ORIGINAL ARTICLE

Human immunodeficiency virus and hepatitis C viruscoinfection in Nepal

Satish Prasad Barnawal & Surya Raj Niraula &

Anand Kumar Agrahari & Nikesh Bista & Nilambar Jha &

Paras Kumar Pokharel

Received: 5 May 2013 /Accepted: 27 August 2013 /Published online: 28 September 2013# Indian Society of Gastroenterology 2013

AbstractObjectives The study aimed at finding prevalence, mode oftransmission, and pattern of CD4 cell count among hepatitis Cvirus (HCV) coinfected human immunodeficiency virus(HIV)-positive individuals in Nepal.Methods This was a descriptive cross-sectional study carriedout in three Volunteer Counseling and Testing clinics, onefromDharan and two fromKathmandu, Nepal. Three hundredand thirteen individuals were recruited.Results Forty-two percent of HIV-infected persons had HCVcoinfection. Significant associations with HIVand HCV coin-fection were male gender (p <0.001) and injection drug use(IDU) (p <0.001). The mean CD4 cell count was significantlylower in HCV coinfected individuals, compared to those with-out coinfection, after 1.5 years (p =0.017), 2 years (p =0.0457),3 years (p =0.011), and 3.5 years (p <0.001) of antiretroviraltherapy.Conclusion HCV coinfection was common in HIV-infectedindividuals in Nepal and was associated with male gender,IDU, and lower CD4 counts.

Keywords CD4 count . Intravenous drug use . Retroviruses

Introduction

The prevalence of hepatitis C virus (HCV) infection has beenestimated to be about 3 % worldwide [1]. In the USA andWestern Europe, approximately one third of individualsinfected with the human immunodeficiency virus (HIV) are

coinfected with HCV [2]. The prevalence of HCVamongHIV-infected individuals with injection drug use (IDU) is approxi-mately 50 % to 70 % [3]. As of 2009, national estimatesindicate that approximately 63,528 adults and children areinfected with the HIV virus in Nepal, with an estimated prev-alence of about 0.39 % in the adult population [4]. The prev-alence of HIVand HCV coinfection in the context of Nepal isunclear.

IDU has become increasingly common in Central andSouth Asia [5]. Due to shared risk factors for transmis-sion, coinfection with HIV and HCV is common, espe-cially among those with IDU and recipients of contami-nated blood or products [6]. HIV increases HCV-relatedliver disease progression [7]. HCV infection has a well-characterized course that is adversely affected at everystage by HIV [8]. Further, the rate of HCV spontaneousclearance is low in HIV coinfection [9]. The effects ofHCV infection on the progression of HIV disease are lessclear with conflicting reports [10, 11]. There is evidencethat chronic liver disease caused by HCV coinfectioncontributes increasingly to the morbidity and mortalityof persons infected with HIV [12].

Antiretroviral therapy (ART) effectively reduces plasmaHIV RNA levels [13] and mortality from HIV infection [14].It is controversial whether HCV coinfection influences theCD4 cell response to ART [15]. The present study sought toestimate the prevalence of HCV coinfection among HIV-positive individuals, to access associations of coinfection,and to determine the effect of coinfection on CD4 cell countresponse to ART.

Methods

Setting The study was carried out in three different places viz.B P Koirala Institute of Health Sciences (BPKIHS), Dharan,

S. P. Barnawal (*) : S. R. Niraula :A. K. Agrahari :N. Bista :N. Jha : P. K. PokharelSchool of Public Health and Community Medicine, B P KoiralaInstitute of Health Sciences, Dharan, Nepale-mail: satishprasadbarnawal@gmail.com

Indian J Gastroenterol (March–April 2014) 33(2):141–145DOI 10.1007/s12664-013-0407-1

Society for Positive Atmosphere and Related Support to HIVand AIDS (SPARSHA) Nepal, Kathmandu, and Sukhra RajTropical and Infectious Disease Hospital, Teku, Kathmandu.It was done with due privacy in their respective VolunteerCounseling and Testing (VCT) clinic by face-to-face inter-view with the HIV-infected individuals based on pretestedsemi-structured questionnaire. Also, an address was given tothe past medical documents for better authenticity of theinformation which most of them had themselves.

Study subjects The target population of the study was theHIV-infected persons visiting the VCT clinic either for takingmedications or for follow up of regular checkup during April2010 to March 2011.

Study design and sample size This was a cross-sectional,descriptive study which included primary and secondary data.Based on an anticipated prevalence of HCV coinfectionamong HIV individuals of 30 % [2], the required sample sizewas taken as 313 with the precision of 5.2 (17.33 % ofprevalence) at 95 % confidence limit after adding 5 % fornonresponse.

Exclusion criteria Those who did not give consent and whocould not report CD4 cell count were excluded from the study.

