ART regimens in patients that are virologically suppressed confers risks including emergence of resistance (i.e. risk of virologic failure), or new toxicities. A central goal of switching ART regimens is to maintain viral suppression, without jeopardizing future treatment options . One should consider prior documented resistance mutations, which are likely to persist in the viral reservoir. A commercially available test can help to detect archived mutations, but its sensitivity and clinical utility is unknown.
Potential reasons to switch
Improve adherence (e.g., simplified regimens with fewer drugs, reduced pill burden or dosing frequency, minimize food requirements)
Improve tolerability (i.e. avoid toxicities of current regimen)
Avoid significant current or future drug-drug interactions
Evidence for Switching ART in patients that are virologically suppressed
The data from switch studies suggests that one should consider the drug class(es) of regimens to which a person is being switched, along with the number of agents in the future regimens, and prior treatment and resistance history.
There is some data to support simplifying to multi-drug regimens (including fixed dosed combinations) which contain an INSTI and/or PI. In some instances, there is data to support 2 drug (class) regimens, but in other situations such strategies have been less successful (e.g., PI + EI). Strategies to simplify to monotherapy with INSTI or boosted PI have found success in niche circumstances, but data is lacking to recommend this strategy broadly.
Our algorithm attempts to incorporate information about why a person may be considering a switch from a suppressive regimen. We attempt to balance the evidence base for simplification of regimen, with maintenance of a similarly constructed regimen
|Score Modification Rule|
|Remaining on the current regimen when virally suppressed|
First, irrespective of our ‘base-rank’ for an individuals regimen (for naive patients), we apply a score of ‘1’ for the individual’s current regimen as its new 'base-rank'. This strategy gives some acknowledgement to the fact that the patient has already reached virologic success, and any change comes with risks for side effects or change in adherence such that remaining on the current regimen may be a preferrable strategy. However, we then apply other rules (mutation penalties, comorbidities) including rules to penalize regimens with less than two active drugs. (see below)
|"Similar" regimens with equal or better pill burden and number of active drugs|
When a regimen has equal or better pill burden, and equal or better Active Drugs (with at least 2 active drugs), AND is a "similar" regimen (1 class different for 2 or 4 ARV containing regimens, or same class for 3 ARV regimens), then apply a base score of 1 to that regimen.
This rule was developed based on the available evidence that has generally found 'within-class' switches (usually for adverse events or safety profile of newer drugs, dosing frequency, lower pill burden) to result in maintained viral suppression. While multiple permutations of within-class switches have been studied, we restricted the rule to additionally having provision for similar or improved pill burden and activity. Thus, the algorithm will continue to recommend staying on a current suppressive regimen over a switch within class that leads to greater pill burden. Comorbidity or other side effect penalties are assessed separately.
|Treatment intensification in a virally suppressed patient|
HIV-ASSIST assesses a number of regimens with 4 drugs. In general, these regimens have a base-rank of 3.5 or lower. They are likely to lead to virologic suppression, but have little role in treatment naive paitents. There role is largely restricted to cases with treatment failure or extensive resistance. Given some of the other algorithm rules listed on this page, these regimens (e.g., TAF/FTC/EVG/c+DRV, TAF/FTC/BIC+DRV/c, etc) may have their base-rank modified to 1-1.5 based on data for components of these regimens that are likely to maintain suppression.
However, tere is little evidence to support treatment intensification to 4 active drugs in a patient that is virally suppressed. A discussion of treatmetn intensification can be found here:
As such, we penalize all regimens with 4 active drugs.
In some situations, a person may be already suppressed on a regimen that only contains 2 active drugs (e.g., suppressed on TAF/FTC+DTG with an M184V). In these circumstances, some 4 drug regimens that have similar pill burden and greater number of active drugs could be considered. However, based on expert opinion and consideration of avoiding unnecessary exposure to extra drug classes, we have applied a modest penalty in these scenarios (i.e. with prior resistance) to all 4 drug regimens. Nonetheless, we also acknowledge that there may be emerging evidence in support of this scenario (see section on TAF/FTC/EVG/c+DRV in patients with prior multi-class failure).
|Regimens with fewer than three active drugs|
Increasingly there is data on dual-therapy for maintaining viral suppression, which is listed in other portions of this page (See sections on INSTI's and PI's).
In general, dual therapy regimens have appeared promising when including DTG from the INSTI class or DRV/boosted from PI class. While data is lacking, we have extrapolated this to include BIC which appears to have higher barrier to resistance and similar potency to DTG.
For other regimens, our algorithms continue to prioritize regimens with 3 active drugs when one of those drugs is not a fully active DRV, DTG or BIC. We apply a penalty when a regimen has 2-2.5 or 2.5-3 active drugs (scaled).
