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Accepted Manuscript Title: Seroprevalence of HBV and HCV co-infection among people living with HIV/AIDS (PLHIV) visiting ART centers in Nepal: A first nationally representative study Authors: Ionita G., Malviya A., Rajbhandari R., Schluter W. William, Sharma G., Kakchapati S., Rijal S., Dixit S. PII: DOI: Reference:
S1201-9712(17)30122-4 http://dx.doi.org/doi:10.1016/j.ijid.2017.04.011 IJID 2926
To appear in:
International Journal of Infectious Diseases
Received date: Revised date: Accepted date:
20-10-2016 11-4-2017 13-4-2017
Please cite this article as: Ionita G, Malviya A, Rajbhandari R, Schluter W William, Sharma G, Kakchapati S, Rijal S, Dixit S.Seroprevalence of HBV and HCV coinfection among people living with HIV/AIDS (PLHIV) visiting ART centers in Nepal: A first nationally representative study.International Journal of Infectious Diseases http://dx.doi.org/10.1016/j.ijid.2017.04.011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Seroprevalence of HBV and HCV co-infection among people living with HIV/AIDS (PLHIV) visiting ART centers in Nepal: A first nationally representative study
(Ionita, G.1, Malviya, A2, Rajbhandari, R.3, Schluter, W. William 4, Sharma, G.5, Kakchapati, S.3, Rijal, S.6, and Dixit, S.3*)
1
United Nations Development Programme, Project Management Unit, Guinea-Bissau
2
UNAIDS |P.O Box: 5580 Addis Ababa, Ethiopia|
3
Center for Molecular Dynamics Nepal, Kathmandu, Nepal
4
WHO - Western Pacific Regional Office (WPRO), Manila, Philippines
5
6
CAMRIS International, Nepal
United Nations Children’s Fund, Kathmandu, Nepal
(*Corresponding author)
Summary: Objectives: To assess the prevalence of HIV, hepatitis C virus (HCV) and hepatitis B Virus (HBV) coinfections among People Living with HIV (PLHIV) in Nepal Methods: A sample of 677 PLHIV representing key affected populations (KAP) in Nepal under antiretroviral (ART) therapy in ART clinics around the country were voluntarily enrolled in the study. Rapid-kit based testing followed by ELISA for validation was carried out focusing on surface antigen for HBV (HBsAg) and antibodies against HCV (anti-HCV). A multivariate logistic regression model was used to identify factors associated with HBV and HCV co-infection. Results: HCV and HBV co-infection with among 77 PLHIV was found to be 19% (95% CI, 16.6 to 22.7) and 4.4% (95% CI, 3.1 to 6.6), respectively. Eastern Region had the highest percentage (48%) of HCV infection. The age group with the highest rates of co-infections was 30 to 39 years (58% and
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70%, respectively for HCV and HBV co-infection). After adjusting for confounding, males were more likely to have HBV co-infection (AOR=4.61, 95% CI, 1.42-14.98). Similarly, PLHIV who were male (AOR=5.7, 95% CI, 2.06- 15.98), had secondary education (AOR=3.04, 95% CI, 1.068.70), or were drug users (AOR=28.7, 95% CI, 14.9- 55.22) were significantly more likely to have HCV co-infection. Conclusion: This first ever national assessment on HIV, Hepatitis B Virus and Hepatitis C Virus coinfection carried out among PLHIV in Nepal demonstrates that HCV and HBV infections are a health threat to this population and interventions are required to mitigate the effects of coinfection and to prevent further morbidity and mortality.
