pol gene sequence variation in Swedish HIV-2 patients failing antiretroviral therapy

• There is limited knowledge about how to treat and interpret results from genotypic resistance assays in HIV-2 infection. Here, genetic variation in HIV-2 pol gene was studied in 20 of 23 known HIV-2 cases in Sweden. Five patients with signs of virological treatment failure were longitudinally studied. Clinical, virological and immunological data were collected and the protease (PR) and first half of the reverse transcriptase (RT) was amplified and directly sequenced from plasma samples. Moderate to extensive genetic evolution was observed in four of the five patients who failed treatment. Some mutations occurred at positions known to confer resistance in HIV-1, but many occurred at other positions in PR and RT. All patients had been treated with zidovudine alone or in combination with other antiretroviral drugs, but none displayed a mutation at position 215, which is the primary zidovudine resistance site in HIV-1. Instead, a E219D mutation evolved in virus from two patients and a Q151M mutation evolved in two other patients. A M184V mutation indicative of lamivudine resistance was detected in three patients. The virus of one patient who had been treated with ritonavir, nelfinavir, and lopinavir successively acquired nine unusual mutations in the protease gene, most of which are not considered primary or secondary resistance mutations in HIV-1. Our data indicate that the evolutionary pathways that lead to antiretroviral resistance in HIV-2 and HIV-1 exhibit both similarities and differences. Genotypic HIV-2 resistance assays cannot be interpreted using algorithms developed for HIV-1, instead new algorithms specific for HIV-2 have to be developed.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Keyword

Adolescent

Adult

Africa

Western/ethnology

Amino Acid Sequence

Amino Acid Substitution

Anti-HIV Agents/pharmacology/therapeutic use

Codon/genetics

Drug Resistance

Multiple

Viral/*genetics

Evolution

Molecular

Female

*Genes

pol

HIV Infections/drug therapy/*virology

HIV Protease Inhibitors/pharmacology/therapeutic use

HIV-1/drug effects/genetics

HIV-2/drug effects/*genetics/isolation & purification

Humans

Lamivudine/pharmacology/therapeutic use

Male

Middle Aged

Molecular Sequence Data

*Mutation

Missense

Nelfinavir/pharmacology/therapeutic use

Prospective Studies

Pyrimidinones/pharmacology/therapeutic use

Reverse Transcriptase Inhibitors/pharmacology/therapeutic use

Ritonavir/pharmacology/therapeutic use

Sequence Alignment

Sequence Homology

Amino Acid

Sweden

Treatment Failure

Variation (Genetics)

Viremia/drug therapy/*virology

Zidovudine/pharmacology/therapeutic use

Publication and Content Type

ref (subject category)

art (subject category)