Frequency and implications of HIV superinfection

Abstract

HIV superinfection occurs when an individual with HIV is infected with a new distinct HIV viral strain. Superinfection has been reported throughout the world, and studies have recorded incidence rates of 0-7·7% per year. Use of next-generation sequencing has improved detection of superinfection, which can be transmitted by injecting drug use and sexual intercourse. Superinfection might have incidence rates comparable to those of initial HIV infection. Clinicians should encourage safe sexual and injecting drug use practices for HIV-infected patients because superinfection has detrimental effects on clinical outcomes and could pose a concern for large-scale antiretroviral treatment plans. The occurrence of superinfection has implications for vaccine research, since it seems initial HIV infection is not fully protective against a subsequent infection. Additional collaborative research could benefit care of patients and inform future vaccine design.

Figure 1. Representative phylogenetic tree for identification and confirmation of HIV-SI

Phylogenetic tree of consensus viral sequences (≥10 NGS reads) of a recent seroconversion sample (red) and a follow-up sample from two years later (blue) demonstrating an inter-subtype superinfection event. The diagnostic requirements for HIV-SI are shown with a selection of subtype reference and random sequences from individuals in Uganda shown (black).

Figure 2. Worldwide cases of documented HIV-superinfection

Countries with HIV-SI cases reported from observational studies are represented in dark green. Countries with documented case reports are represented in light green. HIV-SI has been reported in North America (both United States,^{, , , –} and Canada), Europe,^{, , , , –} Australia, Asia,^, and Africa.^{, , , , , ,} Except for a small study in Brazil which did not find HIV-SI when using less sensitive detection methods than NGS, all countries in gray as reported in the medical literature have not been evaluated for HIV-SI. Text boxes indicate the mode of transmission [heterosexual (HS), female sex workers (FSW), men who have sex with men (MSM), injecting drug users (IDU)] and number of cases/number screened by country for all observational studies that detected HIV-SI.

Figure 3. Hypothetical HIV-SI transmission pattern

Sequence of a typical heterosexual sexual network involving initial transmission with an original viral strain (red) followed by superinfection with a new viral strain (blue). This can result in the newly superinfected partner transmitting one or both of their two strains or a new recombinant strain (purple) to a subsequent partner. Although this demonstrates a heterosexual pattern, a similar pattern would be anticipated for MSM and IDUs.

Figure 4. Representative clinical and virological aspects of HIV-SI

Putative representative graph indicating the HIV viral load (solid black), CD4+ cell count (red), CD8+ cytotoxic T-lymphocyte response (dotted black), and anti-HIV neutralizing antibody (NAb) response (purple)of a typical HIV-SI case. The graph demonstrates a spike in viral load after HIV-SI similar to what is found during acute infection which may or may not result in a higher set-point viral load. An increase in NAb response is also shown post-SI.