Patient-centered Care and Treatment in HIV Infection.

In this issue of EclinicalMedicine, Diaco and colleagues describe a retrospective, secondary analysis of routinely collected data of 103 patients followed by two infectious diseases specialists in the HIV out-patient clinic of the University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, Basel, Switzerland. They found that 70 patients were de-escalated to either dolutegravir/emtricitabine or dolutegravir/lamivudine by stopping tenofovir disoproxil fumarate or abacavir [1]. Viremia remained undetectable in all de-escalated patients at least 48 weeks later. These results confirm those of eight previous, heterogeneous studies in experienced patients on dolutegravir plus lamivudine [reviewed in [2]], which showed a low risk of virologic failure (6 of 727 patients, without emergence of specific resistance mutations) and a high tolerability (only 18 patients interrupted the treatment due to side effects). Although Diaco and colleagues included emtricitabine much more often than lamivudine in their regimen, they acknowledge that the two drugs are interchangeable; lamivudine is available as a low cost generic and a fixed-dose lamivudine-dolutegravir combination is more likely to be available in the future.

Diaco's and colleagues' study is yet another example that the once quite neglected issue of patient-centered medicine in HIV care is finally becoming important and that tailoring of therapy and individual patients' preferences must be taken into strong account. Indeed following patients' preferences is central to the important issue of adherence to treatment, so vital in HIV therapy. The aging HIV-infected population (in 2020, around 50% of infected individuals will be 50 years of age or above in high income countries) [3] suffers from a number of non-communicable diseases, and HIV-infected people are not immune from the epidemic of non-communicable diseases that affects sub-Saharan Africa [4]. Comorbidities imply the use of several drugs with potential interactions and therefore deintensification, i.e. reduction of number of anti-HIV drugs, is an option that will be increasingly adopted in the future and is particularly attractive in those patients who have achieved good control of HIV replication following the initial use of a three-drug regimen. The dual dolutegravir plus lamivudine or emtricitabine regimen combines a drug with high antiviral potency, long half-life, high genetic barrier to resistance and tolerability (dolutegravir) with one with a good tolerability (lamivudine or emtricitabine). In addition, interactions with other drugs are limited, and dual therapy with dolutegravir and lamivudine does not appear to increase genital shedding of HIV-1 [5], hence should not increase the risk of sexual transmission of the virus. The concern regarding the reduced “forgiveness” (i.e., the possibility that viral replication increases) should patients be not fully adherent was highly mitigated in Diaco's patients by the fact that they were followed for many years by the same physician, who had established a very good relationship with them and whom they trusted. This is yet again another extremely important aspect of patient-centered care in HIV infection; patients need to be familiar with their physicians to be able, among other aspects, to openly let them know whether they adhere to treatment, and how much so. We have demonstrated the value of this aspect of care in previous publications [6], [7].

Dolutegravir monotherapy was not considered due to a high risk of virological failure but Diaco and colleagues think that it “may still emerge as a valid de-escalation option in selected patients in the future” [1]. Indeed, in a recent report only three cases (4.8%) of virologic failure (all prior to 24 weeks of treatment) were observed in a median follow-up time of eighteen months in 63 patients on dolutegravir monotherapy, [8] and we have shown that this option could be pursued in highly adherent patients with a zenith HIV-RNA below 100,000 copies/ml [7].

In conclusion, the study from Diaco and colleagues confirms once again the virologic safety and feasibility of a dual regimen including dolutegravir. The results of the ongoing TANGO study (Switch study to evaluate Dolutegravir plus Lamivudine in virologically suppressed human immunodeficiency virus type 1 positive adults), a phase III, randomized, open-label, active-controlled, multicenter, parallel-group study that started enrolling patients in 2018 [9] will obviously be more relevant and should finally show whether indeed this regimen can become the preferred option for deintensification therapy in non-hepatitis B virus coinfected patients. Additional investigations are also needed to identify the factors predicting success of other deintensification strategies and further improve patient-centered anti-HIV therapy.

Author Contributions

Massimiliano Lanzafame wrote the Commentary and Sandro Vento modified/amended it.

Declaration of Interests

No conflicts for either author.