Wednesday, March 21, 2007

Background & Rationale

Acute HIV Infection (AHI) is characterized by high levels of virema and no antibody response. These conditions cause flu like symptoms in 50- 90% of persons within two to three weeks of exposure to HIV and typically last 2-6 weeks; until the time an individual develops an antibody response to HIV. Individuals in AHI can transmit HIV up to 1,000 times more efficiently than persons with established HIV infection as a consequence of high levels of virema which typically range from 500,000 to <>1 By comparison, persons in untreated chronic infection typically carry viral loads between 10,000 and 50,000 copies/ml of plasma. Persons with AHI will always test negative on standard HIV ELISA antibody tests.

As AHI resembles many viral syndromes, is acquired via stigmatized behaviors, which both patients and providers are not comfortable addressing, and is often presented in overburdened settings, the syndrome is typically misdiagnosed. The high rates of misdiagnosis have substantial deleterious public health consequences as persons with AHI are highly infectious to others and mistakenly believe that they are uninfected and as a consequence may be more likely to engage in high risk sexual behaviors. Transmission dynamics originating from acutely infected individuals are likely to be magnified in areas where HIV prevalence is high. One study in Geneva, Switzerland, which assessed the temporal trends in HIV transmission among persons with AHI, found significant clustering (29%) of subsequent HIV transmissions connected closely in time and place to the acutely infected source patient (Yerly et al, 2001).2


Diagnosing AHI

Nucleic acid PCR tests, which detect HIV RNA or DNA can diagnose HIV as early as 5 to 7 days after exposure. ELISA antibody testing by contrast, usually will not detect infection until 21 to 42 days after exposure. Pooling nucleic acid PCR tests alongside standard HIV antibody testing adds about $4.00 per test in the US (Pilcher et al., 2005).3


Figure 1. Comparative effectiveness of diagnostic tests by days since HIV exposure.


Despite the enormous public health benefits of diagnosing AHI which include counseling the acutely infected patient and rapidly contacting, counseling and testing recent sexual partners to interrupt chains of HIV transmission – no health systems in the developing world and few in developed nations, have added pooled viral load testing (PVLT) to ELISA HIV antibody testing protocols among persons at high risk for HIV. In Western nations, blood banking industries now routinely perform pooled PCR viral load testing (PVLT) for all blood donors in an effort to reduce transmission associated HIV infections. As a consequence, HIV transmissions via blood transfusions in the West are now rare; in the United States, about 1 in 1.8/million (Busch et al, 2003).4 Notably, blood donors as a group are at low risk for HIV because of careful pre-screening yet they are afforded the most sophisticated HIV testing algorithms whereas groups at highest risks for HIV infection are routinely denied these more accurate and cost effective protocols for diagnosing HIV infection.

Since ARV therapy is not readily available in most developing nations, prevention technologies are the most effect mechanism available for reducing the transmission of HIV. PVLT is highly cost effective and show promise of preventing substantial secondary HIV transmissions.

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