W. David Hardy, MD Disclosures

Barcelona, Spain; Thursday, July 11, 2002 -- Striking virologic evidence that HIV-infected individuals can become reinfected with a second strain of HIV-1 was reported by Jost and colleagues[1] from the University of Geneva, Switzerland. This phenomenon, known as superinfection, has been commonly demonstrated in vitro, as well as with SIV in subhuman primates. Although there have been previous reports of possible HIV-1 superinfection in humans,[2,3] there has not been conclusive evidence of this phenomenon.

In the case reported today, a 38-year-old man noted to have an acute retroviral syndrome (ARS) following multiple unprotected sexual contacts with male partners was enrolled in a treatment trial (QUEST; zidovudine, lamivudine, abacavir, and amprenavir) and monitored for 25 months. The study also included 6 months of concomitant vaccination with ALVAC vCP 1452 at the end of the study, followed by treatment interruption. The patient's viremia was noted to decline from > 1 million copies/mL to < 200 copies/mL while receiving highly active antiretroviral therapy (HAART). One month after discontinuation of HAART and the therapeutic vaccine, his viremia rebounded to 80,000 copies/mL, then declined to 20,000 copies/mL, and finally rebounded again 2 weeks later to 200,000 copies/mL. Viremia then fluctuated between 200,000 and 400,00 copies/mL for 5 months before HAART was resumed.

Curious about the patient's second and persistent viremic rebound, the investigators undertook intensive gene sequencing of the viral isolates, analyzing the protease (Pr), reverse transcriptase (RT), gag, and C2V3 portion of the envelope genes. This analysis demonstrated that the patient was initially infected with a subtype AE HIV-1 strain during the ARS. However, a subtype B HIV-1 isolate was found at the time of the second rebound of viremia.

To rule out the possibility that the patient was infected with the 2 subtypes from the outset, as opposed to acquiring the subtype-B strain subsequently, the investigators set up a polymerase chain reaction (PCR) assay using subtype-specific primers for AE and B viral isolates, designed according to the patient's viral sequences. The subtype-specific PCR confirmed (1) the absence of subtype-B virus both in plasma and in the form of proviral DNA before the second viremia, and (2) the appearance of subtype-B virus during the second rebound and thereafter as the major viral isolates in both DNA and plasma. In addition, the C2V3 envelope sequences of the subtype-B virus was found to be closely related to subtypes found in Brazil. Of note, the patient had had several unprotected sexual contacts during a vacation in Brazil 3 weeks before the second viral rebound. Viral cultures of the subtype-B primary isolate demonstrated that it had a much higher replicative capacity than the AE subtype.

Thus, these investigators have used sophisticated molecular virology techniques coupled with epidemiologic data to demonstrate conclusively the occurrence of HIV-1 superinfection in this patient. Whereas previous reports strongly hinted at this phenomenon, proof from molecular virology was lacking. The fact that the 2 HIV-1 subtypes acquired by this patient were different subtypes (AE and then B) increases the certainty that superinfection occurred in this patient. Although this report holds significant virologic and epidemiologic interest, its most compelling message is that HIV-1-infected persons must avoid risk behaviors if they wish to avoid reinfection with potentially more virulent or possibly multidrug-resistant virus. HIV-treating physicians and treatment advocates should take heed of this well-documented scientific report to inform their patients and clients of this phenomenon, and encourage them to observe safe sex guidelines.

References

1. Jost S, Bernard MC, Kasise L, Yerly S, et al. HIV-1 super-infection: AE subtype supplanted by B subtype. Program and abstracts of the XIV International AIDS Conference; July 7-12, 2002; Barcelona, Spain. Abstract ThOrA1381.
2. Angel JB, Kravcik S, Balaskas E, et al. Documentation of HIV-1 superinfection and acceleration of disease progression. Program and abstracts of the 7th Conference on Retroviruses and Opportunistic Infections; January 30-February 2, 2000; San Francisco, California. Abstract LB2.
   
3. Daar ES, Frost SDW, Wong JK, et al. Mixed infection with multidrug resistant (MDR) and wild type HIV strains in primary HIV infection (PHI): Early viral rebound suggests loss of immune control. Program and abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, Washington. Abstract 96.
   

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