Complex Subtype Diversity of HIV-1 Among Drug Users in Major Kenyan Cities

Gounder, Kamini; Oyaro, Micah; Padayachi, Nagavelli; Zulu, Thando; Oliveira, Túlio de; Wylie, John; Ndung’u, Thumbi

doi:10.1089/aid.2016.0321

Cited by 11 publications

(12 citation statements)

References 16 publications

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“…The present study detected higher prevalence of subtype A1 (78.4%) followed by AG 16.2%), A1/C (2.7%) and A1/G/AE (2.7%) infection among injection drug users. This is partly consistent with previous study reporting higher prevalence of envelope-gene subtype A1 and the remainder being AD, C and complex subtypes in that order, among injection drug users in Nairobi city (8). Studies assessing in vitro HIV subtype replication capacity found that A has a higher replication fitness hence increased transmission compared to other subtypes (23,24), may explain the expansion of subtype A in the present study.…”

Section: Discussionsupporting

confidence: 93%

HIV-1 Transmission Cluster in Injection Drug Users in Nairobi City, Kenya

Webale¹,

Kilongosi²,

Munyekenye³

et al. 2023

Ethiop J Health Sci

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BACKGROUND: While there is a striking increase in the prevalence of HIV in injection drug users, information on envelope-gene subtypes and transmission clusters in injection drug users is scarce.METHOD: In a cross-sectional study, 247 injection drug users were recruited via out-rich method. Deoxyribonucleic acid was extracted from dry blood spot samples, amplified by Polymerase Chain Reaction and sequenced. Subtyping was performed using COntext-based Modeling for Expeditious Typing (COMET) and Recombinant Identification Program (RIP) tools. Phylogenetic diversity and Transmission clusters were identified using MEGA version 6.0 and TreeLink, respectively.RESULTS: Overall, 42 (17.0%) injection drug users were sero-positive for HIV-1. Of the 37 samples successfully sequenced, 29 (78.4%) sequences were identified as A1, 6 (16.2%) as AG while 1 (2.7%) as A1/G/AE and A1/C recombinants. The HIV subtypes formed clusters with little genetic diversity.CONCLUSION: The high HIV prevalence was associated with transmission clusters and diversity in subtypes indicating ongoing local transmission. Therefore, there is need for comprehensive HIV care tailored to this population.

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Section: Discussionsupporting

confidence: 93%

HIV-1 Transmission Cluster in Injection Drug Users in Nairobi City, Kenya

Webale¹,

Kilongosi²,

Munyekenye³

et al. 2023

Ethiop J Health Sci

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“…At least two of these studies [17,20] tested many subtype samples collected from around the world including Africa. These studies include the predominant HIV subtypes seen in Kenya such as subtype A, D, C, G and recombinants [21,22,36,37]. The good agreement seen between Aptima VL results and Abbott RT seen in this study also suggest that subtype quantification of Aptima is equivalent to that of Abbott RT for the HIV subtypes prevalent in Kenya.…”

Section: Plos Onesupporting

confidence: 70%

“…Several publications demonstrate equivalent performance of the Aptima Assay with other commercially available assays, but most of these were conducted by testing plasma specimens from HIV patients in Europe and the United States [10][11][12][13][14][15][16][17][18][19][20]. Unlike the United States and Europe where the predominant HIV subtype is subtype B, Africa has the greatest genetic diversity of HIV-1 with Kenya having high level of infection with recombinants, subtype A, C and D [21,22].…”

Section: Introductionmentioning

confidence: 99%

Prospective evaluation of accuracy of HIV viral load monitoring using the Aptima HIV Quant Dx assay with fingerstick and venous dried blood spots prepared under field conditions in Kenya

