Bictegravir/emtricitabine/tenofovir alafenamide appears to be safe and effective in women: results from a pooled analysis
24 February 2020. Related: Conference reports, Pregnancy.
Polly Clayden, HIV i-Base
A pooled analysis of women and girls receiving bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in five clinical trials showed high rates of virological suppression at 48 weeks, according to data presented at EACS 2019.
Rates of adverse events (AEs) were similar to those seen among participants receiving comparator regimens.
There were not sufficient numbers of B/F/TAF-exposed pregnancies to draw any conclusions.
Co-formulated B/F/TAF 50/200/25 mg is a once-daily fixed dose combination manufactured by Gilead Sciences.
This analysis included 679 women and girls receiving B/F/TAF or comparators (373 B/F/TAF) across five phase 2/3 originator clinical trials, conducted in ART naive adults and virologically suppressed children, adolescents and adults through 48 weeks. See Table 1.
Table 1: Pooled analysis of women in phase 2/3 bictegravir/emtricitabine/tenofovir alafenamide studies
|Study||Population||Comparator regimen(s)||Women B/F/TAF arm (n)||Women comparator arm (n)|
|1489/1490||ART naive adults||DTG/ABC/3TC (1489) DTG+F/TAF (1490)||69||70|
|1961||Suppressed women||E/C/F/TAF E/C/F/TDF ATV/r/F/TAF||234||236|
|1464||Suppressed (2 NRTIs + 3rd agent) children and adolescents 6– 17 years||59|
|4449||Suppressed (2 NRTIs + 3rd agent) adults 65+||11|
Key: ABC, abacavir; ATV/r, atazanavir/ritonavir; B, bictegravir; DTG, dolutegravir; E, elvitegravir; F, emtricitabine; TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate; 3TC lamivudine
The comparator arm in study 1489 was dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) and in 1490 DTG/F/TAF. Notably the total number of participants in these naive studies was 1274 of which only 139 were women.
Women in study 1961 were previously enrolled in the women-only WAVES study (elvitegravir/cobicistat/emtricitabine/tenofovir E/C/F/TDF or E/C/F/TAF vs atazanavir/r-based ART) and its open label extension in which they all received elvitegravir-based ART.
Paediatric switch study 1464 had 100 participants in total, of which 59 were young women and girls. And switch study 4449, in participants aged 65+, had 86 in total of which 11 were women.
In the pooled analysis, demographics among women and girls by age and baseline treatment group were as follows. Virologically suppressed: 6–17 years (n=59); 18–49 years (n=191); 50–64 years (n=43) and 65–75 (n=11). ART naive: 18–49 years (n=54) and 50–68 (n=15).
There was considerable variation in ethnicity, particularly among virologically suppressed participants: from 78% black among 6–17 year-olds to 91% white in the 65–75 years age group. In the ART-naive group just under half of the participants were black and 35–40% were white.
At week 48 there were high and similar rates of virologic suppression across age and treatment groups (B/F/TAF 87–100% and comparators 88–95%). These findings are consistent with those seen overall in the B/F/TAF studies across both sexes. No treatment-emergent resistance was seen with B/F/TAF across the programme.
Drug-related AEs were similar among participants taking B/F/TAF versus comparators. Overall rates of grade 3/4 AEs were low and similar to comparators. One adolescent (0.1%) discontinued B/F/TAF due to anxiety.
Weight gain was reported as an AE in 3/314 women receiving B/F/TAF (all in ART-naive group aged 18–49); weight loss was reported in 1/314. There was 1/306 weight gain and 1/306 weight loss among the participants receiving comparator ART.
At week 48 the median change from baseline weight in the virologically suppressed participants receiving B/F/TAF was 1.5 kg vs 0.4 kg in the comparators (p<0.001). Among these participants 53% received TAF and the remainder TDF.
The difference in median change between B/F/TAF and comparators in the ART-naive participants was non-significant at weeks 48 and 144. The respective weight gain from baseline at week 144 was 5 kg, 7.9 kg and 4.9 kg in the B/F/TAF (n=50), DTG/ABC/3TC (n=29) and DTG + F/TAF (n=29) groups. But numbers were very small.
The presentation also included weight gain in men. Of note in the ART-naive group differences in weight gain from baseline for men receiving B/F/TAF vs DTG/ABC/3TC were significant: 3 kg vs 1.4 kg (p<0.0001) and 4.2 kg vs 3.2 kg (p=0.03) at 48 and 144 weeks respectively. There were no significant differences in weight gain among men receiving B/F/TAF and DTG+F/TAF. There were over 1000 men in the ART naive group.
Cumulative to 17 October 2019, there were 30 B/F/TAF exposed pregnancies across the Gilead trials: 25 prospective, 4 retrospective and one unknown reports.
Among the prospective reports 21 exposures were preconception/first trimester, 2 were second/third trimester and 2 unknown. The 4 retrospective reports were all preconception/first trimester as was the unknown prospective or retrospective pregnancy.
Of these there were 15 live births with no congenital anomaly; 1 live birth with patent urachus; 3 with unknown outcome; 7 spontaneous abortion; 1 still birth and 3 elective terminations.
There were no cases of CNS congenital anomalies or neural tube defects but no prevalence can be calculated as retrospective reports are drawn from a population in which the number of exposed pregnancies is unknown.
Presenting author Chloe Orkin made a plea to the audience to report pregnancies retrospectively and reminded us that in the US only 10% are reported.
Orkin C et al. Efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide vs comparators in cis-women and girls (living with HIV): an analysis of 5 clinical trials. 17th European AIDS Conference (EACS). Basel, Switzerland. 6–9 November, 2019. Oral abstract PS7/6.