Predictors of HIV virological failure and drug resistance in Chinese patients after 48 months of antiretroviral treatment, 2008–2012: a prospective cohort study

Abstract

ObjectiveTo explore factors associated with HIV virological failure (VF) and HIV drug resistance (HIVDR) among HIV-positive Chinese individuals 4 years after initiating first-line lamivudine-based antiretroviral treatment (ART) in 2008 at five sentinel sites.DesignFirst-line ART initiators who were previously treatment naïve were selected using consecutive ID numbers from the 2008 National Surveillance Database into a prospective cohort study. Questionnaires and blood samples were collected in 2011 and 2012 to assess the outcomes of interest: VF (defined as viral load ≥1000 copies/mL) and HIVDR (defined as VF with genetic drug-resistant mutations). Questionnaires and data from National Surveillance Database assessed demographics and drug adherence data.Results536 individuals with HIV were analysed; the 4-year risk of VF was 63 (11.8%) and HIVDR was 27 (5.0%). Female participants initiating stavudine (D4T)-based regimens were more susceptible to both VF (adjusted OR (aOR)=2.5, 95% CI 1 to 6.1, p=0.04) and HIVDR (aOR=3.6, 95% CI 1 to 12.6, p=0.05) versus zidovudine-based regimens. Male participants missing doses in past month were more susceptible to both VF (aOR=2.8, 95% CI 1.1 to 7, p=0.03) and HIVDR (aOR=9.7, 95% CI 2.1 to 44.1, p<0.01). Participants of non-Han nationality were of increased risk for HIVDR (aOR from 4.8 to 12.2, p<0.05) and non-Han men were at increased risk for VF (aOR=2.9, 95% CI 1.1 to 7.3, p=0.02). All 27 participants detected with HIVDR had non-nucleoside reverse-transcriptase inhibitor mutations, 21 (77.8%) also had nucleoside reverse-transcriptase inhibitor mutations, and no protease inhibitor mutations were detected.ConclusionsOur findings suggest successful treatment outcomes at 4 years for roughly 90% of patients. We suggest conducting further study on whether and when to change ART regimen for women initiated with D4T-based regimen, and reinforcing adherence counselling for men. Increased VF and HIVDR risk among non-Han minorities warrants further exploration, and ethnic minorities may be an important group to tailor adherence-focused interventions.

Characteristics of HBV infection in 705 HIV-infected patients under lamivudine-based antiretroviral treatment from three regions in China

“…CD4 cell count was detected by flow cytometry (FACSCalibur; BD, Franklin Lakes, NJ, USA) within 24 hours after plasma sample collection at provincial CDC laboratories. 16 HIV RNA was quantified with real-time NASBA (Nucli-Sens EasyQ; bioMerieux, Marcy l’Etoile, France) or COBAS (Roche Applied Biosystems, Mannheim, Germany) according to manufacturer’s recommendations. For those with HIV RNA level ≥1,000 copies/mL, HIV-1 partial polymerase genes (protease amino acid [AA] 1–99 and RT AA 1–252) were amplified and sequenced for drug resistance analysis.…”

“…For those with HIV RNA level ≥1,000 copies/mL, HIV-1 partial polymerase genes (protease amino acid [AA] 1–99 and RT AA 1–252) were amplified and sequenced for drug resistance analysis. 16 …”

“…HIV drug resistance analyses used the Stanford University HIV Drug Resistance Database ( https://hivdb.stanford.edu/ ), 16 which was also used for HBV NUCr analyses and genotyping. The 11 classical NUCr-related AA sites (rtL80, rtI169, rtV173, rtL180, rtA181, rtT184, rtA194, rtS202, rtM204, rtN236, rtM250) in HBV RT were carefully studied.…”

“…The TDF-based combination ART was recommended for treatment of HIV/HBV co-infected individuals in China since 2012. 15 , 16 However, TDF/TDF + 3TC-based ART remains unavailable in some resource-limited regions, and the 3TC-based ART has been continually in use. 17 Some HIV-infected patients in China have received 3TC-based ART for almost 10 years.…”

Effectiveness, Safety, and Tolerability of a Switch to Dual Therapy with Dolutegravir Plus Cobicistat-Boosted Darunavir in Treatment-Experienced Patients with Human Immunodeficiency Virus

“…The selection of drug with high resistance barriers is necessary to achieve successful treatment in treatment failure or experienced patient because of the high drug resistance was seen. In several studies, the rate of drug resistance in treatment failure or experienced patients has varied from 42% to 61%; number of patients with drug resistance/number of patients with treatment failure; 33/65 [ 19 ], 27/63 [ 20 ], and 219/359 [ 21 ].…”