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Distinct HIV type 1 strains in different risk groups and the absence of new infections by drug-resistant strains in Lithuania.

ABSTRACT: To analyze HIV-1 genotypes in Lithuania and the transmission of drug-resistant viruses, HIV-1 sequences were obtained from 138 individuals, who were diagnosed as HIV-1 infected in 1990-2008 and represented all major risk groups. Subtype A strains, dominating in the former Soviet Union (90% of cases), were found in 60% of individuals, followed by subtype B (22%) and CRF03_AB (12%) strains. The remaining 7% of the strains included variants belonging to subtype C, CRF01_AE, CRF02_AG, more complex recombinant forms, and strains that could not be reliably genotyped. Analysis of virus genotypes per risk group revealed the circulation of distinct HIV-1 strains in different risk groups: subtype A viruses were present in 82% of injecting drug users (IDUs), but less than a half of heterosexually infected individuals and cases with unknown transmission route, and none of men having sex with men (MSM). We observed no mutations causing drug resistance among 27 newly diagnosed HIV-1 cases.

SUBMITTER: Caplinskas S

PROVIDER: S-EPMC3607974 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Distinct HIV type 1 strains in different risk groups and the absence of new infections by drug-resistant strains in Lithuania.

Caplinskas Saulius S Loukachov Vladimir V VV Gasich Elena L EL Gilyazova Alla V AV Caplinskiene Irma I Lukashov Vladimir V VV

AIDS research and human retroviruses 20130201 4

To analyze HIV-1 genotypes in Lithuania and the transmission of drug-resistant viruses, HIV-1 sequences were obtained from 138 individuals, who were diagnosed as HIV-1 infected in 1990-2008 and represented all major risk groups. Subtype A strains, dominating in the former Soviet Union (90% of cases), were found in 60% of individuals, followed by subtype B (22%) and CRF03_AB (12%) strains. The remaining 7% of the strains included variants belonging to subtype C, CRF01_AE, CRF02_AG, more complex r ...[more]

PMID: 23186249

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Project description:BackgroundHIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load.Methodology/principal findingsMolecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS) DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log(10) HIV-1 copies/10(6) PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug-resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4(+) T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two.Conclusions/significanceAn improved molecular-beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV-1 infected individuals. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furthermore, a correlation found between RNA- and DNA-derived sequences in the pol region suggests that genotypic drug-resistance testing could be carried out on either template.

Project description:BackgroundChina's National Free Antiretroviral Treatment Program (NFATP) has substantially reduced morbidity and HIV/AIDS incidence since 2003. However, HIV resistance to antiretroviral drugs (ARVs) has been a major challenge for the current treatment of HIV/AIDS in China.MethodsIn the current study, we established a nested dynamic model to predict the multi-drug resistance dynamics of HIV among the heterosexual population and evaluated the impact of intervention measures on the transmission of drug resistance. We obtained an effective reproductive number [Formula: see text] from each sub-model held at different stages of the dynamic model. Meanwhile, we applied Bayesian phylogenetic methods to infer the weighted average effective reproductive number [Formula: see text] from four HIV subtypes that sampled from 912 HIV-positive patients in China. It is an original and innovative method by fitting [Formula: see text] to [Formula: see text] by Markov Chain Monte Carlo (MCMC) to generate unknown parameters in [Formula: see text].ResultsBy analyzing the HIV gene sequences, we inferred that the most recent common ancestor of CRF01AE, CRF07BC, CRF08BC, and CRFBC dated from 1994, 1990, 1993 and 1990, respectively. The weighted average effective reproductive number [Formula: see text] dropped from 1.95 in 1994 to 1.73 in 2018. Considering different interventions, we used a macro dynamic model to predict the trend of HIV resistance. The results show that the number of new infections and total drug resistance under the baseline parameter (S1) are 253,422 and 213,250 in 2025, respectively. Comparing with the numbers under the target treatment rate (S2), they were 219,717 and 236,890, respectively. However, under the ideal treatment target (S3, the treatment rate reaches 90% and the treatment success rate reaches 90%), the number of new infections shows a declining trend and will decrease to 46,559 by 2025. Compared with S1 and S2, the total number of resistance also decreased to 160,899 in 2025.ConclusionWith the promotion of NFATP in China, HIV resistance to ARVs is inevitable. The strategy of increasing the treatment rate would not only ineffectively curb the epidemic, but also deteriorate drug resistance issue. Whereas, a combination of intervention strategies (the treatment rate reaches 90% and the treatment success rate reaches 90%) can greatly reduce both infection and drug resistance rate than applying one strategy alone.

Dataset Information

Distinct HIV type 1 strains in different risk groups and the absence of new infections by drug-resistant strains in Lithuania.

Publications

Distinct HIV type 1 strains in different risk groups and the absence of new infections by drug-resistant strains in Lithuania.

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