Prevalence and risk factors for hepatitis c virus co-infection among human immunodeficiency virus-infected patients and effect of hepatitis c virus infection on acquired immunodeficiency syndrome cases at baseline.

Background: Hepatitis C virus (HCV) co-infection with human immunodeficiency virus (HIV) exists as both viruses have the common routes of transmission. HIV infection has adverse effect on the natural history of HCV infection; however, the effect of HCV infection on the natural history of HIV infection is unclear. Materials and
Methods: This study was cross-sectional comprising of treatment-naïve adult HIV-infected patients attending clinics at Usmanu Danfodiyo University Teaching Hospital, Sokoto and Specialist Hospital Sokoto. The study participants were screened for HCV anti]body and assayed for transaminases and CD4+ T-lymphocytes count levels. The symptoms of acquired immunodeficiency syndrome (AIDS)-defining illnesses were asked among the study participants. The questionnaire was used for the collection of data, and SPSS software version 20 was used for the analysis of data. Student's t-tests, Pearson's, Chi-square, and Fisher's exact tests were used for the statistical analysis, and P < 0.05 was considered statistically significant.
Results: The prevalence of HIV/HCV co-infection was 20.6%. Self-intravenous drugs usage was not statistically significant (P = 0.210). HIV mono-infected patients had significantly lower alanine aminotransferase levels compared to HIV/HCV co-infected study participants (P = 0.048). AIDS status at the baseline was comparable between HIV mono-infected and HIV/HCV co-infected study participants. (P = 0.227; 0.200; 0.130).
Conclusion: Moderately high prevalence of HIV/HCV co-infection was observed in the current study. HCV co-infection had no effect on AIDS status at baseline. There is a need for routine screening of HCV infection in HIV-infected individuals.

INTRODUCTION

Hepatitis C virus (HCV) has seven genotypes, greater proportion of those infected with HCV develop chronic course of the infection.[12] About 180 million are infected with HCV worldwide, substantial percentage of patients with chronic HCV infection progress to liver cirrhosis, hepatocellular carcinoma, and liver failure.[345]

Among those at risk of contracting HCV infection are human immunodeficiency virus (HIV) infected patients, intravenous drug users, sex workers, children born to HCV-infected mothers, recipients of blood/blood products transfusions (especially before the advent of HCV screening of blood donors), and those with a history of tattooing, among others.[3]

Hepatitis C virus co-infection in HIV-infected patients causes more liver-related morbidity and mortality than in HCV mono-infected patients.[6] However, HCV infection has little or no effect on anti-retroviral therapy (ART) response or clinical progression of HIV infection.[7] Additionally, Seminari et al. in their study reported that HCV co-infection did not impair late immunological recovery; however, it impaired early immunological recovery after ART initiation.[8]

Identification of HIV/HCV co-infected patients is needed for proper management, as HCV infection is treatable.[3] This study intended to find the prevalence and risk factors for HCV infection among HIV-infected individuals as well as the effect of HCV infection on acquired immunodeficiency syndrome (AIDS) cases at baseline.

MATERIALS AND METHODS

The present study was cross-sectional, conducted from March 2014 to October 2015 at Specialist Hospital Sokoto (SHS) and Usmanu Danfodiyo University Teaching Hospital (UDUTH), Sokoto. The study participants were 180 adult HIV-infected patients.

Patients who were yet to commence anti-retroviral drugs were included in the study. Participants who were below 18 years of age were excluded from the study. The study was approved by the ethical committees of SHS and UDUTH, Sokoto, and informed consent was obtained from the study participants. Questionnaire was used for the collection of respondent's information and interviewer administered technique was adopted.

The study participants were screened for HCV infection using anti-HCV enzyme linked immunosorbent assay kit (Perfemed, South San Francisco United States). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed using Agappe Kit (Agappe Diagnostics Switzerland Gmbh) with the normal range up to 46 IU/L and 49 IU/L, respectively. While CD4+ T-lymphocytes count was determined by Cyflow counter Machine (PARTEC, Germany). The study participants were questioned about the presence of symptoms suggestive of AIDS-defining illnesses such as persistent fever, loss of >10% body weight, persistent diarrhea, multiple skin lesions, persistent cough, and oral ulcerations. The prevalence of HCV infection was compared with the variables of interest, while AST, ALT, and and CD4+ T-lymphocytes levels were compared among HIV study participants with negative and positive anti-HCV.

The data were analyzed with the Statistical Package for the Social Sciences (SPSS), version 20. Student's t-test, Pearson's Chi-square, and Fisher's exact test were used for the statistical analysis, and P < 0.05 was considered as statistically significant.

