Treatment as Prevention Michael Wong, MDBeth Israel Deaconess Medical Center Harvard Medical SchoolMassachusetts 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 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.
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 < 500Patients (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 200Montaner J, et al. CROI 2010. Abstract 88LB..
Considerations whendiscussing 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 Dx1 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 remission3 M 30 PCP, CMV, CNS Died 6 weeks Lymphoma4 M 32 PCP, CMV, KS Doing well; KS 6 months in remission5 M 65 PCP, MAI Doing well 3 months6 M 51 PCP, Burkitt’s Lymphoma Doing well, 6 months Burkitts in remission7 M 48 PCP, Hodgkins Doing well, 3 months Hodgkins in remission8 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.To Providers,HIV therapy is here Maslow’s Hierarchy of Needs
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%
Correlation between Adherence and Virologic Failure
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