Viral dynamics of dolutegravir-based dual versus triple ART

13 November 2018. Related: Conference reports, Antiretrovirals, HIV 14 Glasgow 2018.

Simon Collins, HIV i-Base

Two oral abstracts at the HIV Glasgow 2018 conference included additional analyses of viral dynamics when starting or switching to dolutegravir/lamivudine dual therapy, presented by Babafemi Taiwo from Northwestern University, Chicago.

The first was a new analysis from the phase 3 ASPIRE study on levels of residual viraemia on effective ART but using an ultrasensitive viral load test with a cut off of 0.5 copies/mL. [1] 

This main ASPIRE study reported that switching to dolutegravir/lamivudine was non-inferior compared to remaining on triple therapy, based on maintaining viral suppression <50 copies/mL at 24 weeks. [2]

The new analysis included samples from baseline, week 24 and week 48 timepoints for 82 participants who continued in the study (41 from each arm), with results for all three timepoints available for 73 participants.

Baseline characteristics included median CD4 count of 677 cells/mm³and median time of 5.8 years on ART. Baseline ART was based on integrase inhibitors (40%), NNRTIs (30%) or PIs (29%). Mean viral load was similar at 4.9 vs. 5.3 copies/mL in the dual vs triple therapy groups.

After adjusting for small non-significant baseline levels, the differences in viral loads continued to be similar in both groups at week 24 (difference 1.3 copies/mL, 95%CI: –2.1 to +4.7, p = 0.45) and week 48 (difference 0.5 copies/mL, 95% CI: –2.9 to +3.9, p = 0.77).

There were also no differences when results were analysed by baseline CD4 count (above or below 500 cells/mm³) or previous duration of ART (using cut points of more vs less than six years).

The second study looked at the early viral dynamics of starting dolutegravir/lamivudine in treatment naive participants in the pilot AACTG5353 study compared to dolutegravir-based triple therapy in the SPRING-1 and SINGLE studies. [3]

Samples were available from weeks 0, 2, 4, 8, 12, 16 and 24 to look at 2- vs 3-drug ART and baseline viral load (< vs. > 100, 000 copies/mL).

Overall, there were no significant differences between 2- vs 3-drug groups (p< 0.001), but baseline viral load >100,000 copies/mL was associated with a slower rate of viral decay. Although not statistically significant, the viral decay rate was slightly steeper in the dual therapy study. See Table 1.

 Table 1: Viral decay by baseline viral load

                                 2-drug            3-drug

<100,000 c/mL         1.272               0.969

>100,000 c/mL         0.725               0.596

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These more detailed results from dual therapy studies show similar level of potency for dolutegravir/lamivudine compared to three-drug ART. There was also no evidence of low level viral rebound below the 50 copies/mL cut-off after switching from triple therapy ART.

The same group have recently published an analysis of HIV genital shedding in a sub-study of ASPIRE, reporting no differences between dual and triple dolutegravir-based ART. [4]

The fixed-dose formulation of dolutegravir/lamivudine has already been submitted to the EMA based on results from the GEMINI 1 and 2 studies. [5]

References

Unless stated otherwise, references are to the Abstract from the Glasgow HIV Congress 2018, 28 – 31 October 2018. Available free online. https://onlinelibrary.wiley.com/toc/17582652/2018/21/S8

1. Taiwo B et al. No significant changes to residual viremia after switch to dolutegravir and lamivudine in a randomized trial. Glasgow HIV Congress 2018, 28 – 31 October 2018. Oral abstract O145.
2. Taiwo B et al. Dolutegravir plus lamivudine maintain HIV-1 suppression through week 48 in a pilot randomized trial. Clin Infect Dis. 2017 Dec 26.
3. Gillman J et al. Comparable viral decay with dolutegravir plus lamivudine versus dolutegravir-based triple therapy. Glasgow HIV Congress 2018, 28 – 31 October 2018. Oral abstract O213.
4. Gianella S et al. Genital HIV-1 shedding with dolutegravir (DTG) plus lamivudine (3TC) dual therapy.JAIDS Journal of Acquired Immune Deficiency Syndromes Publish Ahead of Print DOI: 10.1097/QAI.0000000000001863.
   https://journals.lww.com/jaids/Citation/publishahead/Genital_HIV_1_Shedding_with_Dolutegravir__DTG_.96543.aspx
5. Dolutegravir/lamividune FDC submitted to EMA and FDA. HTB 19 October 2018.
   https://i-base.info/htb/35124