The rates of HIV superinfection and primary HIV incidence in a general population in Rakai, Uganda

Abstract

Background: Human immunodeficiency virus (HIV) superinfection has been documented in high-risk individuals; however, the rate of superinfection among HIV-infected individuals within a general population remains unknown.

Methods: A novel next-generation ultra-deep sequencing technique was utilized to determine the rate of HIV superinfection in a heterosexual population by examining two regions of the viral genome in longitudinal samples from recent HIV seroconverters (n=149) in Rakai District, Uganda.

Results: The rate of superinfection was 1.44 per 100 person years (PYs) (95% confidence interval [CI], .4-2.5) and consisted of both inter- and intrasubtype superinfections. This was compared to primary HIV incidence in 20 220 initially HIV-negative individuals in the general population in Rakai (1.15 per 100 PYs; 95% CI, 1.1-1.2; P= .26). Propensity score matching (PS) was used to control for differences in sociodemographic and behavioral characteristics between the HIV-positive individuals at risk for superinfection and the HIV-negative population at baseline and follow-up. After PS matching, the estimated rate of primary incidence was 3.28 per 100 PYs (95% CI, 2.0-5.3; P = .07) controlling for baseline differences and 2.51 per 100 PYs (95% CI, 1.5-4.3; P = .24) controlling for follow-up differences.

Conclusions: This suggests that the rate of HIV superinfection in a general population is substantial, which could have a significant impact on future public health and HIV vaccine strategies.

Figure 1.

A and B, Phylogenetic trees of consensus gp41 viral sequences (≥10 reads) derived from 454 pyrosequences of baseline serum sample (red) and follow-up sample (blue) are shown for 2 representative intrasubtype human immunodeficiency virus type 1 (HIV-1) superinfection events. All consensus sequences were combined in a joint tree for identification of superinfecting strains as indicated (dashed circle). The HIV subtypes A and D are indicated by brackets. The number of repeated sequences represented by each consensus sequence is shown at the end of the consensus identifier. Distance is indicated for each individual tree with scale at bottom of the tree, and samples are grouped with a selection of subtype reference sequences and random sequences from individuals in Rakai (black) [1].

Figure 2.

A and B, Phylogenetic trees of consensus gp41 viral sequences (≥10 reads) derived from 454 pyrosequencs of baseline serum sample (red) and follow-up sample (blue are shown for 2 representative inter-subtype HIV-1 superinfection events. All consensus sequences were combined in a joint tree for identification of superinfecting strains as indicated (dashed circle). The HIV subtypes A and D are indicated by brackets. The number of repeated sequences represented by each consensus sequence is shown at the end of the consensus identifier. Distance is indicated for each individual tree with scale at bottom of the tree, and samples are grouped with a selection of subtype reference sequences and random sequences from individuals in Rakai (black) [1].