. Hepatitis B (and D), hepatitis C, and HIV can all be transmitted variably via blood and sexual contact, and consequently, co-infection is common.Liver-related mortality among PLWH has . Hepatitis B (and D), hepatitis C, and HIV can all be transmitted variably via blood and sexual contact, and consequently, co-infection is common.
Assessment of co-infection requires a multidisciplinary approach with attention to ongoing drug and alcohol use, psychiatric illness, progressive liver disease, and degree of HIV immune suppression. Alcohol should be strongly discouraged. PWID should be supported to enter a maintenance programme.
Vaccination against hepatitis A and/or B should be offered to PLWH who have not previously exposed or vaccinated.
The worldwide rate of HBV in PLWH is between 5 and 20%, equating to around 2.7 million people. For HBV in high endemic areas of sub-Saharan Africa, eastern Europe, south and southeast Asia co-infection rates are highest. In the UK, HBV/HIV co-infection is 5–8% and more common in haemophiliacs, PWID, and those from high prevalence areas. Co-infection rates vary regionally within the UK.
Co-infection is usually associated with a higher HBV viraemia and a more rapid progression to cirrhosis and risk of hepatocellular carcinoma (HCC). HBV does not appear to influence the natural history of HIV. There is risk of hepatotoxicity in relation to antiretroviral therapy. HBV reactivation can occur in those who appear to have cleared their HBV infection with transient HB surface antigenaemia more frequently seen when CD4 counts are 
. In addition, the natural clearance of HBe antigen is , but spontaneous recovery from chronic HBV infection may occur in those whose CD4 count .
Co-infection with hepatitis D (HDV) leads to more rapid progress of liver disease and should be considered if evidence of more significant liver disease in those with ALT despite low HBV VL.
• As for HBV and HIV (
Chapter 25, ‘Diagnosis’, p. 314; Chapter 40, ‘HIV: Diagnosis and assessment’, pp. 469–478). However, if ALT is raised persistently, HBV DNA should be measured to exclude occult HBV disease.
• It is important to repeat HBV serology regularly in immuno-naive patients with HIV infection.
• All HBsAg +ve PWLH should be screened for hepatitis D.
• Alpha-foetoprotein (AFP) and liver ultrasound should be performed in all at diagnosis and 6-monthly if cirrhotic. Furthermore, 6-monthly screening should be considered in those with severe fibrosis, family history of HCC, and if HBV VL high and ALT abnormal.
• If ALT raised, screen for other causes of liver disease.
• Aminotransferase platelet ratio index (APRI) score: a product of ALT, AST, and platelets predicts cirrhosis if >2 and non-cirrhosis if <1.
• Fibroscan® ≥13.1 KPa is suggestive of cirrhosis.
• Liver biopsy may be considered, particularly if other cause of liver disease considered or there is concern regarding more severe disease, despite the above.
See Box 43.1.
Box 43.1 HIV–HBV co-infection management
• Initial investigations: CD4, LFT, FBC, AFP, clotting, albumin, hepatitis B viral load, HDV Ab, US liver.
• Stage liver fibrosis: APRI Score, Fibroscan®, possibly liver biopsy.
• Consider treatment in all patients: ART with HBV activity.
In chronic HBV–HIV co-infection, the aim of HBV treatment is to suppress viral replication. Only rarely is it curative (loss of surface antigen).
• Co-infected patients requiring ART should be treated with a regime containing tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF) and emtricitabine AF or lamivudine. Lamivudine or emtricitabine should not be used without adequate second agent. If ART regimens containing lamivudine with TDF or TAF achieve good HBV response, but need to be changed, TDF or TAF should be maintained in the new ART combination. If TAF or TDF cannot be given entacavir can be used with effective ART, adefovir may need to be added if known HBV resistance.
• PLWH who have co-infection should be assessed for liver transplantati' on if decompensated cirrhosis or HCC develops.
• Co-infection with HDV is very difficult to treat.
