Luận án kết quả lồng ghép điều trị bằng suboxone tại cơ sở điều trị hiv ngoại trö trên người bệnh hiv nghiện các chất ma töy dạng thuốc phiện ở hà nội tt

MINISTRY OF EDUCATION AND TRAINING

MISTRY OF HEALTH

HANOI MEDICAL UNIVERSITY

DINH THI THANH THUY

OUTCOMES OF INTEGRATED SUBOXONE TREATMENT
AT HIV OUTPATIENT CLINIC ON HIV-INFECTED OPIOID
DEPENDENT PATIENT IN HANOI

Specialization
Code

: Public Health
: 9720701

THE MEDICAL DOCTORAL DISSERTATION SUMMARY

HA NOI – 2022


THE RESEARCH WAS COMPLETED IN
HANOI MEDICAL UNIVERSITY

Supervisors:
1. Assoc.Prof. Le Minh Giang, Ph.D
2. Assoc.Prof. Tran Huu Binh, Ph.D
Reviewer 1: Assoc.Prof. Ho Thi Hien, Ph.D

Reviewer 2: Assoc.Prof. Do Thi Nhan, Ph.D

Reveiwer 3: Assoc.Prof. Le Anh Tuan, Ph.D

The dissertation will be defended at the PhD Dissertation Judging
Committee taken place at Hanoi Medical University.
At

hour

, date

month

year 2022

The dissertation can be found at:
- National Library
- Library of Hanoi Medical University


LIST OF PUBLICATIONS

1.

Dinh Thị Thanh Thuy, Le Minh Giang, Todd Korthuis, Pham
Phuong Mai, Lynn Kunkel, Nguyen Thu Hang (2020), Integrated
model of opioid substitution treatment with suboxone at HIV
outpatient clinic in Hanoi: perspective from providers and patients,
Journal of Medical Research, Volume 125, No4 – 6/2020.

2.

Dinh Thi Thanh Thuy, Vu Minh Anh, Tran Huu Binh, Tong Thi
Khuyen, Pham Quang Loc, Todd Korthuis, Le Minh Giang (2020),
Effectiveness of buprenorphine/naloxone treatment on HIVinfected opioid dependent patient at HIV outpatient clinic in Hanoi,
Journal of Medical Research, volume 132, No8, 11/2020.

3.

Dinh Thi Thanh Thuy, Vu Minh Anh, Tran Huu Binh, Todd
Korthuis, Pham Phuong Mai, Le Minh Giang (2021) ARV
adherence among HIV patients receiving buprenorphine/naloxone
treatment in Hanoi, Vietnam Medical Journal, Volume 498, No2,
1/202.


1
INTRODUCTION
Opioid substance abuse is a global public health problem. The total
number of heroin and opium users is 30.4 million, equivalent to 1.2% of
the global population aged 15-64. In Vietnam, the number of drug users
is 246 000 (2019), of which about 40% are heroin users and mainly
injecting behavior. Global use and injection of opiates are responsible
for an increased burden of diseases such as HIV, Hepatitis C (HCV),
and Hepatitis B (HCV).
The current approach method to dealing with opioid substance
abuse is that addiction is a chronic disease and needs to be treated. The
main medications for opioid use disorder are naltrexone, methadone and
buprenorphine, but methadone and buprenorphine are the most

commonly used medications. The most common model of organization
for the treatment of opiate addiction is to organize specialized substance
addiction treatment facilities in the community with the most common
drug being methadone. The trend of integrating opioid addiction
treatment is increasingly popular with the goal of putting the patient at
the center, increasing access, and maintaining treatment.
Buprenorphine with its advantages such as safe, ceiling level, no
interaction with ARV medication, long hafl-life is organized to
integrate treatment in different medical facilities. The integrated model
of opioid addiction treatment with buprenorphine in HIV treatment
facilities is the most popular. International evidence shows that
integrating opioid addiction treatment in HIV treatment facilities
increases service access rates and improves outcomes for addiction and
HIV treatment. However, in the context of Vietnam, whether the this
model can help patients improve the outcomes of opioid use disorder
treatment and HIV treatment, and increase adherence and retention in
care or not? Therefore, we carried out an study “Outcomes of integrated
Suboxone treatment at HIV outpatient clinic on HIV-infected opioid
dependent patient in Hanoi” with two objectives:
Objective 1: Evaluate outcomes of integrated Suboxone treatment at
HIV outpatient facilities on HIV-infected opioid dependent in Hanoi
from 2016 to 2019.
Objective 2: Analyze associated factors with treatment outcomes in this
group of patients.
New contributions of the dissertation:
This is one of the first research projects on the outcomes of


2
integrated Suboxone treatment at HIV outpatient clinics in Hanoi,

Vietnam. The study used a new drug called Suboxone
(buprenorphine/naloxone) to treat opioid use disorder and organized
integrated treatment at the outpatient HIV clinics in Hanoi.
The study provided the first evidence of opioid substituion
treatment with Suboxone among HIV-infected opioid dependence
patients in Hanoi, Vietnam.
The study contributed some valuable lessons on integrating
opioid substitution at outpatient HIV facilities in Hanoi,
The layout of dissertation:
The dissertation consists of 128 pages (excluding references,
appendices), including 4 chapters:
Introduction

03 pages

Chapter 1

Literature review

26 pages

Chapter 2

Methodology

23 pages

Chapter 3:

