Viraemia and HIV-1 drug resistance mutations among patients receiving antiretroviral treatment in Mozambique.

This study was conducted among individuals taking first-line antiretroviral treatment (ART) for at least 12 months under programme conditions in Maputo, Mozambique in order to report on the level of detectable viraemia and the proportion and types of drug resistance mutations among those with detectable viral loads. HIV-1 RNA viral load levels (lower detection limit <50 copies/ml) were measured, and resistance mutations were sequenced. One hundred and forty-nine consecutive patients (69% females, median age 36 years) were included after a mean follow-up time of 23 months. One hundred and seven (72%; 95% CI 64-79) had undetectable viral load, while in 42 (28%, 95% CI 21-36) viral load was detectable (range 50-58884 copies/ml). From 15 patients with viral load >1000 copies/ml, 12 viruses were sequenced: eight were C subtypes and four were circulating recombinant forms (CRF08). Eight (5%; 95% CI 2-9) patients with detectable viral load had one or more major resistance mutations. Nucleoside reverse transcriptase inhibitor (NRTI) and non-NRTI mutations were observed. There were no major mutations for resistance to protease inhibitors. In Maputo, the level of detectable viraemia is reassuringly low. While embarking on ART scale-up, wider surveillance is warranted to monitor programme quality and limit the development of drug resistance, which remains a major potential challenge for the future of ART in Africa

Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Objectives The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were >50 copies/mL in both compartments and bulk genotypic tests were realized. Results On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P = 0.0455) and T215Y (P = 0.0455). Conclusions In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performe

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice