Objectives
We assessed whether changes in community viral load (CVL) over time were associated with the rate of new HIV diagnoses (NDs).
Methods
HIV‐1‐positive individuals referred to our institute ...and permanently residing in our province were considered for inclusion in the study. A total of 861 HIV‐infected adults with at least one HIV RNA measurement (12 530 measurements in total) between 2008 and 2014 were included. Viraemia copy‐years were calculated from all HIV RNA values for each patient using the trapezoidal rule; multiple CVL indicators were considered. Total NDs and recent infections (< 1 year) were analysed separately. The association between NDs and CVL was tested by means of mixed Poisson models, with CVL as a fixed effect and year as a random effect.
Results
The incidence of NDs was 2.28 per 100 000 residents in 2008 and 2.52 per 100 000 residents in 2014. Total numbers of NDs and recent infections did not vary significantly over time (P for trend 0.879 and 0.39, respectively). Mean HIV RNA decreased from 31 095.8 HIV‐1 RNA copies/mL in 2008 to 21 231.5 copies/mL in 2014 (P < 0.001); a downward trend was always observed regardless of the CVL indicator considered. Depending on the indicator, there were some differences in CVL by patient characteristics. The most substantial contributors to CVL appeared to be male individuals, men who have sex with men (MSM), non‐Italians, and untreated subjects (all P < 0.05). The relative risk of ND increased among Italians and MSM with an increasing proportion of subjects having an undetectable HIV RNA, and decreased in the same population with increasing levels of CVL.
Conclusions
In our setting, CVL represented a good marker of access to care and treatment; however, reduced CVL did not coincide with a reduction in the rate of NDs.
Abstract Background In HIV/HCV co-infected patients, HIV-1 gp120 activates human hepatic stellate cells (HSCs) which play a key role in fibrosis pathogenesis. It is still unclear whether ...pro-fibrogenic effects are more attributable to X4 or R5 strains in vivo. Objective To assess if HIV-1 X4 or R5 variants are associated with a different progression of fibrosis. Study design A total of 105 HIV/HCV co-infected patients were submitted to gp120 sequencing on proviral DNA and classified as X4 or R5 based on g2p (20% false positive rate). The fibrosis evolution was retrospectively determined by means of APRI and FIB-4 scores at 3-month intervals from the first anti-HCV-positive test. The association of co-receptor tropism with increased fibrosis scores was evaluated by linear mixed models. Results X4 variants were found in 41 patients (39%). The median observation period was similar in X4 and R5 patients (17 years). No difference was observed between the two groups of patients, except for nadir CD4 which was lower in X4 compared to R5 (percentage, p = 0.005, and absolute number, p = 0.005). X4 and R5 patients did not significantly differ for FIB-4 and APRI score over time ( p = 0.5, and p = 0.1, respectively). No association between HCV-RNA levels over time and co-receptor tropism was noted ( p = 0.9). Conversely, a significant correlation of fibrosis scores with gamma-glutamyl transferase levels, lower current CD4 count, HIV viremia and use of antiretrovirals was observed. Conclusions This retrospective analysis of fibrosis evolution did not support the evidence of a differing pro-fibrogenic activity for X4 and R5 HIV-1 variants in HIV/HCV co-infected patients.
Paired PBMCs and plasma samples from 34 HIV-infected patients were studied to verify the relationship between coreceptor use based on genotyping of V3 region of HIV-1 envelope gp120 and biological ...phenotype with virus isolation and subsequent correlation to clinical characteristics. The “11/25” rule, geno2pheno and PSSM were compared. All SI patients were HIV-1 subtype B (
p
=
0.04) and had a lower CD4 count than NSI patients (
p
=
0.01), while no differences were observed in mean HIV-RNA
log (
p
=
0.6). SI phenotype was not associated with AIDS-defining events (
p
=
0.1) or with concurrent antiretroviral therapy (
p
=
0.4). With geno2pheno, which shows the highest sensibility (83%), an X4 or X4/R5 genotype in PBMC DNA was also associated to B-subtype and lower CD4 count (
p
=
0.01) compared to R5 isolates. Based on plasma RNA sequences, the predicted coreceptor usage agreed with PBMC DNA in 79% of cases with the “11/25” rule, 82% with geno2pheno, and 82% with PSSM. A X4 virus in plasma (but not in PBMCs) was significantly associated with HAART in all three methods (
p
=
0.01 for “11/25” rule,
p
=
0.01 for geno2pheno and
p
=
0.03 for PSSM). Due to viral mixtures and/or difficulties in genotype interpretation, current V3 sequence-based methods cannot accurately predict HIV-1 coreceptor use.
One hundred and ninety-two
pol sequences of drug-naïve and drug-experienced subjects infected with non-B HIV-1 subtypes were analyzed to identify treatment-related amino acid changes which might be ...relevant for drug-resistance and possibly not included in the accepted mutation list for the B subtype. The correspondence analysis identified non-B-specific and subtype-specific polymorphisms which should not be mistaken for mutations. Multiple
χ
2 were performed to detect the differences between naïve vs treated subjects and between different subtypes. To verify the contribution of each single mutation to the resistance levels as predicted by the
Virtual Phenotype™—LM, simple univariate linear regression was used with fold resistance as a dependent variable and individual mutations as predictors. Commonly accepted protease (PR) and reverse transcriptase (RT) positions along with mutants at RT positions 118 and 90 were significantly associated with treatment. Two unusual PR (K14R and I66F) and five RT positions (E28K, S68G, H221Y, L228R/H and P294A) were also associated with treatment (
p
<
0.01). Only minimal variations were observed with respect to commonly accepted amino acid changes. All amino acid changes correlated with treatment influenced the resistance levels to each single drug. Our findings demonstrate that there are no substantial differences regarding known resistance-associated mutations and the newly emergent substitutions between non-B and B subtype strains.
Thirty pol gene plasma-derived sequences clustering with the circulating recombinant form (CRF) 02_AG (IbNG) (bootstrap 100%) were evaluated to analyze the genomic composition. Subtype assignment was ...also phylogenetically confirmed by C2-V3 region analysis for 18/21 sequences evaluated. Thereafter, we compared the genomic recombination of the CRF02_AG/IbNG prototype as predicted by bootscanning and Jumping HMMER software (jpHMM) to that of our strains. With these methods, 27% and 50%, respectively, of our clinical sequences demonstrated the same pol structure as the prototype CRF02_A/G-IbNG. However, in subtrees built for each segment predicted by jpHMM (with a bootstrap value of more than 75%), all fragments clustered with IbNG and were distinct from A and G clades. Overall, our sequences resulted in true members of CRF02_AG-IbNG, which, however, appeared to be a subtype phylogenetically separate from A or G, at least with regard to the pol gene.
Lithium (Li) has been shown to increase the platelet number after chemotherapy. The present paper suggests that Li may increase the platelet aggregation induced by sub-optimal concentrations of ADP. ...Conversely, rubidium does not modify platelet aggregation in the present experiments.
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