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New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations.

ABSTRACT: OBJECTIVE:To estimate the prevalence of HIV drug resistance over time and identify risk factors for multiclass resistance. DESIGN:Prospective clinical cohort of HIV-infected patients at the University of North Carolina. METHODS:Among antiretroviral therapy (ART)-experienced patients in care 2000-2016, we estimated annual prevalences of cumulative resistance, defined as at least one major mutation by drug class. Clinical data and multiple imputation were used when genotypic data were missing, and mutations were carried forward in time. We estimated resistance odds ratios comparing characteristics of patients in care in 2016. RESULTS:A total of 3682 patients contributed 23?169 person-years. Prevalence of at least one major resistance mutation, irrespective of viral suppression, peaked in 2005 with 49% (95% confidence interval 46, 52) and decreased to 38% (35, 40) in 2016. Resistance to nucleoside reverse transcriptase inhibitors, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors also peaked in 2005-2007 and decreased to 28 (26, 31), 14 (12, 16), and 27% (24, 29) in 2016, respectively. In 2016, prevalence of integrase strand transfer inhibitor (INSTI) resistance was 2% (1, 3) and triple-class resistance 10% (9, 12). Over the study period, cumulative resistance was frequent among patients with detectable viremia, but uncommon among patients initiating ART post-2007. Among 1553 patients in care in 2016, ART initiation at an older age, with an INSTI, and with higher CD4 cell counts were associated with resistance to fewer or no classes. CONCLUSION:Prevalence of resistance to older ART classes has decreased in the last 10 years in this clinical cohort, whereas INSTI resistance has increased but remained very low. Patients with viremia continue to have a high burden of resistance even if they initiated ART recently.

SUBMITTER: Davy-Mendez T

PROVIDER: S-EPMC6209541 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations.

Davy-Mendez Thibaut T Eron Joseph J JJ Brunet Laurence L Zakharova Oksana O Dennis Ann M AM Napravnik Sonia S

AIDS (London, England) 20181101 17

<h4>Objective</h4>To estimate the prevalence of HIV drug resistance over time and identify risk factors for multiclass resistance.<h4>Design</h4>Prospective clinical cohort of HIV-infected patients at the University of North Carolina.<h4>Methods</h4>Among antiretroviral therapy (ART)-experienced patients in care 2000-2016, we estimated annual prevalences of cumulative resistance, defined as at least one major mutation by drug class. Clinical data and multiple imputation were used when genotypic ...[more]

PMID: 30134298

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Project description: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.

Project description:ObjectiveDescribe trends in antiretroviral treatments and drug resistance mutations among Swedish HIV-patients over time 1997-2011.MethodsTreatment histories, viral sequences, and demographic and clinical data were retrieved from the national database InfCareHIV. All ART-experienced patients were included (N?=?6537), while resistance tests were restricted to those obtained ?90 days after ART start. This cohort is fully representative for Sweden since the database covers virtually all diagnosed HIV-patients since the start of the epidemic. Patients were grouped according to the year of first ART, and treatments and mutations were analyzed by calendar year.ResultsThe prevalence of major drug resistance mutations decreased dramatically over time, most rapidly between 2003 and 2007. Since then there has been a continued slow decrease for NRTI- and PI-associated mutations with an overall prevalence among all ART-experienced patients at 1.1% (NRTI) and 0.3% (PI) in 2011. NNRTI resistance reached the lowest level in 2007-2009 (0.6%), but is now increasing (0.9% in 2011). Patients with first ART exposure before 2001 are still highly overrepresented among those with PI and, to a lesser extent, NRTI resistance. In contrast, almost half of the patients with NNRTI mutations in 2011 initiated their first ART after 2007.ConclusionsTremendous improvements in ART options and knowledge have resulted in rapidly declining levels of resistance, and most of the current NRTI and PI mutations are found among patients with a history of suboptimal treatments. However, NNRTI resistance is increasing and is primarily found in patients infected in low- and middle-income countries who initiated ART in recent years. It is plausible that these patients were infected with resistant strains and it is therefore suggested that resource-rich countries like Sweden should test for resistance in minor quasispecies or use PI-based first-line regimens in patients who are at increased risk of carrying resistant virus.

Project description:ObjectiveFemale sex workers (FSW) have increased risk of HIV infection. Antiretroviral treatment (ART) can improve HIV outcomes and prevent HIV transmission. We analyzed antiretroviral (ARV) drug use and HIV drug resistance among HIV-positive FSW in the Dominican Republic and Tanzania.MethodsPlasma samples collected at study entry with viral loads >1,000 copies/mL were tested for ARV drugs and HIV drug resistance. ARV drug testing was performed using a qualitative assay that detects 22 ARV drugs in five classes. HIV genotyping was performed using the ViroSeq HIV-1 Genotyping System. Phylogenetic analyses were performed to determine HIV subtype and assess transmission clusters.ResultsAmong 410 FSW, 144 (35.1%) had viral loads >1,000 copies/mL (DR: n = 50; Tanzania: n = 94). ARV drugs were detected in 36 (25.0%) of 144 samples. HIV genotyping results were obtained for 138 (95.8%) cases. No transmission clusters were observed in either country. HIV drug resistance was detected in 54 (39.1%) of 138 samples (31/35 [88.6%] with drugs detected; 23/103 [22.3%] without drugs detected); 29/138 (21.0%) had multi-class resistance (MCR). None with MCR had integrase strand transfer inhibitor resistance. In eight cases, one or more ARV drug was detected without corresponding resistance mutations; those women were at risk of acquiring additional drug resistance. Using multivariate logistic regression, resistance was associated with ARV drug detection (p<0.001), self-reported ART (full adherence [p = 0.034]; partial adherence [p<0.001]), and duration of HIV infection (p = 0.013).ConclusionsIn this cohort, many women were on ART, but were not virally suppressed. High levels of HIV drug resistance, including MCR, were observed. Resistance was associated with detection of ARV drugs, self-report of ART with full or partial adherence, and duration of HIV infection. These findings highlight the need for better HIV care among FSW to improve their health, reduce HIV drug resistance, and decrease risk of transmission to others.

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New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations.

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New antiretroviral agent use affects prevalence of HIV drug resistance in clinical care populations.

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