Lack of Drug Options in HIV Management Unrelated to Virological Treatment Failure

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Lack of Drug Options in HIV Management Unrelated to Virological Treatment Failure

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Lack of Drug Options in HIV Management Unrelated to Virological Treatment Failure

A large-scale study has found that, over a follow-up period of about five years, approximately one in ten people with HIV develop limited treatment options, meaning they can no longer take the standard combination of three antiretroviral drugs.

The most common reason for discontinuing previous antiretroviral drugs and requiring non-standard treatment regimens is the inability to tolerate the drugs in the previous treatment plan, rather than virological treatment failure. The study tracked individuals who had been on treatment for at least five years, and those who developed limited treatment options had a median of 13.5 years on antiretroviral drugs.

The results emphasize the need for new antiretroviral drugs not only due to the emergence of drug resistance but also because complications in HIV-infected individuals mean that some antiretroviral drugs are either poorly tolerated or unsuitable for individuals with multiple health conditions.

In the past, individuals with limited treatment options were often referred to as treatment-experienced, but as Dr. Laura Watts pointed out at the British HIV Association Spring Conference in 2023, individuals with HIV can have limited treatment options without taking a large number of antiretroviral drugs. This situation may occur if they are infected with drug-resistant HIV, cannot tolerate certain antiretroviral drugs, or have complications that limit their treatment options. She noted that if prescribers do not carefully consider the risk of treatment failure when choosing second-line treatment options, resistance to three drugs may develop after only two are taken.

The definition of limited treatment options varies. The European AIDS Clinical Society guidelines explicitly state that treatment options are limited when a patient develops resistance to at least two classes of antiretroviral drugs and/or cannot use regimens containing two to three active drugs from the four major classes of antiretroviral drugs. The guidelines from the UK HIV Association state that treatment options are deemed limited when a fully suppressive regimen cannot be constructed. The U.S. DHHS guidelines do not provide a definition.

To investigate the proportion of HIV-infected individuals with limited treatment options, Professor Amanda Mocroft and colleagues from the RESPOND cohort combined data from 17 cohort studies in Europe, Australia, Argentina, and Israel.

Without resistance data, they used treatment records to study the incidence of new cases with limited treatment options among individuals who had received antiretroviral treatment for at least five years. The study excluded individuals with limited treatment options at baseline (2,794 individuals).

In this study, limited or exhausted treatment options were defined as requiring two anchor drugs in a three-drug regimen (such as darunavir or dolutegravir), or taking a dual-drug regimen consisting of anchor agents (excluding combinations like rilpivirine with dolutegravir or cabotegravir), or taking a regimen with at least three nucleoside reverse transcriptase inhibitors.

Anyone taking a regimen with two nucleoside reverse transcriptase inhibitors and a third drug from a different class was considered to be receiving standard treatment.

The study population included 23,827 HIV-infected individuals who had been on treatment for at least five years and had CD4 counts and viral loads measured in the previous year. Less than three-quarters (73%) were male, 69% were white, and the majority (72%) had been infected with HIV for less than 15 years. The median follow-up time for participants was 5.5 years.

During 130,061 person-years of follow-up, 9% of participants developed limited treatment options (an incidence rate of 1.66 cases per 100 person-years of follow-up). Before developing limited treatment options, participants were exposed to seven antiretroviral drugs over a median of 13.5 years of treatment. Among those who developed limited treatment options, 48% took two anchor drugs and a third drug, 31% took a dual-drug regimen (with 62% of cases involving darunavir), and 15% took three nucleoside reverse transcriptase inhibitors. Almost everyone taking two or more drugs was also taking lamivudine, emtricitabine, and/or tenofovir disoproxil fumarate.

Overall, only 27% of participants stopped taking antiretroviral drugs because of failure of any previous treatment regimen. Participants were more likely to stop antiretroviral drugs in previous treatment regimens because they could not tolerate them (54%).

After adjusting for age and CD4 count, the development of limited treatment options was not associated with an increased risk of death, cardiovascular disease, or non-AIDS-defining malignancies. However, the risk of subsequently developing chronic kidney disease was 47% higher in those who developed limited treatment options.

“The most common reason for discontinuing previous antiretroviral drugs is the inability to tolerate the drugs, not virological failure. For individuals with a history of cardiovascular disease or chronic kidney disease, as well as those with CD4 counts below 350 and a history of AIDS diagnosis, the risk of developing limited treatment options is higher. Compared to Central Europeans, South Europeans and Argentinians have a slightly increased risk of limited treatment choices.

Compared to the period from 2012-2014, the risk of developing limited treatment options was lower in the period from 2018-2021, which may be due to the emergence of second-generation integrase inhibitors (dolutegravir and bictegravir) with higher barriers to developing resistance.

In conclusion, the incidence of exhausted treatment options is lower in an aging population with increased rates of comorbidities and a widespread history of ART, which is a positive finding and may reflect more personalized clinical management, enhancing awareness of potential ART-related toxicities, comorbidities, and drug interactions.”

Lack of Drug Options in HIV Management Unrelated to Virological Treatment Failure

References
Mocroft A et al. Heavy ARV exposure and exhausted/limited ARV options: predictors and clinical outcomes. AIDS, published online, 11 December 2023.

(source:internet, reference only)

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