et al. 2021

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Quantification of HIV-1 RNA is essential for clinical management of HIV patients. The limited throughput and significant hands-on time required by most HIV Viral load (VL) tests makes it challenging for laboratories with high test volume, to turn around patient results quickly. The Hologic Aptima HIV-1 Quant Dx Assay (Aptima), has the potential to alleviate this burden as it is high throughput and fully automated. This assay is validated for both plasma and dried blood spots (DBS), which are commonly used in resource limited settings. The objective of this study was to compare the performance of Aptima to Abbott RealTime HIV-1 Assay (Abbott RT), which was used as reference. This was a cross-sectional prospective study where HIV VL in finger stick (FS) DBS, venous blood (VB) DBS and plasma, collected from 258 consenting adults visiting 5 medical facilities in Kenya, Africa were tested in Aptima. The results were compared to plasma VL in Abbott RT at the medical decision point (MDP) of 1000 copies/mL and across Aptima assay range. The total agreement at MDP between plasma HIV VL in Abbott RT and plasma, FS and VB DBS tested in Aptima were 97.7%, 92.2% and 95.3% respectively with kappa statistic of 0.95, 0.84 and 0.90. The positive and negative agreement for all 3 sample types were >92%. Regression analysis between VL in Abbott RT plasma and various sample types tested in Aptima had a Pearson’s correlation coefficient ≥0.91 with systematic bias of < 0.20 log copies/mL on Bland-Altman analysis. The high level of agreement in Aptima HIV VL results for all 3 sample types with Abbott RT plasma VL along with the high throughput, complete automation, and ease of use of the Panther platform makes Aptima a good option for HIV VL monitoring for busy laboratories with high volume of testing.

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“…HIV gag-protease was amplified by bulk PCR using previously described protocols (19). Single genome amplification (SGA) of gag was performed, as described previously (20), by serial dilution of cDNA to determine a dilution where ≤30% of wells were positive for amplification. The ABI Prism Big Dye Termination V 3.1 cycling sequencing kit (Applied Biosystems, Waltham, Massachussetts) was used to Sanger sequence bulk PCR products and single genome amplicons using previously published primers (19,20).…”

Section: Gag Amplification and Sequencing From Plasma Ln Mononuclear ...mentioning

confidence: 99%

Limited Sequence Variation and Similar Phenotypic Characteristics of HIV-1 Subtype C Gag Variants Derived From the Reservoir and Pre-Therapy Plasma

Ojwach¹,

Gounder²,

Mulaudzi³

et al. 2022

Front. Virol.

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HIV variants present in the reservoir, particularly in tissues, may differ from those present in peripheral blood prior to therapy initiation, and characterisation of these reservoir variants could better inform immune-based interventions for HIV cure. In the present study, Gag sequence differences between variants derived from the lymph node and peripheral blood mononuclear cell (PBMC) reservoirs as well as those derived from pre-therapy plasma, were investigated in 24 HIV-1 subtype C-infected individuals. HIV gag amplification was successful for 20 individuals, where 4 were controls including one untreated individual and 3 early treated individuals with LN collection within 2 weeks of treatment initiation. The remaining 16 individuals with LN and PBMC collection > 3 months after treatment initiation (median = 665 days), were further characterised. Recombinant viruses encoding patient-derived Gag-protease sequences from the pre-therapy plasma, LN reservoir, and PBMC reservoir, were constructed and the replication-competent viruses that grew in vitro were used to further investigate whether there are specific features of Gag reservoir variants that may have relevance for strategies to cure HIV. Virus characteristics measured included replication capacity, interferon-alpha resistance, cell-to-cell spread ability, and induction of antiviral cytokines. A limited number of novel Gag mutations (median = 4) in the reservoir of 3/7 early treated participants and 9/9 late treated participants were observed, where the majority of these mutations were likely cytotoxic T lymphocyte (CTL)-driven and 48% were represented in the replication-competent viruses. The reservoir variants had very few unique potential CTL escape mutations (median = 3) in Gag compared to the number of these Gag mutations that were already present in the plasma-derived virus (median = 23) at the time of treatment initiation, which was similar whether treatment was initiated late or early. The data suggest that the extent of CTL escape in Gag overall is likely similar between early and late treated individuals as well as between the reservoir and pre-therapy variants. The sequence differences in Gag that were unique to the reservoir viruses did not result in significantly altered virus characteristics overall, and are therefore unlikely to affect effectiveness of immune-based interventions for virus eradication.

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Complex Subtype Diversity of HIV-1 Among Drug Users in Major Kenyan Cities

Cited by 11 publications

References 16 publications

HIV-1 Transmission Cluster in Injection Drug Users in Nairobi City, Kenya

HIV-1 Transmission Cluster in Injection Drug Users in Nairobi City, Kenya

Prospective evaluation of accuracy of HIV viral load monitoring using the Aptima HIV Quant Dx assay with fingerstick and venous dried blood spots prepared under field conditions in Kenya

Limited Sequence Variation and Similar Phenotypic Characteristics of HIV-1 Subtype C Gag Variants Derived From the Reservoir and Pre-Therapy Plasma

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