Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) are common viral infections that share routes of transmission through unprotected sex and exchanging needles/syringes. HBV and HCV coinfections are widespread among HIV-infected patients worldwide, which cause long-term illness to chronic hepatitis and death. Viral hepatitis progresses faster in HIV-infected patients compared to those without HIV. Although the antiretroviral therapy (ART) extended the life expectancy of people with HIV, viral hepatitis associated with HBV and HCV becomes the primary cause of morbidity and mortality. As documented, 36.7 million people are living with HIV/AIDS, and 1 million died of HIV-related illness worldwide in 2016. Among them, 3.5 million people are covered by Southeast Asia [
In this case report, we present a rare case of HBV and HCV coinfections in an HIV-1-infected patient with an improved CD4+ count but detectable viral loads after ART. Such triple coinfections in the patient from developing countries like Nepal provide an opportunity to access the effects of viral hepatitis coinfection on immediate and long-standing outcomes after antiretroviral therapy. Also, coinfection could be an exciting model for viral interaction studies and their clearance in response to immune cells.
The patient was a 49-year-old Nepalese man who was an HIV-1-positive injecting drug user coinfected with hepatitis B and C. He was informed and written consent was obtained for collection of blood samples for follow-up investigation. All the necessary tests and analysis were performed at the National Public Health Laboratory (NPHL), Kathmandu, Nepal. The blood sample was collected in a plain and K2 EDTA tube (BD Vacutainer). The rapid diagnostic testing for HIV-1/2, HBV, and HCV was performed using rapid immunochromatography, while syphilis testing was done using the flocculation method for VDRL (RPR). The reactive and nonreactive results were further confirmed by enzyme-linked immunosorbent assay for HBsAg, anti-HCV, and anti-HIV 1/2 (ELISA Human, Germany) and electrochemiluminescence immunoassay for HBeAg, HBsAg, anti-HBs, anti-HBe, anti-HBc, anti-HCV, and HIV Combi PT (ECLIA, cobas Roche Inc., Germany). The ECLIA was performed using cobas e 411 analyzer (Roche Inc., Germany). The whole blood collected in EDTA was used for CD4+ count using a BD fluorescent-activated cell sorter system (BD Biosciences, San Jose, CA, USA). The viral nucleic acid (DNA/RNA) was extracted using the QIAamp® DSP Virus kit (Qiagen, Germany). HBV DNA and HCV RNA were quantified by Corbett Rotor-Gene 6000 Real-Time PCR. The Artus HBV/HCV RG PCR kit (Qiagen, Germany) allows for a viral load detection limit of 10–100,000,000 IU/ml for HBV-DNA and 65–1,000,000 IU/ml for HCV-RNA with 97% specificity. HIV-1 was amplified and quantified by a Cobas® TaqMan® 48 analyzer. The COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Test, v2.0 (Roche Molecular Systems, Inc., USA), has an assay of linearity from 20 to 10,000,000 copies/ml with 100% specificity.
The patient was tested positive for HIV-1/2 infection with hepatitis B and C coinfections first time at a tertiary care hospital of Nepal on 14 August 2017. The initial finding at the time of HIV-1/2 confirmation showed decreased CD4+ nadir and SGOT. The client was informed that he was HIV-1/2 positive, and appropriate counseling was provided regarding the HIV, risk factor, transmission to family, social issues, and availability of ART. He was prescribed a fixed-dose combination of tenofovir disoproxil fumarate (TDF), lamivudine (3TC), and efavirenz (EFV) as the preferred option to initiate ART according to the National HIV Testing and Treatment Guidelines 2017, Nepal. It also covers for HBV infection. However, the patient was not in HCV treatment. He also mentioned that his spouse was positive for HIV-1/2. After ten months of ART initiation, he visited for follow-up on 5 June 2018. The follow-up investigation includes a routine laboratory test on hematological parameters, biochemical parameters, and viral loads. The HCV was tested negative using rapid chromatography but confirmed positive using ELISA and ECLIA. However, the improved CD4+ count was observed after ART. Final testing of viral loads for HIV-1, HBV, and HCV was performed for monitoring of ART. The schematic flowchart of the case presentation is shown in Figure
Laboratory investigation of HBV/HCV coinfection in an HIV-1-infected patient after ten months of antiretroviral therapy.
