Background/Objectives: This study evaluated variation in nodal support for provisional HIV-1 subtype B compatibility across pol, gag, vif, tat and vpr in an institutional cohort from central Mexico. Methods: We performed a secondary descriptive bioinformatics reanalysis of 60 treatment-naïve adults. Paired FASTQ files were available for 58 samples, and 42 were retained across all five regions. Robust support required SH-aLRT ≥ 80 and UFBoot ≥ 95. Additional analyses varied reference-composition thresholds, reselected assignment nodes, harmonized the reference panel and subsampled alignment columns. Results: At the originally recorded nodes, 18/210 sample–region records (8.6%) were robust; 25/42 samples had no robust region, 16 had one and one had two. Node reselection at the 60% composition threshold retained all 18 records and added S42/pol and S29/tat, yielding 20/210 (9.5%). Neither analysis identified robust support in three or more regions. With a common reference panel, the ordering of contextual internal-branch support between pol and vif changed. Conclusions: Support depended on the evaluated node and analytical dataset. Fixed-node threshold stability did not establish stability under node reselection. Differences among regional analyses could not be attributed independently to genomic region. Single-fragment assignments remain provisional and do not establish whole-genome subtype classifications. V3 and ViReMa analyses were exploratory.

Mexico has one of the highest incidences of childhood acute lymphoblastic leukemia worldwide and also reports one of the lowest 5-year overall survival rates; one cause is elevated treatment-related mortality from severe hematologic toxicity, a critical side effect during chemotherapy. Although association studies have identified common genetic variants linked to toxicity, the Mexican population remains incompletely explored. We performed targeted next-generation sequencing of genes involved in methotrexate and mercaptopurine metabolism in 96 Mexican children with ALL, stratified by hematologic toxicity severity according to CTCAE v5.0. Logistic regression revealed nominally significant associations between the TSER*3/TSER*2 genotype (rs45445694) in the 5′ UTR of TYMS severe hematologic toxicity (overdominant model: OR = 3.21; 95% CI = 1.23–8.38; p = 0.014 and codominant model: OR = 3.31; 95% CI = 1.17–9.34; p = 0.047). Additionally, the CCND1 LD block (rs678653/rs7177) also showed nominal associations (overdominant model: OR = 2.60; 95% CI = 1.01–6.71; p = 0.044). None of these associations remained statistically significant after Bonferroni correction for multiple testing (corrected α = 0.000588). Patients with severe toxicity had lower 5-year overall survival than those without severe toxicity (70.2% vs. 90.5%; p = 0.0609), although the difference was not statistically significant. Variants in 5′ and 3′ UTRs regions were markedly enriched compared to coding sequences, underscoring the importance of regulatory region analysis.