Evidence Of Transmitted Drug Resistance Research Articles

Trends and Patterns of HIV Transmitted Drug Resistance in China From 2018 to 2023.

National treatment guidelines of China evolving necessitates population-level surveillance of transmitted drug resistance (TDR) to inform or update HIV treatment strategies. We analyzed the demographic, clinical, and virologic data obtained from people with HIV (PWH) residing in 31 provinces of China who were newly diagnosed between 2018 and 2023. Evidence of TDR was defined by the World Health Organization list for surveillance of drug resistance mutations. Among the 22 124 PWH with protease and reverse transcriptase sequences, 965 (4.36%; 95% CI, 4.1-4.63) had at least 1 TDR mutation. The most frequent TDR mutations were nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.39%; 95% CI, 2.19%-2.59%), followed by nucleoside reverse transcriptase inhibitor mutations(1.35%; 95% CI, 1.2%-1.5%) and protease inhibitor mutations (1.12%; 95% CI, .98%-1.26%). The overall protease and reverse transcriptase TDR increased significantly from 4.05% (95% CI, 3.61%-4.52%) in 2018 to 5.39% (95% CI, 4.33%-6.57%) in 2023. A low level of integrase strand transfer inhibitor TDR was detected in 9 (0.21%; 95% CI, .1%-.38%) of 4205 PWH. Presently, the continued use of NNRTI-based first-line antiretroviral therapy regimen for HIV treatment has been justified.

HIV drug resistance and HIV transmission risk factors among newly diagnosed individuals in Southwest China

BackgroundThe widespread use of antiretroviral therapy (ART) has resulted in the development of transmitted drug resistance (TDR), which reduces ART efficacy. We explored TDR prevalence and its associated risk factors in newly diagnosed individuals in Guangxi.MethodsWe enrolled 1324 participants who were newly diagnosed with HIV-1 and had not received ART at voluntary counselling and testing centres (VCT) in Guangxi, China, who had not received ART. Phylogenetic relationship, transmission cluster, and genotypic drug resistance analyses were performed using HIV-1 pol sequences. We analysed the association of demographic and virological factors with TDR.ResultsIn total, 1151 sequences were sequenced successfully, of which 83 (7.21%) showed evidence of TDR. Multivariate logistic regression analysis revealed that there was significant difference between the prevalence of TDR and unmarried status (adjusted odds ratio (aOR) = 2.41, 95% CI: 1.23–4.71), and CRF08_BC subtype (aOR = 2.03, 95% CI: 1.13–3.64). Most cases of TDR were related to resistance to non-nucleoside reverse transcriptase inhibitors (4.87%) and V179E was the most common mutation detected. We identified a total of 119 HIV transmission clusters (n = 585, 50.8%), of which 18 (15.1%) clusters showed evidence of TDR (36, 41.86%). Three clusters were identified that included drug-resistant individuals having a transmission relationship with each other. The following parameters were associated with TDR transmission risk: Unmarried status, educational level of junior high school or below, and CRF08_BC subtype may be a risk of the transmission of TDR.ConclusionsOur findings indicated that moderate TDR prevalence and highlighted the importance of continuous TDR monitoring and designing of strategies for TDR mitigation.

Low Rates of Transmitted Drug Resistance Among Newly Identified HIV-1 Seroconverters in Rural Rakai, Uganda.

We investigated the rate of transmitted drug resistance (TDR) among HIV-1 seroconverters identified from the Rakai Community Cohort Study (RCCS) survey, a population-based cohort in Rakai District, Uganda. Participants aged 15-49 are interviewed at study visits approximately every 12-18 months and provided a serological sample. Antiretroviral therapy (ART) has been provided free of charge since 2004. RCCS participants with documented negative HIV-1 serology between January 2011 and August 2012 and confirmed seroconversion between November 2012 and October 2013 were included in this analysis. Serum was genotyped for HIV drug resistance mutations in reverse transcriptase and protease genes. Mutations were classified according to the 2009 World Health Organization surveillance of transmitted HIV-1 drug resistance update. Seventy-five (75) seroconverters were identified and genotyped. The mean age was 28 years (range 18-49) and the majority were male, n = 44 (58%). The HIV-1 subtype frequencies were A = 19 (25%), D = 44 (59%), C = 4 (5%), A/D recombinant = 5 (7%), and C/D recombinant = 3 (4%). The majority (72/75, 96%) of individuals were infected with wild-type virus with no evidence of TDR. Two individuals had a single non-nucleoside reverse transcriptase inhibitor mutation each, K101E and K103N, and one had a single protease inhibitor mutation, M46I. No mutations were identified involving nucleoside reverse transcriptase inhibitors. In conclusion, almost 10 years after the introduction of ART in rural Uganda, rates of TDR remain low. Ongoing surveillance for TDR remains an important public health priority and should be conducted among known seroconverters to estimate TDR.

Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe.

Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.

