Study on prevalance of drug resistance and genetic mutation for drug resistance HIV on HIV/AIDS patients with first line antiretroviral treatment failure at Dongda hospital Ha Noi

- STUDY ON PREVALANCE OF DRUG RESISTANCE AND GENETIC MUTATION FOR DRUG RESISTANCE HIV ON HIV/AIDS PATIENTS WITH FIRST-LINE ANTIRETROVIRAL.
- TREATMENT FAILURE AT DONGDA HOSPITAL HA NOI.
- Objectives: To study prevalence of drug resistance and genotype testing for drug resistance HIV on HIV/AIDS patients with first-line antiretroviral treatment failure at Dongda Hospital, Hanoi.
- Subjects and methods: Cross-sectional, descriptive, prospective study on 47 HIV/AIDS patients with first-line antiretroviral treatment failure at Dongda Hospital, Hanoi during period from 6 - 2011 to 12 - 2016.
- Results: The prevalence of drug resistance HIV was 90.7%.
- resisted NNRTIs, following NRTIs: 95.3% and PIs group 11.6%.
- 27.9% and 25.6%, respectively.
- In NNRTIs, the prevalence of NVP resistance was 95.3% and ETR resitance was 4.7%.
- In NRTIs, lamivudine resistance was 93.0% and AZT resistance was 9.3%..
- No LVP/r resistance was recorded.
- Conclusions: Patients with first-line antiretroviral treatment failure had high prevalence of NNRTIs and NRTIs resistance but still susceptible to PIs..
- Drug resistance.
- First-line antiretroviral treatment failure.
- Genetic mutation for drug resistance..
- ARV therapy widely used in patients with indication, contributes to a new pathway in the prevention and treatment of HIV/AIDS by reducing the risk of HIV transmission in the population.
- However, the emergence and widesrpead of drug resistance HIV are inevitable trend due to prolonged treatment..
- Moreover, side effects of ARV are sustainable factors leading to non- adherence to treatment, which contribute to drug resistance HIV and uncontrolled disease in community.
- The development of drug-resistant virus strains predisposes treatment failure and patients who had treatment failure should be changed to use higher-line ARV therapy (higher-level)..
- In Vietnam, drug-resistance HIV testings are extravagant and are not performed regularly..
- Therefore, to help clinicians optimize the effectiveness of ARV treatment, we performed this study with aims: To determine the proportion of drug resistance and genetic mutation for drug resistance in patients with first-line ARV treatment failure..
- 47 HIV patients with fist-line ARV treatment failure in HIV/AIDS outpatient clinic in Dongda Hospital from June, 2011 to December, 2016 were enrolled..
- Patients were treated by first-line ARV (zidovudine + lamivudine + nevirapine or stavudine + lamivudine + nevirapine) and diagnosed treatment failure according to guidelines for diagnosis and treatment HIV/AIDS issue in 2009 [2]..
- No cooperation (compliance) in the research process..
- Nucleotid sequencing testing to indentify the drug resistance mutations:.
- Show each amino acid corresponding to each of Prot and RT sites to detect resistance mutations and estimate resistance levels (potent, low, medium or high) for each drug in the three groups NRTIs, NNRTIs, PIs.
- This drug resistance compiler is based on the International AIDS Society (USA Panel Guidelines) 2010 [6]..
- The propotion of patients having HIV with genetic mutation for drug resistance..
- Among the 47 patients enrolled, 43 patients had genetic mutation for drug resistance (accounted for 90.7.
- Tran Thi Phuong Thuy’s research demonstrated that 5% of patients with HIV-1 treatment.
- failure had not resistance mutation [1]..
- The proprotion of these patients was 2.8% in Nguyen Huu Chi’s study [3]..
- Thus, it can be seen that HIV in patients with treatment failure do not mean that they resist ARV drugs.
- There are many factors that affect the viral replication, which lead to treatment failure with HAART including poor adherence to ARV therapy, factors related to the pharmacokinetics of.
- When drug resistance testing are not used, doctor probably determines to unnecessary conversion to second-line regimens.
- Meanwhile, delaying the transition to second-line regimens upon failure of first-line regimen increases the occurrence of new drug-resistant mutations..
