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Effect of misclassification of antiretroviral treatment status on the prevalence of transmitted HIV-1 drug resistance.

ABSTRACT: Estimates of the prevalence of transmitted HIV drug resistance (TDR) in a population are derived from resistance tests performed on samples from patients thought to be naïve to antiretroviral treatment (ART). Much of the debate over reliability of estimates of the prevalence of TDR has focused on whether the sample population is representative. However estimates of the prevalence of TDR will also be distorted if some ART-experienced patients are misclassified as ART-naïve.The impact of misclassification bias on the rate of TDR was examined. We developed methods to obtain adjusted estimates of the prevalence of TDR for different misclassification rates, and conducted sensitivity analyses of trends in the prevalence of TDR over time using data from the UK HIV Drug Resistance Database. Logistic regression was used to examine trends in the prevalence of TDR over time.The observed rate of TDR was higher than true TDR when misclassification was present and increased as the proportion of misclassification increased. As the number of naïve patients with a resistance test relative to the number of experienced patients with a test increased, the difference between true and observed TDR decreased. The observed prevalence of TDR in the UK reached a peak of 11.3% in 2002 (odds of TDR increased by 1.10 (95% CI 1.02, 1.19, p(linear trend) = 0.02) per year 1997-2002) before decreasing to 7.0% in 2007 (odds of TDR decreased by 0.90 (95% CI 0.87, 0.94, p(linear trend) < 0.001) per year 2002-2007. Trends in adjusted TDR were altered as the misclassification rate increased; the significant downward trend between 2002-2007 was lost when the misclassification increased to over 4%.The effect of misclassification of ART on estimates of the prevalence of TDR may be appreciable, and depends on the number of naïve tests relative to the number of experienced tests. Researchers can examine the effect of ART misclassification on their estimates of the prevalence of TDR if such a bias is suspected.

SUBMITTER: Castro H

PROVIDER: S-EPMC3364874 | biostudies-other | 2012 Mar

REPOSITORIES: biostudies-other

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Effect of misclassification of antiretroviral treatment status on the prevalence of transmitted HIV-1 drug resistance.

Castro Hannah H Pillay Deenan D Sabin Caroline C Dunn David T DT

BMC medical research methodology 20120314

<h4>Background</h4>Estimates of the prevalence of transmitted HIV drug resistance (TDR) in a population are derived from resistance tests performed on samples from patients thought to be naïve to antiretroviral treatment (ART). Much of the debate over reliability of estimates of the prevalence of TDR has focused on whether the sample population is representative. However estimates of the prevalence of TDR will also be distorted if some ART-experienced patients are misclassified as ART-naïve.<h4> ...[more]

PMID: 22416878

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Project description:BackgroundThe aim of this study is to analyse the prevalence of transmitted drug resistance, TDR, and the impact of TDR on treatment success in the German HIV-1 Seroconverter Cohort.MethodsGenotypic resistance analysis was performed in treatment-naïve study patients whose sample was available 1,312/1,564 (83.9% October 2008). A genotypic resistance result was obtained for 1,276/1,312 (97.3%). The resistance associated mutations were identified according to the surveillance drug resistance mutations list recommended for drug-naïve patients. Treatment success was determined as viral suppression below 500 copies/ml.ResultsPrevalence of TDR was stable at a high level between 1996 and 2007 in the German HIV-1 Seroconverter Cohort (N?=?158/1,276; 12.4%; CI(wilson) 10.7-14.3; p(for trend)?=?0.25). NRTI resistance was predominant (7.5%) but decreased significantly over time (CI(Wilson): 6.2-9.1, p(for trend)?=?0.02). NNRTI resistance tended to increase over time (NNRTI: 3.5%; CI(Wilson): 2.6-4.6; p(for trend)=?0.07), whereas PI resistance remained stable (PI: 3.0%; CI(Wilson): 2.1-4.0; p(for trend)?=?0.24). Resistance to all drug classes was frequently caused by singleton resistance mutations (NRTI 55.6%, PI 68.4%, NNRTI 99.1%). The majority of NRTI-resistant strains (79.8%) carried resistance-associated mutations selected by the thymidine analogues zidovudine and stavudine. Preferably 2NRTI/1PIr combinations were prescribed as first line regimen in patients with resistant HIV as well as in patients with susceptible strains (susceptible 45.3%; 173/382 vs. resistant 65.5%; 40/61). The majority of patients in both groups were treated successfully within the first year after ART-initiation (susceptible: 89.9%; 62/69; resistant: 7/9; 77.8%).ConclusionOverall prevalence of TDR remained stable at a high level but trends of resistance against drug classes differed over time. The significant decrease of NRTI-resistance in patients newly infected with HIV might be related to the introduction of novel antiretroviral drugs and a wider use of genotypic resistance analysis prior to treatment initiation.

Dataset Information

Effect of misclassification of antiretroviral treatment status on the prevalence of transmitted HIV-1 drug resistance.

Publications

Effect of misclassification of antiretroviral treatment status on the prevalence of transmitted HIV-1 drug resistance.

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