ความชุกของการดื้อยาด้านไวรัส และปัจจัยเกี่ยวข้องในผู้ติดเชื้อเอชไอวีที่ได้รับการรักษามาแล้ว ซึ่งเข้าโครงการวิจัยต่อเนื่องระยะยาวที่ฮิฟ-แนท (ศูนย์วิจัยเอดส์ สภากาชาดไทย) / สุรสฤษดิ์ ขาวละออ = Prevalence and associated factors of antiretroviral drug resistance in HIV patients treated with antiretroviral therapy in a long term HIV-infected Thai cohort: HIV-NAT, Thai Red Cross Aids Research Center
Background & objective : HIV infection was first reported in Thailand in 1984, the prevalence of this infection has been declined from 1.7% in 2001 to 1.5% , 1.4% and 1.3% in 2003, 2007, 2009 respectively UNAIDS has estimated in 2009 that 530,000 Thais are living HIV. Recent data (n 2010) from National Health Security Office reveals that approximately 130,000 HIV-infected patients are receiving antiretroviral drugs and has predicted that in 2011 will increase to 150,000. Thus, unless the management system is effective, the rise of antiretroviral drug resistance will certainly be a major challenge. This research aims to determine the prevalence and risk factors of antiretroviral drug resistance in a long-term cohort in Bangkok. Methods : We collected the data of patients who are continuing to receipt service in Thai cohort : HIV-NAT,Thai Red Cross Society since 1996 to April 2010 based on data in terms of resistance to antiretroviral drugs at all levels, all formulas and gene mutation for those drugs such as NRTI, NNRTI, PI. In addition to this, the relationship of various factors associated with drug resistance, such as age, baseline CD4, baseline viral load is considered by logistic regression analysis. Results : Of 1,112 cases, the most common antiretroviral regimen was 2NRTIs+NRTI 320/1,112(28.8%), the rest included 2NRTIs+bPI 274/1,112(24.6%), others 518/1,112(46.6%). The prevalence of secondary antiretroviral drug(ARV) resistance was 26.8%(298/1,112 when included dual NRTIs “currently not recommended”), and 15.6% when dual NRTIs were excluded. The major risk of transmission were heterosexual 215(72.2%), other included homosexual 32(10.7%), bisexual 41(1.3%), IVDU 3(1%) and not specified 44(14.8%). Among patients treated with NRTIs, 158/728(21.7%) had virological failure (VF) and 79/158(50%) were resistance genotypic tested. were detected. The most common NRTI-resistant associated mutants(RAMs) is M184V (63.3%). 32.9% had at least 3 TAMs, 51.9% and 45.9% had D67N, M41L respectively. Of 329 who treated with NNRTI regimens, 106/329(32.2%) had virological failure; 64/106(60.4%) had genotype results. The 3 most common NNRTI-RAMs included Y181C, G190A and K103N 45.3%, 39.1%, 31.2% respectively. Of 470 who treated with bPI regimens, 70/470(14.9%) had virological failure; 41/70(58.6%) had resistance genotype results. Only 2/41(4.8%) had PI-major mutation(L90M, V82M), due to HIV-1 non-B subtype(subtype CRF01_AE is the most common subtype in Thailand found >90% of patients). PI polymorphism-related mutations is therefore common(75.6%, 26.8%, 12.2%: M36I, K20R/I, L10V/I respectively). Logistic regression analysis of age, baseline CD4 and baseline viral load showed that patients who had baseline CD4 350 cell/mm³ or less is associated with a 2.5 folds higher risk to HIV drug resistance than those a higher CD4 counts(95%CI0.991-6.401, p value 0.052). Conclusion : If we excluded dual NRTIs, the prevalence of antiretroviral virological failure is 15.6%. Overall patients treated with first-line regimens had a higher rate of failure of 26.8%, whereas failing second and third-line regimens was 24.5, 20.5% respectively. The most common RAMs was M184V (3TC-resistance), the second most common was NNRTI-RAMs and a half were cross-resistance to the new NNRTI-etravirine. One-third of patients who failed NRTI had 3 or more thymidine-analog-associated mutations or TAMs. PI-resistance was uncommon, therefore was not compromised other newer PI-darunavir in particular. Patients with low baseline CD4 counts of ≤350 cells/mm³ were at risk of HIV drug resistance and these patients should therefore require closer counseling and follow-up.
