Long‐term follow‐up of 11 protease inhibitor (PI)‐naïve and PI‐treated HIV‐infected patients harbouring virus with insertions in the HIV‐1 protease gene

Objectives

Amino acid insertions in the protease gene have been reported rarely, and mainly in patients receiving protease inhibitors (PIs). The aim of the study was to assess the long‐term viro‐immunological follow‐up of HIV‐infected patients harbouring virus with protease insertions.

Methods

Cases of virus exhibiting protease insertions were identified in routine resistance genotyping tests. Therapeutic, immunological and virological data were retrospectively collected.

Results

Eleven patients harbouring virus with a protease gene insertion were detected (prevalence 0.24%), including three PI‐naïve patients. The insertions were mainly located between codons 33 and 39 and associated with surrounding mutations (M36I/L and R41K). The three PI‐naïve patients were infected with an HIV‐1 non‐B subtype. Follow‐up of these PI‐naïve patients showed that the insert‐containing virus persisted for several years, was archived in HIV DNA, and displayed a reduced viral replicative capacity with no impact on resistance level. Of the eight PI‐experienced patients, 63% were infected with HIV‐1 subtype B; one had been antiretroviral‐free for 5 years and seven were heavily PI‐experienced (median duration of follow‐up 24 months; range 10–62 months). The protease insertion was selected under lopinavir in four patients and under darunavir in one, in the context of major PI‐resistance mutations, and following long‐term exposure to PIs. The insert‐containing virus persisted for a median of 32 months (range 12–62 months) and displayed no specific impact on phenotypic resistance level or viral replicative capacity.

Conclusion

Our data, obtained during long‐term follow‐up, show that insertions in the protease gene do not seem to have an impact on resistance level. This finding supports the recommendation of PI‐based regimens, although further work is required to confirm it.     

‘Active chronic visceral leishmaniasis’ in HIV‐1‐infected patients demonstrated by biological and clinical long‐term follow‐up of 10 patients

Objectives

The aim of the study was to describe a new evolutionary form of visceral leishmaniasis observed in immunocompromised patients.

Methods

We carried out long‐term clinical and biological follow‐up of 10 HIV‐1/Leishmania‐coinfected patients presenting numerous secondary visceral leishmaniasis episodes despite treatment, with the follow‐up time ranging from 0.5 to 10 years.

Results

Analysis of polymerase chain reaction (PCR) and blood culture results demonstrated continuous multiplication and circulation of parasites despite treatment, both during asymptomatic periods and during secondary visceral leishmaniasis episodes. This condition may be termed ‘chronic’ because of the presence of relapses over a period of several years and ‘active’ because of the continuous blood circulation of the parasite.

Conclusion

We wish to define ‘active chronic visceral leishmaniasis’ as a novel nosological entity observed in HIV‐1/Leishmania‐coinfected patients.