Coreceptor Usage, Diversity, and Divergence in Drug-Naive and Drug-Exposed Individuals from Malawi, Infected with HIV-1 Subtype C for More Than 20 Years

Abstract

There are few cohorts of individuals who have survived infection with HIV-1 for more than 20 years, reported and followed in the literature, and even fewer from Africa. Here we present data on a cohort of subtype C-infected individuals from rural northern Malawi. By sequencing multiple clones from long-term survivors at different time points, and using multiple genotyping approaches, we show that 5 of the 11 individuals are predicted as CXCR4 using (by ≥3/5 predictors) but only one individual is predicted as CXCR4 using by all five algorithms. Using any one genotyping approach overestimates the number of predicted CXCR4 sequences. Patterns of diversity and divergence were variable between the HIV-1 long-term survivors with some individuals showing very small amounts of variation and change, and others showing a greater amount; both patterns are consistent with what has been described in the literature.

Individuals with HIV-1 Subtype C Infection and Cryptococcal Meningitis Exhibit Viral Genetic Intermixing of HIV-1 Between Plasma and Cerebrospinal Fluid and a High Prevalence of CXCR4-Using Variants

“…Although we expected to detect CXCR4 usage by HIV-1C in some individuals in this study, considering that all had an AIDS defining condition, we observed a much higher frequency of CXCR4 usage than expected based on previous studies. It may be that the CPAs overestimated the predicted CXCR4 usage as described previously 74–77. Coreceptor usage tests in vitro may be employed in future to corroborate our findings.…”

Viruses Previously Identified in Brazil as Belonging to HIV-1 CRF72_BF1 Represent Two Closely Related Circulating Recombinant Forms, One of Which, Designated CRF122_BF1, Is Also Circulating in Spain

“…For these analyses, we used a reconstructed BF1 ancestral sequence as outgroup, considering the phylogenetic relationship between B and F subtypes (Zhu et al, 1998), obtained with IQ-Tree. The use of a reconstructed ancestral sequence as outgroup is similar to the approach used in other studies (Travers et al, 2004;Thomson and Fernández-García, 2011;Seager et al, 2014) to prevent the long-branch attraction artifact (Bergsten, 2005) that could be caused by an outgroup whose distance to the ingroup is relatively long compared with the within-ingroup distances. This artifact can result in collapse or a substantial decrease in node support of the clades of the ingroup, particularly in short genome segments.…”

Identification of a HIV-1 circulating BF1 recombinant form (CRF75_BF1) of Brazilian origin that also circulates in Southwestern Europe

“…The analyses with MrBayes were performed using the GTR + G + I substitution model, running two simultaneous independent runs and 8 chains 2–5 million generations long, ensuring that both runs reached convergence, as determined by an average standard deviation of split frequencies <0.01. In bootscan analyses and in phylogenetic trees of genome segments constructed to determine mosaic structures, a reconstructed B-F1 ancestral sequence was used as outgroup to avoid artifacts caused by distant outgroups ( Travers et al, 2004 ; Thomson and Fernández-García, 2011 ; Seager et al, 2014 ; Hill et al, 2022 ). For this reconstruction, the ML method implemented in W-IQ-Tree was used, with the GTR + FR evolutionary model, and sequences with the following GenBank accessions and subtypes: AB253421, AB253429 (A1); K03455, U21135, U63632, AY173951, AY331295, AY423387, DQ853463, MG365763 (B); AY772699, U46016 (C); AB485656, AF005494, FJ771006, FJ771007, FJ771008, FJ771009, MG365763, MG365768 (F1); AF061641, AF084936 (G); AF190127, AF190128 (H); J: AF082394, EF614151 (J); and DQ373063 (SIVcpz), used as outgroup.…”

“…All 4 patients harboring CRF75_BF1 (or a closely related recombinant in one case) viruses studied by us had low CD4 + T-cell counts less than 1 year after HIV-1 diagnosis (3 of them less than 3 months after diagnosis): 219, 96, 92, and 142 cells/mm 3 , respectively. Compared with 3,548 other patients attended at Spanish clinical centers studied by us in the same period in which infections with CRF75_BF1 had been diagnosed (2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020)(2021)(2022), the difference in the proportion of viruses with CD4 + T-cell counts ≤220 cells/mm 3 (100% vs. 29.3%) was statistically significant when analyzed with Fisher's exact test (p = 0.0074).…”