Keywords: HIV HCV HBV coinfection Nepal Introduction: Persons at high risk for Human Immunodeficiency Virus (HIV) infection are also likely to be at risk for other infections including Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV). HIV, HBV and HCV share epidemiological characteristics such as routes of transmission through the exchange of blood or other body fluids during injecting drug use (IDU), sexual contact, or mother to child transmission during the perinatal period.1 HBV and HCV infections have frequently been observed among PLHIV worldwide.2 HBV co-infection, appears to have no impact on the progression of HIV to AIDS.3 However, there are reports that suggest that HIV co-infection modifies the natural history of infection resulting in increased percent of persons with HIV who become carriers of HBV surface antigen (HBsAg).4 Similarly, HIV infection exacerbates HCV infection3, so that HIV-infected persons are less likely to clear HCV viremia, and therefore, have higher HCV RNA loads and be more likely to progress rapidly to develop HCV-related liver disease compared to HIV-uninfected persons.4 HCV co-infection is associated with a 50% increase in mortality among persons diagnosed with AIDS.5 For these reasons, expert guidelines developed in the United States and Europe recommend screening all HIV-infected persons for co-infection with HCV and HBV.6
2
The HIV/AIDS prevalence in Nepal as of December 2009 was estimated at 0.2%, or 39,249 people living with HIV throughout the country.7 Women aged 15-49 accounted for 28.6% of all infected persons. Studies published between 1990 and 2003 reported HBV sero-prevalence of 0.3- 4.0 percent and HCV sero-prevalence of 0.3% - 1.7% in the general population of Nepal.8 In a study of HCVsero-positive persons among blood donors in Kathmandu, 3.6% were also HIV positive and 0.71% were also HBV positive.9 A study on sex trafficked women and girls of Nepal showed that among those infected with HIV, 9.1% were HBV infected. 10 A retrospective study carried out on “healthy” blood donors at a hospital in Nepal found that 2.7% of the total sample size was HBsAg positive. 11 No nationally representative study assessing HIV and hepatitis co-infection has been previously reported from Nepal. A recent study among PLHIV in Kathmandu showed HCV co-infection prevalence of over 43%. The rates among HIV-infected persons using intravenous drugs was even higher at 96%.12 With the advent of highly active antiretroviral therapy (HAART) and the possibility for HIV patients to live longer, clinicians are more likely to be confronted with issues related to co-infection and the management challenges they present, especially in resource-limited settings that exist in developing countries. Further, in occupational settings, it was previously reported that HBV and HCV are 10 and 100 times, respectively, more infectious than HIV, raising concerns not only for patients but also among health care workers.
The UN report of 2010 (Universal Access to HIV Prevention, Treatment, Care and Support Review Report) stated that the issue of HBV and HCV was not being adequately addressed in Nepal. At the time of preparation of this manuscript, there was still is no official guideline for treatment of HCV and HBV mono- or co-infection for Nepal.
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Therefore, this evaluation, conducted in 2010-2011
should provide data to assist with developing policies for HBV and HCV co-infection amongst PLHIV in Nepal.
Methods:
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A cross sectional study was carried out on 800 People Living with HIV/AIDS (PLHIV), aged 17 and over, who were randomly selected from the list of NAP+N volunteers (the association of in Nepal) and female sex workers during 2010-11. The sample size was drawn from 35 districts of the country (Nepal currently has 75 districts). A criterion of a minimum of 100 PLHIVs per district was imposed in order to select the required number of respondents per district cluster yielding a total of 18 eligible districts. There were a total of 3,736 PLHIV in the 18 districts selected. A booster sample was taken purposively to ensure adequate representation of men who have sex with men (MSM) and female sex workers (FSWs) based on the reported prevalence of HIV among these key population groups. For each parameter (questionnaire question), the non-response rate was less than 10% (in the 800 questionnaires), and only valid responses were analysed. Not all PLHIV from among 800 selected for the study agreed to take part in the serological survey. Thus, a total of 677 clients representing 17 ART sites (out of total, at the time, of 36 nation-wide) were enrolled for the sero-survey. The sero survey included testing for antibodies to Human Immunodeficiency Virus (HIV), antibody to Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) Surface Antigen (HBsAg).
