Background
The National HIV/AIDS Care and Treatment Plan (NCTP) for Tanzania Mainland launched in 2004 was charged with the responsibility of providing quality human immunodeficiency virus (HIV) care and treatment services to as many HIV-infected residents of the United Republic of Tanzania as possible. The operational plan was to provide antiretroviral treatment to as many 440,000 AIDS patients by the end of 2008; and to track the disease progression in some 1.2 million HIV-infected persons who were not clinically eligible for ART. The plan recommends that treatment be available through care and treatment clinics (CTC's) established over a five years time, at virtually all public and non-public hospitals down to the district level [
1]. By December 2007, the numbers of health facilities providing HIV care and treatment was 210. These provided non-ART care to estimated 118,286 clients and ART to 69,250 eligible patients [
2].
Despite these achievements, relatively little is known regarding hepatitis viral co-infections among HIV infected patients enrolling at the CTC's. To the best of our knowledge, this is the first study to determine the prevalence and predictors of viral hepatitis co-infection among adults infected with HIV attending a CTC in Tanzania. Thus, findings obtained will provide valuable information for stakeholders within and outside Tanzania involved in scaling up care and treatment services.
Results
Two hundred and sixty HIV infected patients were recruited during the study period, of whom 70.0% were females. Table
1 summarises the characteristics of the study population. The overall mean age was 37.3 (± 9.5) years, ranging from 19 to 81 years. Males were significantly older, with a mean age of 41.4 years compared to females whose mean age was 35.6 years, p < 0.0001. The median CD4+ T-lymphocytes was 202 cells/μl.
Table 1
Socio-demographic characteristics of the study population (n = 260)
Age group
| | | | < 0.01 |
18 – 29 | 3 (3.8) | 48 (26.3) | 51 (19.6) | |
30 – 39 | 38 (48.7) | 87 (47.8) | 125 (48.1) | |
40 – 49 | 28 (35.9) | 31 (17.0) | 59 (22.7) | |
50+ | 9 (11.5) | 16 (8.8) | 25 (9.6) | |
Marital Status
| | | | 0.04 |
Single | 16 (20.5) | 51 (28.0) | 67 (25.8) | |
Married | 47 (60.3) | 83 (45.6) | 130 (50.0) | |
Divorced | 10 (12.8) | 18 (9.9) | 28 (10.8) | |
Widowed | 5 (6.4) | 30 (16.5) | 35 (13.5) | |
Education
| | | | 0.04 |
Primary & below | 44 (56.4) | 125 (68.7) | 169 (65.0) | |
Secondary | 22 (28.2) | 41 (22.5) | 63 (24.2) | |
Post Secondary | 12 (15.4) | 16 (8.8) | 28 (10.8) | |
Baseline CD4+ count (cells/μl)
| | | | |
< 200 | 43 (56.6) | 77 (46.1) | 120 (49.4) | |
200 – 350 | 19 (25.0) | 27 (16.2) | 46 (18.9) | |
> 350 | 14 (18.4) | 63 (37.7) | 77 (31.7) | < 0.01 |
WHO-HIV stage
| | | | 0.66 |
I
| 15 (19.2) | 45 (24.7) | 60 (23.1) | |
II
| 20 (25.6) | 47 (25.8) | 67 (25.8) | |
III
| 32 (41.0) | 72 (39.6) | 104 (40.0) | |
IV
| 11 (14.1) | 18 (9.9) | 29 (11.2) | |
The seroprevalence of HAV (anti HAV IgM), HBV(HBsAg), acute HBV(anti HBcAb) and HCV (anti HCV) were 3.1%, 17.3%, 2.3% and 18.1%, respectively (Table
2). Of the six patients with acute Hepatitis B infection (anti-HBc IgM antibody positive), two had occult HBV infection (anti HBc IgM positive but HBsAg negative), and the remaining four were positive for HBsAg. HBV carrier state, defined as being HBsAg positive and HBc IgM antibody negative, was present in 41 patients (15.8%). The prevalence of any of the four hepatitis markers was found to be 34.6% (Table
2).
