Drug-resistant HIV infection among drug-naive patients in Israel.
BACKGROUND
In Israel, <0.06% of the general population is infected with human immunodeficiency virus (HIV), with a much higher prevalence among specific groups. These groups are distinguished demographically by risk behavior category and by virus subtype. We investigated transmission of drug resistance within groups to assess the impact of these factors.


METHODS
Plasma samples from >15% of all patients with new diagnoses of HIV infection were randomly collected between June 1999 and June 2003. Sequences from 176 drug-naive patients included 20 of subtype A, 20 of subtype AE, 2 of subtype AC, 29 of subtype B, 100 of subtype C, and 5 of subtype F.


RESULTS
Major drug resistance mutations (protease: L90M; reverse transcriptase: M41L, K103N, V106M, M184V, Y181S, G190A, L210W, T215Y/F, and K219R) were detected in 1 subject with A subtype, 3 with subtype B, and 9 with subtype C. In addition, 1 subject with A subtypes, 2 with subtype B, and 10 with subtype C had secondary mutations (protease: M46I; reverse transcriptase: A98G, K101Q, and V108I). Only 1 patient had mutations associated with >1 class of drugs. Among subjects who contracted HIV infection in Israel, 16 of 56 (1 of 7 with subtypes A or AE, 4 of 17 with subtype B, and 11 of 32 with subtype C; P=.7-1.0) carried resistant virus--a significantly higher proportion (P<.001) than in subjects infected in other countries (10 of 120 infected).


CONCLUSIONS
Drug-resistant virus was detected in 14.8% of patients with new diagnoses of HIV infection but in 28.6% of patients known to have been infected in Israel. The implications include a need for pretreatment resistance testing and for better programs aimed at prevention of transmission, directed particularly at patients. We did not find significant differences in transmission of resistant virus between those infected with subtypes B and C, despite the different demographic background. A conclusive analysis and interpretation should await a more extensive study.
Grossman
Z
Z
National HIV Reference Laboratory, PHL, MOH, Central Virology, Sheba Medical Center, Tel Hashomer, 52621 Israel. grossman@sheba.health.gov.il
Lorber
M
M
Maayan
S
S
Bar-Yacov
N
N
Levy
I
I
Averbuch
D
D
Istomin
V
V
Chowers
M
M
Sthoeger
Z
Z
Ram
D
D
Rudich
H
H
Mileguir
F
F
Pavel
R
R
Almaliach
R
R
Schlaeffer
F
F
Kra-Oz
Z
Z
Mendelson
E
E
Schapiro
J M
JM
Riesenberg
K
K
D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D009154:Mutation; D010802:Phylogeny; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000235:genetics
D019380:Anti-HIV Agents; D012367:RNA, Viral; D012194:RNA-Directed DNA Polymerase; D016333:HIV Protease