A case of intraclade HIV-1 superinfection by wild-type virus illustrates the potential to impact disease progression

Graham McKerrow, HIV i-Base

Californian and Scottish researchers report in the 2 May issue of AIDS on a case of intraclade HIV-1 superinfection by wild-type virus in the absence of antiretroviral therapy in a patient initially infected with drug-resistant HIV. They conclude that the substantially different in vivo viral growth characteristics they observed illustrate the potential for superinfection to impact disease progression.

The immunological response to HIV-1 infection has been postulated to impede superinfection with a second virus; however, a few recent reports have documented cases of HIV-1 superinfection in humans either from different viral clades or from the same clade. Kersten K Koelsch, of the University of San Diego, and colleagues set their objective to differentiate between coinfection and superinfection in a patient harboring a distinct wild-type HIV four months after primary infection with drug-resistant HIV.

They used detailed dye primer and clonal sequencing along with length polymorphism analysis to investigate the evolutionary linkage between viral populations sampled at different time points.

They found that after a set point viral load of 6000 copies HIV RNA/ml, viral load jumped to 34,000 copies/ml at month four and, shortly after, to almost 200 000 copies/ml. At that time a second viral strain was first detected by dye primer sequencing of a pol fragment. These findings were confirmed by analysis of a 1300 bp gag-pol fragment and clonal sequencing and phylogenetic analysis of the V3 region. Length polymorphism analysis of the gp120 V4-V5 region showed that the second viral population was absent even as a minority population until month four, when it was found to be the majority population, and the initial variant was present only as a minority. Both strains were subtype B.

In their Discussion the researchers write: “Infection by viral variants with differing replication capacities and their variable susceptibility to the host immune response might be expected to have a significant impact on disease progression. Indeed, in the case described here, an abrupt increase in plasma viremia occurred coincident with the appearance of the second variant and consistent with the hypothesis that this second variant had greater in-vivo fitness than the initial, drug-resistant virus. The theoretical acceleration of disease progression that might result from a higher post-superinfection viral setpoint appears to be reflected in the steeper trajectory of the CD4 cell decline in this patient after superinfection.

“A second issue of importance is the impact of superinfection on treatment response. An obvious scenario for concern is that of a patient with drug-sensitive virus responding well to therapy who then becomes superinfected with drug-resistant virus. The transmission of drug-resistant virus is a common event. However, the case described here highlights a more insidious danger arising as a consequence of superinfection. In this case, standard drug susceptibility testing at late time points would fail to detect the occult drug-resistant virus. Nevertheless, if this patient were to initiate therapy, it seems likely that drug-resistant virus would quickly re-emerge.”

The authors cite a handful of recent publications and conclude: “Together, these recent reports suggest that superinfection may occur more commonly than has previously been assumed, which has broad implications for HIV treatment, epidemiology, vaccine development and pathogenesis.”

Reference:

Koelsch K, Smith DM, Little SJ et al. Clade B HIV-1 superinfection with wild-type virus after primary infection with drug-resistant clade B virus. AIDS 17(7):F11- F16, 2003.

The full text of this article is available online following single free registration:
http://www.medscape.com/viewpublication/744_toc?vol=17&iss=7

Comment

Growing evidence affirms the previous plausibility of re-infection. The frequency of this remains difficult to determine. With the fragility of combination therapy dependent retaining drug sensitivity, drug absorption, food and drug interactions and adherence, the additional risk from reinfection is rarely suspected or investigated.

Large numbers of such cases are never likely to be reported, but this does not mean that they are only occurring infrequently.