Tuberculosis (TB) is associated with an impaired immune
response to antiretroviral therapy, according to Italian research published in
the online edition of Clinical Infectious
The study involved patients starting HIV therapy for the
first time. Individuals with TB had lower CD4 cell gains when compared to
individuals with other AIDS-defining illness and patients who were AIDS-free.
This was possibly because individuals with TB were also less likely to achieve
“HIV-infected patients starting cART [combination
antiretroviral therapy] when ART naïve and with a tuberculosis diagnosis have
an impaired immune recovery,” write the authors. “This impairment seems to
persist over 3 years…and is mainly explained by differences in the level of
viral suppression between patients with and those without tuberculosis.”
Worldwide, TB is the single biggest cause of serious illness
and death in patients with HIV.
Antiretroviral therapy has transformed the prognosis of many
HIV-positive patients, which is now considered normal. Starting HIV treatment
normally achieves suppression of viral load to undetectable levels and an
increase in CD4 cell count.
Factors associated with a poorer immunological response to
treatment are poorly understood and studies exploring the significance of TB to
CD4 cell gains after starting treatment have produced contradictory results.
However, there are two theoretical mechanisms which mean
that individuals with TB have could have lower increases in CD4 cell count.
First, TB can contribute to the death of immune cells. Second, the infection
can be difficult to manage in patients treated with antiretroviral drugs.
Italian investigators wished to establish a better
understanding of the interaction between TB and immune restoration after
starting antiretroviral therapy. They therefore designed a study involving 6528 patients who initiated treatment
between 1996 and 2010.
The patients were divided into three categories according to
their TB and AIDS status when HIV treatment was started:
The investigators then calculated the time taken for
patients in each group to experience an increase in CD4 cell count of 100, 200
and 300 cells/mm3 above baseline and to a CD4 cell count of 500
cells/mm3 or more. The time between starting treatment and suppression
of viral load to below 50 copies/ml was also assessed.
Median baseline CD4 cell count was 269 cells/mm3
and almost two-thirds (64%) of patients started HIV therapy when their CD4 cell
count was below 350 cells/mm3, the current European threshold for
the initiation of therapy.
The 125 patients who had TB had this infection diagnosed a
median of one week before they started HIV treatment. The 1061 individuals with
another AIDS-defining condition had this detected a median of four days
antiretroviral therapy was prescribed.
Compared to patients without AIDS, individuals with TB were
significantly younger, had a lower baseline CD4 cell count and were less likely
to be born in Italy (all p < 0.001).
Overall, CD4 cell count increased by 100 cells/mm3
a median of eight months after treatment was started. The median time to an
increase of 200 cells/mm3 was 18 months, and it took a median of 34
months for CD4 cell count to increase by 300 cells/mm3. Twenty-four
months after treatment was started, 55% of patients had a CD4 cell count above
After controlling for pre-treatment CD4 cell count, the
investigators found that patients with TB had a significantly lower chance of
immune recovery when compared to patients without AIDS, regardless of which CD4
cell threshold was used (above 200 cells/mm3, p = 0.02).
Individuals with TB were also less likely to achieve an
increase in CD4 cell count of 200 or 300 cells/mm3 compared to
patients with another AIDS-defining condition (p = 0.05 and p = 0.02
However, neither TB nor other AIDS-defining illnesses
significantly reduced the chances of CD4 cell count increasing to above 500
Infection with TB also appeared to affect the chances of
suppressing viral load to undetectable levels.
A viral load below 50 copies/ml was achieved at some point
by 74% of patients. It took patients with TB a median of 20 months to suppress
viral load, compared to a median of 15 months for those with another
AIDS-defining illness and 14 months for individuals free of TB and AIDS.
Further analysis found a non-significant association between
taking HIV therapy and TB treatment together and a reduction in the odds of
achieving an undetectable viral load (p = 0.09).
“HIV and tuberculosis coinfection is characterized by
several challenges in terms of patient management, such as poor adherence and
overlapping toxicities,” note the authors. “In addition, interactions with
antituberculosis treatment may cause reduced plasma concentrations of
antiretrovirals, resulting in a reduced chance of virological success.”
They conclude, “our analysis showed that HIV-infected
patients starting cART when ART naïve and with a tuberculosis diagnosis have an
impaired immune recovery with cART, mainly because of differences in levels of
viral suppression between them and both patients with nontuberculosis AIDS and
those without AIDS.” They call for further research exploring interactions between
the two therapies.