[66] PERSISTENCE OF HIV-1 MULTIDRUG RESISTANCE WITHOUT ANY ANTIRETROVIRAL TREATMENT 2 YEARS AFTER SEXUAL TRANSMISSION

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] PERSISTENCE OF HIV-1 MULTIDRUG RESISTANCE WITHOUT ANY ANTIRETROVIRAL TREATMENT 2 YEARS AFTER SEXUAL TRANSMISSION

[AUTHOR(S):] C Delaugerre¹, L Morand-Joubert², O Picard², ML Chaix³, AG Marcelin¹, V Schneider⁴, A Krivine⁵, A Compagnucci⁶, C Katlama¹, PM Girard² and V Calvez¹
¹Pitié-Salpêtrière Hospital; ²Saint-Antoine Hospital; ³Necker- Enfants Malades Hospital; ⁴ Rothschild Hospital; ⁵ Saint Vincent-de-Paul Hospital; and ⁶ Hôtel-Dieu Hospital, Paris, France

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 66
Antiviral Therapy 2003; 8(Suppl. 1):S201

[ABSTRACT:] Objectives: To understand the virological mechanisms of persistence of multidrug resistant virus without any selective antiretroviral pressure in recently HIV-1 infected patients.

Patients and methods: Two patients were contaminated recently by their HIV-1-infected partners, who had received, before the contamination, all available antiretroviral drugs and who died within 6 months after the contamination. The resistance mutations analysis was performed by clonal sequencing of 1.2 kb of pol gene in plasma of index and sources patients. A phylogenetic analysis was done. Sequencing of HIV-1 DNA was performed in the PBMC of index patients.

Results: Genotypic testing performed in index patients at time of seroconversion showed resistance mutations to three classes of drugs. All mutations were present on the same genome viral and all quasispecies carried all mutations. No wild-type virus was detected. The same results were found in source patients, showning that all mutations were transmitted. In the index patients, all mutations persisted over 2 years without antiretroviral treatment. Moreover, the resistance mutations were all archived in cellular reservoir. Viral load and CD4 count of index patients remained stable during 2-years of follow-up.

Discussion: Only multidrug resistant viruses, present in the source patients and well-adapted to the environment, were transmitted. In the index patients, an expansion of predominant MDR quasispecies and the ‘archival’ of all mutations were observed. These results explain the persistence of mutations and suggest the high difficulty to return to a wild-type viral population sensitive to an antiretroviral treatment. The treatment of index patients is limited and the major risk is the transmission of these multidrug resistant viruses.

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