Result

44 pages

Chapter 4:

Conclusion

28 pages

Conclusion

04 pages

Recommendation

01 pages

The dissertation includes: 33 tables, 5 figures, 8 images và 130
references


3
THEORETICAL FRAMEWORK
Individual
factors:
Age
Gender
Carrier
Substance
abuse status

Social Support
Mental Health
Adherence
Treatment
status
Motivation to
treatment

Program level

Clinic level
factors

Individual
level factors

OUTCOMES

Program level factors:
Changing in ARV
treatment modal
The policies on ARV
treatment and
addiction treatment
Stigma

Clinic level factors:
Facility factor
Personel
Training

Addiction treatment
experience

CHAPTER 1: LITERATURE REVIEW
1.1. Current status of opioid addiction in the world and Vietnam
Opioid substance use was recorded in 192 countries out of a total
of 229 countries studied. These countries account for more than 99% of
the world's population aged 15-64, which shows just how widespread
opioids are globally compared to other drugs.
Out of a total of 57.8 million opiate users, 30.4 million use opiatesbased substances (opium, heroin), most concentrated in some parts of
Asia (accounting for 60%).
According to statistics, the number of drug users in Vietnam in
2019 was 235,314 people. Until mid-2015, heroin use accounted for the
majority of drug users, however, the use of synthetic drugs has been
increasing in recent years, the number of drug users synthesis of
methamphetamine and some other drugs increased to 70% in 2019.
1.2.2. The association of opioid addiction with HIV infection and
response measures in the world and Vietnam
Opioid use disorder and injecting drug use (IDUs) have led to
negative health consequences, especially HIV. HIV prevalence among
IDUs is 17,8%, equivalent to 2,8 million people. In Vietnam, HIV
prevalence among IDUs currently is at 12,7% (2019).
Opioid substitution treatment is one of the effective methods to
reduce injecting drug behavior and HIV transmission. It is a common


4
treatment with 81 countries providing methadone treatment and 56
countries providing buprenorphine treatment
In Vietnam, opioid substitution treatment has been implemented

since 2008, currently, there are 335 treatment facilities with 52,200
patients in 63 provinces and cities. Besides, the pilot buprenorphine has
been started since 2019 in 8 provinces and cities with 578 patients.
1.3. Model of opioid substitution treatment
1.3.1. Model of opioid substitution treatment in the world
The most common form of treatment for opioid use disorder is
outpatient treatment in the community. The outpatient treatment model
is organized in two forms: 1) organized into a specialized substance
addiction treatment facility such as a methadone treatment facility and
2) integrated into primary health care facilities, private clinics, HIV and
TB treatment facilities.
Buprenorphine with its advantages such as low overdose risk, long
half-life, and milder withdrawal symptoms than methadone if
discontinued, becomes a pharmacological therapy that fits the different
integrative treatment model.
The studies around the world have provided evidence of the
effectiveness all kinds of treatment settings, but there is no strong
evidence that which treatment model lead to better treatment outcomes.
However, some studies suggest that sucessful opioid substitution
treatment with a high retention rate and good quality of care focus on
intergrated mult-service or integrated with other services.
1.3.2. Model of opioid substitution treatment in Vietnam
The most popular model of opioid substitution treatment
organization in Vietnam is methadone clinic, organized into two levels:
treatment facilities and drug dispensing facilities. Integrating opioid
substitution treatment and ARV treatment has been implemented with
some integrated step and forms.
In summary, a research review on the treatment of opiate addiction
with methadone is the most common form of treatment in the world.
However, the model of integrating treatment of CTDP addiction with

buprenorphine into primary care, private clinics or HIV treatment
facilities is being deployed strongly around the world. The integrated
treatment model aims to increase access to treatment for patients,
especially for HIV-infected patients. Therefore, we integrate the
treatment of opiate addiction with Subxone at an HIV treatment facility
in Vietnam.


5
CHAPTER 2: METHODOLOGY
2.1. Subject
2.1.1. Subjects for quantitative study component
Study subjects are HIV-infected opioid dependent people
2.1.2. Subjects for qualitative study component
The participants include 2 groups: healthcare providers and
patients participating in the study
2.2. Study site and time
The study was conducted at 4 HIV outpatient clinics in Hanoi from
September 2016 to July 2020.
2.3. Study method
Using quasi-experimental (without control group) design and qualitative
design.
2.4. Sample
2.4.1. Sample for quantitative design
Applied the calculating sample size formula:
[

√

(

)
(

In which:


√ (
)

)

(

)]

p1 = 35,2% is an estimated proportion of test negative
morphine of patients at the gate of treatment.
 p2 = 53% is an estimated proportion of test negative
morphine of patients after participating in the treatment

; α = 0.05; Z1-α/2 = 1.96; β = 0.20; Z1-β = 0.84
Minimum sample size is 121 plus 10% loss during the study so the
estimated sample is 135. The study recruited 136 participants.
2.4.2. Sample size for qualitative study
Each clinic invites 5 medical staff and 5 patients to participate. The
study invited 26 health workers and 23 patients.
2.4.3. Sample selection
Convenience sampling method was used in this study. The study
team approached and screened all potential patients from voluntary HIV

testing facilities, HIV outpatient facilities, methadone clinics, and peer
networks during the period. from 2016 to 2018.
2.5. Study and intervention process
2.5.1. Study process
The research process went through 6 phases: screening, baseline, 3


