Tehran University Medical Journal

Background and Aim: The better understanding of immunopathologic mechanism of tuberculosis (TB) is necessary for the production of new vaccines and adjunctive immunomodulator drugs. Intended to this object, the following study including the measurement of serum concentrations of Th1 (Interferon (IFN)-y and interkeukin (IL)-2 and Th2 cytokines(IL-4AND IL-10 ) in patients with sputum smear-positive pulmonary TB and comparisons of them with PPpositive healthy persons, was designed.

Materials and Methods: The HIV-negative patients that had sputum smear-positive pulmonary TB as defined WHO criteria and hospitalized in the infectious diseases ward of Imam Khomeini hospital or referred to health care centers in the south of Tehran, were included in the study. The PPD-positive healthy persons who were close contacts with pulmonary TB patients, were considered as control group.

Results: In this research 34 active pulmonary TB patients (including17men and 17 woman)and 23 healthy persons with PPD skin test results  or = 10mm (including 12men and 11 woman) were studied. The mean ages of the patients and the healthy persons were 73 and 41 years and 74 and 27 years, respectively. The mean serum IFN-Y concentration was significantly higher in TB patients but the mean serum IL-2 IL-4and IL-10 concentrations were significantly higher in healthy persons. The com parison of the mean serum levels of these cytokines before and during treatment (about 2 months after starting treatment) showed that the amounts of IFN-y and IL4 were increased and the amounts of IL2 and IL-10 were decreased but only the changes of IL-10 were statistically significant. There were no effect on the cytokine changes before and during treatment by age and gender of the patients.

Conclusion: The results of the study of serum Th1 and Th2 cytokines in pulmonary TB patients were different in comparison with the results of the studies of peripheral blood mononuclear cells (PBMCs) stimulated with M.tuberculosis antigens. SO, the simultaneous measurement of them in serum, pleural fluid, BAL fluid and the medium culture of PBMCs stimulated with the antigens is recommended.

The combinations of antiretroviral (ARV) drugs have proven effective in controlling the progression of AIDS, but these benefits can be compromised by drug resistance. Thus, drug-resistance testing has become an important tool in the management of HIV-infected individuals.1 Drug resistance develops when mutations in the HIV virus proteins occur due to amino acid substitutions.2 Drug resistance testing is done in two ways: phenotypic test and genotypic test.3 In the first method, virus proliferation is measured in the presence of different concentrations of the drugs. In the second, the genetic structure of viral genome sequences are investigated.4 Although, the first case of HIV infection in Iran was identified 23 years ago (1988), there is still no study published on its drug resistance. The main purpose of this study was to determine the prevalence of drug resistance mutations in patients with HIV/AIDS attending Imam Khomeini Hospital in Tehran. The secondary objectives of the study were to determine the frequency of drug resistance to specific drugs such as nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PI). We collected plasma samples from 25 patients with HIV/AIDS and immunological failure. After the extraction of the viral RNA from plasma, genomic sequencing was performed. Finally, the data for determining drug resistance were analyzed by the Stanford HIV Drug Resistance Database (http://hivdb.stanford.edu) software. Out of the 25 patients under study, 20 were male (80%) and five were female (20%). Routes of HIV transmission were: 56% by needle sharing among injecting drug users (IDUs), 20% through sexual contact, 12% through blood transfusions and 12% by unknown routes. High-level drug resistance for ARV drugs included: 24% to NRTIs, 28% to NNRTIs and zero percent to PI drugs. In addition, 15 patients had been infected with genotype A and 10 patients with genotype B of the virus subtypes. More than half of the patients (56%) had HCV co-infection and 44% had prison histories. Overall, the prevalence of drug resistance was 28% which is lower to those of other countries which range from 30% to 90%. Among NRTI drugs, 24% had high-level drug resistance to Lamivudin while no resistance was witnessed against Tenofovir. Among NRTI drugs, 8% had high-level and 68% had low-level resistance to Stavudine. Among NNRTI drugs, 24% and 28% of the patients showed high-level resistance to Efavirenze and Nevirapine, respectively, although the resistance rate in the present study was much lower in comparison to similar studies in China, Venezuela and Chile with respective resistance rates of 61%, 38% and 84%. In this study, no resistance was seen against PI drugs, while the resistance rates in other countries, such as Venezuela, Chile, Brazil and the U.S. have been respectively reported to be 47%, 45%, 45% and 41%.5 With higher genetic barriers than NNRTI drugs, and lack of resistance to them, PI drugs can be used effectively in health care systems in triple drug regimens. With a compliance rate of 32% in our study, 2NRTI+PI combination seems to be preferable to 2NRTI+NNRTI combination for the treatment of HIV/AIDS patients.