Last week, at the Ninth Retroviruses Conference in Seattle, researchers from the University of Geneva, Switzerland presented a case study of a 38 year old gay man who has been shown to be infected with two different subtypes of HIV on two different occasions more than two and a half years apart.
In November 1998 the man presented with acute retroviral syndrome following multiple unprotected sexual encounters. At that time his CD4 count was 684 cells/ml and his viral load was over 1 million copies. He was quickly enrolled in the QUEST study, which offered AZT, 3TC, abacavir and amprenavir for 25 months, with the addition of the Alvac vaccination at months 19-25. At time of diagnosis he was found to have no primary resistance mutations and to have been infected with a subtype AE virus.
His viral load declined rapidly within 6 weeks of initiating HAART to around 1000 copies. Following a six week treatment interruption due to hepatitis B, treatment was re-started and his viral load declined to below 50 copies.
In January 2001 HAART was stopped, his viral load whilst on treatment had always been below 200 copies. By February his viral load had risen to 18,000 copies and then to 80,000 copies. Two weeks later it had declined again to 21,000 copies (first rebound).
Two weeks later in April a rapid increase in viral load occurred (second rebound) during which time his viral load fluctuated between 200,000 and 400,000 copies.
Sequencing at this point revealed a subtype B infection and the man's symptoms were mild, he had transient fatigue and fever and the patient declined the re-introduction of HAART. Co-infection at the time of acute infection, back in November 1998 and during the following two years was excluded by using subtype specific PCR tests on saved plasma samples.
The patient's history revealed several unprotected sexual contacts in Brazil three weeks before the second viral rebound. Serological data and quantification of hepatitis C RNA also documented an acute HCV infection of genotype 3A.
HIV-1 superinfection has previously been induced in chimpanzees. In this animal model the second infection produces a slower immune deterioration and more efficient control of viraemia in comparison to the initial infection. Superinfection has been considered a rare event and it was thought that it was prevented by previous viral exposure, through a phenomenon called superinfection immunity.
In the man however, the biological course of HIV-1 infection was characterized by the persistence of high viraemia and loss of 300 CD4 cells. This indicates that subtype B produced a rapid disease progression. Natural infection in humans, unlike chimps does not necessarily induce crossclade protection.
Attenuated HIV, it appears, may not induce cross clade protection in humans and circulating HIV-1 strains should be closely monitored in the context of vaccine development.
This case study underlines the importance of the maintenance of safer sexual practices among people living with HIV.
Jost S et al. HIV superinfection: rapid replacement of AE subtype by B subtype. Ninth Retroviruses Conference, abstract 757-W, Seattle, 24-28 February, 2002.