6
months, 6 months, 9 months and 12 months follow up time points.
2.5.2. Intervention process
HIV treatment interventions: Participants will be supported to
access and maintain ARV treatment according to current treatment
guidelines of the Ministry of Health when participating in the study.
Intervention to treat opioid addiction with Suboxone: implemented
according to the Guidelines for opioid substitution treatment with
buprenorphine, issued under Decision 444/QD-BYT dated February 5,
2015 of the Ministry of Health.
2.6. Research variables and indicators
Gereral information: demographic and social characteristics, some
health problems, social support and stigma
Indicators for the outcomes of opiois substitution treatment with
Subxone: substance use behavior in the past 30 days and urine test
results for morphine; adherence and retention in treatment.
Indicator for the outcomes of ARV treatment: CD4 cell count, HIV
viral load results (under 200 copies/ml and over 200 copies/ml),
adherence to ART medication; status of receiving ARV medication.
Topics from indepth-interviews with subjects: Experiences of
integrated treatment models, changes in the treatment process,
challenges and benefits from patients treated in the hair graft model
Topics from indepth-interviews with health workers: clinic

characteristics, integrated activities, advantages and disadvantages in
the process of implementing integration, plans to expand service
integration
2.7. Tools and techniques for collecting information
Information collection tools: Quantitative questionnaire, medical
record extract, urine test for drugs, CD4 test, HIV viral load test and indepth interviews guides.
2.8. Bias and control bias
Bias: bias due to loss of subjects and bias of recall information
before and after the intervention.
Bias control: regular contact and tracking of research subjects and
ensure that all necessary information is collected according to the
research time points; training investigators on research ethics and skills
in working with vulnerable groups; clearly explain to the research
subjects about the research purpose and use of the test results to ensure
the accuracy of research information.
2.9. Data analysis


7
Analyzing quanlitative data
Data were analyzed by using Stata 14.0/MP software. Descriptive
statistics to analyze socio-demographic characteristics (mean, median
and percentage).
Wilcoxone trend analysis method to analyze substance use
behavior, CD4 cell count results and HIV viral load testing results over
time.
Mixed-effect model to analyze factors related to positive urine
morphine test results and adherence to ART.
The Kaplan-Meier method was used to construct a curve describing
the retention rate in the treatment of opioid addiction with Suboxone

and to estimate the discontinuation rate during the follow-up periods.
Cox regression model was used to determine the patient's risk of
stopping treatment after 12 months of follow-up in the study.
Analyzing qualitative data
In-depth interviews will be recorded and taped, cleaned of personal
data and analyzed using Atlas.ti qualitative data management and
analysis software. Using thematic analysis method, the qualitative
content will be coded according to the coding table built based on the
interview guide and the research theoretical framework.
2.10. Research ethics
The study was approved by the Biomedical Research Review Board
of Hanoi Medical University under the approval certificate No. 134
dated October 29, 2013.
CHAPTER 3: RESULTS
3.1. Characteristics of demographic, socioeconomic, health status
and substance use history of participants at baseline.
3.1.1. Characteristics of demographic and socioeconomic of
participants at baseline
- The average age of the subjects was 38 ± 5,8 years old, in which the
age group ranging from 31 to 40 years old accounted for the majority
(63,2%), most of whom are men (96,3%). About 52,9% of the subjects
have not finished high school; 44,1% of the subjects have never been
married; 43,4% of the subjects have jobs and 52,2% of the subjects
have an income of 3 million VND or more.
- The mean score of the stigma related to substance use is 1,6±0,8.
The average score of HIV-related stigma is 2,0±0,7, in which the
highest score of the status of being discriminated is 2,5±0,9 and


8

avoiding/distancing is 2,1 ± 0,9.
- The average score for social support was 3,8 ± 0,7 (minimum 1 point
and maximum score 5 points), where the score for family support and
friend support with the same average score was 4,2 ± 0,6, support from
significant other is 4,0 ± 0,8.
- 83,8% of the participants had been arrested and imprisoned at least
once, 18,4% had been arrested more than 4 times. 64% reported having
had drug treatment at compulsory detoxification centers.
3.1.2. Health status of participants at baseline point.
- The average CD4 level is 411 ± 216 TB/mm3; 8,1% of patients
were positive for Hepatitis B; 66,9% were positive for Hepatitis C.
- 24,2% of study participants had a moderate risk of depression and
7,3% had a severe and very severe; 42,3%, at risk of moderate to very
severe anxiety mental health disorder.
3.1.3. Substance use history of participants at baseline
- The age of first concentrated heroin use is under the age of 30;
53,7% of subjects reported having used drugs for more than 10 years;
94,8% of participants used drugs by injection; 78,7% had ever received
withdrawal treatment for heroin addiction.
- Behavior of using heroin in the 30 days before participating in the
study: 100% of patients used heroin; Median number of days of use is
30 days, number of days of heroin use is from 4 to 30 days/last 30 days.
- 38,2% used more than one substance in the 30 days before
participating in the study, the number of days of multidrug use was
from 1-30/30 days, median of 3,5 days.


9
3.2. Objective 1: Results of integrated Suboxone treatment at
outpatient HIV clinic in Hanoi from 2016 -2019.