Table 2
Sero-prevalence of viral hepatitis markers among the study population (n = 260)
HAV-IgM antibodies
| 8 (3.1) | 1.3 – 6.0 |
HBsAg
| 45 (17.3) | 12.9 – 22.5 |
HBc IgM antibodies
| 6 (2.3) | 0.9 – 5.0 |
HCV Ab
| 47 (18.1) | 13.6 – 23.3 |
HBsAg & HBc IgM
| 4 (1.6) | 0.4 – 3.9 |
HBsAg & HCV Ab
| 10 (3.9) | 1.9 – 7.0 |
Any viral marker
| 90(34.6) | 28.9 – 40.7 |
Co-infection with both HBV and HCV (HBsAg and HCV Ab) occurred in 10 individuals (3.9%) while that of HAV and HBV (anti HAV IgM and HBsAg) occurred in two subjects (0.8%). None of the investigated patients was found to be co-infected with HAV and HCV. Similarly, none of the patients had all the three hepatitis viruses (HAV, HBV and HCV), (Table
2). There was neither an association between the occurrence of HBV and HCV nor between HAV and HBV.
The prevalence of HCV infection increased with age (χ
trend = 4; p = 0.04), with the oldest age group (50+ years) having the highest proportion (Table
3). The prevalence of HBV infection among males (21.8%) was non-significantly higher than that among females (15.4%). Similarly, widowed and divorced subjects had the highest prevalence (39.7%) for HCV while currently married had the lowest prevalence of HCV (13.8%). Subjects who were never married had the highest prevalence (20.9%) of HBV infection. However, there was no statistically significant association between viral hepatitis infection and sex, marital status or education status (table
3). Furthermore, univariate analysis showed no association between the presence of any of the hepatitis viruses with blood transfusion, illicit drug use, uvulectomy and traditional or cosmetic scarification.
Table 3
Sero-prevalence of viral hepatitis markers according to demographic characteristics (n = 260)
Age
| | | | | |
18 – 29 | 51 | 1 (2.0) | 12 (23.5) | 7 (13.7) | 16 (31.4) |
30 – 39 | 125 | 3 (2.4) | 16 (12.8) | 22 (17.6) | 38 (30.4) |
40 – 49 | 59 | 3 (5.1) | 15 (25.4) | 9 (15.3) | 25 (42.4) |
50+ | 25 | 1 (4.0) | 2 (8.0) | 9 (36.0) | 11 (44.0) |
P*-value
| |
**
| 0.06 | 0.09 | 0.28 |
Sex
| | | | | |
Male | 78 | 1 (1.3) | 17 (21.8) | 10 (12.8) | 27 (34.6) |
Female | 182 | 7 (3.8) | 28 (15.4) | 37 (20.3) | 63 (34.6) |
P* value | | 0.442*
| 0.211 | 0.149 | 1 |
Education
| | | | | |
Primary & Below | 169 | 4 (2.4) | 29 (17.2) | 35 (20.7) | 62 (36.7) |
Secondary & Above | 91 | 4 (4.4) | 16 (17.6) | 12 (13.2) | 28 (30.8) |
P* value | | 0.456*
| 0.932 | 0.133 | 0.339 |
Marital status
| | | | | |
Never Married | 67 | 2 (3.0) | 14 (20.9) | 12 (17.9) | 24 (35.8) |
Currently Married | 130 | 5 (3.8) | 23 (17.7) | 18 (13.8) | 41 (31.5) |
Divorced/Widowed | 63 | 1 (1.6) | 8 (12.7) | 17 (27.0) | 25 (39.7) |
P* value | |
**
| 0.460 | 0.084 | 0.522 |
Table
4 shows that out of all patients with HAV infection 50% had nausea and 37.5% had vomiting. These proportions were significantly higher than corresponding proportions among patients without HAV infection. Moreover, patients with acute HBV (HBcAb IgM) were more likely to have jaundice (66.7%), hepatomegaly (66.7%), raised alanine aminotransferase {ALAT} (66.7%) or raised total bilirubin (66.7%). However, when clinical features and biochemical markers were considered together, only 17 out of 90 (18.9%) patients with any of the markers for hepatitis had jaundice (by history or examination), or hepatomegaly or elevated ALAT. Importantly, only 10.0% of the patients co-infected with hepatitis virus A, B or C co-infection had abnormal serum ALAT.
