Background:  Acute tuberculosis (TB) in HIV⁺ patients has been associated with elevated HIV RNA levels that decline with TB therapy. We identified unexpectedly low HIV viral loads among Ugandan adults with untreated HIV and smear-positive TB, and examined predictors of low viral load and evolution of viremia during TB therapy.

Methods:  Subjects were HIV/TB-co-infected adults in 2 different clinical trials, with CD4 >200 cells/mm³ (trial 1, 1999) or CD4 ≥350 cells/mm³ (trial 2, 2005). HIV-1 RNA and CD4 were measured prior to initiating TB therapy. Baseline chest X-ray was classified as mild-moderate or severe disease. In each trial, patients with baseline HIV RNA <4.0 log copies/mL were classified as having “low baseline” viral load, and were compared to patients with baseline HIV RNA ≥4.0 log copies/mL (“high baseline” viral load). 

Results:  Of 187 patients enrolled in trial 1, 28 (15%) had baseline HIV RNA <4.0 log copies/mL (median 3.21, range 1.70 to 3.99), 11 (6%) of whom had baseline HIV RNA <3.0 log copies/mL. Among 93 patients enrolled in trial 2, 18 (19%) had baseline HIV RNA <4.0 log copies/mL (median 3.41, range 2.30 to 3.95); 1 had baseline HIV RNA <3.0 log copies/mL. The 46 patients with low baseline viral load from trials 1 and 2 were compared with 132 patients (56 randomly selected trial 1 patients, and 76 trial 2 patients) with baseline HIV RNA ≥4.0 log copies/mL (median 4.86, range 4.00 to 6.49). Patients with low baseline viral load exhibited no difference by median age (30 vs 29 years, p = 0.63), gender (59% vs 60% male, p = 1.0), median baseline CD4 (427 vs 447 cells/mm³, p = 0.93), or radiographic severity of TB (62% vs 64% severe disease, p = 0.86). These differences did not vary by trial. Among those who received only TB therapy (n = 82), a significantly higher proportion of patients with high baseline viral load (38%) had HIV RNA declines of >0.5 log copies/mL after 3 months compared with low baseline viral load patients (0%), p <0.001. Conversely, a higher proportion patients with low baseline viral load (50%) had paradoxical HIV RNA increases of >0.5 log copies/mL after 3 months of TB treatment  compared to high baseline viral load patients (14%), p = 0.003. 

Conclusions:  Low-level viremia occurs in a subset of patient with acute TB and is not related to baseline CD4 or severity of TB. Paradoxical increases in viral load were observed in this population after TB treatment. Evaluation of viral factors including HIV subtype and tropism and host immune factors to explain these findings are ongoing.