treatment with anti-tuberculosis (TB) drugs and antiretroviral therapy (ART) does not
result in major changes in liver function, investigators report in the International Journal of Infectious Diseases.
Changes in liver function were monitored over twelve months in people who
received rifampicin-based TB therapy and simultaneous HIV treatment containing
either efavirenz (Sustiva or Stocrin, also in the combination pill Atripla) or nevirapine (Viramune). There were modest increases in liver enzyme
levels after HIV therapy was started, but overall these remained within the
normal range. Treatment-limiting toxicities were extremely rare.
“The initiation of
ATT [anti-tuberculosis therapy] led to an expected but not significant increase
in liver enzyme levels. Co-administration of ART with ATT was associated with
elevated ALT [alanine aminotransferase] during the early phase of treatment,” comment the authors.
“However, these elevations were mild, not associated with severe or
rate-limiting toxicity, and decreased over time.”
An estimated 1.1
million people globally HIV and TB co-infection. The World Health
Organization (WHO) recommends that all patients with HIV/TB co-infection should start antiretroviral therapy within a few weeks of starting TB treatment.
Several of the recommended anti-HIV and anti-TB drugs are associated with liver
toxicity. However, there is little information on rates of hepatic dysfunction among people starting simultaneous TB and HIV therapy.
team of investigators therefore designed an observational study involving 168
people with HIV/TB co-infection patients in India, who started therapy for both infections
between 2006 and 2008. All had a CD4 cell count below 250 cells/mm3
and none had hepatic dysfunction at baseline.
consisted of isoniazid, rifampicin, ethambutol and pyrazinamide for two months,
followed by a further four months of therapy with isoniazid and rifampicin.
therapy was started two months after TB treatment was initiated and consisted
of 3TC (lamivudine, Epivir) and ddI (didanosine, Videx) with either efavirenz or nevirapine.
The study participants had a
battery of liver function tests at baseline, including ALT and AST [aspartate aminotransferase] monitoring, together
with assessment of serum alkaline phosphate (SAP) and bilirubin. These tests
were repeated at regular intervals over follow-up, which lasted twelve months.
three-quarters (79%) of the study participants were men and 104 started efavirenz-based
antiretroviral therapy. The participants had advanced HIV disease (median CD4 cell
count 93 cells/mm3; median viral load 243,000 copies/ml). None of
the participants had hepatitis B or C co-infection.
ALT and AST levels
were significantly higher (p = 0.02, p = 0.001, respectively) among people with a CD4 cell count below 90 cells/mm3, whereas a viral load above
300,000 copies/ml was associated with elevations in SAP.
increases in ALT and AST levels were observed two months after TB therapy was
started. These rises were minimal and less than two times the upper limit of normal.
After two weeks of
HIV therapy, ALT levels increased from 26 mg/dl to 32 mg/dl (p = 0.03) and an
increase in AST levels was observed after six weeks of therapy (41mg/dl to 46
mg/dl, p = 0.02).
remained within the ULN [upper limit of normal] range and ART was continued,”
write the authors.
After four months
of concomitant TB and HIV therapy, elevations in ALT levels were noted (31mg/dl
to 36 mg/dl, p = 0.001), but these were
still within normal limits.
Elevations in SAP
slightly above the normal range were noted after eight weeks of HIV treatment
(131mg/dl to 166 mg/dl, p = 0.001).
There were three
cases of serious liver toxicity, all involving people taking efavirenz-based
HIV therapy. These cases were managed by switching TB drugs and temporarily
stopping HIV therapy.
then remained unchanged until the discontinuation of TB therapy.
At month twelve
(six months after TB treatment was stopped), AST and SAP levels had declined significantly
compared to month-four levels (p = 0.01 and p = 0.001, respectively) whereas
ALT levels were comparable.
liver function occurred sooner with efavirenz-based HIV therapy. However, by
the end of follow-up, similar proportions of people treated with nevirapine
and efavirenz had elevated ALT or AST (3 vs 2%).
of aminotransferases occurred, but was transient, improved after
completion/discontinuation of ATT, and was not worse with NVP [nevirapine] than
EFV [efavirenz],” conclude the authors. “Hepatoxicity was rare in this group of
patients with normal liver function at baseline and low rates of hepatitis B/C