The prevalence of transmitted antiretroviral drug resistance in treatment‐naïve patients and factors influencing first‐line treatment regimen selection

Abstract

ObjectivesTo estimate the prevalence of transmitted antiretroviral (ARV) drug resistance, and to assess whether resistance testing influences first-line ARV regimen selection. MethodsData on patients' characteristics were collected through questionnaires. ARV drug resistance was tested by genotypic methods and defined by Quest-Stanford classification rule. Physicians reported the intended and actual treatments and the factors considered in treatment selection. ResultsTwo hundred and twenty-eight patients were included. The prevalence of ARV drug resistance was 12.1%, with 9.8% for non-nucleoside reverse transcriptase inhibitors (NNRTIs), 4.5% for nucleoside reverse transcriptase inhibitors and 1.8% for protease inhibitors (PIs). Pill burdens, dosing frequency and physicians' experience with regimens were the major factors considered in treatment selection. The intended and actual treatment differed for 73 and 44% of the patients with and without ARV drug resistance, respectively [odds ratio (95% confidence interval, CI) 5 3.6 (1.5-9.0), P 5 0.006]. NNRTI-based regimens were intended for 10 patients with resistance to NNRTIs; these patients were prescribed PI-based regimens after genotypic testing. ConclusionsTransmitted ARV drug resistance was detected in 12.1% of treatment-naïve patients, with resistance to NNRTIs the most common. Resistance-testing results played a partial role in first-line treatment selection. However, resistance to NNRTIs pre-empted NNRTI use.Keywords: drug resistance testing, first-line treatment, HIV, transmitted drug resistance IntroductionThe use of highly active antiretroviral therapy has made it possible to prolong the life expectancy and reduce the incidence of opportunistic infection in persons with HIV infection or AIDS [1][2][3][4]. Current recommended initial regimens employ two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI). Unfortunately, under drug-selective pressure, resistance to these drugs may develop, primarily as a result of mutations in viral reverse transcriptase and protease genes. It has been estimated that approximately 40-80% of chronically HIV-infected, treatment-experienced patients with incomplete virus suppression developed resistance to antiretroviral (ARV) therapy [5], leading to poorer survival and opportunities for transmitted ARV drug resistance [6].Transmitted resistance to ARV drugs can persist for years [7][8][9], and hence has implications for treatment strategies. According to the International AIDS Society-USA and the US Department of Health and Human Services guidelines, resistance testing is recommended for patients with acute or recent infection (o6-12 months), and is recommended or should be considered for treatment-naïve patients with chronic infection (1 year or longer) [12,13]. Recently, the use of HIV susceptibility testing was shown to be associated with enhanced survival -even after adjusting for stages of HIV disease, demographics and ag...

Inefficient Vaginal Transmission of Tenofovir-Resistant HIV-1

“…The inherent ability of replicating HIV to revert to a drug-sensitive genotype in the absence of drug pressure makes it difficult to study in patients, especially if (i) the time, duration, and route of infection are unknown, (ii) there is no way to prove ART-naïve status, and (iii) the HIV sequence in the infecting partner is unknown. Despite these difficulties, genotypic analysis of ART-naïve patients has provided evidence that drugresistant HIV-1 is being transmitted and can result in treatment failure (15)(16)(17)(18)(19)(20)(21). Given that animal studies are the best option to overcome the inherent limitations of human studies (22), we utilized humanized mice to investigate in vivo transmission of drugresistant HIV-1.…”

Low Prevalence of Primary HIV Resistance in Western Massachusetts

“…Table 4 compares our data with other recent US studies documenting primary resistance in chronically infected patients. Our study had the lowest rate (5%) among these recent studies [1][2][3][4]6,7 in which the rate of resistance ranged from 8% to 18%. The distribution of resistance among the antiretroviral classes was consistent with the recently published data, which showed that NNRTI resistance prevalence was the highest, followed by NRTI and PI resistance.…”

“…[1][2][3][4][5][6][7][8] Resistance testing for chronically HIV-infected individuals is currently recommended at the time of the first evaluation and at treatment initiation. 9 The prevalence of primary resistance varies by geographic region and may be influenced by local demographics, HIV risk factors, and the penetration of antiretroviral therapy (ART) in the local area.…”

Diagnosing acute HIV infection

“…Several additional laboratory tests should be performed once AHI is diagnosed, including CD4 + T lymphocyte counts, HIV RNA level, screening for other STDs, and hepatitis B and C. Given the reported prevalence of transmitted drug resistance, HIV resistance testing should be strongly considered [80][81][82][83]. Limit of detection of assay for plasma viral RNA Eclipse phase approx.…”