China: rapid rise in drug-resistant HIV among people not previously on treatment
HIV drug resistance among treatment-naïve people in China rising rapidly from 2012 and tops 10% in Central China.
A systematic review and meta-analysis from China finds that transmitted drug resistance (TDR) – when people who have never been on antiretroviral treatment (ART) before are already resistant to first-line ART – was found at 3% of cases overall, with significant regional variation. The analysis also found this type of drug-resistant HIV has been accelerating in China since 2012, mainly due to resistance to a class of ART known as non-nucleoside reverse transcriptase inhibitors (NNRTI).
The review, published in The Lancet’s E-Clinical Medicine, analysed 170 studies to assess the level, trend and geographical distribution of HIV drug resistance between 2001 and 2017, and the most common genetic mutations that cause it.
Studies included in this analysis, the most comprehensive of its kind to date, relate to 21,450 people living with HIV who had not been on antiretroviral treatment (ART) before (otherwise known as treatment or ART-naïve), and 30,475 people who had previously been on treatment.
Significantly, NNRTI-associated transmitted drug resistance was found to have exceeded 10% in Central China since 2015, the threshold at which the World Health Organization (WHO) recommends urgent action is taken.
Acquired drug resistance, whereby resistance occurs among people who have previously been on treatment, was found in around 45% of cases.
The genetic mutations that they found were associated with the most common ART drugs in China – including five drugs that are used in publically-funded (and therefore free) first- and second-line treatment regimens. This suggests the current regimens containing these drugs should be revised.
Central China was found to be the region worst affected by drug resistance, among both treatment-naïve people and those with a history of ART. The region was the first to implement a free ART programme in 2003, and also has higher ART-coverage than North and South China, factors that are likely to be at the root of the region’s higher drug resistance levels.
Overall, NNRTI-resistance was found to be more prevalent than resistance to other classes of antiretrovirals, namely nucleoside reverse transcriptase inhibitors (NRTI) and protease inhibitors (PI).
The analysis’ examination of which genetic mutations contributed most to drug resistance found one NRTI-associated and three NNRTI-associated mutations to be common in both ART-naïve and ART-treated individuals with drug resistance. These mutations conferred high-level resistance to the drugs lamivudine (3TC), efavirenz (EFV) and nevirapine (NVP), suggesting these should no longer be included in first and second line-regimens.
The characteristics of mutations were also found to vary between regions, with Central China’s mutation profile dramatically distinct from other regions and the overall national picture. For instance, the two most commonly observed mutations in North and South China were rarely found in Central China.
This analysis provides compelling evidence that should be used to inform new, region-specific first-line and second-line ART regimens in China. It also suggests that a number of strategies, including increased viral load testing and the scale-up of pre-treatment counselling and enhanced adherence support, should be implemented in the country. These measures will be particularly important as China’s expansion of ART continues.