RESULTS

Sociodemographic characteristics of the study participants

The study participants comprised of 109 (60.6%) females and 71 (39.4%) males. The mean age of the study participants was 32 ± 10 (mean ± standard deviation). Majority of them were married. Only 36 (20.0%) attended tertiary institutions, as shown in Table 1.

Table 1

Sociodemographic features of the study participants

Variable	Frequency (%)
Sex
Male	71 (39.4)
Female	109 (60.6)
Age in years (mean±SD)	32±10
Western education
Primary school	12 (6.7)
Secondary school	43 (23.9)
Tertiary school	36 (20.0)
None	89 (49.4)
Marital status
Married	122 (67.8)
Single	24 (13.3)
Divorced	7 (3.9)
Widowed	27 (15.0)

SD=Standard deviation

Overall prevalence, sex, and age group distribution of human immunodeficiency virus/hepatitis C virus co-infection

The overall prevalence of HIV/HCV co-infection was 37 (20.6%). The prevalence of HIV/HCV co-infection was numerically higher in females 24 (22.0%) compared to males 13 (18.3) (P = 0.547), as shown in Table 2.

Table 2

Overall prevalence and comparison of human immunodeficiency virus/hepatitis C virus co-infection by sex

Variable	HIV/HCV co-infection, n (%)	P
Overall prevalence (n=180)	37 (20.6)
Sex
Male (n=71)	13 (18.3)	0.547
Female (109)	24 (22.0)
Age group (years)
≤45 (n=163)	37 (22.7)	0.016
˃45 (n=17)	0 (0.0)

HIV/HCV=Human immunodeficiency virus/hepatitis C virus

Mean CD4+ T-lymphocytes count, aspartate aminotransferase, and alanine aminotransferase levels between the study participants who were positive and negative for hepatitis C virus co-infection

The mean CD4+ T-lymphocytes count levels were comparable between study subjects who were positive and negative for HCV co-infection (312 ± 220; 279 ± 249 cells/mm3, respectively) (P = 0.472). The mean AST level was numerically higher among the study participants who were positive for HCV infection (43 ± 32 IU/L) compared to study participants who were negative for HCV infection (42 ± 38 IU/L); however, the difference was not statistically significant (P = 0.891). Mean ALT level was significantly lower in study participants who had HCV co-infection (28 ± 19 IU/L) compared to study participants who had no HCV co-infection (37 ± 36 IU/L) (P = 0.048), as shown in Table 3.

Table 3

Comparison of mean CD4+ T-lymphocytes count, aspartate aminotransferase, and alanine amino transferase levels between study participants who were positive and negative for hepatitis C virus infection

Variable	HIV mono-infected, n (37)	HIV/HCV co-infected, n (143)	P
CD4+T-lymphocytes count (mean±SD)	279±249	312±220	0.472
AST level (IU/L), mean±SD	42±38	43±32	0.891
ALT level (IU/L), mean±SD	37±36	28±19	0.048
Elevated ALT level	31 (79.5)	8 (20.5)	0.994
Elevated AST level	39 (73.6)	14 (26.4)	0.209

HIV/HCV=Human immunodeficiency virus/hepatitis C virus, HIV=Human immunodeficiency virus, SD=Standard deviation, AST=Aspartate aminotransferase, ALT=Alanine aminotransferase

Association of hepatitis C virus co-infection with acquired immunodeficiency syndrome cases at baseline

The prevalence of AIDS (based on severe immunosuppression [CD4 T-lymphocytes count less than 200 cells/mm3] or the presence of opportunistic infections or both) cases at baseline was comparable between the study participants who were positive and negative for HCV infection (P = 0.876, 0.845, and 0.623, respectively), as shown in Table 4.

Table 4

Comparison of acquired immuno deficiency syndrome cases in study participants with and without hepatitis C virus co-infection

Variable	HIV mono-infected, (n=143)	HIV/HCV co-infected, (n=37)	P
Severe immunosuppression (CD4+ T-lymphocytes count <200 cell/mm3), n (%)	70 (49.0)	14 (37.8)	0.227
Symptoms of opportunistic infections, n (%)	71 (49.7)	14 (37.8)	0.200
Severe immunosuppression coupled with symptoms of opportunistic infections, n (%)	58 (40.6)	10 (27.0)	0.130

HIV/HCV=Human immunodeficiency virus/hepatitis C virus, HIV=Human immunodeficiency virus

Observed frequencies of symptoms of acquired immunodeficiency syndrome defining illnesses

Weight loss was the most frequent symptom of AIDS defining illness that was observed among the study participants who have either HIV/HCV coinfection 19 (51.4%) or HIV mono-infection 68 (47.6%); however, none of the observed symptoms differed significantly between HIV/HCV coinfection and HIV monoinfection [Table 5].