Antiretroviral drug resistance in HIV‐1 therapy‐naïve patients in Cuba, 2006–2011

In 2009, genotypic drug resistance testing was introduced for HIV‐1 patients failing antiviral therapy in Cuba. The high prevalence of drug resistance in this population indicated the need for surveillance of transmitted drug resistance (TDR) in therapy‐naïve patients. Therefore, the objectives of this study were to analyze the level and patterns of TDR and subtype in therapy‐naïve HIV‐1 patients in Cuba from 2006 to 2011, and to compare it with reported data from 2004 that indicated 4% TDR, solely restricted to NRTI. 153 plasma from HIV‐1 therapy‐naïve patients were collected between June 2006 and December 2011 and subsequently extracted, amplified and sequenced. Drug resistance was interpreted according to HIVdb v.6.1.1 and WHO list for TDR surveillance (2009) using the CPR tool v.6.0. Phylogenetic analysis was performed using Neighbour Joining (Kimura 2) in Mega 4. The majority of patients was male (82.4%), MSM (68.6%) and originated from Havana province (68.1%). 8.4% were recent infections. Subtype B was the most prevalent subtype (31.3%) followed by CRF20‐23‐24_BG (28.1%), CRF19 (18.3%) and CRF18 (13.0%). The prevalence of subtype B declined from 43.7% in the 2004 study to 31.3% in the present study, whereas BG recombinants increased from 14.4% to 28.1%. Overall, 12.4% (19/154) had evidence of TDR. 3.9% carried at least one NRTI, 1.9% at least one NNRTI and 1.9% at least one PI mutation. Drug resistance mutations against both NRTI and NNRTI were observed in 3.9%, whereas triple class resistance was found in only 0.6%. The most frequent NRTI mutations were M184V (55.5%), T215F/Y/rev (16.6%) and K70R (16.6%). The most frequent NNRTI mutations were K103N (61.1%) and G190A (22.2%). The most common PI mutation was L90M (5.5%). From the 19 patients with TDR, 13 (68.4%) were diagnosed with a recent HIV‐1 infection. AZT/D4T + 3TC + NVP may be effective in 6 of the patients with TDR (31.5%), partially effective in 6 (31.5%) and ineffective in 7 (36.8%). AZT/D4T + 3TC + IDV would be effective in 9 of the patients with TDR (47.3%), partially effective in 8 (42.1%) and ineffective in 2 (10.5%). This analysis confirmed the further expansion of BG recombinants in Cuba and revealed that antiretroviral drug resistance in HIV‐1 therapy‐naïve patients has increased to 12.4% in 2006–2011. The current study emphasizes the need to perform surveillance studies for TDR in therapy‐naïve patients, as the extent of TDR might jeopardize the effectiveness of first‐line regimens prescribed in Cuba.

Transmitted Antiretroviral Drug Resistance in New York State, 2006-2008: Results from a New Surveillance System

BackgroundHIV transmitted drug resistance (TDR) is a public health concern because it has the potential to compromise antiretroviral therapy (ART) at the population level. In New York State, high prevalence of TDR in a local cohort and a multiclass resistant case cluster led to the development and implementation of a statewide resistance surveillance system.MethodologyWe conducted a cross-sectional analysis of the 13,109 cases of HIV infection that were newly diagnosed and reported in New York State between 2006 and 2008, including 4,155 with HIV genotypes drawn within 3 months of initial diagnosis and electronically reported to the new resistance surveillance system. We assessed compliance with DHHS recommendations for genotypic resistance testing and estimated TDR among new HIV diagnoses.Principal FindingsOf 13,109 new HIV diagnoses, 9,785 (75%) had laboratory evidence of utilization of HIV-related medical care, and 4,155 (43%) had a genotype performed within 3 months of initial diagnosis. Of these, 11.2% (95% confidence interval [CI], 10.2%–12.1%) had any evidence of TDR. The proportion with mutations associated with any antiretroviral agent in the NNRTI, NRTI or PI class was 6.3% (5.5%–7.0%), 4.3% (3.6%–4.9%) and 2.9% (2.4%–3.4%), respectively. Multiclass resistance was observed in <1%. TDR did not increase significantly over time (p for trend = 0.204). Men who have sex with men were not more likely to have TDR than persons with heterosexual risk factor (OR 1.0 (0.77–1.30)). TDR to EFV+TDF+FTC and LPV/r+TDF+FTC regimens was 7.1% (6.3%–7.9%) and 1.4% (1.0%–1.8%), respectively.Conclusions/SignificanceTDR appears to be evenly distributed and stable among new HIV diagnoses in New York State; multiclass TDR is rare. Less than half of new diagnoses initiating care received a genotype per DHHS guidelines.

Primary Drug Resistance in South Africa: Data from 10 Years of Surveys

HIV-1 transmitted drug resistance (TDR) could reverse the gains of antiretroviral rollout. To ensure that current first-line therapies remain effective, TDR levels in recently infected treatment-naive patients need to be monitored. A literature review and data mining exercise was carried out to determine the temporal trends in TDR in South Africa. In addition, 72 sequences from seroconvertors identified from Africa Centre's 2010 HIV surveillance round were also examined for TDR. Publicly available data on TDR were retrieved from GenBank, curated in RegaDB, and analyzed using the Calibrated Population Resistance Program. There was no evidence of TDR from the 2010 rural KwaZulu Natal samples. Ten datasets with a total of 1618 sequences collected between 2000 and 2010 were pooled to provide a temporal analysis of TDR. The year with the highest TDR rate was 2002 [6.67%, 95% confidence interval (CI): 3.09-13.79%; n=6/90]. After 2002, TDR levels returned to <5% (WHO low-level threshold) and showed no statistically significant increase in the interval between 2002 and 2010. The most common mutations were associated with NNRTI resistance, K103N, followed by Y181C and Y188C/L. Five sequences had multiple resistance mutations associated with NNRTI resistance. There is no evidence of TDR in rural KwaZulu-Natal. TDR levels in South Africa have remained low following a downward trend since 2003. Continuous vigilance in monitoring of TDR is needed as more patients are initiated and maintained onto antiretroviral therapy.