1) Community viral load measurement is a flawed metric for tracking HIV incidence and the impact of antiretroviral treatment (ART) programs. 2) It lacks accurate denominators of total HIV infections and numerators of longitudinal viral load data. 3) It obscures critical information like rates of undiagnosed acute HIV infection which is responsible for a large proportion of transmissions. 4) Reliable outcome measurements that account for undiagnosed infections, lost to follow up patients, geography and treatment failure/resistance are needed to properly measure HIV prevention efforts and effects of ART.

1. Community Viral Load Measurement
Myron S. Cohen
University of North Carolina at Chapel Hill

2. ART STOPS HIV Transmission
NEJM Aug 11, 2011

3. 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”

4. 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

5. Acute HIV-1 Infection
Window of Opportunity Point of No Return
Virus 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

6. 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 this
proportion corresponds with the proportion of all transmissions that occur during EHI at the population level will depend on the epidemic phase and the distribution
of 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 behavior
parameters 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.

7. 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/ml
For 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

8. What is the US Community Viral Load?
Gardner et al CID, 2011
Figure 2. The spectrum of engagement in HIV care in the United States spanning from HIV acquisition to full engagement
in care, receipt of antiretroviral therapy, and achievement of complete viral suppression. We estimate that only 19% of
HIV-infected individuals in the United States have an undetectable HIV load.

9. Reporting HIV Incidence:
A parallel problem
Seroconversion 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

10. 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 (Plos
One, August 2011) see NO decrease in HIV incidence in
spite of widespread usage of ART!

11. British Columbia and ART?
Lancet, Montaner, 2010: “NEW DIAGNOSIS”

12. 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!

13. 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

14. 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”