Table 5

Frequencies of observed symptoms of acquired immunodeficiency syndrome defining illnesses

Symptoms	HIV/HCV co-infection, n (37)	HIV mono-infection, n (143)	P
Chronic cough	9 (24.30)	54 (37.80)	0.127
Persistent fever	12 (32.40)	64 (44.80)	0.176
Chronic diarrhea	6 (16.20)	19 (13.30)	0.646
Weight loss of	19 (51.40)	68 (47.60)	0.680
Musculoskeletal lesions	1 (2.70)	12 (8.40)	0.208
Oral ulceration	0 (0.0)	11 (7.70)	0.073

HIV/HCV=Human immunodeficiency virus/hepatitis C virus, HIV=Human immunodeficiency virus

Observed risk factors for the acquisition of human immunodeficiency virus/hepatitis C virus co-infection and human immunodeficiency virus mono-infection

Self-intravenous drugs usage was numerically higher among study participants with HIV/HCV co-infection compared with study participants with HIV mono-infection, though not statistically significant (P = 0.210). Other acquisition risk factors (blood transfusion, tattooing, and having multiple sexual partners) observed in the study were also comparable between study participants with and without HCV co-infection (P = 0.073; 0.661; 0.682, respectively), as shown in Table 5.

DISCUSSION

The prevalence of HCV co-infection with HIV infection (20.6%) observed in the current study is higher than the values obtained by Eze et al. in Enugu, (6.8%) among pediatric HIV-infected patients, Balogun et al., (14.7%) among adult HIV-infected patients in Lagos and Forbi et al., (11.1%) in Keffi, Nigeria.[91011] However, this finding is lower than what was documented in Poland (71.1%)[12] and in Spain (37.3%).[13] Self intravenous drugs usage which is often the route of HCV infection in Europe was found to be lower in the current study (13.5%) compared to a study in Poland (57.8%) which recorded the higher prevalence of HCV co-infection among HIV-infected patients, and this may explain the disparity.

Gender, blood transfusion, intravenous drugs usage, and tattooing were found not to be associated with HCV co-infection among HIV-infected patients, and this is contrary to a study in Poland in which an association between HCV/HIV co-infection with male gender and intravenous drugs usage was observed.[12] However, Eze et al. and Balogun et al. observed similar results with regard to tattooing and gender, respectively.[910] The risk factors for acquiring HCV infection differ by the region. In developing countries, unscreened blood transfusion (though now rare), unsterilized barber practices, unsafe therapeutic injections due to poor application of universal infection control guidelines, and poorly sterilized surgical equipment are the main risk factors for HCV infection. However, in developed and Western Nations, intravenous drugs usage, sexual route, alcohol abuse, and tattooing are the major risk factors for acquiring HCV infection.[3]

Study participants aged ≤45 years were observed to have significantly higher prevalence of HCV/HIV co-infection. This finding is in contrast to what was observed by Bhattarai et al. in their study in Nepal in which they documented that age >40 years was associated with HCV co-infection in HIV-infected individuals,[14] and Chen et al. who observed that age >50 years was associated with HCV co-infection.[15] Risky behaviors are frequently found in younger ages than in middle or old age in our environment; therefore, this may explain the disparity.

The current study observed that HCV infection has no influence on the elevation of ALT and AST. In a similar study in Ukraine among HIV-infected child-bearing women, elevated ALT and AST levels were observed to be higher in HIV/HCV co-infected than in HIV mono-infected women.[16]

ALT is an important marker associated with liver damage and progression to chronic liver diseases. Reason for the disparity between these results may probably be due to recruitment of treatment-naïve study participants in the current study, whereas previous study under the discussion recruited study participants some of whom were on ART. ART restores immune functions and can have adverse effect on hepatocytes, and liver damage in viral hepatitis is immunologically mediated.

The current study found that HCV co-infection in HIV-infected patients did not have effect on AIDS cases at baseline. This finding is similar with what was reported in a meta-analysis study in which HCV co-infection in HIV-infected individuals was observed not to have effect on developing AIDS-defining events.[17] These results indicate that HCV infection did not influence the natural history of HIV infection.

Our study was limited by the fact that HCV RNA was not done; hence, it may not be clear whether the presence of anti-HCV meant chronic or resolved HCV infection. However, it is well-known that majority of medium- and low-income countries where HIV treatment is given free, HCV RNA assay is seldom carried out during treatment.[15] Better methods (such as aminotransferase/platelet ratio and fibrosis-4 score) of assessing severity of liver injuries were not employed in the current study.

CONCLUSION

Moderately higher prevalence of HIV/HCV co-infection was observed compared to previous studies in Nigeria. HCV co-infection had no adverse effect on the natural history of HIV infection at baseline. There is need for routine screening of HCV infection in HIV-infected patients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.