Prevalence of HIV-1 Drug Resistance among Patients with Antiretroviral Therapy Failure in Sichuan, China, 2010-2016

Abstract

Antiretroviral therapy (ART) has been introduced recently and has significantly impacted morbidity and mortality, but can also engender drug resistance. To identify the prevalence of HIV-1 drug resistance (HIVDR) among patients with antiretroviral therapy failure in Sichuan during the period from 2010 to 2016, we carried out a longitudinal study in Sichuan, a province with the highest HIV/AIDS prevalence in China. The data and blood samples were collected from HIV/AIDS patients who received ART for more than half a year. Overall 5,512 sequences were completed from 7,059 ART-failure patients, and 2,499 individuals were identified as drug resistant. Among those with HIVDR mutations identified, 25.37% were against non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.60% was against nucleoside reverse transcriptase inhibitors (NRTIs). NRTI-resistant drugs were mainly lamivudine (3TC) (57.77%) and emtricitabine (FTC), while NNRTI-resistant drugs were mainly nevirapine (NVP) (91.13%) and efavirenz (EFV) (72.81%). The most common recombination subtypes of HIV-1 in sequenced samples were CRF07_ BC (circulating recombinant form, CRF) (41.42%), followed by CRF01_AE (40.77%). Moreover, drug resistance rate increased with the prolongation of treatment time (χ 2 = 14.758, P < 0.05). The overall prevalence of acquired drug resistance in HIV-1 infected patients in Sichuan was 5.47%, which has remained relatively stable from 2010 to 2016. HIV-1 CRF01_AE and CRF07_BC subtypes were the main epidemic strains, and the possibility of resistance was higher in CRF01_AE subtypes. The current study highlights the importance of acquired drug resistance surveillance over a long period.

Multidrug-resistant tuberculosis (MDR-TB) and multidrug-resistant HIV (MDR-HIV) syndemic: challenges in resource limited setting

“…In our case, the patient had M184 mutations conferring resistance to 3TC, emtricitabine (FTC), didanosine (ddI) and abacavir (ABC), while K65R causes intermediate to high-level phenotypic and clinical resistance to TDF, ddI, ABC and d4T and low level to intermediate phenotypic and clinical resistance to 3TC and FTC. Drug resistance surveillance of CRF01_AE subtype in a Chinese cohort experiencing ART failure reported occurrence of M184V and K65R mutations at 64.98% and 15.97%, respectively, among treatment failures 38. The M184 mutation is not a contraindication to a continued treatment with 3TC or FTC, thus 3TC remained a part of our patient’s ART regimen.…”

“…INSTIs comprise a key drug class that has been shown in randomised controlled trials to be more effective in rapidly decreasing HIV viral load within 12 weeks when compared with the standard NNRTI and NRTI combinations,33 and this effect is similar across most INSTIs 33 34. Reports have shown an increasing numbers of pretreatment NNRTI resistance among ART-naïve patients35–37 and can be >25% among those experiencing ART failure 38. In our case, HIV genotyping revealed mutations in K101E and Y181C, causing resistance to EFV and Y181I/V mutations causing resistance to NVP, etravirine and rilpivirine.…”

“…These transmitted drug resistance (TDR) patterns were reported to occur in 2.2% in a patient cohort in Malawi 35. On the other hand, NRTI mutations are less prevalent, ranging from 1.6%38 to 4%39 among ART-experienced and ART-naïve, respectively. In the Philippines, overall HIV-1 TDR by conventional Sanger-based sequencing is 9.7% overall (NNRTI: 6.2%, NRTI: 1.8% and PI: 2.7%) and was even higher on next-generation sequencing at 5% minority variant cut-off (19.5% overall, NNRTI: 13.3%, NRTI: 2.7%, PI: 4.4%, INSTI 1.8%) 40.…”

Prevalence and determinants of virological failure, genetic diversity and drug resistance among people living with HIV in a minority area in China: a population-based study

“…The findings confirmed that the prevalence of virological failure on ART (41.81%) among PLWH was high in this area, which was higher than that in other high HIV epidemic areas of China (11.8%-17.5%) [22], and even higher than that in East and West Africa (9.1%-25.4%) [23][24][25]. The prevalence of drug-resistance was as high as 32.10%, which is lower than that of other places of Sichuan province (35.4%-50.7%) [21,26] and other HIV epidemic areas of China (50%-65%) [27,28]. A high prevalence of subtype CRF07_BC (95.62%) was observed among PLWH with virological failure on ART, which was different from other areas of China.…”

HIV-1 reverse transcriptase and protease mutations for drug-resistance detection among treatment-experienced and naïve HIV-infected individuals

“…Moreover, 42.0%-86.2% of the HIV-infected individuals had at least one resistance mutation in Iran [5,9,20]. It was also reported in China that with the increase in the coverage of ART, drug resistance increased from 23.0% to 74.0% from 2010 to 2016 [35].…”