3.2.1 Results of integrated Suboxone treatment at HIV outpatient clinic.
3.2.1.1. Status of substance use during participating in integrated
Suboxone treatment at HIV outptient clinic.
Table 3.1: Substance use behaviors at study time points of participants
9
12
Characteristic Baseline 3 months 6 months
p-trend
months months
s
(n= 136) (n = 115) (n = 99)
value*
(n = 95) (n = 96)
Heroin
Using status in
136
79
63
57
62
the last 30
<0,001
(100%)
(68,7%) (63,6%) (60%)
(64,6%)
days
Number days
of using in the
30
5

3
3
4
last 30 days
<0,001
(4 – 30)
(0 – 30) (0 – 30) (0 – 30) (0 – 30)
(Median, minmax)
Craving (177,6
31,3±
32,8±33, 30,5 ±
100, Mean ±
35,8±36,8 <0,001
±19,9
31,1
8
33
SD)

100% of subjects used heroin in the past 30 days at baseline,
decreasing to 68,7%, 63,6%, 60% and 64,6% at 3, 6, 9 and 12 month
respectively. The rate of self-reported drug use behavior tends to
decrease (p<0,001). The median number of days of drug use in the last
30 days tended to decrease over the follow-up periods from 30 days at
baseline to 4 days at 12 months (p<0,001).
The mean level of craving for heroin was 77,6±19,9, decreasing to
35,8 ± 36,8 at 12 months. The trend of reducing craving after 12 months
is statistically significant (p<0.001)
The rate of using synthetic drugs in the last 30 days was 14,7% at
baseline, decreasing to 10,4%, 13,1%, 7,3%, and 8,3% at 3, 6, 9, and 12

months of follow-up respectively.
Methamphetamine use behavior in the past 30 days had a rate of
23,5% at baseline, 18,3% at 3 months, 20,2% at 6 months, 17,9% at 9
months,s and 18,7% at 12 months.


10
100%

100%

80%

6.9%

6.4%

6.0%

6.5%

2.4%

1.8%

2.0%

1.8%

1.9%

1.5%

1.0%

p-trend value<0,001

60%
40%
20%
0%

p-trend value<0,076

1.3%

(n = 136) (n = 115) (n = 99)

0.7%
(n = 95)

p-trend value<0,384

0.8%
(n = 96)

Baseline 3 months 6 months 9 months 12 months
Heroin

Amphetamine

Methamphemine

Figure 3.1: Results of urine test for drug at study time points
Urine test results showed 100% positive for morphine at baseline,
68,7%, 61,6%, 62,1%, and 67,7 % at 3, 6, 9 and 12 months respectively.
The trend towards decreasing morphine positive test results after 12
months was statistically significant. The rate of positive results for
amphetamine synthetic drugs was 11.8% at baseline, 11,3% at 3
months, 16,2% at 6 months, 12,6% at 9 months, and 13,5% at 12
months. There were 22,8% of study participants with positive results for
methamphetamine at baseline and 22,6% at 3 months, 21,2% at 6
months, 20% at 9 months. and 18,8% at 12 months.
3.2.1.2. Adherence to opioid substituion treatment with Suboxone at HIV
outpatient clinics at follow up perioids
80
60

62,5

5.4

52,4 47,6

52,4 47,6

(n = 124)

(n = 82)

(n = 56)

(n = 50)

3 months

6 months

9 months

12 months

37,5

40

4.6

20
0

Yes

No

Figure 3.2: The rate of opioid substitution treatment with
Suboxone adherence during follow up periods
The rate of opioid substitution treatment with Suboxone adherence

11
at the 3-month follow-up was 52%, 52,4%, 62,5%, and 54% at 3, 6, 9
and 12-month follow-up. (see figure 3.2)
3.2.1.3. Retenton in opioid substitution treatment with Suboxone during study
time points

Figure 3.3: Retention rate in opioid substitution treatment with
Suboxone
The cumulative retention rate at 3, 6, 9 and 12 months respectively
is 91,2%; 59,6%; 39% and 29,9%.
Table 3.2: The rate of discontinuation of Suboxone treatment over
time (100 person-month)
Treatmen time

N

Personmonth

0 – 3 months
3 – 6 months
6 – 9 months
9 – 12 months
Total

136
124
81
53
-

408
372
243
159
1182

# of
discountinuation
12
43
28
7
90

Incidence
rate/ 100
personmonth
2,9
11,6
11,5
4,4
7,6

CI - 95%
1,67 – 5,18
8,57 – 15,59
7,96 – 16,69
2,10 – 9,24
6,19 – 9.36

The average rate of stopping opioid treatment with Suboxone after
12 months of follow-up was 7,6/100 person-months, 95% CI : 6,2 –
9,4/100 person-months (see Table 3.2)
The main reasons for drop out were arrested or going to prison
with 32,6%, 15,2% of patients died, 13% refused treatment, 10,9% were
sent to the center for treatment or force to self-treat at home.
There was no difference in demographic, socio economic and substance
use history between groups of retention and drop out at baseline.
3.2.2 Results of ARV treatment during receiving integrated Suboxone


