Treatment as Prevention

Michael Wong, MD

Beth Israel Deaconess Medical Center

Harvard Medical School

Massachusetts Department of Public Health

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

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.

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

Das-Douglas M, et al. CROI 2010. Abstract 33.

Mean CVL

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*Data insufficient to prove significant association with reduced HIV incidence.

Newly diagnosed and reported HIV cases

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• 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, chlamydia

Montaner J, et al. CROI 2010. Abstract 88LB..19

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Reduction in New HIV Diagnoses in BC: Testing, HAART, and

Community VL

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Censored at the time of death or move

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HIV-1 RNA, copies/mL

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New HIV+diagnoses (all)

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Considerations when discussing ARVs with a newly

diagnosed patient

• 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…

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

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?

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.

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,

Pt Gender Age Presenting Conditions Outcome Time to Dx

1 M 34 KS, PCP, CMV and diffuse large B cell lymphoma (DLBCL)

Died 4 months

2 M 45 KS, PCP, multicentric Castleman’s Dz, DLBCL

Doing well, KS and lymphoma in remission

8 months

3 M 30 PCP, CMV, CNS Lymphoma

Died 6 weeks

4 M 32 PCP, CMV, KS Doing well; KS in remission

6 months

5 M 65 PCP, MAI Doing well 3 months

6 M 51 PCP, Burkitt’s Lymphoma Doing well, Burkitts in remission

6 months

7 M 48 PCP, Hodgkins Doing well, Hodgkins in remission

3 months

8 M 49 KS, Hodgkins Starting chemo 9 months

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.

Maslow’s Hierarchy of Needs

To Providers, HIV therapy is

here

Conventional wisdom is that adherence must be 95% to reduce

risk of mutationThis 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%

Correlation between Adherence and Virologic Failure

FDA Approved ARV Agents, 2010

Simplification of therapy, evolution from 1996-2006

Declining rates of virologic failure of first regimens

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

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

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

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