Letters to the Editor
To the Editors:
Antiretroviral (ARV) therapy improves survival among patients who have a virological and immunologic responses.1 Unfortunately, some patients do not respond to ARVs, generally because of resistance, intolerance, or nonadherence. To better characterize patients managed in the New Orleans HIV Outpatient Program (HOP) with prolonged virological failure (defined as having a HIV RNA levels consistently >10,000 copies for a year), a retrospective study was performed.
A line listing of patients having at least 3 HIV RNA levels and 1 CD4 cell count between July 31, 2011 and July 31, 2012 was generated. For inclusion into the study, all HIV RNA levels had to be >10,000 copies and all CD4 cell counts had to be <350 per cubic millimeter during this time frame. Charts were retrospectively reviewed back to time of initiation of electronic records (April 1, 2004) to present (June 6, 2013). A comparison group was defined as patients on ARVs with all HIV RNA levels <400 copies during the study period.
Of a total clinic population of 1960 patients, 37 met inclusion criteria for the study population and 538 met criteria for the comparison group. The study population was significantly more likely to be female, African American, and severely immunocompromised compared to the comparison group (Table 1). All of the study population stated that they were taking ARVs during the study time period. Over half of the study population reported ever having gastrointestinal intolerance (57%) or other nonspecific adverse reactions to ARVs (51%). Nearly, half (49%) had documentation of ever illicit substance use, and the majority (78%) had at least 1 time frame of ≥6 months between clinic visits. Sex and body mass index were not associated with any of these characteristics. Of the 35 study group patients with known genotype results, the proportions ever with a M184V mutation, other reverse transcriptase inhibitor mutation, any nonnucleoside reverse transcriptase inhibitor mutation, or any protease inhibitor mutation were 66%, 91%, 60%, and 43%, respectively. Over half (57%) had mutations in ≥2 classes.
The mean time subjects were followed in clinic was 90 months. The majority (70%) did ever achieve a HIV RNA level <1000 copies outside the study period but this occurrence was transient among patients who had low HIV RNA levels before the study period. No characteristics were associated with ever having a HIV RNA levels <1000 copies. Among the 26 patients with ever a HIV RNA level <1000 copies, the mean total number of HIV RNA levels performed was 22 and the mean number <1000 copies was 5 (21%).
Ten of the 26 patients achieved HIV RNA levels <1000 copies after the study time period. Seven of the 10 reached levels <400 copies (n = 3 for <50 copies and n = 4 for 50–400 copies) and 3 had suboptimal suppression (400–1000 copies). Seven of the 10 had highly resistant genotypes that directed their ARV regimen, and 1 patient had their regimen simplified to 1 pill daily. Comparison of the 10 recent virological responders to the remaining study population showed recent responders to be less likely to ever have a CD4 cell count <50 (50% vs. 81%, P = 0.094) or a baseline body mass index <18.5 (30% vs. 81%, P = 0.01) suggesting the recent virological responders to be healthier. No other characteristics were associated with recent response. Multiple resistance mutations were infrequent (n = 2) among the 16 patients with current uncontrolled viremia who had an early brief period of low HIV RNA levels. Half of these 16 patients were on once day regimens (atazanavir based: n = 7, efavirenz based: n = 1).
The results from this study are consistent with previous reports, which have found predictors for poor retention in care include female sex and racial or ethnic minority status along with several other characteristics.2 The strong association between virological failure and medication intolerance and resistance mutations has also been described.3 A unique finding from this study was the temporal patterns of virological responses. Many patients had a brief time period of low HIV RNA levels. They subsequently developed sustained virological failure even though they were on optimal ARV regimens and generally had minimal resistance mutations. In contrast, a small proportion of patients (10 of 37 or 27%) eventually did have a virological response even with a high background prevalence of resistant mutations. Success in the recent responders is likely because of behavioral changes and the availability of newer ARVs. The results from this study demonstrate an encouraging take home message for clinicians. Selected patients with prolonged clear virological failure eventually may respond to ARVs, even in the presence of several resistant mutations. Continued support, medication changes to reduce side effects and improve tolerability, interventions to improve adherence, and periodic repeat resistance testing are all strategies to achieve virological suppression in this challenging population.
1. Hogg RS, Heath KV, Yip B, et al.. Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. JAMA 1998;279:450–454.
2. Giordano T. Retention in HIV care: what the clinician needs to know. Top Antiv Med. 2011;19:12–16.