French study confirms that people with HIV born abroad are less likely to receive integrase inhibitors than those born in France

Data from across France shows that the choice of the antiretroviral regimen is influenced by the birth country of patients, without clear clinical, virological or immunological justification. These results confirm what was revealed by a recent study from a Paris hospital.

Dr Romain Palich from the Hôpital Pitié-Salpêtrière and his colleagues used the French national Dat’AIDS cohort to assess patients’ characteristics associated with the choice of antiretrovirals in people starting therapy in recent years. The team’s second objectives were to analyse the time to reach viral suppression and the time to treatment discontinuation.

Information was collected from 26 HIV clinics. Eligibility criteria were being over 18 years old, starting triple therapy between 2014 (when dolutegravir became available in France) and 2020, and having a viral load above 400 copies before starting therapy.

Among participants’ characteristics collected were sex, place of birth (“France” or “abroad”), HIV acquisition mode, year of diagnosis, type of third drug in the first regimen (integrase inhibitor, boosted protease inhibitor, non-nucleoside reverse transcriptase inhibitor or “other”), viral load and CD4 cell count at the time of HIV diagnosis, chronic hepatitis B and tuberculosis at the time of starting antiretroviral therapy.

Of note, collecting data on ethnicity or race is illegal in France, with exceptions to the rule only occasionally allowed, hence the frequent use in research of “place of origin” or “place of birth” as a proxy.

Duration of the first antiretroviral therapy was also collected, until the occurrence of death, loss to follow-up, switch to another centre not participating in Dat’AIDS, or the year 2021.

Data from 9,094 persons living with HIV whose place of birth was available were analysed: 48% were born in France, 29% in sub-Saharan Africa. While men who have sex with men were mostly (74%) born in France, 77% of women were born abroad.

Compared to those born in France, people born abroad had lower CD4 cell counts at the time of HIV diagnosis: 404 [interquartile range 234-580] vs 290 [147-441], respectively. Tuberculosis and hepatitis B were more frequent in patients born abroad than in those born in France: 4.2% vs 0.5%, and 8.2% vs 1.5%, respectively. There was no difference in viral load.

Time from HIV diagnosis to antiretroviral prescription was slightly longer for people born abroad, but remained below three months in 75% of cases.

In total, 4,535 patients received an integrase inhibitor-based regimen as first antiretroviral therapy: 1,723 had dolutegravir, 1,227 had boosted elvitegravir, 1,153 had bictegravir and 432 had raltegravir. For 69% of those taking integrase inhibitors, the treatment was given as single-tablet regimen.

However, an integrase inhibitor-based therapy was less frequently started in patients born abroad than in those born in France (44% vs 56%, respectively). This difference was almost entirely made up of people born abroad being prescribed boosted protease inhibitors, which might be appealing to clinicians when it comes to limiting the emergence of resistance mutations when they anticipate sub-optimal adherence.

Characteristics significantly associated with the choice of an integrase inhibitor-based regimen were:

• Starting therapy in more recent years.
• A high viral load before treatment.
• Tuberculosis, reflecting caution regarding interactions between anti-TB drugs and protease inhibitors.
• Being born in France (increasing the chances to have an integrase inhibitor in the first combination by 1.73).

This latter finding remained similar (1.47) when restricting the analysis to men only. The investigators included this analysis to make sure the finding was accurate as doctors may have had concerns around prescribing the integrase inhibitor dolutegravir to women – predominantly born abroad – after a few cases of neural tube defects in babies born to women taking dolutegravir. 

Time to viral suppression (below 50 copies) was three months on average in people receiving an integrase inhibitor-based regimen, whatever their country of birth or clinical characteristics.

There was little difference in the rate of changing treatment (67-68%) or how soon it occurred (median 19 months in those born in France, 17 months in those born abroad). The main reasons for modifications were reducing the number of pills (29-30%) or switching to a two-drug regimen (18% among patients born in France, 11% in those born abroad).

Timing of treatment modification was found to be related to the choice of the first antiretroviral regimen (sooner in the case of boosted protease inhibitors), the person’s gender, the presence of tuberculosis and the viral load level at the start of therapy. However, country of birth was not a factor: in other words, treatment modifications were driven by the same factors in both populations.

The association between being born in France and having a better chance to receive an integrase inhibitor in a first antiretroviral combination is however real, confirming previous findings.

The authors discuss potential explanations for this association, including misperceptions such as doctors assuming people born abroad are unable to adhere to antiretroviral therapy. This study proves them outdated – the absence of a difference in time to viral suppression between patients born in France and those born abroad very clearly indicates high adherence. Moreover, second-generation integrase inhibitors have a high genetic barrier and fewer side effects.

“With this work, we hope to encourage the questioning of current practices, promoting more equity in prescriptions according to geographical origin so as to offer all persons living with HIV the best therapeutic options,” Palich and colleagues conclude.