HIV Pretreatment Drug Resistance Trends in Mexico City, 2017-2020.
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ABSTRACT:
SUBMITTER: Garcia-Morales C
PROVIDER: S-EPMC8708254 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Pretreatment HIV drug resistance (HIVDR) to NNRTIs has consistently increased in Mexico City during the last decade. OBJECTIVES:To infer the HIV genetic transmission network in Mexico City to describe the dynamics of the local HIV epidemic and spread of HIVDR. PATIENTS AND METHODS:HIV pol sequences were obtained by next-generation sequencing from 2447 individuals before initiation of ART at the largest HIV clinic in Mexico City (April 2016 to June 2018). Pretreatment HIVDR was estimated using the Stanford algorithm at a Sanger-like threshold (?20%). Genetic networks were inferred with HIV-TRACE, establishing putative transmission links with genetic distances <1.5%. We examined demographic associations among linked individuals with shared drug resistance mutations (DRMs) using a???2% threshold to include low-frequency variants. RESULTS:Pretreatment HIVDR reached 14.8% (95% CI 13.4%-16.2%) in the cohort overall and 9.6% (8.5%-10.8%) to NNRTIs. Putative links with at least one other sequence were found for 963/2447 (39%) sequences, forming 326 clusters (2-20 individuals). The inferred network was assortative by age and municipality (P?<?0.001). Clustering individuals were younger [adjusted OR (aOR) per year?=?0.96, 95% CI 0.95-0.97, P?<?0.001] and less likely to include women (aOR?=?0.46, 95% CI 0.28-0.75, P?=?0.002). Among clustering individuals, 175/963 (18%) shared DRMs (involving 66 clusters), of which 66/175 (38%) shared K103N/S (24 clusters). Eight municipalities (out of 75) harboured 65% of persons sharing DRMs. Among all persons sharing DRMs, those sharing K103N were younger (aOR?=?0.93, 95% CI 0.88-0.98, P?=?0.003). CONCLUSIONS:Our analyses suggest age- and geographically associated transmission of DRMs within the HIV genetic network in Mexico City, warranting continuous monitoring and focused interventions.
| S-EPMC7021100 | biostudies-literature
Project description:The increased antiretroviral therapy (ART) coverage of patients in the absence of routine genotyping tests and in the context of active labor migration highlight the importance of HIV-1 drug resistance (DR) surveillance in Armenia. We conducted a two-phase pretreatment DR (PDR) study in 2017-2018 (phase I; 120 patients) and 2020-2021 (phase II; 133 patients) according to the WHO-approved protocol. The analysis of HIV-1 genetic variants showed high degrees of viral diversity, with the predominance of A6. The prevalence of any PDR was 9.2% in phase I and 7.5% in phase II. PDR to protease inhibitors was found only in 0.8% in phase II. PDR to efavirenz and nevirapine was found among 5.0% and 6.7% of patients in phase I, and 6.0% and 6.8% of patients in phase II, respectively. The prevalence of PDR to nucleoside reverse-transcriptase inhibitors decreased from 5.0% in phase I to 0.8% in phase II. In addition, we identified risk factors associated with the emergence of DR-male, MSM, subtype B, and residence in or around the capital of Armenia-and showed the active spread of HIV-1 among MSM in transmission clusters, i.e., harboring DR, which requires the immediate attention of public health policymakers for the prevention of HIV-1 DR spread in the country.
| S-EPMC9698750 | biostudies-literature
Project description:BackgroundTransmitted drug resistance (TDR) remains an important concern for the management of HIV infection, especially in countries that have recently scaled-up antiretroviral treatment (ART) access.Methodology/principal findingsWe designed a study to assess HIV diversity and transmitted drug resistance (TDR) prevalence and trends in Mexico. 1655 ART-naïve patients from 12 Mexican states were enrolled from 2005 to 2010. TDR was assessed from plasma HIV pol sequences using Stanford scores and the WHO TDR surveillance mutation list. TDR prevalence fluctuations over back-projected dates of infection were tested. HIV subtype B was highly prevalent in Mexico (99.9%). TDR prevalence (Stanford score>15) in the country for the study period was 7.4% (95% CI, 6.2?8.8) and 6.8% (95% CI, 5.7?8.2) based on the WHO TDR surveillance mutation list. NRTI TDR was the highest (4.2%), followed by NNRTI (2.5%) and PI (1.7%) TDR. Increasing trends for NNRTI (p?=?0.0456) and PI (p?=?0.0061) major TDR mutations were observed at the national level. Clustering of viruses containing minor TDR mutations was observed with some apparent transmission pairs and geographical effects.ConclusionsTDR prevalence in Mexico remains at the intermediate level and is slightly lower than that observed in industrialized countries. Whether regional variations in TDR trends are associated with differences in antiretroviral drug usage/ART efficacy or with local features of viral evolution remains to be further addressed.