12
treatment at HIV outpatient clinics
3.2.2.1. HIV status and ARV treatment information at baseline
The average number of years of HIV infection among patients
participating in the study was 7,5 ± 5,5 years. Out of a total of 136
patients enrolled in the study, 103 were on ART in the past. Most
patients (93,4%) received ART with first-line regimens (TDF – 3TC –
EFV/NVP) at baseline.
3.2.2.2. Outcomes of ARV treatment at follow up periods
At baseline, 30,4% had a CD4 cell count over 500 cell/mm3, the
percentage of CD4 cell count over 500 cell/mm3 accounted for 42% at 6
monts and 12 months. The change in CD4 cell count after 12 months
was not statistically significant.
Table 3.3: The rate of HIV viral load suppression at study time points
Results
HIV viral load supression
<1000 copies/mL
HIV viral load supression
<200 copies/mL

Baseline
(n=136)

6 months
(n=91)

12 months
(n=89)

p-trend
value

99 (72,8%)

75 (82,4%)

75 (84,3%)

0,052

96 (70,5%)

74 (81,8%)

73 (81,8%)

0,217

The rate of HIV viral load suppression <200 copies/mL at baseline

was 70,5%, and was 81,8% at 6 and 12 months. The change in viral
load suppression rate <200 copies/mL after 12 months of follow-up was
not statistically significant.
3.2.2.3. Adherence to ARV treatment at study follow up periods
Table 3.5: Adherence to ARV treatment at study time points
Result
Self-estimated %
taking ARV
medication on time
< 90%
≥ 90%
a

Baseline
n=
%
98a

17
79

17,4
80,6

6 months
n = 94
%

12
80

13,0
87,0

12 months
n=
%
102

ptrend
value

21
81

0,577

20,6
79,4

: thiếu thông tin của 2 bệnh nhân
The proportion of patients who self-reported taking medication on
time according to the VAS scale of 90% or more within the past 7 days
was 80,6% at baseline, 87% at 6 months and 79,4% at 12 months.


13
100
80
60

40
20
0

78,6

92

21,4

21

8
(n=126)
Baseline

83,6

79

(n=125)
3-month

(n=124)
6-month
Yes

89,9

16,4

10,1

(n=122)
9-month

(n=119)
12-month

No

Figure 3.4: The rate of receiving ARV medication at study time points
At baseline, the rate of receiving ARVs was 78,6% at baseline, 92% at 3
months, 79% at 6 months, 83,6% at 9 months, and 89,9% at 12 months.
3.3. Objective 2: Associated factors with outcomes of integrated
Suboxone treatment at HIV outpatient clinic in Hanoi from 2016 - 2019.
3.3.1. Associated factors from patient level with outcomes of integrated
Suboxone treatment at HIV outpatient clinic: Quantitative results
3.3.1.1. Associated factors with test positive with morphine
Table 3.6: Associated factors with test positive morphine
(multivariate model )
Regression model
Factors
OR
p-value
(KTC 95%)
Age
0,98 (0,91 – 1,06)
0,580
Job status

No
1
0,252
Yes
0,66 (0,32 – 1,35)
Substance Use stigma
2,51 (1,39 – 4,53)
0,002
HIV stigma
0,52 (0,25 – 1,07)
0,074
Social Support
0,89 (0,49 – 1,62)
0,696
Mental Health – anxiety level
Normal and mild
1
0,070
Moderate and Severe
2,32 (0,93 – 5,74)
Suboxone treatment adherance
No
1
0,348
Yes
0,68 (0,31 – 1,52)


14
The results of analysis of some factors related to test positive with

morphine during Suboxone treatment from a multivariable mixed-effect
logistic regression model showed that patients with substance use
stigma were more likely to result in test positive with morphine
(OR=2,51; 95% KTC: 1,39 - 4,53).
3.3.1.2. Associated factors with retention in integrated Suboxone
treatment att HIV outpatient clinics
Table 3.7: Associated factors with retention in integrated Suboxone
treatment (multivariate model)
Factors
Regression model
Age

aHR (KTC 95%)

p-value

0,91 (0,80 – 1,03)

0,154

1

0,207

Gender
Male
Female

2,71 (0,58 – 12,68)

Job status
No

1

Yes

0,66 (0,31 – 1,41)

0,286

Number of arrests
Less than 2 times
From 2 times or more

1

0,495

1,24 (0,66 – 2,35)

Age of first heroin use

1,03 (0,92 – 1,12)

0,557

Number years of regular heroin use

1,16 (0,48 – 2,77)

0,739

Social Support

0,87 (0,56 – 1,37)

0,559

Dose of Suboxone medication

0,94 (0,91 – 0,98)

0,002

HIV stigma
1,01 (1,00 – 1,03)
0,024
Applied the multivariable Cox regression model, the results
showed that the factors related to retetention in opioid substitution
treatment with Suboxone includes: Suboxone dose and HIV stigma.
Specifically, patient with the higher the dose of Suboxone, they have a
lower drop-out rate (aHR = 0,94; 95% CI: 0,91 - 0,98); The patients
with high level of HIV stigma, they have a higher level of drop out rate


15
(aHR=1,01, 95% KTC: 1,00 - 1,03)
3.3.1.3. Associated factors with HIV viral load supression
Table 3.8: Associated factors with HIV viral load supression

(multivariate model)
Regression modal
Factors
aOR (KTC 95%)
p-value
Job status
No

1

Yes

0,45 (0.19 – 1,06)

No

1

Yes

1,64 (0,59 – 4,53)

0,070

Morphine positive result
0,336

Methamphetamine positive result
No

1

Yes

1,96 (0,79 – 4,83)

