Prevalence and evolution of drug resistance HIV-1 variants in Henan, China

Abstract

ABSTACTTo understand the prevalence and evolution of drug resistant HIV strains in Henan China after the implementation of free antiretroviral therapy for AIDS patients. 45 drug naïve AIDS patients, 118 AIDS patients who received three months antiretroviral therapy and 124 AIDS patients who received six months antiretroviral treatment were recruited in the southern part of Henan province. Information on general condition, antiretroviral medicines, adherence and clinical syndromes were collected by face to face interview. Meanwhile, 14ml EDTA anticoagulant blood was drawn. CD4/CD8 T cell count, viral load and genotypic drug resistance were tested. The rates of clinical improvement were 55.1% and 50.8% respectively three months and six months after antiretroviral therapy. The mean CD4 cell count after antiretroviral therapy was significantly higher than in drug naïve patients. The prevalence rate of drug resistant HIV strains were 13. 9%, 45.4% and 62.7% in drug naïve patients, three month treatment patients and six month treatment patients, respectively. The number of resistance mutation codons and the frequency of mutations increased significantly with continued antiretroviral therapy. The mutation sites were primarily at the 103, 106 and 215 codons in the three-month treatment group and they increased to 15 codon mutations in the six-month treatment group. From this result, the evolution of drug resistant strains was inferred to begin with the high level NNRTI resistant strain, and then develop low level resistant strains to NRTIs. The HIV strains with high level resistance to NVP and low level resistance to AZT and DDI were highly prevalent because of the AZT+DDI+NVP combination therapy. These HIV strains were also cross resistant to DLV, EFV, DDC and D4T. Poor adherence to therapy was believed to be the main reason for the emergence and prevalence of drug resistant HIV strains. The prevalence of drug resistant HIV strains was increased with the continuation of antiretroviral therapy in the southern part of Henan province. Measures, that could promote high level adherence, provide new drugs and change ART regimens in failing patients, should be implemented as soon as possible.

Approaches to antiretroviral therapy in China

“…Initially, China explored the use of ZDV, ddI and NVP as well as d4T, ddI and NVP. Both these choices were associated with high treatment failure rates as noted above 9 . Tab.…”

“…Choice of regimens which may include thymidine analogs [27,28] and nevirapine (NVP) [29] must be balanced by accumulating toxicities of long term therapy, increased cost, and potential for development of resistance prior to onset of symptomatic AIDS. This is highlighted by the 62.7% resistance seen after 6 months of ZDV/ddI/NVP in China [9]. In addition, the presence of co-morbidities such as HBV must also be factored into the selection of antiretroviral agents, especially given the high prevalence of HBV in China.…”

“…This has led to an increase in the prevalence of resistance mutations in both those on ART and those who are newly infected [7,8]. Indeed, a report in this issue demonstrates that 62.7% of patients developed ARV drug resistance after only 6 months of ART in one region in China [9]. These high failure rates and the spread of resistance within populations are important realities to consider when developing and managing ART programs in China and worldwide.…”

Commentary on “Prevalence and evolution of drug resistance HIV-1 variants in Henan, China”

“…In order to obtain this information monitoring and evaluation or operational research must be done in each country or population. The article by Li et al in this issue represents an outstanding example of the importance of data obtained in the populations treated [1]. The authors proactively evaluated the outcomes at 3 and 6 months of 118 and 124 HIV infected individuals, respectively, treated with zidovudine, didanosine and nevirapine in one region in China.…”

Trade-Related Aspects of Intellectual Property Rights

“…However, this combination is plagued by drug resistance, as highlighted in recent reports revealing an alarming 62.7% rate of drug-resistant mutations in a group treated for 6 months in Henan. 6,7 Furthermore, this combination has particularly strong side-effects and is potentially dangerous for hepatitis B patients. All first-line WHOrecommended HIV treatments now incorporate 3TC (lamivudine), a drug patented by GSK that MSF reports remains fairly inaccessible in China.…”