1. Treatment as Prevention
Michael Wong, MD
Beth Israel Deaconess Medical
Center
Harvard Medical School
Massachusetts Department of
Public Health

2. Accumulating Data that ART
Reduces HIV transmission
• Sullivan et al, CROI 2009
– Evaluated the effect of ART on HIV transmission rates in 2993
serodiscordant, monogamous heterosexual couples
– ART was prescribed to the HIV+ partner only if clinically indicated by
contemporaneous HHS guidelines
– Seronegative partner at time of study entry underwent q 3 month HIV
testing
• Risk for HIV seroconversion:
– Partner not on ART: 171 linked events, 3.4/100 CY
– Partner on ART: 4 linked events, 0.7/100 CY
– This difference is statistically significant

3. HIV Transmission Risk in
Heterosexual Serodiscordant
Couples Initiating ARV
 92% lower HIV transmission risk in African serodiscordant
couples with HIV-infected partner receiving ARV therapy
vs couples with infected partner not receiving ARVs
• 102 of 103 cases of confirmed HIV transmission
occurred in couples with HIV-infected partner not
receiving ARV therapy
– ARV use in seropositive partner, adjusted for visit
and CD4+ cell count at initiation:
• Unadjusted relative risk: 0.17 (95% CI: 0.004-0.94; P = .037)
• Adjusted relative risk: 0.08 (95% CI: 0.002-0.57; P = .004)
Donnell D, et al. CROI 2010. Abstract 136.

4. Community Viral Load Mirrors Reduced
Rate of New HIV Cases in San Francisco
• Retrospective analysis of relationship between community viral load
(mean of summed individual HIV-1 RNA results per yr) and new HIV
diagnoses
30,000 P = .005 for Mean CVL
Mean Community Viral Load
association* 1200
25,000 Newly diagnosed and
Diagnosed HIV Cases
reported HIV cases 1000
Number of Newly
(copies/mL)
20,000
800
15,000 798
600
642
10,000 523 518 400
434
5000 200
0 0
2004 2005 2006 2007 2008
Yr
*Data insufficient to prove significant association with reduced HIV incidence.
Das-Douglas M, et al. CROI 2010. Abstract 33.

5. Reduction in New HIV Diagnoses
in BC: Testing, HAART, and
Community VL
• Period of declining new HIV diagnoses in BC coincident with increased HIV
testing rates, increased uptake of antiretroviral therapy, and decrease in
community viral load (1996-2008)
– Decline in new HIV diagnoses despite increases in syphilis, gonorrhea,
12,000
chlamydia 1400
HIV-1 RNA,
New HIV+ Diagnoses (n)
10,000 Censored at the time of death or move
1200 copies/mL
8000 1000 < 500
Patients (n)
New HIV+ 500-3499
6000 diagnoses (all) 800
3500-9999
600
4000 10,000-49,999
400 ≥ 50,000
2000 200
0 0
6 7 8 9 0 1 2 3 4 5 6 7 8 9
1 99 199 199 199 200 200 200 200 200 200 200 200 200 200
Montaner J, et al. CROI 2010. Abstract 88LB..

6. Considerations when
discussing ARVs with a newly
diagnosed patient

7. • What we say to
patients: I have some
news for you; your HIV
test is positive. Now
that doesn’t mean you
have AIDS, but we
should…
• What patients hear:
Blah, blah, blah, HIV,
blah, blah, blah, AIDS…

8. Why does ART fail?
• Adherence
• Baseline resistance
• Prior ART not disclosed or not recorded
• Drug levels and drug-drug interactions
• Tissue reservoir penetration
• Provider inexperience
• Other unknown or yet to be identified
causes

9. Adherence Considerations
• Patient lifestyle (shift work, full time new
parent, travel, existing responsibilities)
• Concurrent medical history (drug-drug
interactions; DM; dual or triple diagnosis)
• Patient acceptance (“I feel fine; why should I
take medications?” “I heard these
medications can make you …..”)
• Patient life chaos (Is the patient’s medical
care their top priority, or are they worried
about housing, heating, food, running water?)
• Can the patient take medications reliably?

10. Dual and Triple diagnoses
• Dual diagnosis: active mental health disorder
and substance abuse (injection, prescription,
nonprescription)
• Triple diagnosis: includes dual diagnosis and
HIV diagnosis.
The impact of dual or triple diagnosis cannot be
overemphasized in this population.

11. Other medical considerations
• Concurrent active/chronic HBV infection
• Undiagnosed HCV infection
• Undiagnosed or untreated STD
including syphilis
• Undiagnosed/untreated LTBI; active
MTB infection
• HTN, DM, CAD, tobacco/ETOH use,

12. Pt Gender Age Presenting Conditions Outcome Time to Dx
1 M 34 KS, PCP, CMV and diffuse Died 4 months
large B cell lymphoma
(DLBCL)
2 M 45 KS, PCP, multicentric Doing well, KS 8 months
Castleman’s Dz, DLBCL and lymphoma
in remission
3 M 30 PCP, CMV, CNS Died 6 weeks
Lymphoma
4 M 32 PCP, CMV, KS Doing well; KS 6 months
in remission
5 M 65 PCP, MAI Doing well 3 months
6 M 51 PCP, Burkitt’s Lymphoma Doing well, 6 months
Burkitts in
remission
7 M 48 PCP, Hodgkins Doing well, 3 months
Hodgkins in
remission
8 M 49 KS, Hodgkins Starting chemo 9 months

13. Always work with your patient where they
are and remember this is dynamic.
For many patients, HIV therapy is
up here, not a basic need.
To Providers,
HIV therapy is
here
Maslow’s Hierarchy of Needs

14. Conventional wisdom is that adherence
must be 95% to reduce risk of mutation
This means:
• If you are on a bid regimen and you miss 1
dose out of 14 your adherence is 93%
• If you are on a bid regimen and you miss 2
doses out of 14, your adherence is 86%
• If you are on a qd regimen and you miss 1
dose out of 7 your adherence is 86%

15. Correlation between Adherence
and Virologic Failure

16. FDA Approved ARV Agents,
2010

17. Simplification of therapy,
evolution from 1996-2006

18. Declining rates of virologic failure
of first regimens

19. Transmission of Resistant Virus:
2006, pooled data from 8 US city
assessment, and Vancouver
• 0-14% of new infections are ZDV resistant
• 0-10% of new infections have PI
resistance mutations
• 2-14% of new infections have a significant
NNRTI mutation
• Reports of transmission of HIV resistance
to all ARVs exist

20. Conclusion
• HIV Treatment is an effective
prevention and public health strategy
– Requires infrastructure and funding to
sustain medications for existing and newly
diagnosed HIV+ patients especially with
universalized testing

21. Conclusion
• Treatment is not merely writing a prescription
for 1 of 4 first line regimens. Must consider:
– Baseline resistance genotype with reliable
interpretation*
– Assess the patient for support, life chaos, life style,
and readiness to take HAART
• I always hope to get them to be an HIV expert before we
start ARVs.
– Assess the patient for concurrent medical and
mental health conditions, and carefully assess for
drug-drug interactions

22. Conclusion
• Have an established team working with
you:
– Mental health expert
– Social worker/case manager
– HIV expert who can help comanage the
patient with you and assist with other
medical conditions