Dataset Information

Prevalence and virologic consequences of transmitted HIV-1 drug resistance in Uganda.

ABSTRACT: Few reports have examined the impact of HIV-1 transmitted drug resistance (TDR) in resource-limited settings where there are fewer regimen choices and limited pretherapy/posttherapy resistance testing. In this study, we examined TDR prevalence in Kampala and Mbarara, Uganda and assessed its virologic consequences after antiretroviral therapy initiation. We sequenced the HIV-1 protease/reverse transcriptase from n=81 and n=491 treatment-naive participants of the Uganda AIDS Rural Treatment Outcomes (UARTO) pilot study in Kampala (AMU 2002-2004) and main cohort in Mbarara (MBA 2005-2010). TDR-associated mutations were defined by the WHO 2009 surveillance mutation list. Posttreatment viral load data were available for both populations. Overall TDR prevalence was 7% (Kampala) and 3% (Mbarara) with no significant time trend. There was a slight but statistically nonsignificant trend indicating that the presence of TDR was associated with a worse treatment outcome. Virologic suppression (?400 copies/ml within 6 months posttherapy initiation) was achieved in 87% and 96% of participants with wildtype viruses versus 67% and 83% of participants with TDR (AMU, MBA p=0.2 and 0.1); time to suppression (log-rank p=0.3 and p=0.05). Overall, 85% and 96% of study participants achieved suppression regardless of TDR status. Surprisingly, among the TDR cases, approximately half still achieved suppression; the presence of pretherapy K103N while on nevirapine and fewer active drugs in the first regimen were most often observed with failures. The majority of patients benefited from the local HIV care system even without resistance monitoring. Overall, TDR prevalence was relatively low and its presence did not always imply treatment failure.

SUBMITTER: Lee GQ

PROVIDER: S-EPMC4151058 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Prevalence and virologic consequences of transmitted HIV-1 drug resistance in Uganda.

Lee Guinevere Q GQ Bangsberg David R DR Muzoora Conrad C Boum Yap Y Oyugi Jessica H JH Emenyonu Nneka N Bennett John J Hunt Peter W PW Knapp David D Brumme Chanson J CJ Harrigan P Richard PR Martin Jeffrey N JN

AIDS research and human retroviruses 20140729 9

Few reports have examined the impact of HIV-1 transmitted drug resistance (TDR) in resource-limited settings where there are fewer regimen choices and limited pretherapy/posttherapy resistance testing. In this study, we examined TDR prevalence in Kampala and Mbarara, Uganda and assessed its virologic consequences after antiretroviral therapy initiation. We sequenced the HIV-1 protease/reverse transcriptase from n=81 and n=491 treatment-naive participants of the Uganda AIDS Rural Treatment Outcom ...[more]

PMID: 24960249

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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.

Project description:Background:Transmitted drug resistance (TDR) compromises clinical management and outcomes. Transmitted drug resistance surveillance and identification of growing transmission clusters are needed in the Southeast, the epicenter of the US HIV epidemic. Our study investigated prevalence and transmission dynamics in North Carolina. Methods:We analyzed surveillance drug resistance mutations (SDRMs) using partial pol sequences from patients presenting to 2 large HIV outpatient clinics from 1997 to 2014. Transmitted drug resistance prevalence was defined as ?1 SDRMs among antiretroviral therapy (ART)-naïve patients. Binomial regression was used to characterize prevalence by calendar year, drug class, and demographic and clinical factors. We assessed the transmission networks of patients with TDR with maximum likelihood trees and Bayesian methods including background pol sequences (n = 15 246). Results:Among 1658 patients with pretherapy resistance testing, ?1 SDRMs was identified in 199 patients, with an aggregate TDR prevalence of 12% (95% confidence interval, 10% to 14%) increasing over time (P = .02). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs; 8%) was common, followed by nucleoside reverse transcriptase inhibitors (4%) and protease inhibitors (2%). Factors associated with TDR were being a man reporting sex with men, white race, young age, higher CD4 cell count, and being a member of a transmission cluster. Transmitted drug resistance was identified in 106 clusters ranging from 2 to 26 members. Cluster resistance was primarily NNRTI and dominated by ART-naïve patients or those with unknown ART initiation. Conclusions:Moderate TDR prevalence persists in North Carolina, predominantly driven by NNRTI resistance. Most TDR cases were identified in transmission clusters, signifying multiple local transmission networks and TDR circulation among ART-naïve persons. Transmitted drug resistance surveillance can detect transmission networks and identify patients for enhanced services to promote early treatment.

Project description:IntroductionHIV-1 transmitted drug resistance (TDR) prevalence increased during the initial years of the antiretroviral therapy (ART) global scale-up. Few studies have examined recent trends in TDR prevalence using published genetic sequences and described the characteristics of ART-naïve persons from whom these published sequences have been obtained.MethodsWe identified 125 studies published between 2014 and 2019 for which HIV-1 reverse transcriptase (RT) with or without protease from ≥50 ART-naïve adult persons were submitted to the GenBank sequence database. The population characteristics and TDR prevalence were compared to those in 122 studies published in the preceding five years between 2009 and 2013. TDR prevalence was analysed using median study-level and person-level data.Results and discussionThe 2009 to 2013 and 2014 to 2019 studies reported sequence data from 32,866 and 41,724 ART-naïve persons respectively. Studies from the low- and middle-income country (LMIC) regions in sub-Saharan Africa, South/Southeast Asia and Latin America/Caribbean accounted for approximately two-thirds of the studies during each period. Between the two periods, the proportion of studies from sub-Saharan Africa and from South/Southeast Asia countries other than China decreased from 43% to 32% and the proportion of studies performed at sentinel sites for recent HIV-1 infection decreased from 33% to 22%. Between 2014 and 2019, median study-level TDR prevalence was 4.1% in South/Southeast Asia, 6.0% in sub-Saharan Africa, 9.1% in Latin America/Caribbean, 8.5% in Europe and 14.2% in North America. In the person-level analysis, there was an increase in overall, NNRTI and two-class NRTI/NNRTI resistance in sub-Saharan Africa; an increase in NNRTI resistance in Latin America/Caribbean, and an increase in overall, NNRTI and PI resistance in North America.ConclusionsOverall, NNRTI and dual NRTI/NNRTI-associated TDR prevalence was significantly higher in sub-Saharan Africa studies published between 2014 and 2019 compared with those published between 2009 and 2013. The decreasing proportion of studies from the hardest hit LMIC regions and the shift away from sentinel sites for recent infection suggests that global TDR surveillance efforts and publication of findings require renewed emphasis.

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.

Dataset Information

Prevalence and virologic consequences of transmitted HIV-1 drug resistance in Uganda.

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Prevalence and virologic consequences of transmitted HIV-1 drug resistance in Uganda.

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