Overcoming HIV DR with Vigilance & Surveillance
On March 5, the World Health Organization (WHO) released a HIV Drug Resistance (HIVDR) Report which stated that drug resistance is growing and issued recommendations for countries to monitor and respond to the potential challenges. The report highlights high levels of HIV viral load suppression (>90 per cent) in populations receiving dolutegravir (DTG)containing antiretroviral therapy (ART). However, observational and country-generated survey data indicate that levels of HIVDR to DTG are exceeding levels observed in clinical trials.
The WHO has recommended use of DTG, since 2018, as the preferred first- and second-line HIV treatment for all population groups. It is more effective, easier to take, and has fewer side effects than other drugs currently in use. It also has a high genetic barrier to developing drug resistance. However, among the four surveys reported, levels of resistance to DTG ranged from 3.9 per cent to 8.6 per cent, and reached 19.6 per cent among people experienced with treatment and transitioned to a DTG-containing ART while having high HIV viral loads. To date, only a few countries have reported survey data to the WHO.
HIV remains a major global public health issue, having claimed 40.4 million lives so far with ongoing transmission in all countries globally; with some countries reporting increasing trends in new infections when previously on the decline. There were an estimated 39.0 million PLHIV at the end of 2022. In 2022, 630,000 people died from HIV-related causes and 1.3 million people acquired HIV.
The WHO noted that by 2025, 95 per cent of all people living with HIV (PLHIV) should undergo a diagnostic test, 95 per cent of those should be taking life saving ART and 95 per cent of PLHIV who are on treatment should achieve a suppressed viral load for the benefit of the person’s health and to reduce onward HIV transmission. In 2022, these percentages were 86 per cent, 89 per cent and 93 per cent respectively.
The world has witnessed an unprecedented increase in the use of ART, which has saved the lives of tens of millions of people living with HIV/ AIDS. At the end of 2021, 28.7 million people, out of an estimated 38.4 million PLHIV, were receiving ART globally. Increased use of HIV medicines has been accompanied by the emergence of HIV drug resistance – the levels of which have steadily increased in recent years.
The WHO has recommended oral pre-exposure prophylaxis (PrEP) as a prevention option for those at risk of acquiring HIV. In 2021, more than 1.6 million people received oral tenofovir disoproxil fumarate + emtricitabine (TDF + FTC) PrEP, and in the past two years the PrEP arsenal expanded to include two new ARV drugs recommended by the WHO: dapivirine containing vaginal rings (DPV-VR) and injectable long acting cabotegravir (CAB-LA).
The use of CAB-LA PrEP reduces the risk of acquiring HIV. However, there are concerns about the potential emergence of integrase-strand transfer inhibitors (INSTI)-resistant HIV. INSTI resistance has been observed in some cases with recent CAB exposure, and delayed detection and confirmation of HIV infection can increase the risk of selection of INSTI drug resistance–associated mutations. Despite the risk, the roll-out of CAB-LA PrEP should not be hindered. Since limited quantities of CAB-LA are anticipated to be available over the next 3–5 years, there is an opportunity to carefully monitor for the emergence of CAB drug resistance and to characterise the potential risk of DTG cross-resistance in well-defined populations using CAB-LA PrEP.
The introduction of DTG-containing regimens coupled with the expansion of PrEP for preventing HIV infection, including new drugs such as CAB-LA, promises to revolutionise HIV care and prevention. However, early signals of DTG resistance among people for whom DTG-containing regimes fail to achieve viral suppression highlight the ongoing need for vigilance and intensified efforts to optimise the quality of HIV care delivery to maximise individual and population-level outcomes coupled with standardised routine surveillance of HIV drug resistance to prevent, monitor and respond to the potential threat of HIV drug resistance.