Abstract
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Dolutegravir, thanks to its potency and tolerability, has been tried as monotherapy in virologically suppressed HIV-1-infected patients. 3 The results of several randomized clinical trials and clinical cohort studies have shown a high rate of resistance after virological failure, discouraging this approach. 3
In this context we want to report our clinical case about a multidrug-resistant HIV-infected patient who became aviremic (HIV RNA <20 copies/mL) after introduction of dolutegravir 50 mg twice daily as monotherapy.
A 74-year-old woman was diagnosed with HIV infection (HIV-1 subtype B) in 1986 (CDC C3).
She suffered for disseminated tuberculosis (pulmonary, bone, and kidney disease) in 1996, treated with antibiotic regimen for 1 year. In 2008, she had a diagnosis of a nasal squamous cell carcinoma, with two relapses in 2009 and 2010, treated with surgery and chemotherapy plus radiotherapy with clinical healing and complete remission. She is now on clinical and radiological follow-up with positron emission tomography.
She started antiretroviral therapy few years after diagnosis with nucleoside reverse transcriptase inhibitor regimen, as usual, starting with zidovudine monotherapy (in 1992).We added didanosine to zidovudine 3 years later (1995) switching to zidovudine plus lamivudine in 1996. At this point, with the introduction in the clinical practice of protease inhibitors, she started protease inhibitor-based highly active antiretroviral therapy (HAART). Her HAART regimen was changed several times in the following years due to virological failure as showed in Table 1.
Patient's Therapeutic History
After 5 years of successful HAART consisted of darunavir/ritonavir (600/100 mg twice daily) plus raltegravir (400 mg twice daily), she failed on February 2015. After the last virological failure her HIV RNA was 10,800 copies/mL with a CD4+ cell count of 406/μL. Her antiretroviral Trugene HIV-1 genotyping resistance test showed: M41L, D67N, V75M, V108I, E138A, M184V, G190A, H208Y, L201W, and T215Y for NRTI and non nucleoside reverse transcriptase inhibitors; L10F, V32I, M36I, M46I, I54V, Q58E, A71I, L76V, I84V, and L90M for PIs. Coreceptor usage prediction from geno2pheno (version 2.5) showed an X4-type, whereas integrase resistance mutations detected were 32I, 201I, 218S, 220M, and 227F considered as polymorphisms. We decide to introduce a new antiretroviral regimen consisted only of enfuvirtide and dolutegravir (50 mg twice daily); our patient after 3 days stopped enfuvirtide for serious side effects. After a month (March 2015) HIV RNA was <20 copies/mL. HIV RNA was <20 copies/mL at following virological controls (June and August 2015; April and September 2016; February and December 2017). In August 2018 her CD4 cell count was 502 cells/μL and HIV RNA was still <20 copies/mL.
Demarest et al. in their article underline that dolutegravir could disclose a clinical utility and keep strong virological efficacy, also in setting with less antiretroviral options because of complicated virological profile. In those situations, dolutegravir was used as part of investigator-selected background therapy, and included at least one fully active agent. Of course we are aware of the risk to patient outcome with dolutegravir monotherapy, as shown by Wijting et al. 4 ; but, however, we believe that in a very few selected patients, this strategy must be considered, even if it is an off-label treatment. Prolonged virological success of dolutegravir monotherapy in our patient was certainly related to her full adherence to last regimen, never experienced in the past, probably due to good tolerable profile.
Footnotes
Author Disclosure Statement
No competing financial interests exist.