Dual HIV infection in long term nonprogressor elite controllers

Researchers from Spain led by Maria Pernas analysed the prevalence, host genetic polymorphisms and the clinical consequences of HIV-1 dual infection (DI) in a cohort of 20 HIV long-term nonprogressor elite contollers (LTNP-EC).

The analysis included median of 15.5 samples per patient over a median follow-up of 10.2 years (range 2.5-17.2 years) . All participants had maintained undetectable HIV viral load (<50 copies/mL) without treatment since their diagnosis. During follow up, they remained clinically asymptomatic. Phylogenetic analysis was performed used 1-5 samples per patient, with follow up in 13-21 samples.

Maximum likelihood (ML) analysis of multiple envelope sequences was performed and showed that all patients had subtype-B. Monophyletic groups were detected above 80% significance except for nine patients, yet four of those patients were clustered in monophyletic groups less than 80%. Five patients had nucleotide sequences that were segregated in 2 or 3 different clusters with greater than 80% significance. The investigators looking at longer gene fragment in these five participants to ensure these five did not generate viral evolution. Four of the 20 LTNP-EC patients were identified as having dual HIV-1 infection.

During the follow-up, there was no statistical difference in epidemiological and clinical markers between those who were single and dual infected. The predominant route of transmission was IV drug use (which is also associated with a higher number of transmitted founder viruses). During follow-up, LTNP-EC status was maintained over 20 years by three out of the four people with dual infection.

There was no difference in median CD4 count between people with single and dual infection (~990 cells/mm3; range 597-1355). However, in the dual infected group, the mean difference in CD8 count was significantly higher [median 1213 (range 882-2438) vs 808 (range 234-1227), p <0.02] and the CD4/CD8 ratio was lower [median 0.8 (range 0.2-1) vs 1.3 (range 0.6-3.0), p < 0.01].

Other host factors such as MHC class I group B and HLA alleles were associated with viral control in this cohort. Dual infections was also associated with several host genetic polymorphisms that are indicated in viral control in single infected LTNP-EC, including the HLA-B*35 allele.