Change in the Prevalence of HIV-1 and the Rate of Transmitted Drug-Resistant HIV-1 in Haiphong,Northern Vietnam

Abstract

We previously reported a significant decrease in HIV-1 prevalence, with no increase in drug-resistant HIV-1 among injecting drug users (IDU), female sex workers (FSW), and blood donors (BD), in Haiphong, Vietnam, from 2007 to 2009. In 2012, 388 IDU, 51 FSW, and 200 BD were recruited for further analysis. None had a history of antiretroviral treatment. From 2007 to 2012, HIV-1 prevalence was reduced from 35.9% to 18.6% (p<0.001), 23.1% to 9.8% (p<0.05), and 2.9% to 1% (p=0.29) in IDU, FSW, and BD, respectively. Of 79 anti-HIV-1 antibody-positive samples, 61 were successfully analyzed for the pol-reverse transcriptase (RT) region. All HIV-1 strains were CRF01_AE. Nonnucleoside RT inhibitor-resistant mutations, Y181C/I, were detected in three subjects; one had the nucleoside RT inhibitor-resistant mutations L74V and M184V and one had E138K. The prevalence of transmitted drug-resistant HIV-1 in Haiphong increased slightly from 1.8% in 2007 to 6.6% in 2012 (p=0.06).

Introduction

Since the first reported case of HIV infection in 1990, the estimated number of people living with HIV has increased, reaching 256,000 people in Vietnam as of 2014.¹ The number of newly reported HIV cases rapidly increased in the early 2000s, peaked in 2006 and 2007, decreased sharply between 2007 and 2009, then remained stable thereafter, paralleling the expansion of antiretroviral therapy (ART) coverage in Vietnam.^1,2 From 2005 to the end of 2011, ART coverage was scaled up from 11% to 53% of HIV-infected adults who needed treatment.² This rapid expansion of ART coverage might induce the emergence of transmitted drug-resistant HIV-1 (TDR).³ Our previous studies, conducted in 2007 and 2009, showed no change in the TDR rate among different risk groups in Haiphong, northern Vietnam,^4,5 whereas other multicenter studies from different areas in Vietnam reported various TDR rates from 2.7% to 7.6% among treatment-naive individuals during similar periods.^6

–13 Thus, consecutive monitoring of TDR is necessary to confirm the trend of circulating drug-resistant HIV-1 in Haiphong.

Materials and Methods

In 2012, we recruited 639 individuals (mean age±SD: 31.2±7.9 years), consisting of 388 male injecting drug users (IDU) (32.1±6.9 years), 51 female sex workers (FSW) (30±7.0 years), and 200 (161 males and 39 females) blood donors (BD) (29.7±9.7 years). After informed consent was obtained, blood samples were collected and the isolated plasma samples were stored at −80°C until use. Anti-HIV-1 antibody (HIV-Ab) was screened using an immunochromatography assay (Determine HIV-1/2; Inverness Medical Japan Co., Ltd., Tokyo, Japan). RNA was extracted from 100 μl of plasma samples positive for HIV-Ab using SMITEST EX-R and D (Genome Science Laboratories, Fukushima, Japan) according to the manufacturer's instructions. The HIV-1 pol-reverse transcriptase (RT) gene was amplified and population sequencing was performed as described previously.^4,5,8

The HIV-1 pol-RT nucleotide sequences obtained were compared to the reported drug-resistant mutations in the Stanford University HIV database (http://hivdb.stanford.edu/pages/algs/HIVdb.html/) and determined from the mutation panel of the International AIDS Society, USA (IAS-USA), in 2014.¹⁴ HIV-1 subtypes were predicted by phylogenetic trees that were constructed through web-based Clustal W (http://clustalw.ddbj.nig.ac.jp/), with the reference HIV-1 strains retrieved from the Los Alamos database. Pairwise comparisons between the results obtained at different sampling periods were conducted by chi-square and Fisher's exact tests.