Statistical analysis The data was entered intoMicrosoft Excel2007 and analyzed in SPSS 17.0 and appropriate statisticaltests applied.

Ethical consideration Ethical approval was taken from insti-tutional review board, BPKIHS, Dharan, SPARSHA, Nepal,Kathmandu and Sukhra Raj Tropical and Infectious DiseaseHospital, Teku, Kathmandu. Verbal consent was taken fromthe participants prior to interview. Privacy of participants wasmaintained during interview with due consideration of theemotional aspect.

Results

The mean age of the individuals was 33.7 years. More than25 % were females. Males were significantly more commonlycoinfected with HCV (p <0.001). Seventy-three percent weremarried, 8 % unmarried, 14.1 % single, and 5.1 % widowed.Sixty-five percent admitted to IDU. The majority (94.2 %)were receiving ART. HCV coinfection was very high com-pared to hepatitis B virus (HBV) coinfection (41.5 % vs.5.7 %). Tuberculosis coinfection was common among HIVcases (36.1 %) .

Figure 1 shows that almost two thirds of HIV-infectedindividuals had a history of IDU, more than a quarter admittedto multiple sexual partners, 18.5 % did not give a history ofextramarital sexual relationships, and 0.6 % each had historyof blood transfusion and vertical transmission.

HCV coinfection was significantly more among those whopracticed IDU (62 %) than nonusers (OR=56.9, CI=17.4–

Table 1 Presence of different types of hepatitis coinfection among HIV-infected IDU in three VCT centers (n =313)

Category IDU Total(n =313)

OR (CI) p-value

Yes (n=205), % No (n =108), %

HBV coinfection alone Yes 6.8 3.7 18 1.906 (0.612–5.938) 0.259

No 93.2 96.3 295

HCV coinfection alone Yes 62 2.8 130 56.987 (17.480–185.785) <0.001

No 38 97.2 183

Both HBVand HCV coinfection Yes 4.9 0 10 – NA

No 95.1 100 303

IDU injection drug use, HBV hepatitis B virus, HCV hepatitis C virus, NA not applicable, VCT Volunteer Counseling and Testing

Fig. 1 Glance of risk behavior(%) for acquiring HIV infectionamong HIV-infected individualsin three VCT centers (n =313)

142 Indian J Gastroenterol (March–April 2014) 33(2):141–145

185.7, p <0.001) as shown in Table 1. Almost 14 % of HCVcoinfected cases had multiple sex partners.

Table 2 demonstrates that the mean CD4 cell count did notdiffer between patients with and without coinfection before1 year of ART and at 2 years of ART. However, at ARTduration of 1.5 years (p =0.017), 2 years (p =0.0457), 3 years(p =0.011), and 3.5 years (p <0.001), the HCV coinfectedcases had significantly less mean CD4 cell count comparedto HCV uninfected individuals.

When we compared the change in mean CD4 cellcount among separate HBV and HCV coinfection, the HCV

coinfected patients appeared to have higher counts than HBVcoinfected patients. Increments in mean CD4 cell count wereleast in patients with dual coinfection (Fig. 2).

Discussion

People infected with HIVare frequently coinfected with HCVdue to shared modes of transmission [16]. HCV transmissionis more efficient through exposure to contaminated blood orblood products, especially through the use of injection drugs

Table 2 Change and comparisonof CD4 cell count in HIV infectedpersons six-monthly among thosewho had HCV coinfection andthose who had not during thecourse of ART for three and halfyears (n =313)

p-value was calculated byMann–Whitney test (nonparametric test)

ART antiretroviral therapy; HCVhepatitis C virusa Significant valueb First abrupt decline inmean CD4

cell countc Second decrease in CD4 cellcount

CD4 count (six monthly) HCV coinfection Total (n =313) p-value

Present (n =130) Absent (n =183)