- Table 1: Variation in expression of ARV resistance mutation in patients with treatment failure..
- Drug resistance mutations Quantity (n = 43) Percentage.
- NNRTI resistance mutations 42 97.7.
- NRTI resistance mutations 41 95.3.
- PI resistance mutations 5 11.6.
- NNRTI + NRTI resistance mutations.
- PI non-resistance mutations 35 81.4.
- NNRTI + NRTI + PI resistance mutations 5 11.6.
- NNRTI resistance mutations.
- NRTI and PI non-resistance mutations 2 4.7 NRTI resistance mutations.
- NNRTI and PI non-resistance mutations 1 2.3.
- Nguyen Huu Chi investigated drugs resistance mutation in 71 treatment failure patients who had drug resistance mutation testing.
- Among them, the highest percentage resistance was seen in NRTI, accounted for 97.2%, followed by NNRTI resistance with 87.3% and PI resistance with 5.6% [3].
- According to Vietnamese researchers, the rates of PIs resistance were low in our country due to the PI drugs are rarely used and transmitted drug resistance HIV is also rare in Vietnam [3].
- Adversely, NRTI resistance was the most common as it is the first-choice drug..
- Drug resistance mutations..
- Table 2: The location of NNRTIs resistance mutations..
- The percentage in patiens with drug resistance.
- The percentage in patients with treatment.
- G190A is highly resistant to NVP and has a moderate resistance to EFV as well as causing resistance in the NNRTI group.
- All mutations were associated with cross-resistance in the NNRTI group.
- Therefore, patients with NNRTI resistance mutations should avoid using these agents in the alternative regimen..
- Table 3: The location of NRTIs resistance mutation..
- This may explain that lamivudine which was a selected drug for this mutation is present in all first-line regimens..
- Lamivudine is a widely used drug in Vietnam for the treatment of chronic hepatitis B, which is a highly prevalent disease in the population.
- This drug is considered to have poor resistance barrier and has a very high rate of drug resistance after initial treatment in chronic hepatitis B [7].
- Table 4: The location of PIs resistance mutation..
- The percentage in drug resistance mutation.
- The percentage in treatment failure patients (n = 47).
- In Doan Thu Tra’s study on patients with L89M, I13V mutation accounted for 6.3% and 5.1%, respectively.
- Huynh Hoang Khanh Thu indicated that the two main mutants recorded were M46I (0.9%) and V82V .
- NVP is a low genetic barrier drug, one mutation in the center of RT (Reverse Transctiptase) activity will occur drug resistance.
- The occurrence of major mutations at high frequency has resulted in the ineffectiveness of NVP (95.3% drug resistance)..
- Therefore, the rate of EFV resistance was low with 55.8% due to less common.
- The level of resistance to ETR was lower than that of other drugs in the group because ETR resistance mutations occurred when at least 3 new mutations were accumulated..
- The percentage of patients with 3TC resistance was high (93.
- In patients with combination regimens of d4T or AZT, TAM mutations and secondary mutations occurred, which resulted in multiple drug resistance (41.9% D4T resistance.
- The rate of patients with TDF resistance was 25.6%..
- Among 5 patients with resistant mutation genes to the PI group, however, only two cases were ability to be resistant to SQV/r.
- In 47 patients with first-line ARV therapy failure, 90.7% had HIV with drug resistance genes.
- Among them, the highest resistance rate was seen in NNRTI group with 97.7%, followed by NRTIs (95.3%) and PIs (11.6%)..
- In the NRTI- resistant mutant genotypes, the highest percentage was seen in M184V accounted for 88.4%.
- In the location of PIs resistance mutation, M36I and K20R accounted for 9.3%.
- In the NNRTI group, NVP had the highest resistance rate of 95.3%.
- In NRTIs, lamivudine had the highest resistance rate (93.0%) and the lowest rate was seen in AZT with 9.3%.
- In PIs, no LVP/r resistance was recorded but might be resistant to SQV/r..
- Determination of drug resistance of HIV in patients with first-line therapy failure and evaluation of the efficacy of second-line antiretroviral therapy in HIV- infected patients.
- Update of the drug resistance mutations in HIV-1: December 2010

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