HIV drug resistance is rising and needs urgent attention, says World Health Organization
Without urgent action, HIV drug resistance is set to derail the HIV response and presents a significant threat to public health, the World Health Organization (WHO) warns today.
Growing levels of HIV drug resistance (HIVDR) to key antiretroviral drugs commonly used across low- and middle-income countries (LMICs) are revealed by the World Health Organization (WHO) today in Geneva.
Several countries in LMIC regions are reporting high levels of pre-treatment drug resistance – that is, resistance detected in a person starting HIV treatment for the first time – at over 10%. This level of HIVDR or greater will require the triggering of a national public health response in those countries, says the WHO.
The findings are revealed in advance of the International AIDS Science Conference, opening in Paris on Sunday (23 July), at a press conference announcing the launch of three major WHO reports – a 2017 Global Report on HIVDR, updated antiretroviral treatment (ART) guidelines, and a Global Action Plan on HIVDR.
Drug resistance – an emerging public health threat
Increased levels of HIVDR in low-resourced contexts are largely the result of poor treatment service quality, pharmacy stock-outs and treatment interruptions – an inevitable impact of the drive to reach every person living with HIV with antiretroviral treatment. This is evident in the fact that pre-treatment drug resistance has increased more rapidly in recent years, in the era of ‘treat all’.
Without action, the realities of HIVDR are bleak – it limits treatment options, increases treatment programme costs, and if left untreated, the level of virus resistant to drugs can increase in the body to the extent that it can be transmitted to others.
Globally, it is resistance to the non-nucleoside reverse transcriptase inhibitor (NNRTI) drug class which is contributing to rising levels of HIVDR. This drug class includes key drugs such as nevirapine and efavirenz, which are regularly used for first-line treatment in LMICs, as recommended by the WHO.
NNRTIs are relatively affordable and available in these countries, whereas access to more expensive, second-line treatment options are limited – at least that is, without innovative partnerships and negotiations.
But health outcomes for people with NNRTI resistance are poorer. They are less likely to be virally suppressed; more likely to experience treatment failure, or death; more likely to stop their treatment; and more likely to acquire drug-resistant mutations.
Of 11 LMICs with surveys on pre-treatment drug resistance reported to the WHO between 2014 and 2016, all had HIVDR prevalence approaching or above the 10% mark, with six reporting levels in excess
Of 11 LMICs with surveys on pre-treatment drug resistance reported to the WHO between 2014 and 2016, all had HIVDR prevalence approaching or above the 10% mark, with six reporting levels in excess – Argentina, Guatemala, Namibia, Nicaragua, Uganda and Zimbabwe. In Africa, NNRTI resistance ranged from 8.1% in Cameroon, to 15.4% in Uganda. In Latin America, HIVDR prevalence of any drug class ranged from 9.8% in Brazil, to 23.4% in Nicaragua.
People who had previously been exposed to treatment, either through prevention of mother-to-child transmission (PMTCT) programmes, or because they re-started treatment, were at an increased risk of having drug-resistant HIV. HIVDR prevalence among the treatment-exposed was 21.6%, compared to just 8.3% among those with no treatment exposure.
While the expansion of PMTCT programmes has meant that significantly less children are now being born with HIV, the fewer children that do become infected have a greater risk of developing drug resistance because they may have already been exposed to ART.
Even where children have not been exposed to PMTCT, they have unique challenges in sticking to a drug-taking regime – they depend entirely on caregivers to take their treatment and are more affected by unpalatable drugs, among other factors – putting them at greater risk of developing resistance through lack of adherence.
While data is limited, the reports reveal high rates of HIVDR among infants and children. In South Africa, the only survey submitted to the WHO for this group, 63.7% of children under 18 months had some form of HIVDR. Other non-WHO led studies have confirmed this. In a Togo national PMTCT programme, 60% of a cohort of newly diagnosed children had relevant drug resistant mutations – with high levels (81.8%) of NNRTI resistance detected.
New treatment options
In countries where HIVDR has increased to above 10%, the WHO now recommends a public health response be launched. In this context, alternative treatment options should be considered for countries where HIVDR levels are high. While not an official recommendation, guidelines now say that a non-NNRTI-containing regime, using the integrase inhibitor dolutegravir, may be a preferable option.
In addition to the alternate treatment choice, testing for HIVDR may also be considered for people who are at-risk of pre-treatment drug resistance – such as those with previous treatment exposure.
Individual-level HIVDR genotype testing is not generally recommended by the WHO in LMICs, as it requires significant human resource and laboratory capacity. But with the increasing levels of drug resistance, countries should now consider using this as a tool to combat drug resistance.
In both these scenarios, cost and cost-effectiveness, as well as feasibility were a concern. But these were outweighed by the wider, long-term, public-health benefits for countries with drug resistance levels in excess of 10%.
A Global Action Plan
If HIV drug resistance is not dealt with, the number of AIDS deaths attributed to HIVDR in the next 15 years could be around 890,000 – around 16% of total AIDS deaths. We could see 450,000 new HIV infections – 9% of all new HIV infections. ART could cost an extra $6.5 billion – around 8% of total ART needs to 2030.
If HIVDR levels remain at 10%, ART could cost an extra $6.5 billion – around 8% of total ART needs to 2030.
As such, the WHO have put together a five-year Global Action Plan – centred on five key objectives – which aim to support countries to prevent HIVDR through effective monitoring, interventions to strengthen treatment programmes, research and innovation, increasing laboratory capacity, and ensuring country ownership on this issue.
What is clear is that concerns over the rising prevalence and potential impact of HIV drug resistance should not stop global treatment expansion.
Dr Shannon Hader of the U.S. Centers for Diseases Control said: “We must be forward-thinking in our efforts to combat resistance: scaling up viral load testing, improving the quality of treatment programs, and transitioning to new drugs like dolutegravir."
“Overall high rates of viral suppression across three recent national Population-based HIV Impact Assessments showed that present first-line regimens remain largely effective. However, special attention to populations at-risk for higher resistance, such as pediatrics, adolescents, pregnant women and key populations, will be critical to target more urgent interventions. We call on the global community for continued vigilance and responsiveness.”