Just before starting ART

Mean±SD 186.80±95.24 201.76±136.21 195.55±120.94 0.842

Median, no. 178.50, 130 165.00, 183 172.00, 313

At 6 months duration

Mean±SD 269.09±112.37 272.12±128.20 270.79±121.27 0.991

Median, no. 255.50, 128 256.50, 162 255.50, 290

At 1 year duration

Mean±SD 290.92±119.87 312.92±161.27 303.03±144.24 0.464

Median, no. 290.00, 103 299.00, 126 293.00, 229

At 1.5 years duration

Mean±SD 295.86±118.95 355.15±160.98 328.57±146.30 0.017a

Median, no. 300.00, 78 336.00, 96 317.50, 174

At 2 years duration

Mean±SD 308.88±104.93 365.45±177.50 342.07±153.82 0.045a

Median, no. 317.00, 50 356.00, 71 330.00, 121

At 2.5 years duration

Mean±SD 332.14±146.09 427.89±215.38 391.98±196.53 0.125

Median, no. 317.00, 21 361.00, 35 347.00, 56

At 3 years duration

Mean±SD 303.46±110.68b 422.30±150.62b 379.39±147.69b 0.011a

Median, no. 291.00, 13 437.00, 23 376.50, 36

At 3.5 years duration

Mean±SD 283.64±92.62c 509.79±146.86 410.28±168.47 <0.001a

Median, no. 271.00, 11 484.00, 14 387.00, 25

Fig. 2 Change and comparisonof mean CD4 cell count in in HIVinfected persons six-monthlyamong those who had HBValone,HCValone, and both HBVandHCV coinfection during thecourse of ART for three and halfyears (n =313)

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[17]. The prevalence of HCV infection among HIV-positivedrug injectors lies between 50 % and 90 % [18]. We found acoinfection rate in concordance with these statistics. HCVcoinfection was significantly more among patients with his-tory of IDU than among nonusers and more among malescompared to females, which could be due to male dominancein society that gives additional freedom to stay outdoors, andhence, higher exposure to IDU.

HIV pathogenesis is characterized by a progressive deple-tion of CD4 cells in the course of the disease [19]. Conflictingdata have emerged regarding the effect of ART on HCVdisease [20]. Eleven cohort studies have shown that ART isassociated with a reduced rate of progression of HCV liverdisease, and four of these studies have demonstrated a reduc-tion in liver-related mortality [21]. In our study, HCVuninfected individuals had higher mean CD4 cell count com-pared to HCV coinfected ones until 1 year of ART. Then, at1.5 years duration (p =0.017) and 2 years duration (p =0.0457),the mean CD4 cell count was significantly more among HCVuninfected cases. However, at 2.5 years duration, there was nosignificant association on average CD4 count. Again, at 3 yearsduration (p =0.011) and 3.5 years duration (p <0.001), theHCV coinfected cases had significantly less mean CD4 count(Table 2). HIVand HCV coinfected patients respond less wellto therapy [22]. Chronic immune activation and cytokine pro-duction in coinfected individuals may result in increased HIVreplication and diminished CD4 cell count. Even direct HCVinfection of monocytes/macrophages and CD4 cell has beenproposed as a potential mechanism [23]. After an initial rapidincrease because of redistribution of cells trapped in thelymphoreticular system to the peripheral blood, CD4 cellcounts may plateau after the first year of ART [24]. As shownin Table 2, we also observed rapid rise of mean CD4 cell countin the first year of ART and then it remained near static in thesecond year in both HCV coinfected and uninfected individ-uals. It is to be noted that after 3 and 3.5 years duration of ART,we observed fall in mean CD4 cell count. Due to longer courseof treatment, compliance to drugs could be a major reason forfall in mean CD4 cell count. Adherence to ART is paramount toits effectiveness [25]. IDU has been identified as an importantpredictor of treatment interruptions among HIV/HCVcoinfected persons [26]. Both the HIV and the HIV/HCVcoinfected population are found to have very high rates ofmental health illness, particularly depression and low levelsof education, income, psychosocial supports, and insight[27–29].

Though we had very few persons coinfected with isolatedHBV coinfection (18) and both HCVand HBV infection (10),when we compared the change in mean CD4 cell count amongseparate HBV and HCV coinfected individuals, the HCVcoinfected ones had higher level every 6months until 3.5 yearsexcept at 2 years of time. Further, when we compared thesetwo with persons having both HBV and HCV infection, the

latter had poor increment (Fig. 2). Coinfection of HIV signif-icantly modifies the natural history of HBV infection [30].When both HBVand HIV coinfect a patient, the mortality ratefrom chronic hepatitis B is increased above that of eitherinfection alone [19]. Besides, drug-related hepatotoxicity ofART for HIV infection is more frequent among patients whoare coinfected with hepatitis viruses and has become a grow-ing cause of morbidity and mortality among HIV-infectedpatients [31–33].

The epidemiologic data suggest that HIVamong drug usingpopulations will continue to fuel the spread of the infection[34]. In the resource limited setting, primary prevention reliesmainly on reducing the risk of exposure for which one of theoptions could be syringe exchange programs and pharmacysales of sterile injection equipment though quoted controver-sial by some of the authors [35–37]. Public awareness cam-paigns, education of infected individuals, screening of allHIV-infected patients for HCV infection [38], and inclusionof a psychiatrist and addictions specialist in the care team willimprove prevention and management of HIV–HCV coinfec-tion [39].

HIVand HCV coinfection is an emerging medical issue inNepal. HCV coinfection was associated with IDU and re-duced the effectiveness of ART for HIV infection. Sensitiza-tion of caregivers and patients and earlier recognition andmanagement may alter this scenario.

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