TB doesn't always increase HIV viral load

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A quarter of Ugandan HIV-positive patients with active tuberculosis (TB) had a viral load below 10,000 copies/ml, investigators report in a letter published in the December 1st edition of the Journal of Acquired Immune Deficiency Syndromes. Furthermore, the investigators found that viral load increased in a significant proportion of patients whose viral load was below 1000 copies/ml after they started treatment with anti-TB drugs.

These findings are unexpected as TB is usually associated with an increase in HIV viral load. The investigators could find no obvious patient characteristics associated with a lower viral load during active TB infection.

Two studies involving a total of 202 HIV-positive patients with sputum smear-positive TB were reported by the investigators. Median baseline viral load was approximately 40,000 copies/ml and median CD4 cell count was 472 cells/mm3.

Glossary

subtype

In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.

active TB

Active disease caused by Mycobacterium tuberculosis, as evidenced by a confirmatory culture, or, in the absence of culture, suggestive clinical symptoms.

viraemia

The presence of virus in the blood.

 

sputum

Material coughed up from the lungs, which can be examined to help with diagnosis and management of respiratory diseases.

pathogenesis

The origin and step-by-step development of disease.

However, 49 patients had a baseline viral load below 10,000 copies/ml, with twelve of these individuals having a viral load below 1000 copies/ml.

Tests to determine HIV subtype were conducted on 35 of these patients and the investigators found that 21 (60%) were infected with subtype A, eleven (31%) with subtype D, with two patients (6%) having subtype A/D and one patient subtype C infection.

The investigators then compared the 40 patients who had a viral load below 10,000 copies/ml to the 153 individuals with higher viral loads. There was no difference between these patients with respect to age, sex or severity of TB disease. Nor did CD4 cell count differ.

The investigators then looked at the effect initiating TB therapy had on viral load. They restricted their analysis to the 109 patients who received standard four drug short-course TB treatment without antiretroviral therapy.

When TB treatment was started, 19 (21%) of these patients had a viral load below 10,000 copies/ml. The investigators found that after three months of TB therapy, patients whose baseline viral load was above 10,000 copies/ml were significantly more likely to experience a fall in their viral load of at least 0.5 log10 (p = 0.001).

However, patients whose viral load was below 1000 copies/ml when they started TB treatment were significantly more likely than patients with a higher baseline viral load to experience an increase in their viral load of at least 0.5 log10.

The investigators note that multiple studies have observed an association between active TB and higher viral load. They write, “contrary to these observations, we detected low-level HIV viremia…in almost 25% of Ugandan patients with untreated HIV-TB coinfection in 2 different clinical trials and found that low-level viremia was not related to baseline CD4 cell count or severity of TB.”

They conclude that investigation of “host and viral factors may shed further light on potential causes of low-level HIV viremia in the setting of active TB and provide additional insights into HIV and TB pathogenesis.”

References

Srikantiah P et al. Unexpected low-level viremia among HIV-infected Ugandans adults with untreated active tuberculosis. J Acquir Immune Defic Syndr 49: 458-60, 2008.