Role of Rilpivirine and Etravirine in Efavirenz and Nevirapine-Based Regimens Failure in a Resource-Limited Country: A Cross- Sectional Study

<div><p>Introduction</p><p>Etravirine(ETR) can be used for patients who have failed NNRTI-based regimen. In Thailand, ETR is approximately 45 times more expensive than rilpivirine(RPV). However, there are no data of RPV use in NNRTI failure. Therefore, we assessed the susceptibility and mutation patterns of first line NNRTI failure and the possibility of using RPV compared to ETV in patients who have failed efavirenz(EFV)- and nevirapine(NVP)-based regimens.</p><p>Methods</p><p>Clinical samples with confirmed virological failure from EFV- or NVP-based regimens were retrospectively analyzed. Resistance-associated mutations (RAMs) were interpreted by IAS-USA Drug Resistance Mutations. Susceptibility of ETR and RPV were interpreted by DUET, Monogram scoring system, and Stanford University HIV Drug Resistance Database.</p><p>Results</p><p>1,279 and 528 patients failed EFV- and NVP-based regimens, respectively. Y181C was the most common NVP-associated RAM (54.3% vs. 14.7%, p<0.01). K103N was the most common EFV-associated RAM (56.5% vs. 19.1%, P<0.01). The results from all three scoring systems were concordant. 165(11.1%) and 161(10.9%) patients who failed NVP-based regimen were susceptible to ETR and RPV, respectively (p = 0.85). 195 (32.2%) and 191 (31.6%) patients who failed EFV-based regimen, were susceptible to ETR and RPV, respectively (p = 0.79). The susceptibility of ETV and RPV in EFV failure was significantly higher than NVP failure (p<0.01).</p><p>Conclusion</p><p>The mutation patterns for ETR and RPV were similar but 32% and 11% of patients who failed EFV and NVP -based regimen, respectivly were susceptible to RPV. This finding suggests that RPV can be used as the alternative antiretroviral agent in patients who have failed EFV-based regimen.</p></div

Top 10 NNRTI-RAMs found in patients who failed either the NVP- or EFV-based regimen.

<p>Top 10 NNRTI-RAMs found in patients who failed either the NVP- or EFV-based regimen.</p

Number of patients susceptible to etravirine and rilpivirine.

<p>Number of patients susceptible to etravirine and rilpivirine.</p

Baseline characteristics of the patients.

<p>Baseline characteristics of the patients.</p

Susceptibility pattern of etravirine and rilpivirine in patients who failed nevirapine and efavirenz-based regimens.

<p>Susceptibility pattern of etravirine and rilpivirine in patients who failed nevirapine and efavirenz-based regimens.</p

Factors associated with primary HIV drug resistance by duration of HIV infection - univariate logistic regression.

<p><b>Abbreviations:</b> HBsAg – hepatitis B surface antigen, anti-HCV – antibody to hepatitis C virus.</p>*<p>p-value is for test for trend (excluding missing values) for age groups, CDC category, and HIV RNA.</p

Distribution of reverse transcriptase resistance-associated mutations among 1,798 antiretroviral-naive HIV-infected patients.

<p>Abbreviations: NRTI; nucleoside reverse transcriptase inhibitor, NNRTI; non-nucleoside reverse transcriptase inhibitor.</p

Association between Tests for <i>M. tuberculosis</i> and Graded Exposure to Tuberculosis.

<p>Association between Tests for <i>M. tuberculosis</i> and Graded Exposure to Tuberculosis.</p

Association between Covariates of Interest and Response to IGRAs and TST.

a<p>Non-household contact with TB was excluded from the models due to 0 cells.</p><p>NA: not applicable.</p

Correlation of Tests for <i>M. tuberculosis</i> with Graded Exposure to Tuberculosis.

<p>Correlation of Tests for <i>M. tuberculosis</i> with Graded Exposure to Tuberculosis.</p