There is less data on regimens with less than 2 active drugs, and relatively strong data advocating against monotherapy. Please see sections on PI or INSTI monotherapy elsewhere on this page. In the absence of more data we have penalized regimens with less than 2 active drugs
Switching for ART toxicities or side effects
|Score Modification Rule|
|Switching for CNS toxicity|
If EFV is in the current suppressive regimen, we consider it to be the likely offending agent. There are clinical data in this setting of switching to 2NRTI + NVP , 2 NRTI + ETR , RAL , TAF/FTC/EVG/c , 2 NRTI + RPV . We have extrapolated the data for RAL and EVG/c to DTG containing regimens as well.
|Switching for dyslipidemia or cardiovascular toxicities/comorbidities|
If ABC is in the regimen, we consider the potential for its contribution to the dyslipidemia. There are clinical data to support a switch to TDF/FTC in this setting (and we extrapolate this to include TAF)  .
If ritonavir-boosted PI is in the regimen, we consider its potential for contribution to dyslipidemia. There is data to support switch from LPV/r to ATV/r in this setting. There is also data to support switch from LPV/r to RAL , which we extrapolate to include DTG and other INSTIs.
|Switching for diarrhea|
|If ritonavir boosted PI is in the regimen,we consider its potential for contribution to diarrhea. This was more frequent with LPV/r. There is data in this setting to switch to RAL(9), TDF/FTC/EVG/c , TDF/FTC/RPV , and ETR containing regimens . As such, we prioritize these regimens.|
Switching or Simplifying to INSTI based regimens
|Score Modification Rule|
|Switching to 3-drug fixed-dose combination regimens (2 NRTI + 1 INSTI)|
Based on the data below, we generally considered a switch to ABC/3TC/DTG or TAF/FTC/BIC or TAF/FTC/EVG/c or TAF/FTC+DTG to be an acceptable option, and apply a base rank of 1.0 to these regimens when a person is virally suppressed. We considered it less desirable (SWITCHMRK below) to switch from PI regimens to RAL regimens (acknowledging that in subgroup analysis, those without background history of failure had similar rates of suppression to LPV/r).
DTG/ABC/3TC, from heterogenous pre-enrollment regimens
STRIIVING Study: 553 suppressed patients were randomized to switch pre-enrollment regimen to fixed dose ABC/3TC/DTG or remain on their pre-enrollment regimen. Subjects were HIV-1-positive men and women ≥18 years of age who had achieved and maintained virological suppression (HIV-1 RNA <50 copies/ml) on an ART regimen that had been stable for ≥6 months prior to screening. The inclusion criteria required that subjects have achieved plasma HIV-1 RNA level <50 copies/ml within 6 months of starting an initial ART regimen with no plasma HIV-1 RNA level >200 copies/ml following initial suppression. Patients had no history of dual therapy and no history of treatment failure. Subjects were randomly assigned to switch to ABC/DTG/3TC once daily for 48 weeks (early-switch group) or continue current ART for 24 weeks and then switch to ABC/DTG/3TC (late-switch group). At week 24, 85% and 88% of subjects who switched to ABC/DTG/3TC or remained on current ART, respectively, were virologically suppressed At week 48, 83% and 92% were virologically suppressed in the early- and late-switch groups, respectively. Adverse events were reported more frequently with ABC/DTG/3TC (66%) than with current ART (47%) by week 24, and in the late-switch group, 60% of subjects reported adverse events post-switch. Pharmacokinetic data supported immediate switch. HIV Treatment Satisfaction Questionnaire scores improved in participants switching to ABC/DTG/3TC versus current ART. Note, that background resistance mutations was not provided.
We applied a CHANGE BASE SCORE TO 1.0 for this regimen IF NO HISTORY OF TREATMENT FAILURE.
EVG/c/TAF/FTC or EVG/c/TDF/FTC, from heterogenous
2 NRTI + RAL, from 2 NRTI + LPV/r
Suppresseive INSTI or PI based regimen, to TAF/FTC/BIC
Early data suggests this may be an effective strategy; Consequently when there is multi-class resistance, we prioritized regimens that included EVG/c, DTG, or BIC (extrapolated data) with 2NRTI's and a boosted DRV.
In Virally suppressed patients with baseline ≥2 ARV class mutations, but no INSTI mutations and no DRV mutations, were randomized to continue current regimen vs EVG/c/FTC/TAF plus DRV. At 48 weeks, 94% of patients on EVG/c/FTC/TAF + DRV maintained Vl <50 copies/mL vs 76% on their baseline regimen.
|Simplifying to DTG + NRTI|
There isevidence from treatment naïve patients that DTG + 3TC is effective. We considered the data to be sufficient to Apply a Base-Rank of 1.0 to regimens that included DTG plus 3TC. based on DHHS (2019) guidelines. While data is more limited, we also applied a base rank of 1.5 to scenarios of DTG+ an additional unspecified ARV.
