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New Initiatives for HIV Taking Off This Year

Advancements in the management of HIV over the past several decades have led to remarkable improvements in patient survival and quality of life. Yet, disparities in diagnosis, retention in care, and treatment failure continue to hinder the goal of disease eradication, hence propelling new initiatives. A multifaceted approach to global HIV control now routinely involves such strategies as pre-exposure prophylaxis (PrEP) in high-risk populations, widespread screening, treatment as prevention, and ongoing efforts to dispel the stigma of living with the disease. Maximizing antiretroviral (ARV) potency, convenience, and tolerability is another constantly moving target. In 2017, significant progress in HIV treatment was achieved with approval of the first 2-drug maintenance regimen for select patients with HIV and the early clinical success of long-acting injectable therapy. Additional October 2017 adult and adolescent ARV guideline updates by the US Department of Health and Human Services (DHHS) for implementation into clinical practice are listed in Table.1


Since the advent of combination antiretroviral therapy (cART) in the early 1990s, standard HIV regimens consist of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a third agent from a different therapeutic class to maximize antiviral efficacy. However, as patients now initiate treatment earlier and live longer, they also become more vulnerable to long-term medication toxicities. This has led to a re-emerging interest in simplified, drug-sparing regimens.2 Secondary benefits of these regimens may include antiretroviral therapy (ART) preservation, improved convenience, fewer drug interactions, and reduced costs.

In November 2017, the US Food and Drug Administration approved the first 2-drug regimen to treat HIV.3 Juluca is a fixed-dose regimen that contains the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG) and the non-nucleoside reverse transcriptase inhibitor rilpivirine (RPV).4 This is the first complete single-tablet regimen that does not incorporate NRTIs, thus sparing patients potential toxicity from these agents. Clinical use of this regimen likely preceded its formal approval, as published data of real-world application populates the literature.5,6

The data behind the approval of this regimen come from 2 open-label, multicenter phase 3 clinical trials, SWORD 1 and SWORD 2, presented at the 2017 Conference on Retroviruses and Opportunistic Infections.7 All patients (N = 1024) enrolled in this study were suppressed, with HIV-1 RNA <50 cells/ mL for at least 12 months with no history of virologic failure. Patients either continued their cART suppressive regimen or switched to DTG / RPV. Results demonstrated noninferiority of viral suppression for the 2-drug regimen at 48 weeks compared with traditional 3- or 4-drug regimens.

DTG / RPV does not necessarily translate into success of all simplified regimens. Other published attempts at 1- or 2-drug regimens produced varying results or unclear applicability.2 A prime example was the initial promise of DTG monotherapy. However, in a randomized trial comparing DTG with cART in virologically suppressed patients, several patients experienced virologic failure with DTG alone, prompting premature study discontinuation.8 Subsequently, phase 1 investigation of DTG with lamivudine has shown greater promise in select virologically suppressed patients, although further study is needed.9


Despite a multitude of available fixed-dose regimens, adherence to daily lifelong ART still challenges many patients. The development of long-acting (LA) ARVs to facilitate HIV treatment and prevention seems intuitive and mimics modern approaches to many other chronic disease states. Transdermal, injectable, and implantable drug delivery options may reduce pill fatigue and thus improve adherence, overcome oral bioavailability concerns, and potentially expand options for medication access. In a study of patient attitudes toward LA ARVs, 84% of patients indicated they would “definitely” or “probably” try injectable therapy offered on a monthly basis.10 Although properties such as aqueous solubility, metabolism, elimination, and dosing volume limit the repertoire of potential injectables, several ARVs have recently entered advanced clinical study for emerging use. Physiologically based pharmacokinetic modelling simulations have been applied and validated to identify and characterize candidate drugs.11 Most favorable at this time is the novel combination of cabotegravir (GSK1265744; CAB) and RPV, 2 ARVs with physiochemical compatibility, yet unique mechanisms of action that lack significant pharmacokinetic interactions.12,13

Is there a cure? How long until we find it? And will it work for the majority of people living with HIV?