Emerging epidemic of transmitted HIV drug resistance in low- and middle-income countries, with highest burden seen in MSM

Prevalence of transmitted drug-resistant HIV has doubled in low- and middle-income countries in recent years, results of a meta-analysis published in AIDS show. Between 2004-08 and 2009-13, rates of transmitted resistance increased markedly in all key populations in these settings.

The increase coincides with the expanded roll-out of antiretroviral therapy (ART) in resource-limited settings; however testing for drug resistance before the initiation of therapy is rare.

“The scale-up of ARV [antiretroviral] use should be accompanied by cost-effective assays for early detection of virologic failure, surveillance of TDR [transmitted drug resistance] and GART [genotypic antiretroviral resistance testing] for individual patient management,” comment the authors of an editorial.

It is possible for HIV to become resistant to the drugs used in its treatment and drug-resistant strains of virus can be transmitted.

There is some evidence that rates of transmitted drug resistance are stabilising in richer countries. This is due to improvements in care – such as the routine use of sensitive resistance tests to help select ART combinations and regular viral load monitoring – and the introduction of more powerful anti-HIV drugs that are active against drug-resistant strains of the virus.

In contrast, emergent epidemics of transmitted resistance in low- and middle-income countries have been detected. Access to ART has expanded rapidly in these settings in recent years. However, viral load and resistance testing are rare and treatment relies on standardised, fixed-dose combinations.

An international team of investigators wanted to establish a better understanding of global trends in rates in transmitted resistance and variations according to world region and risk group.

They therefore conducted a meta-analysis, analysing the results of 212 studies conducted between 1999 and 2013 that reported on rates of transmitted drug resistance.

The authors examined trends in industrialised and low- and middle-income countries. They also compared rates between the main HIV risk groups: men who have sex with men (MSM); people who inject drugs (PWID); and heterosexuals.

Overall, North America was the world region with the highest burden of transmitted drug resistance, which was present in 14% of MSM, 9% of PWID and 11% of heterosexuals.

Western Europe was the next-worst affected region, with transmitted resistance present in 11% of MSM, 6% of PWID and 7% of heterosexuals.

There was also a notable epidemic of transmitted resistance in South America, where prevalence in the key populations were 8% for MSM, 14% in PWID and 8% in heterosexuals.

High rates of transmitted resistance were observed among MSM in Oceania (Australia 16%), Eastern Europe/Central Asia (10%) and East Asia (8%).

The epidemics of transmitted resistance in high-income countries stabilised between 1999 and 2013. In these settings, prevalence was significantly higher among MSM (11-13%) compared to PWID (5-8%) and heterosexuals (6-9%).

There were limited data concerning transmitted resistance in low- and middle-income countries before 2004. However, prevalence across all risk groups in 2009-2013 was more than double that observed in the 2004-08 period (MSM: 8 vs 4%, p = 0.001; heterosexuals: 4 vs 2.6%, p < 0.001; PWID: 5 vs 2%, p = 0.2). MSM have been the group most affected by transmitted drug resistance in these settings, with especially severe epidemics observed in China and Cuba.

The risk of transmitted drug resistance was compared between risk groups. In high-income countries, the risk was 28% higher in MSM compared to heterosexuals. Comparison of these two groups in low- and middle-income countries showed that MSM had a 42% higher risk.

The authors also looked at prevalence of transmitted resistance according to antiretroviral drug class. In MSM, prevalence of transmitted resistance to NRTIs (nucleoside reverse transcriptase inhibitors) fell from 7% before 2004 to 5% in 2009-2013. However, resistance to both NNRTIs (non-nucleoside reverse transcriptase inhibitors) and protease inhibitors increased (2 to 4%, p < 0.001; 0.6-2%, p < 0.001). Among heterosexuals and PWID, prevalence of transmitted resistance to all antiretroviral classes remained low.

The authors suggest that the geographical differences revealed in their study are “largely dependent on ART coverage, drug regimens used, clinical experience and patient adherence to treatment.” They conclude there is a “need for ongoing surveillance of TDR in all settings to regularly update knowledge of levels of TDR and to ensure timely initiation of therapies which effectively suppress viral load.”

The authors of the editorial write that “low-cost assays are needed that can be performed while patients wait in the clinic. An ideal assay would detect both virologic failure and important resistance mutations on a single platform at the point of care.”