scholarly journals Demonstration of Sustained Drug-Resistant Human Immunodeficiency Virus Type 1 Lineages Circulating among Treatment-Naïve Individuals

2009 ◽  
Vol 83 (6) ◽  
pp. 2645-2654 ◽  
Author(s):  
Stéphane Hué ◽  
Robert J. Gifford ◽  
David Dunn ◽  
Esther Fernhill ◽  
Deenan Pillay
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
United Kingdom ◽  
Phylogenetic Analyses ◽  
Antiretroviral Drugs ◽  
Cross Resistance ◽  
Transmitted Drug Resistance ◽  
The United Kingdom ◽  
Immunodeficiency Virus

ABSTRACT Transmission of human immunodeficiency virus (HIV) drug resistance is well-recognized and compromises response to first-line therapy. However, the population dynamics of transmitted resistance remains unclear, although previous models have assumed that such transmission reflects direct infection from treated individuals. We investigated whether population-based phylogenetic analyses would uncover lineages of resistant viruses circulating in untreated individuals. Through the phylogenetic analysis of 14,061 HIV type 1 (HIV-1) pol gene sequences generated in the United Kingdom from both treatment-naïve and -experienced individuals, we identified five treatment-independent viral clusters containing mutations conferring cross-resistance to antiretroviral drugs prescribed today in the United Kingdom. These viral lineages represent sustainable reservoirs of resistance among new HIV infections, independent of treatment. Dated phylogenies reconstructed through Bayesian Markov chain Monte Carlo inference indicated that these reservoirs originated between 1997 and 2003 and have persisted in the HIV-infected population for up to 8 years. Since our cohort does not represent all infected individuals within the United Kingdom, our results are likely to underestimate the number and size of the resistant reservoirs circulating among drug-naïve patients. The existence of sustained reservoirs of resistance in the absence of treatment has the capacity to threaten the long-term efficacy of antiretroviral therapy and suggests there is a limit to the decline of transmitted drug resistance. Given the current decrease in resistance transmitted from treated individuals, a greater proportion of resistance is likely to come from drug-naïve lineages. These findings provide new insights for the planning and management of treatment programs in resource-rich and developing countries.

scholarly journals Antiretroviral Drug Resistance Surveillance among Treatment-Naive Human Immunodeficiency Virus Type 1-Infected Individuals in Angola: Evidence for Low Level of Transmitted Drug Resistance

2009 ◽  
Vol 53 (7) ◽  
pp. 3156-3158 ◽  
Author(s):  
Inês Bártolo ◽  
Cheila Rocha ◽  
José Bartolomeu ◽  
António Gama ◽  
Marlene Fonseca ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Transcriptase Inhibitor ◽  
Transmitted Drug Resistance ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor

ABSTRACT The prevalence of transmitted human immunodeficiency virus type 1 drug resistance in Angola in 2001 in 196 untreated patients was investigated. All subtypes were detected, along with unclassifiable and complex recombinant strains. Numerous new polymorphisms were identified in the reverse transcriptase and protease. Two (1.6%) unrelated patients harbored nucleoside reverse transcriptase inhibitor- and nonnucleoside reverse transcriptase inhibitor-resistant viruses (mutations: M41L, D67N, M184V, L210W, T215Y or T215F, and K103N). Continued surveillance of drug resistance is required for maximization of ART efficacy in Angola.

scholarly journals Phylogenetic Surveillance of Viral Genetic Diversity and the Evolving Molecular Epidemiology of Human Immunodeficiency Virus Type 1

2007 ◽  
Vol 81 (23) ◽  
pp. 13050-13056 ◽  
Author(s):  
Robert J. Gifford ◽  
Tulio de Oliveira ◽  
Andrew Rambaut ◽  
Oliver G. Pybus ◽  
David Dunn ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Human Immunodeficiency Virus ◽  
United Kingdom ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
The United Kingdom ◽  
Viral Genetic Diversity ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT With ongoing generation of viral genetic diversity and increasing levels of migration, the global human immunodeficiency virus type 1 (HIV-1) epidemic is becoming increasingly heterogeneous. In this study, we investigate the epidemiological characteristics of 5,675 HIV-1 pol gene sequences sampled from distinct infections in the United Kingdom. These sequences were phylogenetically analyzed in conjunction with 976 complete-genome and 3,201 pol gene reference sequences sampled globally and representing the broad range of HIV-1 genetic diversity, allowing us to estimate the probable geographic origins of the various strains present in the United Kingdom. A statistical analysis of phylogenetic clustering in this data set identified several independent transmission chains within the United Kingdom involving recently introduced strains and indicated that strains more commonly associated with infections acquired heterosexually in East Africa are spreading among men who have sex with men. Coalescent approaches were also used and indicated that the transmission chains that we identify originated in the late 1980s to early 1990s. Similar changes in the epidemiological structuring of HIV epidemics are likely to be taking in place in other industrialized nations with large immigrant populations. The framework implemented here takes advantage of the vast amount of routinely generated HIV-1 sequence data and can provide epidemiological insights not readily obtainable through standard surveillance methods.

scholarly journals 3′-Azido-3′-Deoxythymidine (AZT) and AZT-Resistant Reverse Transcriptase Can Increase the In Vivo Mutation Rate of Human Immunodeficiency Virus Type 1

