A striking report from the Royal Free Hospital has demonstrated the first confirmed case of HIV superinfection in the UK with drug-resistant HIV, in a young gay man recently infected with HIV. The findings were presented at the European HIV Drug Resistance Workshop, held from March 29th to 31st in Monte Carlo.
In addition to the British HIV Association (BHIVA) Treatment Guidelines recommendation for testing in newly diagnosed individuals, the team at the Royal Free has been additionally performing repeat pol sequencing for the past 6 months in HIV-infected patients considered at risk of superinfection, defined as those with reported unprotected sexual intercourse, a diagnosis of STI or sudden fluctuations in CD4 or viral load. Of four patients with repeat baseline genotypes available, one case was identified of possible superinfection.
Case profile
A 23 year old gay man was diagnosed in May 2005 when he sought HIV testing. The diagnosis had been negative when he was tested five months previously. He reported several unprotected sexual encounters within the preceding four months and in April 2005 experienced symptoms indicative of seroconversion illness. He was diagnosed with HIV-1, subtype B with a viral load over one million copies/ml and a CD4 cell count of 278 cells/mm3. The HIV IgG avidity index (a validated technique with values determining seroconversion within the first four to six months), showed a strong correlation with early infection. By July 2005 his CD4 count had increased to 423 and viral load had fallen to around 40,000 copies/ml (4.6 log).
Over the following few months, he further reported several unprotected exposures and at the end of September 2005 again experienced similar symptoms to the time of his first seroconversion with a concomitant drop in CD4 count to 247 cells/mm3 and rise in viral load to approximately 160,000 copies/ml (5.2 log). Tests for co-infections with hepatitis A, B, C, Epstein-Barr virus, gonorrhoea and chlamydia all proved negative.
By February 2006, viral load had stabilised around 80,000 copies/ml (4.9 log), slightly higher than at the first baseline, while the CD4 count remained considerably lower at 274 cells/mm3 compared to 423 at initial infection. His viral subtype was confirmed as clade B at both infections, but of interest, phylogenetic analysis of the pol sequences obtained at the different time points (May and July, October and November) revealed separate and phylogenetically distinct clusters. Worthy of note, resistance mutations were not observed in the earlier viral samples at the RT region but secondary mutational changes were observed on the protease enzyme at positions L10I and L63T. The later sequences however, showed a host of additional mutations at V179D and G333E in RT as well as L63P, A71T and I93L in the protease. In November 2005, the patient presented with an episode of genital herpes and in February 2006, he received treatment following contact with acute syphilis.
The authors conclude that whilst routine pol sequencing may not be required, targeted testing for individuals engaging in repeated high-risk behaviours may be helpful in identifying cases of superinfection. As with previous reports of superinfection, this case highlights infection with the same subtype confirming the lack of cross-protective immunity. Most importantly, this case emphasises the urgent need to reinforce safer sex messages through targeted public health campaigns, they conclude.
Booth C et al. Divergent pol sequences as markers of HIV-1 superinfection in a case of recurrent acute seroconversion illness. European Drug Resistance Workshop, Monte Carlo, abstract 101, 2006.