Frequency of HIV-1 co and super-infection in intravenous drug users

L. Perrin, S. Yerly , M. Monnat , A. Telenti , P. Burgisser.

Geneva University Hospital, Geneva (Switzerland)

Background: The frequency of HIV-1 co/super-infection is unknown despite their implications for public health and vaccine development. We addressed this issue during an epidemic of both CRF11 and B subtype among intravenous drug users (IVDUs) living in the western part of Switzerland.

Methods: Systematic plasma and lymphocyte collection at baseline and during follow-up in recently infected IVDUs from the western part of Switzerland in 19982002 and in IVDUs with chronic infection living in the same area and presenting with an unexpected rise of viremia (> 1 log). We performed bulk sequencing of reverse transcriptase, protease and C2V3 regions. A subtype specific nested PCR was performed in plasma and proviral DNA (In the first generic RT-PCR, a 1399 bp gag/pol fragment (1872-3271, Numbers in reference to HXB2) was amplified. Primers for the nested PCR were designed based on gag and RT sequences of IVDUs infected with either B or CRF-11 strains.

Findings: In 58 recently infected patients, we detected at baseline 3 B/CRF-11 co-infections, 25 B, 28 CRF-11 and 2 other subtypes. In the 3 co-infected patients, both CRF-11 and B were detected in plasma and proviral DNA and persisted during a follow up of more than 2 years. B and CFR-11 specific PCR performed on follow-up samples of 40/58 recently infected patients (total follow-up of 59,6 years) revealed a transient B super-infection in a patient initially infected by CRF-11. At this time the concentration of B subtype in plasma was 1000 fold lower than that of CRF-11. This patient was not treated and its viremia was around 500.000 HIV-1 RNA copies and viremia and CD4 count did not change at the time of super-infection. Five of 156 chronic IVDUs (total follow-up: 346 years) had an unexpected rise of viremia. In two of them, aviremic without treatment for years after an initial B infection, a symptomatic CRF-11 super-infection occurred and was associated with high viral load and a fall of CD4.

Conclusions: In recently infected IVDUs, co-infection is frequent (>5%). In chronically infected IVDUs super-infection is not rare and may occur in patients controlling efficiently HIV infection by the initial strain. However, the detection of a transient super-infection, using a very sensitive technique, may suggest that most super-infections are unnoticed and that transient super-infection is the rule rather than the replacement of the first strain by the second one as shown in few case reports.