Table 4
Clinical characteristics of patients with viral hepatitis markers (n = 260)
Fever | 3 (37.5) | 17 (37.8) | 2 (33.3) | 18 (38.3) |
Nausea | 4 (50.0)* | 5 (11.1) | 1 (16.7) | 7 (14.9) |
Vomiting | 3 (37.5)* | 6 (13.3) | 1 (16.7) | 4 (8.5) |
Jaundice | 0 | 5 (11.1) | 4 (66.7)* | 4 (8.5) |
Hepatomegaly | 0 | 5 (11.1) | 4 (66.7)* | 3 (6.4) |
Biochemical characteristics, n (%)
|
Elevated ALAT | 1 (12.5) | 4 (8.9) | 2 (33.3)* | 2 (4.3) |
Elevated Total bilirubin | 0 | 5 (11.1) | 4 (66.7)* | 5 (10.6) |
Immunological characteristic
|
Mean CD4+ T-cells (cells/μl) | 113 | 198 | 134 | 222 |
Table
4 also shows that the mean CD4+ T-lymphocyte counts among patients co-infected with either HAV, or HBV, or HCV were not significantly different from the mean values among patients without the corresponding hepatitis co-infection.
A set of variables was selected to search for predictors of the viral hepatitis infections including, age, sex, blood transfusion, scarification, nausea and vomiting, jaundice, palpable hepatomegaly and the presence of other viral hepatitis infection. Significant predictors of co-infection with the respective viral hepatitis are summarised in table
5. Presence of nausea, history of prior blood transfusion, and presence of jaundice were the independent predictors of HAV, HBV and acute HBV co-infections respectively.
Table 5
Likelihood of viral hepatitis co-infection using clinical features presented as odds ratios (OR) with 95% confidence intervals (CI) (n = 243)*
HAV | Nausea | 4.18 (1.46 – 11.96) |
< 0.01
|
HBsAg | Blood transfusion | 2.59 (1.09 – 6.15) |
0.03
|
HBcAb | Jaundice | 41.07 (6.78 – 248.89) |
< 0.01
|
Discussion
This study reveals a high burden of hepatitis viral co-infection among HIV infected, ART naïve patients who sought care at a tertiary public health facility in Tanzania, with more than a third of the study participants being co-infected.
HCV was the most prevalent infection (18.1%) which is in keeping with the findings of Telatela et al [
6] who documented HCV sero-prevalence of 13.8% among HIV infected children in the same institution [
6]. This prevalence is higher than that reported among among blood donors at the same hospital [
7‐
9] probably due to the fact that all our subjects were HIV-infected and that HCV has similar transmission modes as HIV. The lower prevalence of HCV reported by Wadell et al. [
8] could also be due to the fact that they used an HCV RNA assay, which is a more stringent assay [
10]. The increase in the prevalence of HCV infection with age that was observed is a reflection of a cumulative risk with time [
11].
We found a higher prevalence of HBsAg (17.3%) compared to a study conducted among blood donors (8.8%–11.0%) at the same setting [
7,
9]. Three main reasons are postulated; firstly, the shared modes of transmission between HIV and HBV [
12]. Secondly, is the known phenomenon of reactivation of HBV in the setting of HIV immunodeficiency [
13] and lastly, the higher rates of childhood horizontal HBV transmission in sub-Saharan Africa [
14]. It is important to note two subjects with anti HBc IgM antibodies but negative HBsAg who may have had occult HBV viremia as demonstrated previously in HIV subjects [
15]. Notably occult HBV infection is likely to be missed diagnosis when HBsAg is employed as a routine screening test, which may consequently lead to silent liver damage.
