Examination of a Second Region of the HIV Type 1 Genome Reveals Additional Cases of Superinfection

Abstract

HIV-1 superinfection may occur at a rate similar to that of initial infection, raising concerns for HIV-1 vaccine strategies predicated on eliciting immune responses similar to those in natural infection. Because of the high rate of recombination during HIV-1 replication, studies examining only one region of the HIV-1 genome are likely to miss cases of HIV-1 superinfection. We examined HIV-1 gag sequences from 14 high-risk Kenyan women in whom superinfection was not detected in a previous study of env sequences. We detected two additional cases of HIV-1 superinfection: one intersubtype superinfection that occurred between 1046 and 1487 days postinfection (DPI) and one intrasubtype superinfection that occurred between 341 and 440 DPI. Our results suggest that studies that examine only small genome regions may lead to underestimates of the risk of superinfection, highlighting the need for more extensive studies examining multiple regions of the HIV-1 genome.

Association between Cellular Immune Activation, Target Cell Frequency, and Risk of Human Immunodeficiency Virus Type 1 Superinfection

“…Cases and controls did not differ significantly in their sex frequencies (mean of 1.4 versus 1.5 self-reported sex acts in the preceding week averaged over follow-up prior to sample collection; Table 1). CD4 counts were not routinely available but were Ͼ200 cells/mm 3 either immediately prior to or within 2 years of superinfection in all cases (30)(31)(32). As expected based on prior results (1,(40)(41)(42)(43), HIV-infected individuals showed higher levels of CD4 ϩ and CD8 ϩ T cell activation markers (Ki-67, CD38, HLA-DR, CCR5) and had perturbations in the expression of memory and differentiation markers in comparison to HIV-1-uninfected controls ( Fig.…”

“…A subset of these women went on to become superinfected with a second HIV-1 strain (30)(31)(32). Superinfection provides a unique opportunity to evaluate correlates of HIV-1 acquisition, since both immune activation and HIV-1-specific immune responses can be evaluated.…”

Partial Protection of Simian Immunodeficiency Virus (SIV)-Infected Rhesus Monkeys against Superinfection with a Heterologous SIV Isolate

“…There is accruing evidence for HIV-1 intra-and intersubtype superinfection in settings of intravenous drug use, structured treatment interruptions, and with strains that are resistant to antiretroviral drugs (2,4,6,22,26,28,32,39,42,43,52,60,66). Epidemiologic studies have suggested that the frequency of superinfection ranges from rare to as high as 5% per year in high-risk populations (9,10,15,20,24,27,31,40,41,51,59,65,67). However, it remains unclear how readily superinfections occur after exposure of an infected individual to a heterologous strain of virus.…”

Clinical Relevance of HIV-1 Superinfection

“…So, in this female African cohort, HIV-1 superinfection was not correlated with plasma viral load increases. In 2008, two more superinfected women from this cohort were described (Piantadosi et al, 2008). One woman was intrasubtype superinfected with two subtype A strains, and also showed no significant plasma viral load increases after more than 3.5 years of follow-up, although her viral load had increased from 4.3 log 10 copies/ml to 4.9 log 10 copies/ml directly after superinfection.…”