Drug resistance or side effects might limit ART in up to 1 in 10 people living with HIV

2 May 2024. Related: Antiretrovirals, Treatment strategies, Side effects, Drug resistance.

Simon Collins, HIV i-Base

Results from an international cohort collaboration published in AIDS are useful for recognising how some people living with HIV might still have limited options for ART due to multidrug resistance (MDR) or intolerance to current drugs. [1]

This analysis was based on identifying people on ART for more than five years who were using alternatives to standard combinations (2NRTIs plus third component). This definition is a substitute for direct evidence of genotypic resistance which was not recorded. It has the advantage however of perhaps picking up people with limited treatment options due to intolerance of commonly used drugs.

This collaboration of 17 national databases was a largely male (74%), white (70%) cohort, but mixed demographics included 44% MSM, 36% heterosexual and 13% people who inject drugs. Geographically, 45% were from central Europe, 24% northern Europe/Australia, 11% eastern Europe and 20% southern Europe/Argentina.

Of the 23,827 participants included in this analysis, 2164 developed limited/exhausted treatment options (termed LExTO) during approximately 130,000 person-years follow-up (PYFU), median 5.5 years of follow-up. This was an incidence of 1.66/100 PYFU (95% CI: 1.59 to 1.73).

Independent risk factors for developing LExTO were longer duration of HIV infection (>15 years), incident kidney or cardiovascular disease, advanced HIV disease and a CD4 count below 350 cells/mm³ and detectable viral load (>200 copies/mL), see Table 1.

Table 1: Independent risk factors for developing LExTO

Incident chronic kidney disease (CKD) was the only clinical event associated with LExTO (aIRR: 1.74; 1.48 to 2.05). In adjusted analyses, LExTO was not associated with increased mortality.

Baseline criteria associated with a higher risk of LExTO included longer duration of HIV, older age, lower CD4 and CD4 nadir and geographical region (all p <0.0001).

Importantly, LExTO was steadily lower in recent calendar years, even though this will be an ageing population, likely due to development of second-generation integrase inhibitors.

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This study is important for highlighting that a significant minority of people are in need of alternative ART.

An indication of the limitations of the study in terms of lack of information about drug resistance, includes that higher rates of LExTO might also reflect greater access to non-standard HIV combinations. For example, approximately 10% of participants in central and northern Europe developed LExTO (998/10,691 and 575//5790, respectively) compared to 6% in eastern Europe (180/2636).

The study also censored data at the end of December 2021 so no one was using fostemsavir, ibalizumab or lenacapavir, which would be the more direct signal of current MDR.

However, a retrospective cohort analysis of HIV multidrug resistance and intolerance in Spain reported much lower rates of people dependent on new drugs. [2]

This study reported that 69/14,995 participants on ART had confirmed drug resistance to three or more ARV classes or intolerance to two or more classes. Of these, 46/69 had undetectable viral load on their current combination, 10/69 were detectable and 13/69 were undetectable but had drug intolerance.

The researchers estimated that approximately 200 people in Spain might have extremely limited treatment options based on the 0.15% prevalence reported in their study.

References

1. Mocroft A et al for the RESPOND cohort collaboration. Heavy antiretroviral exposure and exhausted/limited antiretroviral options: predictors and clinical outcomes. AIDS 38(4):p 497-508. DOI: 10.1097/QAD.0000000000003798. (15 March 2024).
   https://journals.lww.com/aidsonline/fulltext/2024/03150/heavy_antiretroviral_exposure_and.8.aspx
2. Llibre JM, García F, Blanco JL, et al. Prevalence of people living with multidrug-resistant HIV and limited treatment options in Spain. HIV Med. 2024; 1–12. doi:10.1111/hiv.13650