Results and Discussion

HIV-Ab was positive in 18.6% (72/388) of IDU, 9.8% (5/51) of FSW, and 1.0% (2/200) of BD (Table 1). The HIV-1 prevalence was significantly reduced in IDU, from 35.9% in 2007 and 26.8% in 2009 to 18.6 % in 2012 (the current study) (2007 vs. 2012, p<0.001; 2009 vs. 2012, p=0.01), and in FSW from 23.1% in 2007 and 13.4% in 2009 to 9.8% in 2012 (2007 vs. 2012, p<0.05; 2009 vs. 2012, p=0.48), while it stayed relatively low and stable in BD: 2.9% in 2007, 0.5% in 2009, and 1.9% in 2012 (2007 vs. 2012, p=0.29; 2009 vs. 2012, p=0.62).^4,5

Table 1.

The Change in HIV-1 Prevalence in Different Risk Groups in Haiphong

	Year			p-values
Risk group	2007 ⁴	2009 ⁵	2012 ^a	2012 vs. 2007	2012 vs. 2009	2009 vs. 2007
IDU	35.9% (273/760)	26.8% (81/302)	18.6% (72/388)	<0.001	0.01	<0.01
FSW	23.1% (21/91)	13.4% (38/284)	9.8% (5/51)	<0.05	0.48	0.03
BD	2.9% (6/210)	0.5% (1/206)	1.0% (2/200)	0.29	0.62	0.12

Current study.

IDU, injecting drug users; FSW, female sex workers; BD, blood donors.

Of the 79 HIV-Ab-positive samples, 61 were successfully analyzed for pol-RT sequences. Phylogenetic analysis showed that all of the HIV-1 strains detected belonged to CRF01_AE (data not shown), which was consistent with our previous results in 2009,⁵ although a few other HIV subtypes, such as subtype A, B, and BC recombinants, were detected in 2007.⁴

Major nonnucleoside RT inhibitor (NNRTI) resistance mutations, Y181C/I, were detected in three individuals: two IDU and one BD, who also had the nucleoside RT inhibitor (NRTI) resistance mutations L74V and M184V (Table 2). One HIV-1 strain harboring E138K, a rilpivirine resistance-associated mutation, was found in an IDU, and was the first found in Vietnam. Because rilpivirine, an NNRTI, has not been included in the current treatment guidelines in Vietnam,^15,16 the E138K-harboring HIV-1 strain might have been transmitted from one of the surrounding countries. The total TDR rate increased slightly from 1.8% in 2007⁴ to 6.6% in 2012 in the current study; however, the difference was not significant (2007 vs. 2012, p=0.06) (Table 2).

Table 2.

Proportion of Transmitted Nonnucleoside pol-Reverse Transcriptase Inhibitor Drug-Resistant Mutations in Various Risk Groups in Each Year

				p values
Risk group	2007 ⁴	2009 ⁵	2012 ^a	2012 vs. 2007	2012 vs. 2009
IDU	K103N (3), M184I (1), K219E (1)	0	Y181C (2), E138K (1)
FSW	0	Y181C (1), K101E (1)	0
BD	0	0	L74V, Y181I, M184V, K101E (1)
Total	1.8% (5/273)	2.0% (2/102)	6.6% (4/61)	0.06	0.20
ART coverage^1,2	28.4%	53.7%	53.0%

Current study.

Data are shown as amino acid position (n).

IDU, injecting drug users; FSW, female sex workers; BD, blood donors; ART, antiretroviral therapy.

Interestingly, the profile of dominant NNRTI resistance-associated mutations changed from K103N in 2007⁴ to Y181C in 2012. Y181C is a more nevirapine-related mutation than K103N in HIV-1 CRF01_AE strains.¹⁷ Therefore, the quasispecies with the K103N mutation tend to decrease, and the population with the Y181C mutation emerges during long-term nevirapine-containing ART¹⁸ and/or the enhancement of prevention of mother-to-child transmission using a single dose of nevirapine,¹⁹ such that the Y181C mutation might have been accumulated as a TDR in this area.

In Haiphong, northern Vietnam, the prevalence of HIV-1 was significantly reduced without a significant increase in the TDR rate among high-risk groups from 2007 to 2012. This might be due to the success of HIV prevention program(s) in Vietnam, such as harm reduction interventions for IDU and FSW, distribution of clean needles/syringes and condoms, and methadone maintenance therapy, as well as peer education.^1,2 It is also suggested that a transmitted NNRTI resistance mutation, K103N, might have been replaced by Y181C in northern Vietnam.

GenBank Accession Numbers

The GenBank accession numbers are KF453803–KF453863.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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