New HIV Medications Being Studied in 2017Nelson Vergel
| Antiretroviral treatment – where we are now / New HIV Drugs & Treatments
|Joseph J. Eron MD Professor of Medicine University of North Carolina at Chapel Hill
The CROI meeting in Seattle this year was again a terrific mix of basic, translational, clinical and epidemiological research. This year perhaps we are seeing more clinical data than we have seen in the last few CROI with some terrific late breaker presentations.
Antiretroviral treatment – where we are now
There were two very nice poster presentations from Thibaut Davy-Mendez who is a PhD candidate at UNC. Working with data from our UNC CFAR HIV Clinical Cohort he described trends in antiretroviral treatment and HIV resistance, prevalence and incidence over the last several years.
In his presentation on Increased Persistence Of Initial Art With INSTI-containing Regimens [Davy et al Abstract 465] he demonstrates the dramatic shift to initial therapy with integrase- inhibitor based regimens in the last several years. By 2014 over 80% of new treatment starts were with INSTI-based regimens in our cohort. This shift has resulted in substantial differences in persistence of first-line therapy (by that we mean how long someone stays on their first regimen before switching or discontinuing their anchor agent) and also in the rates of virologic failure. Davy-Mendez showed that the median time to moving away from or stopping INSTI-based therapy was greater than 6 years and that patients on an INSTI-based therapy were significantly and substantially less likely to stop or switch from INSTI-based therapy compared to NNRTI based therapy (HR = 0.49 (0.35, 0.69). Those patients started on INSTI-therapy were also less likely to experience virologic failure. These data are only likely to improve as much of the data were captured before single tablet integrase inhibitor therapy became the norm.
Davy-Mendez also looked at prevalence of resistance in our cohort in Low Prevalence Of HIV Drug Resistance With Modern Agents [Davy et al Abstract 483]. In this analysis he did two things: first he looked at prevalence of resistance in all patients who were active in the cohort in a given year. All previous and current resistance tests were used and resistance was counted even if the patient’s viral load was suppressed. For example if in 2006 a patient has viremia and a resistance test that show NRTI, NNRTI and PI resistance that information is captured for that year. If in 2007 she suppressed on raltegravir, etravirine and darunavir/r (like many patients did) that resistance burden still exists in the cohort even though she is suppressed on therapy. The resistance remains in every year she stays in the cohort. The second analysis looks only at resistance in patients who have viremia in a given year and the resistance assessment includes all past tests (cumulative resistance). So if our patient listed above rebounds in 2010 and has INSTI-resistance documented her cumulative resistance would include 4 classes. You can think of this like an iceberg of resistance. The first analysis is the whole iceberg and gives you an idea of the total resistance burden – hopefully most in underwater (i.e. suppressed). The second analysis is the part of the iceberg that is visible – so circulating resistance in viremic patients. Patients who are lost to follow-up, move away or die no longer contribute to the resistance analysis in the subsequent year. Perhaps a picture is worth 1000 words
This figure is the whole iceberg (notice the y-axis only goes to 60%). We see that the burden of resistance in our cohort (and I suspect most cohorts in the US) is declining. PI and NRTI resistance has declined substantially as has 1-, 2- and 3-class resistance. Fortunately integrase resistance remains very low, less than 5% of patients in the cohort (recall that we are a referral center for much of North Carolina so we may be enriched for “Viking” like patients1).
Here the story is a little different – the proportion with resistance is higher and the downward trends are not nearly as obvious (except for maybe protease inhibitor resistance). The good news is that viremic patients are a small proportion of our total patient populations (approximately 10% or less). We also looked at patient who started therapy with modern preferred regimens (2007 to 2014). In this group emergent resistant virus was even much less common – with resistance to at least one drug in 2 classes emerging in only 5% of 685 patients and resistance to one or more drugs in 3 classes emerging in only 1%. However resistance is likely to be with us as long as we have HIV and we are treating people who are – like us – human.