The prevalence of HAV-IgM (3.1%) reported in this study is much lower than that of 41.0% found in a Kenyan study [
16]. The difference is most probably due to the fact that the latter study investigated patients who already had clinical hepatitis as evidenced by jaundice.
About 4% of our study population had dual HBV/HCV infection evidenced by co-existence of HBsAg and anti-HCV total antibodies. However, the occurrence of the two viruses (HBV and HCV) was not significantly associated, corroborating the findings of previous studies done in the country [
6,
7].
In this study, the association of hepatitis viral co-infection with serum alanine aminotransferase (ALAT) as well as clinical features was very limited. Only 10% of HIV/hepatitis co-infected patients had elevated ALAT and clinical features suggestive of acute liver disease were insignificantly associated with hepatitis co-infection. The asymptomatic pattern of co-infection in our study population would probably be due to the fact that we detected less subjects with acute hepatitis (HAV-IgM 3.1%, HBsAg 2.3%) compared to those with chronic HBV and HCV co-infection. The paucity of signs and symptoms of liver damage has been documented in HIV patients with chronic viral hepatitis co-infection [
17,
18] and has been attributed to decreased hepatocellular injury associated with the HIV-induced immunodeficiency [
19].
In this study, except for the association between age and HCV infection, demographic characteristics were not associated with the occurrence of any of the investigated hepatitis infections. Our results show that HCV co-infection was associated with increasing age, which may reflect a cumulative risk over time as previously reported by Kondili [
11]. Notably, we observed no statistically significant association between the occurrence of the either HBsAg or HCV and sex and marital status, which is in keeping with other studies conducted in the country [
20].
In this study there was no association between absolute CD4+ T-lymphocyte count and the presence of hepatitis co-infection. Indeed the association between hepatitis viral co-infection and CD4+ T lymphocytes count is currently a subject of debate, with some studies showing no existence of a relationship [
21] and others showing the association [
22]. The lack of association is probably due to the impaired qualitative response to hepatitis virus in HIV infection rather than impairment in the absolute numbers of CD4+ T-lymphocytes [
23]. However, the lack of association in our study could also be due to that fact that most of our study patients had low CD4 counts, (median < 202 cells/mm
3) at baseline.
Evidently from this study is the fact that most (> 80%) of the patients with hepatitis viral co-infection, presented with no specific liver damage-related signs and biochemical changes, emphasizing the need for routine screening of viral markers in HIV patients. This is currently not part of the Tanzanian HIV care and treatment guidelines [
24]. Secondly, there are implications for the choice of an appropriate regimen for the hepatitis co-infected patients that should include two active anti HBV agents to avoid viral mutations and thus enhance outcome [
25,
26]. The, current first line ART regimen in Tanzania (stavudine, lamivudine and nevirapine or efavirenz) [
24] does not sufficiently cover for HBV [
25]. Moreover, a prolonged use lamivudine against HIV infection in undiagnosed viral hepatitis infection may result in resistant HBV mutants [
27]. Flexibility in the regimen under such circumstances to include appropriate drugs to take care of HBV or HCV co-infections should be considered. In addition, it is likely that the undiagnosed cases of hepatitis co-infected patients may be kept on nevirapine based ART combinations leading to nevirapine hepatotoxicity [
28], and thus defeating the national objective of improving the quality of life of these patients [
24]. Finally, patients with HIV/Hepatitis co-infection may complicate ART with an immune reconstitution syndrome (IRIS), which may be confused with drug toxicity or acute hepatitis infection. It is therefore important for health care workers to be cognisant of these facts to improve the care of patients infected with HIV
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
TJN designed the study, conducted the interviews and clinical examinations. MB assisted study design and supervised interviews and clinical examination. MIM assisted study design and supervised laboratory work. Finally, all authors participated in the preparation of the manuscript, read and approved the final manuscript.