIV-negative women and MSM • Celum et al. Lancet 2008;371:2209-19

HIV Treatment for HIV Prevention

• Post-exposure prophylaxis (PEP)

• Pre-exposure prophylaxis (PrEP)

• Chronic suppressive therapy among those infected to prevent ongoing transmission

HIV Suppressive Treatment for HIV Prevention?

• Fact: HIV viral load among HIV-infected is strongly associated with HIV transmission to un-infected partners

Quinn et al, N Engl J Med 2000

HIV Suppressive Treatment for HIV Prevention?

• Question: Can (chronic) HIV suppression prevent transmission?

• Answer: Maybe…– Mathematical modeling using South African data

suggests that annual HIV testing and starting HIV treatment immediately could dramatically reduce HIV incidence within 10 years and drive prevalence <1% in 50 years.• Granich et al. Lancet 2008; Nov 25, epub ahead of print.

HIV Treatment as Prevention

• Dilemma’s:– Is (chronic suppressive) treatment for prevention ethical if

there is no clear clinical benefit?– Will extensive treatment with variable adherence lead to

emerging (transmission of) resistant virus?– Can adequate coverage be achieved to make epidemiologic

impact?– How well are viral loads in plasma and genital secretions

correlated?• How well do current treatments penetrate in the genital tissue

compartments?

• Can intercurrent STIs elevate viral load in genital compartment and thus increase transmission risk?

HIV Viral Load and STIs

Acute HIV STI episode STI episode AIDS

Adapted from Cohen and Pilcher, JID 2005

6

5

4

3

2

HIV RNA Log10 Copies/Ml

Behavioral Interventions for HIV Prevention

Behavior Change and HIV Prevention

• Fact: Widespread behavior change occurred in the beginning of the HIV epidemic and resulted in dramatic decrease in HIV and STI incidence

Rietmeijer et al. Sex Transm Dis 2003;30:562-7

Incidence of gonorrhea and primary or secondary (P&S) Syphilis among MSM, Denver Metro Health Clinic, 1982-2001

Behavior Change and HIV Prevention

• Question: Can behavioral interventions induce change in risk behaviors and subsequently reduce HIV and STI incidence?

• Answer: Yes

http://www.effectiveinterventions.org/

Results of the RCT to test the community popular

opinion leader (C-POL) intervention in five countries • Large, controlled, randomized trial to test a community-level HIV

risk reduction intervention in five countries accounting for the majority of HIV: China, India, Peru, Russia Zimbabwe.

• Intervention: Fifteen percent of the populations in experimental venues were trained as popular opinion leaders to diffuse HIV prevention messages to others.

• Both Intervention and Control:– AIDS information– Access to free or affordable condom– Completed in-depth interviews concerning their sexual

practices during the past three months– Received HIV testing and intensive test-related counseling at

baseline and at one and two year follow-ups.

Results of the RCT to test the community popular

opinion leader (C-POL) intervention in five countries

• Results– Sexual risk practices reduced by 33.3% in C-POL intervention

group compared to 32.0% in comparison group after 2 years

– Disease incidence outcomes through follow-up were similar in both conditions

• Conclusion– Ethically-required comparison condition activities can produce

substantial risk behavior reductions, and future intervention packages must be tested against those already known to produce behavior change.

NIMH Collaborative HIV/STD Prevention Trial Group: XVII International AIDS Conference.

Behavioral Interventions: Do They Still Work?

• Most developed and evaluated in the pre-HAART era

• Most used self-reported behavioral outcomes

• Effectiveness may be dependent on stage of the epidemic– Effective in early stages

– Less effective in later stages when those who have changed behaviors are removed from the “risk pool”

• Increasingly compared to improving standard of HIV prevention practice

Behavioral InterventionsA New Focus

• Shift away from development of “new” interventions to development of standard of prevention practice–Healthy sexual behaviors

–HIV/STI testing, treatment, and partner services

–Counseling

• Enhance infrastructure to deliver these services

Behavioral InterventionsA New Focus

• Prevention intervention in HIV care settings–Using concepts of client-centered counseling in day-

to-day provider-client interactions are shown to be effective and can be introduced in the busy practice setting

http://www.effectiveinterventions.org/

Project RespectMain Results

• Compared to standard education messages, client-centered counseling resulted in overall STD reduction of –30% after 6 months

–20% after 12 months

• 2-session prevention counseling was as effective as the 4-session enhanced counseling

Kamb et al. JAMA 1998;280:1161

Project Respect

Relative effectiveness was greatest among those at highest risk for STI

# STI prevented per 100 persons counseled

– 20 years and younger 9.1– Exchange sex for money or drugs 5.9– STD at baseline 5.3– Lower education (<12th grade) 4.3– Female 3.9– African American 3.2

Bolu et al. Sex Transm Dis 2004;31:469.

Ask

Screen

Intervene

A modular training curriculum for providers to enhance prevention among HIV-infected patients in care settings

National Network of STD/HIV Prevention Training Centers

Effective behavior change at the patient level begins with behavior

change at the provider level…

A Case for Structural Interventions

• Even if highly effective, individual and group level interventions are resource-intensive and unlikely to reach at-risk populations in sufficient numbers to make an impact on HIV/STI epidemiology

• Structural/environmental interventions:– Are targeted to at-risk populations where they congregate,

i.e., bars, bath houses, Internet

– Are not resource-intensive

– Reach people who would not seek prevention

– Combine small impact with wide coverage

http://www.effectiveinterventions.org/

Safe in the City

• 23-minute video

• 3 story lines

• 2 cartoon animations

– Condom variety and selection

– Instructions for use

• Posters in waiting and exam rooms

Story Line 1

Things are getting more serious between Paul and Jasmine, but Paul “slips” and has a sexual encounter with Teresa.

Teresa gets an STD and tells Paul. Now Paul has to tell Jasmine

Overall Intervention Effect on incident Laboratory-Confirmed Infection

Hazard Ratio (95% CI)

All patients 0.90 (0.81-1.00)

Warnet et al. PLoS Medicine 2008 Jun 24;5(6):e135.

COMING SOON TO AN STI

CLINIC NEAR YOU!!

THANKS!!

kees.rietmeijer@dhha.org

www.stdpreventiononline.org