Worldwide HCV is found among 2–15% of PLWH (2.75 million people), 90% of those co-infected are PWID. In the UK, HCV co-infection is found in 10–12% of PLWH, it is found more commonly in patients from high endemic areas, PWID and MSM. HCV transmission is seen in MSM particularly if anal sex, chemsex, co-existing STI, or low CD4 count.
Heterosexual HCV transmission is infrequent, but may be more likely with anal sex or with co-existing STIs.
Co-infection with HCV accelerates the progression of HIV and results in a poorer CD4 increase with ART.
HCV/HIV co-infected patients have a faster progression to cirrhosis if untreated (median time decreases from 32 to 23 years with ~50% cirrhotic at 30 years post-HCV infection) with death from ESLD more common. Vertical transmission of HCV from 1-5% to 14–17% if co-infected.
Otherwise clinical features as for mono-infection ( Chapter 25, ‘Clinical features’, p. 318).
• As for HCV and HIV ( Chapter 25, ‘Diagnosis and investigations’, pp. 318–319; Chapter 40, ‘HIV diagnosis and assessment’, pp. 469–478), including HCV genotype testing. HCV Ab should be checked at diagnosis and yearly if MSM, PWID, or others at risk. HIV patients may have occult HCV (3.2% HCV PCR +ve, HCV Ab –ve; with low CD4) and HCV VL should be measured if ALT persistently raised and HCV Ab –ve.
• APRI score or Fibroscan® should be considered, there may be overestimation of fibrosis in co-infection if standard cut-off of 12 kPa used for cirrhosis.
• Patients with cirrhosis should be monitored with AFP and 6-monthly ultrasound liver for HCC.
See Box 43.2.
Treatment should be considered in all patients. Directly acting antiviral drugs (DAA) acting against HCV are highly effective with no difference in effectiveness due to HIV co-infection ( Chapter 25, ‘Hepatitis C virus (HCV) infection’, pp. 318–321).
Box 43.2 HIV–HCV co-infection management
• Baseline tests: LFTs, clotting, albumin, HCV genotype, HCV RNA, CD4.
• Liver fibrosis assessment: APRI score and if available Fibroscan® or fibrosis biomarkers.
• ART + DAA +/– ribavirin: consider drug interactions/toxicity.
• During treatment measure HCV RNA at 4 and 12.
• Duration of treatment: dependent on genotype and treatment.
• Check HBV, HCV genotype, HCV VL, consider resistance testing if previous HCV treatment, not normally needed.
• ART should be started in patients with HCV co-infection. Potential interactions should be considered (see Box 43.3).
• Those with CD4>500 cells/µL with low HIV VL can be considered for DAA for HCV prior to ART, if no significant delay.
• Didanosine and zidovudine should be avoided in combination with ribavirin (increased side effects).
Box 43.3 HCV drug interactions with HIV medications
• Sofosbuvir: no significant interaction.
• Daclatasvir: decrease dose to 30 mg when used with atazanavir (ATV)/r or EVG/c, increase dose to 90 mg with efavirenz (Elvitegravir, EFV)
• Elbasvir/Grazoprevir: cannot be co-administered with PIs, EVG/c, or NNRTI. Integrase no significant interaction.
• Paritaprevir/r/ombitasvir/dasabuvir: cannot be co-administered with regimes containing cobicistat, NNRTI (rilpivirine may QT can be used with significant caution), Maraviroc may need to be . Unboosted ATV or DRV (Darunavir, dose 800 mg od) may be used.
• Paritaprevir/r/ombitasvir: as above; in addition DRV or ATV should not be co-administered.
• Sofosbuvir/Ledipasvir: need to carefully monitor renal function if TDF used in regime.
• Sofosbuvir/Velpatasvir: should not be administered with NNRTI other than rilpivirine. Need to carefully monitor renal function if TDF used in regime.
• Treatment for HIV/HCV co-infection does not differ significantly from mono-infection (see Chapter 22, ‘Management’, pp. 319–321).
• Check HCV VL at 4 weeks, end of treatment, 3 months and 6 months post treatment.