It is estimated that a third of the world’s population is infected with tuberculosis (TB).
This epidemic is fueled by HIV, with reactivation rates of 8-10% / year and overall lifetime risk of 30% in HIV patients. Uganda has both a high TB and HIV prevalence of 646/100000 population and 6.4% respectively with over 1,000,000 people living with HIV and AIDS (PLWA).
HIV makes the diagnosis of TB infection difficult. Tuberculin skin test (TST) is negative in up to 70% of HIV patients. In Uganda about 80,000 people are on antiretroviral drugs (ARVS). These drugs lead to recovery of the immune system. It is not known whether this immune system recovery leads to a corresponding improvement in the performance of TST. This would allow use of TST in the diagnosis of latent TB infection and subsequently institution of prophylaxis therapy in HIV infected patients on HAART.
In this study we evaluated whether HAART restores PPD reactively and the factors associated with this PPD reactively.
The overall objective of this study was to determine the effect of HAART on the in vivo PPD reactivity and the associated factors among HIV patients at the Makerere University adult Infectious Diseases Clinic (IDC).
This was a prospective cohort study of 130 HIV positive patients who initiated antiretroviral therapy at the adult IDC at mulago hospital. We enrolled consenting HIV positive ART naïve adults who had history and physical examination done to exclude active tuberculosis (TB). All patients had a chest X-ray examination. 0.1ml of purified protein derivative (PPD) (RT-23) was administered. Patients with negative baseline TST received a second TST at 2 months and those who were still negative at this time got a third TST at 6 months. At all these intervals patients were clinically evaluated to exclude active TB and blood samples for CD4 cell counts were taken at six months interval. Patients with positive TST but no active TB were given a nine month course of isiniazid prophylaxis.
Data was abstracted from the patients’ cohort files using pre-tested tools and entered into Epidata version 3.1 and later exported to STATA version 10 for analysis.
Patients with skin indurations of 5mm and over were considered positive. We calculated the proportion of patients with positive PPD at enrolment and after two and six months of HAART. We compared the clinical, radiological and CD4 cell counts of TST positive and negative patients at enrolment and follow up.
Of the 155 patients screened 130 fulfilled eligibility criteria… fourty one (31.5%) were TST positive at baseline and this was significantly associated with history of weight loss and cough, as well as higher CD4 cell counts. Twelve patients (13.5%) had TST conversion during six months of follow up of whom 8 were in the first 2 months and this was associated with a greater increase in CD4 cell counts after six month of HAART (mean CD4 rise in converters 174 vs 91, p=0.03. Five out of 89 (5.6%) patients followed up to 6 months developed active TB.
Among ART naïve HIV positive patients TST positively is low and after six months of HAART, less than 50% were TST positive. Patients with higher CD4 cell count increase are more likely to have TST conversion during HAART.
Diagnosis of latent TB in HIV patients is difficult and repeat TST testing should be considered for those HIV positive patients with negative TST before ART who have experienced favourable immunological recovery if clinicians have a need to diagnose latent TB infection.
Active TB screening is needed before ART and during the early months of ART because the burden of TB is high during this period as shown in this study.
TB control measures are needed in HIV care settings to prevent TB transmission as we showed in this study that 1 in 10 of the pre-HAART patients have undiagnosed active TB.