D. Pieniazek et al., Protease sequences from HIV-1 group M subtypes A-H reveal distinct amino acid mutation patterns associated with protease resistance in protease inhibitor-naive individuals worldwide, AIDS, 14(11), 2000, pp. 1489-1495
Background: Although numerous mutations that confer resistance to protease
inhibitors (PRI) have been mapped for HIV-1 subtype B, little is known abou
t such substitutions for the non-B viruses, which globally cause the most i
Objectives: To determine the prevalence of PRI-associated mutations in PRI-
naive individuals worldwide.
Design: Using the polymerase chain reaction, protease sequences were amplif
ied from 301 individuals infected with HIV-1 subtypes A (79), 8 (95), B' (1
9), C (12), D (26), A/E (23), F (26), A/G (11), and H (3) and unclassifiabl
e HIV-1 (7). Amplified DNA was directly sequenced and translated to amino a
cids to analyze PRI-associated major and accessory mutations.
Results: Of the 301 sequences, 85% contained at least one codon change givi
ng substitution at 10, 20, 30, 36, 46, 63, 71, 77, or 82 associated with PR
I resistance; the frequency of these substitutions was higher among non-B (
91%) than B (75%) viruses (P < 0.0005). Of these, 25% carried dual and trip
le substitutions. Two major drug resistance-conferring mutations, either 20
M or 30N, were identified in only three specimens, whereas drug. resistance
accessory mutations were found in 252 isolates. These mutations gave disti
nct prevalence patterns for subtype B, 63P (62%) > 771 (19%) > 101/V/R (6%)
= 361 (6%) = 71T/V (6%) > 20R (2%), and non-B strains, 361 (83%) > 63P (17
%) > 10/V/R (13%) > 20R(10%) > 771 (2%), which differed statistically at po
sitions 20, 36, 63, 71, and 77.
Conclusions: The high prevalence of PRI-associated substitutions represent
natural polymorphisms occurring in PRI-naive patients infected with HIV-1 s
trains of subtypes A-H. The significance of distinct mutation patterns iden
tified for subtype B and non-B strains warrants further clinical evaluation
. A global HIV-1 protease database is fundamental for the investigation of
novel PRI. (C) 2000 Lippincott Williams & Wilkins.