Sample Size: The sample size for the study was calculated using following formula: pˆ Z1 / 2
p (1 p) , n
Where Z1 - α/2 is the (1 - α/2)% quintile from a standard normal distribution for a 95 per cent confidence interval Z1 - α/2 = 1.96. From this, we note that the precision of the estimate (or size of the half interval) is precision Z1 / 2
p (1 p) . n
The probability proportionate to size (PPS) technique was used to determine the district-specific sample size by sex. Finally, a systematic random sample technique was used for the selection of the male and female respondents.
4
Testing: A total of 677 participants took part in the sero-prevalence study of the 800 study participants completing the PLHIV survey. Interviewers of the PLHIV survey guided respondents to MoHP health facilities (ART treatment centers) for the blood draw with a reminder card.
A total of 5 ml of whole blood was collected by venipuncture in EDTA vials. Serum was separated from whole blood either by centrifugation or by gravity separation and was tested for HBV and HCV by rapid kits. The rapid kits used were HCV Tri-Dot (J Mitra and Co. Pvt Ltd, India] with sensitivity and specificity values of 100% and 98.9% respectively; And HBsAg Hepacard [J Mitra and Co. Pvt Ltd] with sensitivity and specificity values of 100% and 99.4% respectively. All positives and 10% of negative samples were futher validated by ELISAs as follows: Anti HCV Ab ELISA test [ Delta Biologicals USA] and HBsAg ELISA [general biological corporation, Taiwan]. Statistical Analysis SPSS version 17 for Window (IBM-SPSS, 2008, USA) was utilized to perform statistical analysis and to generate tables and graphs. Following this, bi-variate analysis of hepatitis infection status of PLHIV using demographic variables was conducted. Since the underlying assumptions necessary to perform multivariate analysis were met, the data were fit into a binary logistic regression model. The default enter method was utilized and categorical covariates were set under "indicator" contrast. Only "main" effects of independent variables were considered.
Logistic regression analysis was performed to examine the effects of explanatory variables with HBV and HCV co-infection among PLHIV. All variables, both explanatory and dependent, were coded as binary variables prior to fitting in the model. Initially, explanatory variables were included in the model one at a time to examine their univariate relationship with HBV and HCV co-infection. Multiple logistic regressions were used to identify the most important determinants for HBV and HCV co-infection. Statistical analyses were conducted using the Statistical Package for the Social Science (SPSS) version 17.0. A p-value of less than 0.05 was used to define statistical significance.
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Role of Funding Source: Funding Source for this study (DFID) played no role in planning and implementation of the study.
Results: General Characteristics Of the total PLHIV, 78 percent were below 30 years, 51 percent were male, 36 percent were illiterate, 98 percent were married and 15 percent were employed full-time. One-fourth of the participants were from Western Region followed by Far Western Region (22%) and Eastern Region (21%) (Nepal is divided east to west into five regions- Eastern, Central, Western, Mid-Western and Far-Western). About 30 percent of PLHIV migrated to another region within six months. More than one third of PLHIV were currently enrolled in ART. About 18 percent of them had multiple sex partners. About 31 percent of PLHIV never belonged to any of the identified risk groups, 24 percent of PLHIV were migrants and 21 percent were injecting drugs users (Table 1).
HBV and HCV co-infection The prevalence of HBV co-infection in the study population was 4.4% (95% CI, 3.1 to 6.6). HCV coinfection was 19.4% (95% CI, 16.6 to 22.7). (Figure 1). Triple infection (HIV and HCV and HBV) prevalence was 1%. The prevalence of both HBV and HCV infection was highest among IDUs (6.7% and 16%, respectively) whereas commercial sex workers (CSWs) had the lowest prevalence of either co-infection (figure 2). It appears that among clients already infected with HIV and HBV and HCV, there was a high percentage also infected with tuberculosis (TB). In all, (figure not shown) 27% of HBV and 31% of HCV infected clients were also infected with TB. The Western Development Region had the highest incidence rate of HBV co-infection (6%). In terms of age groups, 25-49 year
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old clients were much more likely to be infected with Hepatitis B (90%) compared with other age groups. Most of the infected clients (n= 657) were from the 30-39 age group. Further, 21 among 30 HBV positive PLHIV clients (or 70%) were found to be in this age group. Similarly, a total of 76 among 132 HCV positive clients (58%) were found to be in this same age group (Figure 4). The Eastern Development Region of Nepal had the highest percentage of HCV co-infection (48%). The Far Western Region had the lowest HCV co-infection incidence of 2% (Figure 3).
