Sashindran V K, Sashwat S, Kumar Suman, Kumar Ashwani, Namgyal K Armed Forces Medical College, Pune, India

TB cases in 2007 – 9. 27 million (55% in Asia, 31% in Africa) TB cases in 2007 – 9.27 million (55% in Asia, 31% in Africa). India had highest number of incident TB cases – 2 million TB accounted for 23% of the 2 million HIV deaths in 2007 Risk of developing TB in HIV+ people 20.6% in countries with HIV epidemic cART has decreased incidence of TB in HIV+ by > 80%

269/632 (42.56%) had TB at some point during their follow up 39/269 h/o tb before ART started, 17/269 developed TB while on ART and of these 11/17 had reactivation of TB after start of ART with 8 manifesting TB within first 3 m of ART and the rest between 8 – 11m. 176/269 were put on ATT and ART concurrently. 3

cART alone is better than concurrent ATT & ART Concurrent ATT-ART leads to many adverse effects (AE) & early treatment failure of ART owing to drug interactions & poor drug compliance.

To study the effect of factors like: age To study the clinical efficacy and adverse effects (AEs) of concurrent ATT-ART To study the effect of factors like: age baseline BMI and CD4 count changes in BMI & CD4 count with therapy ART regimen Timing of ART vis a vis ATT

Prospective case-control study Cases HIV-TB patients on concurrent ATT-ART ( already on ART or ATT started by 2 m of starting ATT) Controls Age-matched HIV patients without TB initiating ART Follow up minimum 12 m after starting therapy Patients with < 95% adherence to ART excluded

Case definition of TB based on WHO TB/HIV Clinical Manual TB cure – clinical resolution/radiological clearance/ sputum conversion ART failure as defined by API & DHHS guidelines IRIS – diagnostic criteria as proposed by MA French ATT regimen 2EHRZ 4 - 10 HR

Statistical programme - R 2.9.1 (R Development Core Team (2009). Linear mixed effects model, Fisher’s exact test, t test for difference between two means & Wilcoxon rank sum test for difference between two median were used

Parameter ART only (n = 50) ATT-ART (n = 92) Total p Value Statistical Test Median age (IQR) 37.5 (33.2,41.8) 36 (31.8, 41) 36 (32, 41) 0.274 Rank sum Sex M (%) F (%) 43(86) 7(14) 89(96.7) 3(3.3) 132(93) 10 (7) 0.033 Fischer’s exact test Median duration of follow up in months (IQR) 24.5 (16.5, 32.8) 22 (16, 34.2) 24 (16, 33) 0.472 Baseline median CD4 count cells/µL (IQR) 138 (109, 161.8) 108 (56.5, 154.5) 123 (66, 158) <0.031 Baseline BMI kg/m2 20.7(3.6) 18.5 (3.1) 19.2(3.4) <0.001 tTest (140 dF) = 3.7

Timing of ART vis a vis ATT Type of TB in subjects Disseminated TB - 53/92(57.61%) Localized TB - 39/92 (42.39%) had localized TB, 14.13% had sputum negative pulmonary TB Timing of ART vis a vis ATT Simultaneously - 33.7% At 2m of ATT – 31.52% At 2 weeks of ATT - 26.9% Already on ART – 8.69%

Linear Mixed –effect modeling used Effect on BMI Duration of therapy – significant bearing (p = 0.01) ART regimen (p = 0.03) Significant difference between cases & controls after nullifying effect of duration of therapy & ART regimen. BMI increase was 66% more in cases as compared to controls Effect on CD4 count Duration of therapy had an effect (p=0.02) No difference in change in CD4 cell count in cases & controls

ART failure commoner in HIV-TB group ( 14. 13% vs 4. 1%, p=0. 1) ART failure commoner in HIV-TB group ( 14.13% vs 4.1%, p=0.1). Mean time to treatment failure 27m Mortality in the 2 groups not significantly different Recurrence of TB seen in 5.43% cases. Mean time of recurrence 26.6m Timing of ART – no bearing on outcome

To ATT 31.52% Drug – induced hepatitis 23.9%, peripheral neuropathy (4.35%), rash (3.26%) To ART Cases 25%, controls 14% AZT –induced anaemia in 14% of cases & controls, mean time for anaemia 12m Not influenced by type of TB or timing of ART

Commoner in HIV-TB than HIV alone - 19.6% vs 6%, (p=0.045)

Temporal distribution of the two main types of IRIS in the study group

T1W Axial T1W Sagittal

ATT does not significantly worsen the success of concurrently administered ART IRIS is commoner suggesting good immediate immune recovery Despite IRIS being commoner in the ATT-ART group, the immune restitution though present was not significantly different from the ART-only group. Explanation?