But … Community Viral Load? Wood et al. BMJ, 2008• Mean “one-time” blood viral load in a cohort• Has been used to “associate” cohort viral load with HIV “incidence”
Community Viral Load: A BAD IDEA• No denominators (who actually has HIV?)• No true numerator -longitudinal viral load not measured - patients “lost to care” disappear -spacial geography may not be noted -report of a mean confuses evaluation• Obscures the role of acute infection
Acute HIV-1 Infection Window of Opportunity Point of No ReturnVirus Concentration in Extracellular Fluid 108 107 Symptoms 106 105 Set Point Plasma (Copies/ml) 104 103 Reservoir 102 101 or 0 Virus Limit of detection of 10-1 dissemination assay for plasma 10-2 Transit virus 10-3 10-4 10-5 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 Time Post Exposure (days) Transmission
Effect of Acute and Early HIV Infection on Spread Cohen et al, NEJM, 2011 Pinkerton & Abramson 1996** Kretzschmar & Dietz 1998**† Powers et al 2010 Salomon & Jacquez et al 1994 Hayes & Koopman et al 1997** White Hogan 2006* 2008* Xiridou et al 2004 Pinkerton 2007 Prabhu et al 2009 Hollingsworth Abu-Raddad et al 2008 & Longini 2008†* Range of estimates reflects the proportion of all transmissions during an individual’s entire infectious period that occur during EHI. The extent to which thisproportion corresponds with the proportion of all transmissions that occur during EHI at the population level will depend on the epidemic phase and the distributionof sexual contact patterns in the population.** Transmission probabilities were drawn from the population category shown, but the reported estimates result from a range of hypothetical sexual behaviorparameters that do not necessarily reflect a specific population. † The range of estimates shown was extracted from the endemic-phase portion of graphs showing the proportion of new infections due to EHI over calendar time.
The Real Community Viral Load?For each new diagnosis 10% AHI missed (Patel, Archives Int Med, 2010)SO…multiply CVL x 10% X 1,000,000 copies/mlFor Example: San Francisco (Das, PLoS, 2010) 434 “new diagnosis” in 2008 - Reported community viral load ~15,000? But 43,000,000 copies of HIV are missing!Community viral load obscures critical information
What is the US Community Viral Load? Gardner et al CID, 2011Figure 2. The spectrum of engagement in HIV care in the United States spanning from HIV acquisition to full engagementin care, receipt of antiretroviral therapy, and achievement of complete viral suppression. We estimate that only 19% ofHIV-infected individuals in the United States have an undetectable HIV load.
Reporting HIV Incidence: A parallel problemSeroconversion in a cohort: (the gold standard)• Biological cross-sectional assay of “new” antibodies? -BED? - avidity -new assays (IgG3) -algorithms• New Diagnosis modeled for incidence (Wand, AIDSBehav.2011) ? New diagnosis is NOT incidence, and relationship to incidence depends on population specific assumptions about disease progression
Ecology and ART• San Francisco Das et al. PLoS One, 2010• British Columbia Montaner et al Lancet, 2010 No Denominator No Numerator No measurement of actual HIV “incidence”…and Australia, the Netherlands and the US (PlosOne, August 2011) see NO decrease in HIV incidence inspite of widespread usage of ART!
British Columbia and ART?Lancet, Montaner, 2010: “NEW DIAGNOSIS”
IDU , BC and Adherence to ART Nolan et al. AIDS Care, 2011• 267 antiretroviral naïve IDU (1996-2007)• 51 months of treatment follow-up• 81 (30.3%) 95% adherent in 1st year of HART• 187 (70.0%) achieved HIV suppression once once over the study• These subjects are not reliably suppressed!
Measuring HIV Prevention and Effects of ART• Focus on a REAL denominator -undiagnosed HIV in the population -lost to follow up -acute infection• Generate a REAL numerator -longitudinal viral load(s) -more geography -treatment resistance and failure• Acute HIV Infection: Ignorance is NOT bliss
Why is this Important?• HIV prevention depends on implementation of a clear, evidenced based strategy• ART STOPS heterosexual transmission of HIV!• Observational ecologic reports may or MAY NOT reflect reduced “incidence” of HIV• We need reliable outcome measurements …not “community viral load”