In the ANRS 167 LAMIDOL study, an open Label single arm study of switching from suppressive Triple ART to DTG+3TC. Patients had to have viral suppression for greater than or equal to 2 years on first line ART with less than 2 ART modifications and have CD4>200. 101/104 maintained suppression at 48 weeks. There were 3 virologic failures, none with INSTI resistance.
The GEMINI studies (see education sheet for DTG+3TC) have suggested that DTG_3TC may be an acceptable regimen in patients that are newly initiating ARV's. We extrapolate this data to infer that this regimen may therefore be acceptable when already virally suppressed.
--Unresolved question: whether this regimen would be effective in patients with baseline 3TC resistance.
|Simplifying to DTG + NNRTI|
We have applied a base-score change to 1.0 for DTG/RPV, if there is no history of treatment failure. Otherwise, DTG+one other active drug is modified to a 1.5.
New DHHS guidelines suggest that DTG/RPV may be an acceptable regimen in patients with virologic suppression without history of treatment failure. As such, we assign a 'base-score' of 1.2 (preferred regimen) for DTG/RPV in suppressed patients without prior treatment experience or failure. Given lack of data (but emerging data) on this regimen in patients with history of treatment failure, we prioritize it but not to the same degree in such cases (base score of 2.0).
|Simplifying to DTG Monotherapy|
Pending more data, avoid DTG monotherapy, particularly if there is a history of INSTI exposures.
Switching or Simplifying to PI based regimens
|Score Modification Rule|
|Switching to PI/r + 3TC, or INSTI+3TC, or PI + XXX|
There is evidence that a boosted PI with 3TC/FTC can maintain viral suppression in ART naïve patients without baseline resistance, and in patients with viral suppression. There is also emerging evidence for other 3TC based dual therapies. We considered this evidence to be nearly on par with the evidence for a INSTI + 3TC, but felt data was stronger for DTG+3TC (or other ARV). We assigned a Base-Rank of 1.4 to regimens of DRV/r +NRTI, and 1.2 if switching from 2 NRTI+PI to PI +XTC.
ATV/r + 3TC, from ATV/r + 2 NRTI
DRV/r + 3TC
LPV/r + 3TC
3TC based Dual therapy, despite M184V
PI plus second drug
|Switching to PI +INSTI|
|Simplifying to PI Monotherapy|
The DHHS guidelines recommend against simplification to a boosted PI monotherapy regimen. A systematic review has suggested lower rates of long term side effects, but there may be an increased risk of virologic failure.In a meta-analysis of 2303 patients in 13 randomized trials, HIV suppression was lower in the PI/r monotherapy arm comared with triple therapy arm
Switching or Simplifying to NNRTI based regimens
|Score Modification Rule|
|Switching to RPV based regimens from EFV or boosted PI regimens|
Switching from EFV to RPV
A phase 2b, open-label, multicenter study evaluated the efficacy and safety of switching from EFV/FTC/TDF (≥3 months duration) to RPV/FTC/TDF. At weeks 12 and 24, all 49 dosed subjects remained suppressed on RPV/FTC/TDF. At week 48, 46 (93.9%) subjects remained suppressed and virologic failure occurred in 2/49 (4.1%) subjects with no emergence of resistance .
Switching from a boosted PI to RPV
In an RCT of switching from 2NRTI +PI/r in virally suppressed patients to TDF/FTC/RPV, primary objective of noninferiority at week 24 was met(11): 93.7% of RPV/FTC/TDF versus 89.9% of protease inhibitor+RTV+ Through week 48, 89.3% of participants in the immediate switch group maintained virologic suppression. High rates of suppression were maintained with RPV/FTC/TDF regardless of participant's pre-antiretroviral HIV-1 RNA level. Overall development of resistance mutations after switching to RPV/FTC/TDF was low. Decreases in total cholesterol, low-density lipoprotein (LDL), and triglycerides were significantly greater among RPV/FTC/TDF recipients than those in the protease inhibitor+RTV+ two NRTIs group .
|Switching from boosted PI or NNRTI therapy to EFV/TDF/FTC|
|The A1266-073 study randomized suppressed patients on NNRTI or PI based therapy to stay on their regimens or switch to TDF/FTC/EFV, and found that switching to TDF/FTC/EFV was non-inferior with regards to virologic suppression, and had benefits of improvements in TG and quality of life measurements .|
Switching or Simplifying to EI based regimens
|Score Modification Rule|
|Switching to a Boosted PI + Maraviroc, from Boosted PI + 2 NRTI|
|Not recommended. In the MARCH study , patients with R5 tropic virus, who were virally suppressed on 2NRTI + 1 PI/r, were randomized to MVC + PI/r. Patients switched to the MVC + PI/r regimen had lower rates of maintaining viral suppression (84%) , compared to 98% who continued on the 2 NRTI + 1 PI regimen.|
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