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HIV-1/2 | Immunochromatography | Positive | |
HBsAg | Immunochromatography | Positive | |
Anti-HCV Ab (IgM) | Immunochromatography | Negative | |
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Glucose R | 158.27↑ | 70–150 mg% | |
ALP | 85 | 44–147 IU/L | |
SGPT/ALT | 36 | 7–57 IU/L | |
SGOT/AST | 43↑↑ | 37 IU/L | |
HDL | 33.750↓↓ | >50 mg/dl | |
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Complete blood count (CBC) is in normal limit | |||
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Percentage of T lymphocytes (CD3+ and CD45+) | 75 | 55–84% | |
Absolute count of T lymphocytes (CD3+) | 1160 | 690–2540 cells/ | |
Percentage of T-helper lymphocytes (CD3+ CD4+/CD45+) | 15 | 31–60% | |
Absolute count of T-helper lymphocytes (CD3+ CD4+) | 300↓↓ | 410–1590 cells/ | |
Absolute count of lymphocytes (CD45+) | 1551 cells/ |
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HBsAg | 2.894 | COI: 0.15, reactive: >0.15, nonreactive: <0.15 | Reactive |
HCV | 3.067 | COI: 0.165, reactive: >0.165, nonreactive: <0.165 | Reactive |
HIV-1/2 | 3.107 | COI: 0.131, reactive: >0.131, nonreactive: <0.131 | Reactive |
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HBeAg | 887 | >1.0 reactive, <1.0 nonreactive, boarder line 0.9-<1.0 | Reactive |
HbsAg | 1602 | >1.0 reactive, <1.0 nonreactive, boarder line 0.9-<1.0 | Reactive |
Anti-HBs | 3.86 | <10.0 nonimmune, >10.0 immune | Nonimmune |
Anti-HBe | 4.92 | <1.0 reactive, >1.0 nonreactive | Nonreactive |
Anti-HBcIgM | 0.135 | <1.0 reactive, >1.0 nonreactive | Reactive |
Anti-HCV | 74.3 | >1.0 reactive, <1.0 nonreactive, boarder line 0.9-<1.0 | Reactive |
HIV-COMBI PT | 376.9 | >1.0 reactive, <1.0 nonreactive, boarder line 0.9-<1.0 | Reactive |
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HBV DNA | 20 IU/ml | 10–100,000,000 IU/ml | Detected |
HCV RNA | 75 IU/ml | 65–1,000,000 IU/ml | Detected |
HIV-1 RNA | 19,800 copies/ml | 20–10,000,000 copies/ml | Detected |
Hepatitis B and C co-primary infections in the HIV-infected population have inconsistent prevalence among the reported studies and countries. The primary determinant for such dual coinfections in key HIV-infected population might be associated with routes of HIV transmission. Even HBV, HCV, and HIV share routes of transmission, but coinfection with viral hepatitis has independent predictors; that is, HCV infection is more closely linked to injection drug use and HBV is associated with unsafe sexual intercourse. In comparison to females, the males showed a significant association of HBV and HCV dual coinfection among HIV-infected population [
In Nepal, the seroprevalence of HBV and HCV infections in blood donors nationwide is 0.82% and 0.47%, respectively, while at central blood transfusion center (CTBS) in Kathmandu, the seroprevalence was 0.92% and 0.71%, respectively [
In conclusion, triple infections are rare cases neither investigated nor reported from Nepal. Our case of triple infections reveals good immune response and no cirrhosis due to high-level adherence (>95%) to ART. However, the detectable viral loads might be due to the influence of late response, effects of coinfections, and/or viral interactions in HIV-1 genome. Therefore, current prevention strategies on the parenteral transmission of HBV and HCV should be revised to alert the importance of using standard needles, avoiding sharing equipment, and unprotected sexual intercourse that could be based on family and community.
(i) We report the first evidence of HCV and HBV coinfections in an HIV-1 patient who revealed late response of ART which might be due to viral nucleic acid interaction. (ii) Hepatitis virus coinfection in HIV-infected patients is common, but lack of systemic and categorized studies leads to a low prevalence rate. (iii) Detection and quantification of plasma viral nucleic acid should be considered for true prevalence and also for monitoring therapy in the long-term follow-up investigation. (iv) Thus, the impact and evolution of viral hepatitis in HIV-viral response to ART remain unclear and matter of research.
Written and duly signed informed consent of the patient was obtained for this case report.
This is a case report based on the retrospective analysis of laboratory report and patient history taken care at Sukraraj Tropical and Infectious Diseases Hospital, Kathmandu, Nepal. The laboratory investigation was performed at National Public Health Laboratory, Kathmandu, Nepal. All necessary data are included in the case report, and the review of the literature supporting this case was obtained via PubMed.
The authors declare that they have no conflicts of interest.
SK, SP, and RP performed a retrospective analysis of the laboratory report, collected the data, and performed the laboratory investigation. AP helped with the discussion and interpretation of ART response and clinical scenario of coinfection. RS and SK analyzed the draft of the case and wrote the manuscript. All authors read and approved the final manuscript for publication.
The authors would like to thank the patient for his support for follow-up investigation and informed decision allowing the right to publish.