0,143

CD4 cell count
< 500 cells/mm3

1

≥ 500 cells/mm

0,24 (0,09 – 0,64)

3

Social Support

0,004

0,99 (0.97 -1,02)

0,853

1

0,139

Suboxone treatment adherence
No

Yes 0,56 (0,26 – 1,21)
Results from the multivariable mixed-effect logistic regression
model showed that CD4 levels were associated with HIV viral load
supresssion. Specifically, patients with CD4 cell count from 500
cells/mm3 and over were 0.24 times higher more likely to achieve HIV
viral load supression < 200 copies/mL than patients with CD4 cell count
under 500 cells/mm3 (OR=0,24; 95% KTC: 0,09 – 0,64).
3.3.1.4. Associated factors with outcomes of ARV treatment
Table 3.9: Associated factors to ARV treatment adherence
(multivariate model)


16
Factors

Regression modal
aOR (KTC 95%) p-value
0,99 (0,92 – 1,07)
0,845

Age
Job status
No
Yes

1

1,53 (0,72 – 3,30)

0,269

Morphine positive result
No
1
0,027
Yes 0,22 (0,06 – 0,84)
Mental Health – depression level
Mild and normal
1
0,137
Moderate and severe
0,52 (0,– 1,23)
Social Support
1,02 (0,99 – 1,05)
0,138
Drug use stigma
0,99 (0,98 – 1,00)
0,323
Addiction treatment
Drop out
1
0.873
Retention 1.07 (0.46 – 2.48)
The results of analysis of factors related to ARV adherence from
the multivariable mixed-effect logistic regression model showed that
the patient had a test positive morphine (OR=0, 22; 95% CI: 0,06-0,84),
they were less likely to adhere to ART treatment.

3.3.2. Facilitators from individual level, clinic level and program
level influence on integrating Suboxone treatment and outcomes of
integrated treatment at HIV outpatient clinics.
Table 3.10: Facilitators
Level
1. Individual
2. Clinic
3. Program

Factors
The satisfaction with the addiction treatment
medication
Improving the relationship between
healthcare staff and patient
Improving travel for patient
Providing comprehensive healthcare service

Integrating opioid use disorder in the outpatient HIV clinic has
favorable factors from the patient, clinic and the program level such as
the satisfaction with the medication, improved relationship between
patients and medical staff, convenience in travel and comprehensive
care and treatment.
3.3.3. Challenges from individual level, clinic level and program


17
level influence on integrating Suboxone treatment and outcomes of
integrated treatment at HIV outpatient clinics.
Treatment motivation and substance use are challenges from the
patient's level during receiving this treatment model. Factors from

treatment facilities such as physical facilities, human resources, training
and capacity building, and experience in substance abuse treatment are
challenges towards the process of integrated implementation. The
process of integrating treatment faces challenges from the program such
as changing the ART treatment model, changed policies on ART and
opioid use disorder treatment, and stigma.
CHAPTER 4: DISCUSSION
4.1 Characteristics of demographic, socioeconomic and substance
use history participants at baseline.
4.1.1 Characteristics of social economic demographic of participants
at baseline
The characteristics of age, gender, education and income of the
study subjects were quite similar to other studies among patients receiving
opioid substitution treatment with methadone in Dien Bien, Lai Chau and
Yen Bai in 2014. However, it is lower than the average income of
methadone patients in Hai Phong and Ho Chi Minh City in 2009.
The rate of criminal activities is higher than that of the studies
among methadone patients in Dien Bien, Lai Chau and Yen Bai in 2019
and Hai Phong, Ho Chi Minh City in 2009. The rate of detoxification is
64%. It is higher than that of methadone patients in the northern
mountainous provinces in 2014 (41%).
4.1.2. Health status of participant at baseline point.
The mean CD4 cell count was 411 ± 216 cells/mm3. This CD4
level is higher than the CD4 level in the group of injecting drug patients
who had access to ARV treatment early in Thai Nguyen and Thanh
Hoa, where up to 34% of patients had CD4 cell count under <100
cells/mm3 at baseline.
The prevalence of HBV infection was 8,1%, it is lower than that of
methadone patients in Hai Phong (11,6%) and Ho Chi Minh (20,8%) in
2009. The prevalence of HCV (66,9%) infection was similar to this in

the patient group. Methadone patients in Ho Chi Minh City (69,8%) and
higher than patients in Hai Phong (40%).
Some mental health disorders such as the risk of depression have
24,2% at moderate and 7,3% at severe and very severe level, 42,3%
have a risk of mental health disorder anxiety from moderate to very
severe. This mental health disorder is much higher than the assessment


