Abstract
Background
to evaluate circulation of drug resistance mutations (DRMs), sub-types (ST) and Herpesviruses replication among subjects recently diagnosed as HIV infected (pts) in Veneto (Italy), over 16 years, comparing previously reported trends with the most recent one, updated to 2019.
Methods
on plasma from 2919 patients diagnosed from July 2004 to April 2019, protease (PR), reverse transcriptase (RT) and recently Integrase (In) were analyzed for DRMs, susceptibility profile (Stanford db) and ST. Potential low-level resistances were excluded. CMV-DNA and EBV-DNA were evaluated by in-house Real-Time-PCR in PBMCs.
Results
in 5 periods (2004/06, 07/09, 10/12, 13/16, 17–19) 334, 796, 752, 750 and 287 patients were recruited; non-B-ST were 21.9, 29.3, 33, 32.7 and 48.1% (33.5% Italians in 17–19), respectively. A significant increase of non-B-ST (P < 0.0001 for trend) and of the percentage of Italians with non-B-strains (P = 0.029) were observed. Resistance to PR or to multiple classes declined but not to non-nucleoside RT inhibitors (NNRTI) (Fig 1). E138A alone, not included in the previous evaluations, increased from 2.3 to 1.8, to 3.2, to 3.6, to 4.7% in 2017-19. No primary TDRM to In-Inhibitors (InIn) were found in 469 B-ST-Pts enrolled in 2014–19; 16% had major TDRM for RT/PI. Among 231 non-B patients, 12,5% with other TDRMs, only a 143C and a 66I were found. Accessory InIn-TDRMs were detected (Figures 2 and 3). Nevertheless, from 2009 to 2019 in Veneto 114 InIn-failed and potentially transmitters patients with In-DRMs were found. In 2017–19 17,3% of patients had CMV-DNA in PBMCs, with a median CD4 of 55 (8%), HIV-RNA 247251 cps/mL and EBV-DNA of 811 cps/106 PBMCs (3% were neg); Patients CMV-DNA-negative (82,7%) had median CD4 of 334 (18,9%), HIV-RNA 47770 cps/mL and a significantly lower EBV-DNA of 194 cps/106 PBMCs (15% were neg): differences between immuvirological variables were significant.
Conclusion
An increase of non-B strains and a slight increase of TDRMs among B-ST were observed. The persistent circulation of NNRTI-DRMs, the shortage of major In-TDRMs but a circulation of many In-polymorphisms have implications on the screening at baseline and on the selection of the first-line HAART. Many patients with lower CD4 and higher HIV replication has an incomplete control of co-infecting herpesviruses, which contribute to immunoactivation.
Disclosures
All authors: No reported disclosures.