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Subtype Distribution and Drug Resistance Patterns Among HIV-1 Strains Prevalent in Makassar, Indonesia

Khairunisa, Siti Qamariyah Megasari, Ni Luh Ayu Ueda, Shuhei Kotaki, Tomohiro Hidayati, Afif Nurul Nasronudin Kameoka, Masanori 神戸大学

2023.03

概要

Human immunodeficiency virus type 1 (HIV-1) is characterized by a large degree of genetic variability because of high rates of recombination and mutation, sizable population sizes, and rapid replication. Therefore, this study investigated HIV-1 subtype distribution and the appearance of drug resistance mutations (DRMs) in viruses that are prevalent in Makassar, South Sulawesi, Indonesia. The HIV-1 pol, env, and gag genes were amplified from 63 infected individuals and sequenced for a subtyping analysis. CRF01_AE was identified as the predominant HIV-1 circulating recombinant form (CRF) in Makassar, South Sulawesi, Indonesia. Subtype B and recombinant viruses containing CRF01_AE, CRF02_AG, and/or subtype B gene fragments were also detected. Several major DRMs against non-nucleoside reverse transcriptase inhibitors were found among antiretroviral therapy (ART)-experienced subjects, whereas ART-naive subjects did not possess any transmitted drug resistance. The prevalence of DRMs was very high among ART-experienced subjects; therefore, further surveillance is required in this region.

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参考文献

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14

Figure legends

FIG. 1. Phylogenetic tree analysis of HIV-1 RT, PR, env, and gag genes collected in

Makassar, Indonesia.

Phylogenetic trees were constructed for the HIV-1 RT (A), PR (B), env (C), and gag genes

newly sequenced in the present study (D). The corresponding viral genes of reference

HIV-1 strains representing subtypes A1, A2, B, C, D, and G as well as CRF01_AE

(01_AE), CRF02_AG (02_AG), CRF15_01B (15_01B), CRF33_01B (33_01B), and

CRF34_01B (34_01B) were included in analyses (shown in Italic letters). Sequence IDs

are presented as a GenBank accession number, sample ID, or the ID of the reference HIV-

10

1 strain and the subtype or CRF of the reference strain (shown in parentheses) in that

11

order. New sequences identified in the study are highlighted by bold letters, while those

12

derived from recombinant viruses are denoted with circles. Bootstrap values were shown

13

if they were >70.

14

Table 1. Demographic characteristics of study participants

Characteristics

Value (n = 63)

Age, mean years (SD)

34.2 (6.3)

Sex, n (%)

Male

46 (73.0%)

Female

17 (27.0%)

Marital status, n (%)

Married

33 (52.4%)

Single

30 (47.6%)

Ethinicity, n (%)

Makasar

23 (36.5%)

Bugis

23 (36.5%)

Jawa

5 (7.9%)

Toraja

2 (3.2%)

Batak

1 (1.6%)

Other

9 (14.3%)

Transmission risk category, n (%)

Heterosexual intercourse

19 (30.2%)

Homosexual intercouse

12 (19.0%)

Intravenous drug use

22 (34.9%)

Commercial sex worker

7 (11.1%)

Unidentified

3 (4.8%)

Types of ART used, n (%)

3TC+AZT+NVP

13 (20.6%)

3TC+AZT+EFV

15 (23.8%)

3TC+TDF+EFV

31 (49.2%)

3TC+TDF+NVP

1 (1.6%)

Naïve

3 (4.8%)

Oppoturnistic infection, n (%)

No

49 (77.8%)

Yes

51 (22.2%)

Table 2. Drug resistance mutations and HIV-1 subtypes/CRFs detected in viral genes

derived from HIV-1-infected individuals receiving ART

Sample

ID

MK9

Type of ART; Subtype

3TC, AZT, EFV;

CRF01_AE/CRF02_AG

3TC, TDF, EFV;

CRF01_AE/CRF02_AGrecombinant

Drug Resistance Mutations*

NRTI

NNRTI

PI

V90I

G16E

EFV, NVP

K20I

D30N

M36I

M46I

L63P

L89M

I93L

MK26

3TC, TDF, EFV;

E138A

G16E

ETR, RPV

CRF01_AE

K20R

M36I

V77I

L89M

I93L

MK27

3TC, AZT, NVP;

V179D

L33V

ETR

subtype B

I64V

I93L

MK41

3TC, AZT, EFV;

V90I

G16E

ETR

CRF01_AE/CRF02_AGK20I

recombinant

D30N

M36I

M46I

I62V

L63P

V77I

L89M

* Mutations associated with high resistance according to the guidelines published by

the International AIDS Society United States (IAS-USA) are shown. Major mutations

are shown in bold.

MK10

K103N

Conferred

Resistance to

ETR

...

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