African migrants living in France less likely to benefit from antiretroviral innovations than people born in France

A French study reveals large differences in antiretroviral therapy prescriptions between people with HIV born in sub-Saharan Africa and those born in France. It also shows that these differences exist both at the time of starting treatment and after long-term viral suppression, without any clinical, virological or immunological justification.

In Western Europe today, different therapeutic options are available for people with HIV. For those starting antiretroviral therapy (treatment-naive), integrase inhibitor-based regimens are preferred, although reverse transcriptase inhibitor or protease inhibitor-based combinations may still be prescribed. Separately, patients with prolonged viral suppression while on treatment can be offered to switch to drug-reduced strategies such as two-drug combinations or four to five days-a-week-regimens.

When clinically appropriate, all people with HIV in high-income countries should have equal access to these innovations. However, the extent to which migrants receive them is a question that few studies have explored. Migrants with HIV are known to typically have poorer clinical outcomes – e.g higher rates of AIDS, lower CD4 cell counts at entry in HIV care and a higher risk of virological failure once in care – when compared with individuals born in the country. Furthermore, they represent an increasing proportion of new HIV diagnoses in high income countries, 66% in the case of France, half of whom are women.

Believing there might be differences in antiretroviral prescriptions between migrant and French-born patients, Dr Romain Palich and his colleagues from the Hôpital Pitié-Salpêtrière compared which regimens were received in the two populations, both at the start of antiretroviral therapy and in the context of sustained viral suppression.

The investigators reviewed medical records of all new patients at their clinic born either in France or in sub-Saharan Africa who started treatment between 2000 and 2018, which they called the treatment-naive group. They also reviewed all patients from the same two populations who attended in 2018 and had a viral load below 50 copies, called the virally suppressed group. The study only includes patients at a single, major Paris hospital and it’s unknown whether its findings reflect wider issues in France.

It should also be noted that the analysis is based on country of birth, not race. In France, collecting data on ethnicity and race is illegal, with exceptions to the rule only occasionally allowed, hence the frequent use of ‘place of origin’ as a proxy.

Results

Overall, 1,944 treatment-naive patients were enrolled: 915 born in sub-Saharan Africa and 1,029 born in France. Most of the migrants were women (58% vs 11%, p<0.001) and heterosexual (86% vs 26%, p<0.001), and were younger than those born in France (35 years of age vs 37, p<0.001).

At time of HIV diagnosis, patients born in Africa had a lower median CD4 cell count (231 vs 345, p<0.001) and higher rates of AIDS (22% vs 14%, p<0.001), hepatitis B (10% vs 2%, p<0.001) and tuberculosis (7% vs 1%, p<0.001) than patients born in France. These results probably explain that patients born in Africa had a shorter median time between entry into care and starting HIV-treatment than those born in France (1.7 months, CI: 0.7-7.2 versus 2.2 months, CI: 0.6-18.8).

In terms of first antiretroviral prescriptions, patients born in Africa were 1.6 times more likely to receive protease inhibitor-based combinations (58% vs 47%, p<0.001) and around half as likely to receive integrase inhibitor-based regimens (13% vs 24%, p<0.001), compared to those born in France. Integrase inhibitors were more commonly prescribed in the last period of the study (2013-2018), as they were more widely available, and in case of a high viral load.

Adjustment of these results for confounders (relevant clinical and demographic differences between groups) confirmed that patients’ geographic origin had a significant impact on what class of antiretrovirals was prescribed to treatment-naive patients.

Turning to the 968 virally suppressed patients – 431 born in sub-Saharan Africa and 537 in France – the investigators found that by 2018 the first group had used antiretroviral therapy for longer (11 vs 9 years, p<0.001), had lower CD4 cell counts (588 vs 714, p<0.001) and were less likely to be treated by a full-time physician (52% vs 63%, p<0.001), in comparison with the second group. However, the median duration of viral suppression – 76 months – was similar in both groups, making the following results astonishing.

Compared to persons born in France, those born in Africa received in 2018:

• more nucleoside reverse transcriptase inhibitors (92% vs 88%, p=0.043),
• more protease inhibitor-based regimens (21% vs 10%, p<0.001),
• fewer integrase inhibitor-based regimens (37% vs 48%, p=0.017) and,
• less drug-reduced antiretroviral therapy such as two-drug combinations or four days-a-week-regimens (22% vs 40%, p<0.001).

Again, after adjustment for confounders, the geographic origin had an independent impact on the type of antiretroviral strategy prescribed.

The investigators note several reasons that could explain doctors’ choice of protease-based regimens for migrants born in Africa starting antiretroviral therapy. Protease inhibitors have a lower risk of emerging HIV resistance in case of poor adherence to treatments than non-nucleoside reverse transcriptase inhibitors and first-generation integrase inhibitors, despite their side-effect profile also being known to make adherence challenging. Another reason is pregnancy and the desire to have children which may be more common in the group of patients born in Africa, with its high proportion of women: a combination of nucleoside reverse transcriptase inhibitors and a protease inhibitor was the standard treatment for pregnant women in the earlier years of the study.  

With regards to virally suppressed patients not receiving drug-reduced antiretroviral therapy, one explanation may be the fear that those born in Africa are more likely to carry archived resistance mutations following past treatment failures (and the implicit perception that they might not fully adhere to their therapy).

“We believe, however, that patients born in sub-Saharan Africa do not receive the most innovative strategies as much as patients born in France, despite similar virological situations, and that they all pay the price for therapeutic difficulties observed in only a small proportion of patients,” say the investigators.

They also point to previous studies from other countries highlighting inequalities in access to treatment based on race, implicit biases and false beliefs about racial differences.  

It is urgent and essential to investigate these disturbing results further – and in more than one HIV clinical centre – in order to correct these biases and improve clinical practice.