Tehran University Medical Journal

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.