Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 14;16(6):962.
doi: 10.3390/v16060962.

Human Immunodeficiency Virus Type-1 Genetic Diversity and Drugs Resistance Mutations among People Living with HIV in Karachi, Pakistan

Abdur Rashid  1   2 , Li Kang  2   3 , Feng Yi  2 , Qingfei Chu  2   4 , Sharaf Ali Shah  5 , Syed Faisal Mahmood  6 , Yimam Getaneh  4   7 , Min Wei  1 , Song Chang  2 , Syed Hani Abidi  8   9 , Yiming Shao  1   2   3   4   10
Affiliations

Human Immunodeficiency Virus Type-1 Genetic Diversity and Drugs Resistance Mutations among People Living with HIV in Karachi, Pakistan

Abdur Rashid et al. Viruses. .

Abstract

The human immunodeficiency virus type-1 epidemic in Pakistan has significantly increased over the last two decades. In Karachi, Pakistan, there is a lack of updated information on the complexity of HIV-1 genetic diversity and the burden of drug resistance mutations (DRMs) that can contribute to ART failure and poor treatment outcomes. This study aimed to determine HIV-1 genetic diversity and identify drug-resistance mutations among people living with HIV in Karachi. A total of 364 HIV-positive individuals, with a median age of 36 years, were enrolled in the study. The HIV-1 partial pol gene was successfully sequenced from 268 individuals. The sequences were used to generate phylogenetic trees to determine clade diversity and also to assess the burden of DRMs. Based on the partial pol sequences, 13 distinct HIV-1 subtypes and recombinant forms were identified. Subtype A1 was the most common clade (40%), followed by CRF02_AG (33.2%). Acquired DRMs were found in 30.6% of the ART-experienced patients, of whom 70.7%, 20.7%, and 8.5% were associated with resistance to NNRTIs, NRTIs, and PIs, respectively. Transmitted DRMs were found in 5.6% of the ART-naïve patients, of whom 93% were associated with resistance against NNRTIs and 7% to PIs. The high prevalence of DRMs in ART-experienced patients poses significant challenges to the long-term benefits and sustainability of the ART program. This study emphasizes the importance of continuous HIV molecular epidemiology and drug resistance surveillance to support evidence-based HIV prevention, precise ART, and targeted AIDS care.

Keywords: HIV-1; Karachi; Pakistan; antiretroviral therapy; drug resistance; genetic diversity; phylogeny.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
HIV-1 subtype distribution in Karachi. (A) Maximum likelihood (ML) phylogenetic tree consisting of 268 pol sequences amplified from PLHIV and 50 HIV-subtype reference sequences (colored black). Tree branches are colored according to subtype. The scale bar at the center indicates the number of substitutions per site along the tree branches. (B) The pie chart represents the proportion of subtypes in the study groups.
Figure 2
Figure 2
Distribution of antiretroviral drug resistance among the study participants. Predicted resistance levels were based on Stanford HIV drug resistance scores. Scores < 10 indicate susceptibility, scores of 10–14 indicate potential low-level resistance, scores of 15–29 indicate low-level resistance, scores of 30–59 indicate intermediate resistance, and scores ≥ 60 indicate high-level resistance. Resistance to antiretroviral drugs among (A) ART-naïve group, (B) ART-experienced group, and (C) unknown ART status group individuals. Overall drug resistance against any antiretroviral class among the different groups is indicated as follows: * ART-naïve, ** ART-experienced, *** unknown status individuals. PIs, protease inhibitors, NRTIs, nucleoside reverse transcriptase inhibitors, NNRTIs, and non-nucleoside reverse transcriptase inhibitors.
Figure 3
Figure 3
Prevalence of drug resistance against PIs, NRTIs, and NNRTIs. Antiretroviral drugs abbreviations: PIs. ATV/r, Atazanavir/ritonavir; DRV/r, darunavir/ ritonavir; FPV/r, fosamprenavir/ritonavir; IDV/r, indinavir/ritonavir; LPV/r, lopinavir/ritonavir; TPV/r, tipranavir/ritonavir; NFV, nelfinavir; SQV/r, saquinavir/ritonavir. NRTIs. ABC, abacavir, AZT, zidovudine; D4T, stavudine; DDI, didanosine; FTC, emtricitabine; 3TC, lamivudine; TDF, tenofovir. NNRTIs. DOR, doravirine; EFV, efavirenz; ETR, etravirine; NVP, nevirapine; RPV, rilpivirine.
Figure 4
Figure 4
Maximum-likelihood phylogenetic tree indicating relationships between transmission clusters and mutations among the three study groups. Tree branches are colored according to the following scheme: green: ART-experienced; blue: ART-naïve; lavender: unknown status; and black: HIV-1 subtypes reference sequences. Tree branch tips are colored to indicate resistance against different antiretroviral drugs: orange: protease inhibitors (PIs); light blue: nucleoside reverse transcriptase inhibitors (NRTIs); rose: non-nucleoside reverse transcriptase inhibitors (NNRTIs); purple; PIs+NNRTIs; yellow; NRTIs+NNRTIs; dark; PIs+NRTIs+NNRTIs. The scale bar at the center indicates the number of substitutions per site along the tree branches. The two transmission clusters, URF DG and A1G, with reference sequences, are highlighted in light purple.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. The Path that Ends AIDS: 2023 UNAIDS Global AIDS Update. [(accessed on 6 June 2024)]. Available online: https://www.aidsdatahub.org/resource/path-ends-aids-2023-unaids-global-a....
    1. Guidelines on the Public Health Response to Pretreatment HIV Drug Resistance. World Health Organization (WHO); Geneva, Switzerland: 2017.
    1. Wittkop L., Günthard H.F., de Wolf F., Dunn D., Cozzi-Lepri A., de Luca A., Kücherer C., Obel N., von Wyl V., Masquelier B., et al. Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): A European multicohort study. Lancet Infect. Dis. 2011;11:363–371. doi: 10.1016/S1473-3099(11)70032-9. - DOI - PubMed
    1. Parczewski M., Sulkowska E., Urbańska A., Scheibe K., Serwin K., Grabarczyk P. Transmitted HIV drug resistance and subtype patterns among blood donors in Poland. Sci. Rep. 2021;11:12734. doi: 10.1038/s41598-021-92210-2. - DOI - PMC - PubMed
    1. Zhao B., Song W., Kang M., Dong X., Li X., Wang L., Liu J., Ding H., Chu Z., Wang L., et al. Molecular Network Analysis Reveals Transmission of HIV-1 Drug-Resistant Strains among Newly Diagnosed HIV-1 Infections in a Moderately HIV Endemic City in China. Front. Microbiol. 2021;12:797771. doi: 10.3389/fmicb.2021.797771. - DOI - PMC - PubMed

Substances

LinkOut - more resources

-