| S-EPMC3217006 | biostudies-literature
Project description:BackgroundPretreatment drug resistance (PDR) can limit the effectiveness of HIV antiretroviral therapy (ART). The aim of this study was to assess the prevalence of PDR among HIV-positive individuals that initiated antiretroviral therapy in 2014-2020 in southwestern China.MethodsConsecutive cross-sectional surveys were conducted in Qinzhou, Guangxi. We obtained blood samples from individuals who were newly diagnosed with HIV in 2014-2020. PDR and genetic networks analyses were performed by HIV-1 pol sequences using the Stanford HIV-database algorithm and HIV-TRACE, respectively. Univariate and multivariate logistic regression models were used to explore the potential factors associated with PDR.ResultsIn total, 3236 eligible HIV-positive individuals were included. The overall prevalence of PDR was 6.0% (194/3236). The PDR frequency to NNRTI (3.3%) was much higher than that of NRTI (1.7%, p < 0.001) and PI (1.2%, p < 0.001). A multivariate logistic regression analysis revealed that PDR was significantly higher among individuals aged 18-29 (adjusted odds ratio (aOR): 1.79, 95% CI 1.28-2.50) or 30-49 (aOR: 2.82, 95% CI 1.73-4.82), and harboring CRF08_BC (aOR: 3.23, 95% CI 1.58-6.59). A total of 1429 (43.8%) sequences were linked forming transmission clusters ranging in size from 2 to 119 individuals. Twenty-two individuals in 10 clusters had the same drug resistant mutations (DRMs), mostly to NNRTIs (50%, 5/10).ConclusionsThe overall prevalence of PDR was medium, numerous cases of the same DRMs among genetically linked individuals in networks further illustrated the importance of surveillance studies for mitigating PDR.
| S-EPMC8590229 | biostudies-literature
Project description:IntroductionMolecular surveillance systems could provide public health benefits to focus strategies to improve the HIV care continuum. Here, we infer the HIV genetic network of Mexico City in 2020, and identify actively growing clusters that could represent relevant targets for intervention.MethodsAll new diagnoses, referrals from other institutions, as well as persons returning to care, enrolling at the largest HIV clinic in Mexico City were invited to participate in the study. The network was inferred from HIV pol sequences, using pairwise genetic distance methods, with a locally hosted, secure version of the HIV-TRACE tool: Seguro HIV-TRACE. Socio-demographic, clinical and behavioural metadata were overlaid across the network to design focused prevention interventions.ResultsA total of 3168 HIV sequences from unique individuals were included. One thousand and one-hundred and fifty (36%) sequences formed 1361 links within 386 transmission clusters in the network. Cluster size varied from 2 to 14 (63% were dyads). After adjustment for covariates, lower age (adjusted odds ratio [aOR]: 0.37, p<0.001; >34 vs. <24 years), being a man who has sex with men (MSM) (aOR: 2.47, p = 0.004; MSM vs. cisgender women), having higher viral load (aOR: 1.28, p<0.001) and higher CD4+ T cell count (aOR: 1.80, p<0.001; ≥500 vs. <200 cells/mm3 ) remained associated with higher odds of clustering. Compared to MSM, cisgender women and heterosexual men had significantly lower education (none or any elementary: 59.1% and 54.2% vs. 16.6%, p<0.001) and socio-economic status (low income: 36.4% and 29.0% vs. 18.6%, p = 0.03) than MSM. We identified 10 (2.6%) clusters with constant growth, for prioritized intervention, that included intersecting sexual risk groups, highly connected nodes and bridge nodes between possible sub-clusters with high growth potential.ConclusionsHIV transmission in Mexico City is strongly driven by young MSM with higher education level and recent infection. Nevertheless, leveraging network inference, we identified actively growing clusters that could be prioritized for focused intervention with demographic and risk characteristics that do not necessarily reflect the ones observed in the overall clustering population. Further studies evaluating different models to predict growing clusters are warranted. Focused interventions will have to consider structural and risk disparities between the MSM and the heterosexual populations.
| S-EPMC8583431 | biostudies-literature
Project description:BackgroundTo know the current status of the epidemiological and geographic distribution of tuberculosis and its complication meningeal tuberculosis in Mexico, this work analyzes national surveillance data (ten years) issued by the General Directorate of Epidemiology (GDE).MethodsAn observational and retrospective analysis of monthly and annual reports of pulmonary and meningeal tuberculosis cases from January 2007 to December 2017 was performed on the annual reports issued by the GDE in Mexico. The number of cases and incidence were classified by year, state, age group, gender, and seasons.ResultsA national case distribution map of pulmonary and meningeal tuberculosis incidence was generated. During this period, a total of 184,003 and 3,388 cases were reported with a median of 16,727.5 and 308 cases per year for pulmonary and meningeal tuberculosis diseases, respectively. The number of cases and incidence of pulmonary and meningeal tuberculosis per year showed that male gender presented a continuous increase in both parameters. The geographic analysis of the distribution of cases of tuberculosis showed that states like Guerrero, Tabasco, and Veracruz presented higher means of tuberculosis cases during this period. Northern states had the highest number of cases in the country compared to other states. In Mexico, pulmonary tuberculosis and meningeal tuberculosis are seasonal. Interestingly, cases of meningeal tuberculosis show an increase during October and November (autumn).ConclusionsIn Mexico, during the years 2007-2017, there has been an increase in the proportion of male TB patients. It remains necessary to implement strategies to detect TB in the adult population, especially among men, because tuberculosis could be difficult to recognize in an early stage in the population, and the appearance of resistant strains can cause an increase in the incidence of the disease.
