Key facts
- The emergence of acquired resistance to dolutegravir - the antiretroviral drug of choice - exceeded the expected level, with levels reaching 19%.
- Dolutegravir resistance increases the urgent need for standardized surveys to characterize the prevalence and patterns of dolutegravir resistance mutations and their associated clinical determinants.
- As the use of dolutegravir-based antiretroviral therapy expands, continued vigilance in preventing and monitoring HIV drug resistance among newly diagnosed HIV-infected infants is needed.
- To stop HIV drug resistance, we must: make optimal antiretroviral drugs available; retaining patients in care and ensuring their adherence to treatment; Expanding the availability and use of viral load testing; And quickly replace therapeutic courses in the event of confirmed treatment failure.
Overview
Over the past decade, the world has witnessed an unprecedented increase in the use of antiretroviral therapy, saving the lives of tens of millions of people living with HIV. At the end of December 2022, the number of people receiving antiretroviral therapy was 29.8 million, up from 7.7 million in 2010.
The increasing use of anti-HIV drugs has been accompanied by the emergence of resistance to these drugs, and resistance levels have continued to increase in recent years.
Drug resistance of HIV results from changes in the genetic structure of the virus that affect the ability of drugs to prevent viral replication. All antiretroviral drugs, including newer classes, are at risk of losing their efficacy partially or completely due to the emergence of drug-resistant viruses. If resistance to anti-HIV drugs is not curbed, it will threaten the effectiveness of the drugs used to treat it (1) , which will lead to an increase in the number of infections and the resulting rates of morbidity and mortality (2).
Scope of the problem
HIV drug resistance surveillance provides countries with evidence that can be used to improve treatment outcomes at the patient and population level. WHO recommends that countries conduct national drug resistance surveys on a routine basis, among various population groups, including adults, children, adolescents, and people on pre-exposure prophylaxis who have been diagnosed with the virus.
The WHO HIV Drug Resistance Summary Report 2024 summarizes recent information, with a focus on HIV drug resistance in the era of integrase inhibitors for HIV prevention and treatment.
Acquired resistance to anti-HIV drugs
Viral load suppression, the goal of HIV treatment, contributes greatly to preventing the emergence of drug resistance. When viral load suppression is achieved and maintained, the likelihood of drug-resistant virus emergence is reduced.
As documented in the WHO Summary Report on HIV Drug Resistance 2024 , global data remain limited regarding the emergence of HIV resistance to dolutegravir; However, in published cohort studies, dolutegravir resistance was observed in up to 4.8% of participants who did not achieve viral suppression. Recent studies supported by the US President's Emergency Plan for AIDS Relief in four low- and middle-income countries indicate that the estimated prevalence of dolutegravir resistance among individuals on dolutegravir-based antiretroviral therapy who have a detectable level of virus in the blood ranges from 3.9% in people who did not achieve viral suppression and who had undergone antiretroviral therapy for at least 9 months, and 19.6% in people who had previously undergone intensive treatment. More data from standardized surveys of acquired antiretroviral drug resistance and from longitudinal observational cohort studies are needed in countries in all regions, in order to achieve enhanced insight into the risk factors and patterns of emergence of drug resistance among individuals on HIV-based antiretroviral therapy (ART) regimens. Dolutegravir.
WHO recommends that countries implement routine surveillance for acquired antiretroviral drug resistance among adults, children and adolescents on antiretroviral therapy, using a laboratory method based on viral loads, a clinical method based on ART or a sentinel survey approach , which method is used depending on coverage. National viral load testing, availability of non-identifying demographic information, and funding.
Resistance to previous anti-HIV therapy drugs
Drug resistance may develop in some people before they start treatment. This type of resistance may be transmitted at the time of infection or acquired during previous treatments.
WHO recommends surveillance for anti-HIV drug resistance in adults starting or re-initiating antiretroviral therapy, or in infants starting antiretroviral therapy who have never been on antiretroviral therapy , to guide the determination of the optimal choice of first-line treatment regimens.
Eleven countries reported data to WHO on the prevalence of drug resistance prior to dolutegravir treatment among adults starting ART. Dolutegravir resistance was detected in one country at a very low prevalence of 0.2%, attributable to a rare non-polymorphic mutation in the integrase. However, these surveys were conducted before the adoption of dolutegravir or in the early transitional stages in these countries, and therefore cannot provide evidence of the absence of dolutegravir resistance in populations starting or re-initiating ART as dolutegravir-based ART continues to expand. And maintain it.
Pre-treatment levels of rilpivirine resistance among individuals who initiated ART and had not received prior antiretroviral therapy ranged between 0.0% (95% CI 0.0-9.4%) in Tajikistan in 2016 and 16.6%. (95% confidence interval 11.2-24.0%) in Eswatini. These data suggest that if rilpivirine is used in combination with cabotegravir as long-acting antiretroviral therapy, drug resistance testing before treatment will be needed in some settings to identify individuals who do not have rilpivirine-resistant virus, because these pre-treatment resistance mutations are risk factors for failure. Viral load suppression in subjects receiving long-acting treatment with cabotegravir in combination with rilpivirine.
To date, only one country has reported data from a survey of HIV drug resistance among infants after adopting a course containing dolutegravir. One infant was identified with dolutegravir resistance, and his mother had undergone dolutegravir-based antiretroviral therapy.
Surveillance of HIV drug resistance among previously untreated and newly diagnosed HIV-infected infants remains important in the era of dolutegravir-based antiretroviral therapy, and rapid implementation of such surveys is needed. Furthermore, effective management of high viral loads among pregnant and lactating women is critical to prevent transmission of the virus to infants.
Pre-exposure prophylaxis for HIV to prevent it
Many people who live in circumstances that pose a high risk of exposure to HIV receive medications to reduce their chances of contracting the disease. The organization recommends providing preventive treatment before exposure to the virus as an additional option to prevent the virus.
HIV infection is rare among individuals who undergo pre-exposure prophylaxis. But the emergence of drug resistance is common among people who become infected with the virus despite undergoing pre-exposure prophylaxis. Drug resistance limits HIV treatment options due to overlapping resistance characteristics between antiretroviral drugs used for pre-exposure prophylaxis and treatment.
A review of the literature published in the WHO HIV drug resistance report 2024 found that of 310 cases of seroreactivity reported during oral pre-exposure prophylaxis containing tenofovir between 2020 and 2023 in clinical settings, 20 were % of these are resistant to tenofovir or lamivudine, with the prevalence of drug resistance increasing more than 10-fold when pre-exposure prophylaxis is initiated in the presence of undiagnosed infection.
Although the risk of HIV infection has decreased significantly among people using long-acting cabotegravir PEP, 10 cases of resistance to integrase inhibitor drugs have been reported to date among people receiving long-acting cabotegravir PEP, and mutations have been found Cross-resistance with dolutegravir occurred in all ten cases.
To monitor the effectiveness of anti-HIV medicines used for both treatment and prevention, WHO recommends that countries implement nationally representative surveys to monitor levels of anti-HIV drug resistance among people initiating treatment and among people on pre-exposure prophylaxis who become infected with the virus.