18
of mental health disorders in methadone patients in Nam Dinh in 2018,
with only 1% having a depression risk level from moderate or higher,
8,1% had a mental health risk of moderate anxiety.
4.1.3. Substance use history of participant at baseline.
The age of first use is less than 30 years old, the life-time using is
longer than that of methadone treatment patients in some northern
mountainous provinces. Injecting drug use made up 94,8%, this rate is
higher than the study in the Northern mountainous areas (67,3%) in
2014 and Hai Phong and Ho Chi Minh City in 2009 at 84,2%. Although
the injection rate is high, the shared needle use behavior is lower (1,5%)
than in Dien Bien, Lai Chau and Yen Bai (10,7%) and Hai Phong. and
Ho Chi Minh City (23,8%).
The prevalence of multiple substance use in the last 30 days prior
to study participation is 38,2%. 25% of the subject use methamphetamine
and 14,7% use amphetamine. The rate of synthetic drug use is quite similar
to this rate in the group of methadone treatment patients at two treatment
facilities in Ho Chi Minh City (23,4%) in 2018.
Thus, the group of patients receiving integrated Suboxone
treatment at an outpatient HIV treatment facility had some sociodemographic characteristics that were quite similar to the group of
methadone patients in terms of age, education level, marital status, etc.
individual and occupational status and HBV and HCV co-infection

status. However, the proportion of patients with a criminal record and
compulsory treatment at centers is higher than in other studies. Longer
history of heroin use, higher injection rates, but lower overall injection
rates. The proportion of patients using synthetic drugs is quite similar to
that of methadone patients in Ho Chi Minh City and Hanoi.
4.2. Outcomes of integrated Suboxone treatment at HIV outpatient
clinic on HIV- infected opioid dependent patient at Hanoi between
2016 -2019.
4.2.1. Outcomes of integrated Suboxone treatment at HIV outpatient
clinic.
The results of the analysis showed that the self-reported heroin use
behavior and morphine positivity rate tended to decrease after 12
months of follow-up, 64,4% reported heroin use behavior and 67,7%
had positive results. positive test result for morphine. Median number of
days of use over the past 30 days and levels of heroin craving decreased
at the time points of follow-up. The positive rate for morphine after 12
months of treatment in this study was about 2,5 times higher than the
2003 study in Sweden and nearly 2 studies in the US (35,3%). The rate


19
of reporting substance use behavior after 12 months was 3 times higher
than this rate among patients treated with methadone in Hai Phong
(22,2%) and Ho Chi Minh City (23,8%). However, the rate of using
synthetic drugs of amphetamine (13,5%) and methamphetamine
(18,8%) after 12 months of treatment was lower than that of patients
treated with Suboxone in the US (41%).
The results of the analysis of adherence to substance addiction
treatment showed that at 12 months, 54% of patients were compliant with
treatment. This rate is higher than the compliance rate (48%) from a

retrospective study of 50 patients treated with buprenorphine/naloxone in
the US. However, the adherence rate in this study was lower than the
methadone adherence rate in Vietnam (82,3%).
At 12 months, the maintenance rate in treatment was 29,9%. This
rate is lower than the retention rate in treatment (57%) after 12 months
of the study in Ho Chi Minh City and in the US (49%). This rate is
much lower than that of methadone patients in Hai Phong and Ho Chi
Minh City, with a 12-month maintenance rate of 89,8%.
Substance addiction treatment outcomes such as urine positivity for
morphine, adherence rates, and retention rates for integrated Suboxone
substance abuse treatment at an outpatient HIV facility are all lower
than those of treatment. substance addiction treatment with methadone
in Vietnam. This shows that the results of the treatment of opioid
addiction with Suboxone at the integrated facility are not as good as the
results of the treatment of opioid addiction with methadone in the
Vietnamese context. Lessons learned from the integration of substance
addiction treatment with Suboxone in the HIV outpatient setting are
reflected in the challenges that staff and patients mentioned in the in-depth
interviews demonstrated in objective 2. This is a lesson for the future
expansion of the treatment of opioid addiction with buprenorphine.
4.2.2. Outcomes of ARV treatment of participants receiving
intergrated Suboxone treatment at HIV outpatient clinic.
Integrating the treatment of opioid addiction with Suboxone at an
outpatient HIV clinic in Hanoi showed that after 12 months of followup, there was a trend of increasing CD4 cell count although this
increase was not statistically significant. This result is quite similar to
an integrated study of buprenorphine in an HIV care facility in the US,
which correlated between the opioid addiction replacement treatment
intervention and the increase in CD4 cells over time of treatment.
As for the HIV viral load suppression rate, at 12 months of followup, 81.8% of the patients achieved viral suppression below 200

20
copies/mL. This rate is lower than the rate of achieving viral
suppression in the general population of ARV patients in Vietnam in
2019. However, this rate is higher than the result (41%) after 52 weeks
of follow-up in the IDU group receiving the intervention. ART
interventions, substance abuse treatment and psycho-behavioral support
in Ukraine, Indonesia and Vietnam.
The rate of adherence to ART ≥ 90% was 80,6% at baseline,
87,0% at 6 months and 79,4% at 12 months, respectively. The ARV
adherence rate is higher than the ARV adherence rate of 65,2% in
France. The rate of adherence to ART in this study is quite similar to
the rate of adherence to ART of HIV patients in Hai Phong, Hanoi and
Ho Chi Minh with a compliance rate of 74,1% with a threshold of
compliance treatment ≥95%.
4.3. Associated factors with outcomes of integrated Suboxone
treatment at HIV outpatient clinics.
4.3.1 Individual factors: quantitative results
4.3.1.1 Associated factors with test positive with morphine.
The results of univariate and multivariate mixed logistics
regression model analysis showed that the factor of substance use
stigma was associated with a higher probability of a positive urine test
result for morphine (OR=2,51 ; 95%CI = 1,39 – 4,53). However, studies
around the world do not come to the same conclusion, but show that
stigma and self-stigmatization about drug use status has an impact on
access to substance addiction treatment and maintenance in treatment.
4.3.1.2. Associated factors with retention in integrated Suboxone
treatment at HIV outpatient clinic.
Multivariate Cox regression analysis results showed that Suboxone
dose and HIV-related stigma were related to retention in treatment. The