2000 ◽  
Vol 74 (20) ◽  
pp. 9532-9539 ◽  
Author(s):  
Louis M. Mansky ◽  
Lisa C. Bernard
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Reverse Transcriptase ◽  
Mutation Rate ◽  
Human Immunodeficiency Virus Type ◽  
Antiretroviral Drugs ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT How antiretroviral drug resistance influences human immunodeficiency virus type 1 (HIV-1) evolution is not clear. This study tested the hypothesis that antiretroviral drugs such as 3′-azido-3′-deoxythymidine (AZT) can influence the in vivo mutation rate of HIV-1. It was observed that AZT can increase the rate of HIV-1 mutation by a factor of 7 in a single round of replication. In addition, (−)2′,3′-dideoxy-3′-thiacytidine (3TC) was also found to increase the mutation rate of HIV-1 by a factor of 3. It was also found that HIV-1 drug-resistant reverse transcriptase (RT) variants can influence the in vivo mutation rate. Replication of HIV-1 with AZT-resistant RTs increased the mutation rate by as much as a factor of 3, while replication of HIV-1 with a 3TC-resistant RT (M184V) had no significant effect on the mutation rate. It was observed that only high-level, AZT-resistant RT variants could influence the in vivo mutation rate (i.e., M41L/T215Y and M41L/D67N/K70R/T215Y). In total, these observations indicate that both antiretroviral drugs and drug resistance mutations can influence the in vivo mutation rate of HIV-1.

scholarly journals Increased Multinucleoside Drug Resistance and Decreased Replicative Capacity of a Human Immunodeficiency Virus Type 1 Variant with an 8-Amino-Acid Insert in the Reverse Transcriptase

2005 ◽  
Vol 79 (6) ◽  
pp. 3536-3543 ◽  
Author(s):  
Lia van der Hoek ◽  
Nicole Back ◽  
Maarten F. Jebbink ◽  
Anthony de Ronde ◽  
Margreet Bakker ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Amino Acid ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Antiretroviral Drugs ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Resistance to antiretroviral drugs is generally conferred by specific amino acid substitutions, rather than insertions or deletions, in reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1). The exception to these findings is the amino acid insertions found in the β3-β4 loop of the RT enzyme in response to treatment with nucleoside reverse transcriptase inhibitors. This insert consists most commonly of two amino acids, but we describe in detail the evolution of a variant with an 8-amino-acid (aa) insert in a patient treated with zidovudine (ZDV) and 2′-3′-dideoxycytidine (ddC). The 24-nucleotide insert is a partial duplication of local sequences but also contains a sequence segment of unknown origin. Extensive sequence analysis of longitudinal patient samples indicated that the HIV-1 population prior to the start of therapy contained not the wild-type amino acid 215T in RT but a mixture with 215D and 215C. Treatment with ZDV and subsequent ZDV-ddC combination therapy resulted in the evolution of an HIV-1 variant with a typical ZDV resistance genotype (41L, 44D, 67N, 69D, 210W, 215Y), which was slowly replaced by the insert-containing variant (41L, 44D, insert at position 69, 70R, 210W, 215Y). The latter variant demonstrated increased resistance to a wide range of drugs, indicating that the 8-aa insert augments nucleoside analogue resistance. The gain in drug resistance of the insert variant came at the expense of a reduction in replication capacity when assayed in the absence of drugs. We compared these data with the resistance and replication properties of 133 insert-containing sequences of different individuals present in the ViroLogic database and found that the size and actual sequence of the insert at position 69 influence the level of resistance to nucleoside analogues.

scholarly journals Detection of human immunodeficiency virus type 1 transmitted drug resistance among treatment-naive individuals residing in Jakarta, Indonesia

2020 ◽  
Author(s):  
Siti Qamariyah Khairunisa ◽  
Ni Luh Ayu Megasari ◽  
Retno Pudji Rahayu ◽  
Adiana Mutamsari Witaningrum ◽  
Shuhei Ueda ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Capital City ◽  
Transmitted Drug Resistance ◽  
Immunodeficiency Virus ◽  
Treatment Naïve ◽  
Hiv 1

The presence of transmitted drug resist- ance (TDR) in human immunodeficiency virus type 1 (HIV-1) infected individuals naive to antiretroviral therapy, may affect the effectiveness of treatment. Jakarta, the capital city of Indonesia, recorded the high- est number of cumulative HIV infection cases in the country. This study aimed to identify on the appearance of TDR, as well as to identify HIV-1 subtypes circulating among treatment-naive individuals in Jakarta. Whole blood samples collected from 43 HIV-1 infected, treatment-naive individuals. Viral subtyping and drug resist- ance testing were performed on HIV-1 pol genes amplified using nested polymerase chain reaction. CRF01_AE was detected most frequently in Jakarta (73.08%). Drug resistance-related major mutation was not detected in protease fragments of pol gene, but two major mutations, K103N (6.67%) and Y181C (6.67%), were detected in reverse transcriptase fragments of pol gene. Our results suggest that TDR was emerged in Jakarta at a certain extent, thus further surveillance study to monitor the TDR prevalence and circulating HIV-1 subtypes in this region is considered to be necessary.

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