Factors Associated with HBV co-infection among PLHIV As shown in Table 2, gender was significantly associated with HBV co-infection among PLHIV (p50
HepB
3.3%
.0%
6.7%
70.0%
13.3%
6.7%
HepC
%
1%
14%
58%
26%
2%
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Table 1 General Characteristics of PLHIV
Characteristics
Number
Percent
(N=677) Age Below 30 years
531
78.4
Above 30 years
146
21.6
Male
347
51.3
Female
330
48.7
Eastern
140
20.7
Central
136
20.1
Western
174
25.7
Mid-Western
81
12.0
Far-Western
146
21.6
No formal education
242
35.7
Primary
195
28.8
Secondary
217
32.1
University
23
3.4
Married
663
97.9
Single
14
2.1
Fully employed
104
15.4
Partially/Non employed
573
84.6
202
29.8
Gender
Development Region
Education qualification
Marital status
Occupation
Migration more than 6 months Yes
18
No
475
70.2
Yes
452
66.8
No
225
33.2
Yes
119
17.6
No
558
82.4
IDU
144
21.3
FSW
13
1.9
Migrants
166
24.5
GBT
24
3.5
Never belong the mentioned group
210
31.0
Other (Refugee/Indigenous group
100
14.8
Not recorded
20
3.0
Currently on ART
Have multiple sex partners
Type
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Table 2 Factors Associated with HBV co-infection among HIV positive people in Nepal
Variable
Hepatitis B Positive
Negative
Univariate OR
P-value
95%(CI)
Multiple OR
P-value
(95% CI) 0.001
Gender Male
25(7.2)
322(92.8)
Female
5(1.5)
325(98.5)
5.0 (1.91-13.35)
0.01 4.61(1.42-14.98)
Note: Rest of the variables, namely Respondent’s age, education qualification, marital status, occupation, migration status, currently on ART, having multiple sex partner, respondent type (IDUs or non-IDUs) were not significant and thus are not shown.
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Table 3. Factors Associated with HCV co-infection among HIV positive people in Nepal
Variable
Hepatitis C Positive
Negative
Uni-variate OR
P-value
95%(CI)
Multiple OR
P-value
(95% CI) 0.04
Age Above 30 years
20(13.7)
126(86.3)
Below 30 years
112(21.1)
419(78.9)
1.68 (1.01-2.82)
0.89 0.94(0.40- 2.20)
< 0.001
Gender Male
126(36.3)
221(63.7)
Female
6(1.8)
324(98.2)
30.7(13.34-71.0)
< 0.001 5.7( 2.06- 15.98)
< 0.001
Education qualification
0.05
Primary
40(20.5)
155(79.5)
8.6(3.78- 19.83)
1.91(0.66- 5.53)
Secondary
74(34.1)
143(65.9)
17.3(7.78- 38.7)
3.04(1.06- 8.70)
University
11(47.8)
12(52.2)
30.7(10.1-93.47)
4.69 (0.93- 23.59)
7(2.9)
235(97.1)
No formal education
< 0.001
Currently on ART Yes
72(15.9)
380(84.1)
No
60(26.7)
165(73.3)
1.92 (1.3-2.83)
1.68 (1.06-2.67)
Have multiple sex partners Yes
32(26.9)
87(73.1)
No
100(17.9)
458(82.1)
0.24 1.44(0.77- 2.70)
0.02
0.45 1.31( 0.63- 2.69)
< 0.001
Type
< 0.001
Injecting Drug User
110(76.4)
34(23.6)
Others
22(4.1)
511(95.9)
75 (42.3-133.4)
28.7(14.9- 55.22)
Note: Remaining variables, namely marital status, occupation and migration status were insignificant and thus are not shown.
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