HTB

Further results using dolutegravir monotherapy: urgent need for controlled studies

NOTE: AT CROI 2017, A HIGHER RISK OF VIRAL REBOUND AND DEVELOPMENT OF INTEGRASE INHIBITOR DRUG RESISTANCE MEANS THAT DOLUTEGRAVIR MONOTHERAPY IS NOT RECOMMENDED. ANYONE USING DOLUTEGRAVIR IS RECOMMENDED TO SWITCH TO DUAL OR TRIPLE THERAPY. 
http://i-base.info/htb/31289

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Simon Collins, HIV i-Base

A small case study using dolutegravir monotherapy in treatment naive patients [1] has reported similar results to several other independent studies presented at the 15th EACS conference last year. [2, 3]

Given the significance of these results in showing a lack of viral rebound, this highlights the importance of larger, randomised controlled studies.

The current study was reported in a letter to JAIDS from Massimiliano Lanzafame from University Hospital Verona, and colleagues. [1]

It included retrospective results from nine HIV positive people (2 women, 7 men) who began initial therapy using dolutegravir after having “refused NRTIs”. All participants were treatment-naive with baseline viral load <100,000 copies/mL (range 16,000 to 90,000) and no genotypic drug resistance (to NRTIs, NNRTIs, PIs or INSTIs). Mean age was 45 (range 36 to 76 years) and been time since diagnosis was about eight years. [4]

After four weeks, viral load was <50 copies/mL for all participants. This was reported as undetectable in 3 patients, <20 copies/mL in another 3 and at 31, 35 and 45 copies/mL in the remaining three.

Viral load at the last result, after a mean follow-up of 7.3 months (range 6 to 10 months) was <20 copies/mL for all participants. This was reported as undetectable in seven patients, and <20 copies/mL in the remaining two. CD4 counts increased in all participants. The mean increase was 152 cells/mm3 (range 94 to 284 cells/mm3).

Comment

The limited details on the JAIDS study mean that these results are largely case reports.

However, it shows that another research group independently initiated a study of dolutegravir monotherapy almost a year ago in early 2015.

At least half a dozen groups are now running small uncontrolled studies of monotherapy [2] and dual therapy with 3TC [3].

Given the potential savings in drug exposure and financial cost of treatment (if proved successful) it is a considerable missed opportunity for future research not to include a standard of care arm in a randomised design. Should this strategy not prove successful, there is an urgency to establish these concerns quickly, as off-label switching to reduced therapy in the absence of data is otherwise very likely.

For example, the NIH-sponsored ACTG dual therapy study is already enrolling but has no control group. [5]

This means that it might take several years until a sufficiently powered study establishes whether or not a significant risk exists for this strategy.

References:

  1. Massimiliano L et al. Dolutegravir monotherapy in HIV-infected naive patients with <100,000 copies/mL HIV-RNA viral load. Letter to the editor. JAIDS, 08 January 2016, Publish Ahead of Print. doi: 10.1097/QAI.0000000000000931.
    http://journals.lww.com/jaids/toc/9000/00000
  2. Collins S. Remarkable results with dolutegravir monotherapy. HTB November/December 2015.
    http://i-base.info/htb/29154
  3. Collins S. First-line ART with dolutegravir plus 3TC: 24-week early results. HTB November/December 2015.
    http://i-base.info/htb/29212
  4. clinicaltrials.gov. Dolutegravir plus lamivudine dual therapy in treatment naïve HIV-1 patients. (not yet recruiting).
    https://clinicaltrials.gov/ct2/show/NCT02582684

Links to other websites are current at date of posting but not maintained.