| S-EPMC6501252 | biostudies-literature
Project description:BackgroundSouth Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naïve adults from South Africa.MethodsWe included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naïve adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect.FindingsWe identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11·9% (95% confidence interval (CI) 9·2-15·0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4-11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13-1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05-1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001).InterpretationIncreasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV.Source of fundingThis research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package.DisclaimerThe contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC.
| S-EPMC6510720 | biostudies-literature
Project description:BackgroundEthiopia is among the highly HIV-affected countries, with reported 12,000 and 12,000 AIDS-related deaths and incidents as per reports from 2021. Although the country has made a promising progress in antiretroviral therapy, recent studies have indicated that pretreatment drug resistance (PDR) is alarmingly increasing, which has become a challenge for the effectiveness of HIV treatment. Epidemiologic data on PDR is necessary to help establish ART regimens with good efficacy. Thus, this systematic review aimed to determine the trend analysis of PDR among ART-naïve individuals along with HIV variant dynamics in Ethiopia.MethodHIV-1 pol sequences from studies conducted between 2003 and 2018 among ART-naïve Ethiopian individuals were retrieved from GenBank and analyzed for the presence of PDR mutations (PDRM) along with the analysis of HIV-1 variant dynamics. The Calibrated Population Resistance (CPR) tool Version 8.1 and the REGA HIV-1 Subtyping Tool Version 3 were used to determine the PDRM and HIV-1 genetic diversity, respectively.ResultWe identified nine studies and analyzed 1070 retrieved HIV-1 pol sequences in this systematic review. The pooled prevalence of PDR was 4.8% (51/1070), including 1.4% (15/1070), 2.8% (30/1070), and 0.8% (9/1070) for nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI (NNRTI), and protease inhibitor (PI) resistance, respectively. NRTI and NNRTI concurrent PDRM were observed among 0.2% (2/799) of the analyzed sequences. The overall PDR prevalence has been increasing over the years. Though the prevalence of the NNRTI, NRTI, and PI PDR also increased over the years, the NNRTI increment was more pronounced than the others, reaching 7.84% in 2018 from 2.19% in 2003. The majority (97%; 1038/1070) of the genetic diversity was HIV-1 subtype C virus, followed by subtype C' (2%; 20/1038) and other subtypes (1%; 10/1038).ConclusionsAccording to this systematic review, the overall pooled prevalence of PDR is low. Despite the low prevalence, there has been an increasing trend of PDR over the years, which implies the need for routine surveillance of PDRMs along with preventive measures. Hence, this supports the recently endorsed transition of ART regimens from NNRTI to integrase strand transfer inhibitor-based regimens recommended by the WHO. In addition, this finding underscores the need for routine baseline genotypic drug resistance testing for all newly diagnosed HIV-infected patients before initiating treatment to halt the upward trend of PDR.
| S-EPMC10601210 | biostudies-literature
Project description:HIV-1 drug resistance can compromise the effectiveness of antiretroviral therapy (ART). A survey of pretreatment HIV-1 drug resistance (PDR) was conducted in Lincang Prefecture of Yunnan Province. From 372 people living with HIV/AIDS initiating ART for the first time during 2017-2018, 322 pol sequences were obtained, of which 11 HIV-1 strain types were detected. CRF08_BC (70.2%, 226/322) was the predominant strain, followed by URF strains (10.6%, 34/322). Drug resistance mutations (DRMs) were detected among 34.2% (110/322) of the participants. E138A/G/K/R (14.3%, 46/322) and V179E/D/T (13.7%, 47/322) were the predominant DRMs. Specifically, E138 mutations commonly occurred in CRF08_BC (19.9%, 45/226). Among the DRMs detected, some independently conferred resistance, such as K65R (1.6%, 5/322), Y188C/F/L (0.9%, 3/322), K103N (0.6%, 2/322) and G190A (0.3%, 1/322), which conferred high-level resistance. The prevalence of PDR was 7.5% (95% CI: 4.6-10.3%) and the prevalence of non-nucleotide reverse transcriptase inhibitor (NNRTI) resistance was 5.0% (95% CI: 2.6-7.4%), which is below the threshold (?10%) of initiating a public health response. In conclusion, HIV-1 genetic diversity and an overall moderate level of PDR prevalence were found in western Yunnan. PDR surveillance should be continually performed to decide whether a public health response to NNRTI resistance should be initiated.
| S-EPMC7315466 | biostudies-literature
Project description: Not available
| S-EPMC5906747 | biostudies-literature