Incidence of HIV dual infections in US men who have sex with men

Gareth Hardy, HIV i-Base

A new study published in the Journal of Infectious Diseases confirms that HIV dual infection and HIV reinfection are common.

Researchers at University of California in San Diego and colleagues used new sequencing technology and phylogenetic analyses to determine the incidence and prevalence of dual infection by more than one strain of HIV in the same individual. [1]

Dual infection can include either:

Co-infection, in which infection with a second viral strain occurred simultaneously or very soon after primary infection; or
Superinfection, in which a second viral strain is acquired after immune responses to the first strain have been established.

These dual infections can either be intra-subtype, where both strains are from the same viral clade, or inter-subtype, where the dual infections are established by different clades. Dual infection has previously been associated with faster rates of CD4 count decline more rapid rises in viral load and more rapid disease progression. [2]

The recent development of next generation sequencing technology enables the more accurate and efficient detection of dual infection, with the ability to detect circulating minority variants that are as low as 0.25% of the viral population. This could help reveal valuable information about the impact of dual infection on disease progression as well as potential correlates of protection against superinfection.

In this longitudinal study, plasma samples were collected at regular time points between January 1998 and January 2007 from 118 treatment-naïve participants with recent HIV infection in the San Diego Primary Infection Cohort. Those patients that initiated ART were followed until their viral load became undetectable (<50 copies/mL). The median time from the estimated date of infection to the baseline time point in these subjects was 71 days (IQR: 70–133).

Seven cases of co-infection were detected at baseline using this technique. The median time from the estimated date of infection for the detection of co-infection was 2.8 months (IQR: 2.3–3.2). This result translated to a coinfection prevalence of 5.9% (95% CI, 2.4–11.8%). Over a total of 201 person-years of follow up (PYFU), 10 subjects were found to have acquired superinfection. The incidence of superinfection was 4.96 per 100 PY (95% CI, 2.67 – 9.22).

Six of these infections occurred within the first year of the estimated date of infection, and four of those within the first six months. The incidence rate of superinfection in the first year was 2.92 (95% CI, 1.31–6.50) per 100 PYFU. In the second year, in which 4 infections occurred, the incidence rate was 9.47 (95% CI, 3.56–25.23) per 100 PYFU. The median time from the estimated date of infection to superinfection was 10.5 months. Taking these results together, the cumulative prevalence of dual infection (both co-infection and superinfection) was 14.4% (95% CI, 8.6% – 22.1%). In all cases, dual infections had occurred with subtype B clade viruses. In contrast the prevalence of new HIV infections in a related Early Test Program cohort, was 4.37 per 100 PYFU (95% CI, 3.56- 5.36).

The prevalence of dual-infection identified in this study was high, at 14.4%. Interestingly the incidence of superinfection in the first year of infection was comparable to that of initial HIV infection (4.96 versus 4.37 per 100 PYFU respectively), but this rate of superinfection seemed to decline rapidly afterwards, suggesting that the establishment of HIV-specific immune responses may protect against subsequent infection. A different theory might be that potential host central memory T cells are already saturated with virus to the extent that superinfecting viral strains are unable to gain sufficient foot-hold. The small number of cases in this study together with shorter follow up from access to ART could mean that the apparent decline in incidence of superinfection may be the result of bias.

References:

Wagner GE et al. Incidence and prevalence of intrasubtype HIV-1 dual infection in at-risk men in the United States. JID (2014), 209 (7): 1032-8. doi: 10.1093/infdis/jit633. Free full text:
http://jid.oxfordjournals.org/content/209/7/1032
Cornelissen M et al. HIV-1 dual infection is associated with faster CD4+ T-cell decline in a cohort of men with primary HIV infection. CID (2012), 54: 539-47. Free full text:
http://cid.oxfordjournals.org/content/54/4/539.full.pdf (PDF)