Background:  HIV/TB co-infection is associated with increased levels of immune activation, viral replication, CD4 T cell dysfunction and decline contributing to accelerated morbidity and mortality. The study objective was to determine if 6 months of ART given concurrently with TB therapy would produce sustained reductions in immune activation and viral load, and improvements in CD4 T cell counts and function, when compared to TB treatment alone.

Methods:  CD4 T cell counts, viral load, markers of immune activation, and T cell effector function (interferon-gamma production/IFN-g), were measured among HIV-TB co-infected patients (CD4 T cell counts >350 cells/mL) at enrollment and every 3 months during 6 months of therapy and 6 months of observation in 2 arms:  38 patients treated with 6 months’ TB treatment (control); 38 patients treated with 6 months’ ART given concurrently with TB treatment (intervention).

Results:  At enrollment, mean CD4 T cell counts (642.3 cells/mL±242 and 579.1 cells/mL±235) and viral load (4.4±0.78 log ₁₀ copies/mL and 4.3±1 log ₁₀ copies/mL) were similar in control and intervention arms, respectively. Significant changes in CD4 T cell count were not observed in either arm during the study. Viral load in the intervention arm declined at 3 (2.1±0.45 log ₁₀ copies/mL, P <0.001) and 6 months (2.3±0.77 log ₁₀ copies/mL, P <0.0001) that was not sustained after ART was stopped. Within both arms, reductions in CD4/HLA-DR⁺/CD38⁺ and CD8/HLA-DR⁺/CD38⁺ were observed during 6 months of therapy and maintained through 6 month observation (P <0.01). The intervention arm had lower levels in CD8/HLA-DR⁺/CD38⁺ at 3 and 6 months of treatment when compared with the control (P <0.01). IFN-g production in response to PHA increased significantly in the intervention arm during the 6 months of therapy and was maintained through 6 month observation (P <0.01). Preliminary analysis of IFN-g production in response to MTB culture filtrate, MTB Ag85b, and HIV p24 antigens, did not demonstrate any significant differences or changes in either arm throughout the study.

Conclusions:  In patients with HIV/TB co-infection and CD4 T cell counts >350 cells/mL, both TB treatment and concurrent HIV/TB treatment produce sustained decreases in immune activation, and this reduction is most pronounced in patients receiving ART, while on therapy. Patients receiving concurrent HIV/TB treatment had sustained increases in global T cell effector function measured by IFN-g production in response to PHA.