higher the dose of Suboxone, the lower the dropout rate (aHR = 0,94;
95% CI: 0,91 – 0,98). This result is similar to the results of a literature
review of 21 clinical trials on the effectiveness of buprenorphine,
showing that patients receiving high doses (from 16-32 mg/day) retain
better than the group receiving the low dose (less than 16mg/day) (P =
0,009, R2 adjusted = 0,4).
The higher the stigma associated with HIV status, the higher the
dropout rate (aHR=1,01; 95% CI: 1,00 - 1,03). We have not found
evidence that stigma associated with HIV status correlates with
maintenance of opioid addiction treatment in studies around the world.
4.3.1.3 Associated factors with ARV adherence among patient receiving
integrated Suboxone treament at HIV outpatient clinic


21
The results of analysis of some factors related to ARV adherence
from the multivariate mixed-effect logistic regression model showed
that factors such as having a morphine positive test result for morphine
(OR=0,24; 95%CI: 0,06-0,90) is associated with nonadherence to ART.
4.3.1.4. Associated factors with HIV viral load suppression among
patient receiving integrated Suboxone treament at HIV outpatient clinic
The results of mutivariable mixed-effect logistic regression model
showed that the factor of CD4 cell counts were associated with HIV
viral load suppression <200 copies/mL. This result is quite similar to
the study of the author Shrestha et al.(2018) in the US. It means patients
with high CD4 cell count (CD4 500 cells/mm3) were more likely to
suppress HIV viral load than the group with low CD4 cell count (aOR =
2,483; p = ,045). In Vietnam, a study showed that patients with low
CD4 counts (less than 200 cells/mm3) at baseline were unlikely to
achieve viral load suppression.

4.3.2. Facilitators and challenges from patient level to outcomes and
retention in integrated Suboxone treatment at HIV outpatient clinic:
qualitative resutls
Integrating opioid addiction treatment with Suboxone at an
outpatient HIV clinic in Hanoi offers patients the opportunity to have
more choice of form and medication in addition to a methadone
program. However, patient factors such as treatment motivation and multisubstance use status are challenging factors for treatment maintenance and
outcomes. This result is similar to the results of a qualitative study on
integrating Suboxone treatment into the HIV treatment facility, patients
highly and satisfied with the treatment effect of Suboxone such as rapid
reduction of cravings, side effects and recovery.
The results of this study show that treatment motivation and
drug use status are challenging factors on the part of patients for
treatment maintenance and outcomes. Research by Teruya et al
(2014) shows that if the patient's treatment goal is not to stop using
drugs completely, the possibility of quitting treatment is very high
because Suboxone's ability to block the effect of heroin is very good.
4.3.3. Facilitators and challenges from healthcare systerm to
integrated Suboxone treatment at HIV outpatient clinic: qualitative
resutls
Integrated treatment helps to improve the relationship between
healthcare providers and patients, and to provide comprehensive health
care. However, this treatment model also faces challenges such as
funding cuts, stigma, human resources and facilities condition and the


22
capacityand skills of staff to work in addiction treatment field. A French
study examined how the interaction between doctors and patients on
buprenorphine plays an important role in treatment adherence and the

success of substance abuse treatment programs.
In addition, treatment integration helps health workers better
monitor HIV and substance abuse treatment progress to ensure that
appropriate counseling services and drug dosages are provided to
patients. This is similar to the study that integrated Suboxone treatment
of patients in the US from 2004-2009, which showed that favorable
treatment integration improved the outcomes of substance abuse and
HIV treatment.
On the other hand, factors from the health system at different levels
impact treatment organization, maintenance and treatment outcomes. In our
study, health system challenges include programmatic factors such as
funding cuts and stigma, clinic-level factors such as staffing conditions,
facility facilities and addiction treatment capacity of health workers.
4.5. Limitations
The study have some limittation: without a control group, selfreported and recalled information bias and conducting intervention with
high risk and unstable group.
CONCLUSION
1. Outcomes of integrated Suboxone treatment at HIV outpatient
clinic in Hanoi between 2016 and 2019.
1.1. Outcomes of integrated Suboxone treatment at HIV outpatient clinic
Heroin use behavior in the past 30 days decreases after 12 months of
treatment. Heroin use rate in the last 30 days was 100% at baseline,
decreasing to 68,7%, 63,6%, 60% and 64,6 % at 3, 6, 9 and 12 months
respectively. The trend to decrease heroin use behavior in the last 30 days
after 12 months of treatment was statistically significant (p<0,001).
Adherence rate for opioid substittution treatment with Suboxone at
HIV outpatient clinics was 52%, 52,4%, 62,5%, and 54% at 3, 6, 9 12
months respectively.
The cumulative rate of retention in Suboxone treatment at 3, 6, 9
and 12 months was 91,2%; 59,6%; 39% and 29,9% respectively.

1.2 In terms of ARV treatment results, there was an improvement in
the rate of HIV viral load <200 copies/mL, but this rate did not meet
the requirements of the 3rd target 90 of the national HIV/AIDS
prevention program.
The proportion of patients with CD4 cell count >500 cells/mm3
was 30,4% at baseline, increasing to 42% at 6 months and 12 months.