Although HIV increases the risk of TB it has long been assumed that
this was primarily due to falling CD4 cell counts seen with advancing HIV
disease progression. The early effect seen in the study, conducted by
researchers from the London School of Hygiene and Tropical Medicine, was
The retrospective study analysed data drawn from the medical records of
23,874 workers from four South African gold mines. The mines provided the
perfect opportunity to assess how HIV affects the risk of tuberculosis
over time. The mines have a stable population, provide regular medical
care and keep good medical records. There is a well-established TB control
programme and a confidential database of all HIV test results of the mine
workers has been kept since 1989. HIV test results could therefore be
linked to routinely collected TB and demographic data.
At the beginning of the study, 3371 miners were HIV-positive (these are
referred to as having prevalent HIV) and 20,503 were HIV-negative.
Over the course of several years, many of the workers had subsequent HIV
tests. Of these, 2737 received positive HIV results (these cases are
referred to as having incident TB) 1962 (72%) within two years
or less of a previous HIV negative result.
A total of 740 cases of pulmonary TB (first episode) were analysed
during a seven-year period. TB was found to be at least three times more
common in those who were HIV-positive. The incidence of pulmonary TB was
2.9 cases per 100 patient years at risk (pyar) in the HIV positive workers
[95% confidence interval CI, 2.53.4] and 0.8 cases/100 pyar in the
HIV negative workers.
Investigators then assessed the relative risk (RR) of developing TB by
age and calendar period (1991-92, 93-94, and 95-9) and according to when
workers tested HIV positive. Age and calendar were significantly
associated with an increased risk of TB (Ps &8804 .0001). Interestingly,
the incidence of TB per pyar doubled during the last time period, with an
adjusted case rate ratio of 2.21 (95% CI1.652.95). This could reflect
the impact that the HIV pandemic was having on the overall incidence of TB
in the southern African region.
The relative risk (RR) of developing TB was greater in those who were
HIV-positive when the study began, which is to be expected as they had
been infected longer and their immune systems would be less able to fight
off TB. But what was not expected, as mentioned earlier, was the increase
in incidence of pulmonary TB so soon (within a year) after seroconversion,
with an adjusted case rate ratio of 2.11 (1.453.09).
An editorial accompanying the article in JID suggested that there could
have been a small bias in detecting TB in patients with HIV because
HIV-positive miners may present to medical facilities more frequently
because of the development of HIV-related clinical symptoms of illness,
thus potentially biasing toward greater evaluation for, and detection of,
TB among HIV-positive miners. However, the study authors state that
We do not believe that TB is more likely to be diagnosed in
HIV-positive than in HIV-negative miners because TB is so very common
in this setting that all workers are closely monitored for TB.
Minor differences aside, the editorial writers believe the study
provides sufficient data to demonstrate the doubling of the incidence of
TB within the first year of HIV seroconversion.
The editorial suggests two possible explanations for the increased TB
risk 1) the profound immune dysregulation that occurs soon after [HIV]
infection or 2) that those patients who develop tuberculosis within the
first year of HIV infection have a rapidly progressing form of HIV
High levels of HIV seen during acute seroconversion or the immune
response to HIV could also activate latent TB infections in some patients.
If TB is activated in this setting, any CD4 cell response to could be
quickly wiped out by HIV leaving the patient defenceless.
Investigators evaluated whether the increased risk of TB early during
the course of HIV infection is due to reactivation or to a newly acquired
M. tuberculosis infection by performing molecular fingerprinting on
available isolates. Unique isolates are more likely to have been due to
reactivated TB acquired before working in the mines, while the isolates of
TB acquired in the mines would be the same.
Among HIV seroconverters, unique TB isolates were present in 57% (8/14)
of miners who developed TB within 2 years of HIV seroconversion, compared
with 20% (3/15) who developed TB later. The finding is intriguing though
numbers are too small to draw any firm conclusions. However, it suggests
that patients with latent TB are more likely to develop pulmonary TB
within the first year of seroconversion.
The studys findings have a number of major implications for TB and
HIV control programmes. The editorial points out that while current models
for TB control do factor an increase in TB incidence where there is a high
adult HIV prevalence, they do not account for the increased risk of TB
early during the course of HIV infection. Reframing these models in the
context of these new data is likely to affect the calculated burden of
TBand not just for HIV-positive persons, but for the general community
It is also important to note that TB that occurs later in HIV disease
is usually not centred in the lungs but is extrapulmonary. This study
showed a doubling in pulmonary TB which is far more infectious.
Another issue that the study brings up is whether treatment of latent
M. tuberculosis infection may be the most feasible way to reduce the risk
of TB. Isoniazid prophylaxis is not routinely administered in all
developing world settings, partly because of the high risk of re-infection
with TB and partly because of the difficulty in excluding active TB
Finally both teams agree that there is an immediate need to expand
reliable and affordable HIV testing services in areas where TB is endemic
and, conversely, to improve surveillance for TB among patients testing
positive for HIV. ( Source: Aidmap,  January 05, 2005)
Sonenberg P et al. How soon after infection with HIV does the risk
of tuberculosis start to increase? A retrospective cohort study in South
African gold miners. The Journal of Infectious Diseases. 191:1508,
Srikantiah P, Charlebois E, Havlir DV. Rapid increase in
tuberculosis incidence soon after infection with HIVa new twist in the
twin epidemics. The Journal of Infectious Diseases. 191:1479, 2005.