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.
This study in Italy aimed to evaluate the epidemiological, clinical and therapeutic aspects of hepatitis B virus (HBV) infection in a population of recent (< 6 months) immigrants. Between February ...2003 and December 2004, 83 (9.3%) out of 890 immigrants tested positive for hepatitis B surface antigen. All were men and 62.6% came-from Africa, 21.6% from Asia and 16.8% from Eastern Europe. About half (54.3%) of the patients had elevated alanine aminotransferase levels and detectable serum HBV DNA. Genotype distribution was as follows: E (20 cases), D (14 cases) and A (11 cases). Our study underscores the potential of migratory flow to introduce genotype non-D hepatitis B virus into our country.
Doravirine is a novel, nonnucleoside reverse transcriptase inhibitor with demonstrated efficacy in treatment-naive adults with HIV-1.
In this open-label, active-controlled, noninferiority trial, ...adults with HIV-1 virologically suppressed for ≥6 months on 2 nucleoside reverse transcriptase inhibitors plus a boosted protease inhibitor, boosted elvitegravir, or a non-nucleoside reverse transcriptase inhibitor were randomized (2:1) to switch to once-daily, single-tablet doravirine 100 mg with lamivudine 300 mg and tenofovir disoproxil fumarate 300 mg (DOR/3TC/TDF) or to continue their current therapy (Baseline Regimen) for 24 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA <50 copies/mL (defined by the FDA Snapshot approach), with the primary comparison between DOR/3TC/TDF at week 48 and Baseline Regimen at week 24 and a secondary comparison between the groups at week 24 (noninferiority margin, -8%).
Six hundred seventy participants (447 DOR/3TC/TDF, 223 Baseline Regimen) were treated and included in the analyses. At week 24, 93.7% on DOR/3TC/TDF vs 94.6% on Baseline Regimen had HIV-1 RNA <50 copies/mL difference -0.9 (-4.7 to 3.0). At week 48, 90.8% on DOR/3TC/TDF had HIV-1 RNA <50 copies/mL, demonstrating noninferiority vs Baseline Regimen at week 24 difference -3.8 (-7.9 to 0.3). In participants on ritonavir-boosted protease inhibitor at entry, mean reductions in fasting LDL-C and non-HDL-C at week 24 were significantly greater for DOR/3TC/TDF vs Baseline Regimen (P < 0.0001). Adverse events occurred in 68.9% on DOR/3TC/TDF and 52.5% on Baseline Regimen by week 24, leading to treatment discontinuation in 2.5% and 0.4%, respectively.
Switching to once-daily DOR/3TC/TDF is a generally well-tolerated option for maintaining viral suppression in patients considering a change in therapy.
ClinicalTrials.gov NCT02397096.
In patients with HIV, immune reconstitution after antiretroviral therapy (ART) is often incomplete. We assessed the probability of patients reaching a CD4/CD8 ratio of 1 or more after the start of ...ART and its association with the onset of non-AIDS-defining events and death.
We did an analysis of the ICONA cohort, which recruited treatment-naive patients with HIV in Italy. We included participants in the cohort who started ART, reached an undetectable viral load (≤80 copies per mL), and had a CD4/CD8 ratio of less than 0·8 at the time of an undetectable viral load. We defined ratio normalisation in patients as two consecutive values of 1 or more. We used Kaplan-Meier curves to estimate the cumulative probability of ratio normalisation. We then used Poisson regression models to identify factors independently associated with normalisation and with progression to non-AIDS-defining events or death.
We included 3236 participants, enrolled between Jan 22, 1997, and Feb 25, 2013. At the start of ART, median CD4/CD8 ratio in our population was 0·39 (IQR 0·26-0·55). 458 (14%) patients reached a CD4/CD8 ratio of 1 or more; the estimated probability of normalisation was 4·4% (95% CI 3·7-5·2) by 1 year from baseline, 11·5% (10·2-13·0) by 2 years, and 29·4% (26·7-32·4) by 5 years. Factors associated with normalisation were high pre-ART CD4 cell counts, a high CD4/CD8 ratio at baseline, and negative cytomegalovirus serological findings. The incidence rate of non-AIDS-defining events for patients with a CD4/CD8 ratio of less than 0·30 (4·2 per 100 patient-years, 95% CI 3·4-5·3) was double that for those with a ratio of 0·30-0·45 (2·3, 2·1-2·5) or more than 0·45 (2·2, 1·7-2·9). A ratio of less than 0·30 was independently associated with an increased risk of non-AIDS-defining events or death compared with one of more than 0·45.
Few patients had normalised CD4/CD8 ratios, even though they had viral suppression. Low ratios were associated with increased risk of serious events and deaths. The CD4/CD8 ratio could be used by clinicians to identity patients at risk of non-AIDS-related events.
AbbVie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp & Dohme, ViiV Italy.
To better understand whether potent antiretroviral therapies can modify the natural history of HIV-1-associated microsporidiosis and cryptosporidiosis, the response to antimicrobial treatment of ...these opportunistic infections was evaluated in patients with or without antiretroviral treatment. Fifty patients with diarrhoea, all positive for Cryptosporidium parvum or Enterocytozoon bieneusi, were included in the study. Retrospective data were collected concerning demographics, clinical and microbiological characteristics of the parasitic infection, antiretroviral therapy and prophylaxis against opportunistic infections. Faecal samples were prepared using the Richie formalin-ethyl acetate method and stained using the modified Ziehl-Neelsen method for detection of Cryptosporidium parvum and Isospora belli, the modified trichrome and calcofluor white technique for detection of Enterocytozoon spp., and iodine for detection of ova, cysts or vegetative forms. Diarrhoea was defined as an abnormal increase in stool liquidity, an abnormal increase in stool frequency and a daily stool weight of more than 250 g for a period of at least 4 days. Patients treated with double antiretroviral therapy or protease inhibitors demonstrated an excellent response and a sustained therapeutic effect after follow-up (range, 5-36 months). The relapse of cryptosporidiosis in two patients who discontinued antiretroviral therapy suggests that the infection might remain in a latent stage. The resolution of the diarrhoea seems to be related to an increased CD4+ cell count rather than to the viral load. In conclusion, these data strongly support the hypothesis that combination antiretroviral therapy is able to greatly modify the course of cryptosporidiosis and microsporidiosis in patients infected with HIV-1.
To assess the prevalence of cryoglobulinemia in three groups of patients: HCV-positive/HIV-negative, HCV/HIV co-infected and HIV mono-infected.
From September 2002 to December 2003, 58 patients with ...documented HCV infection, 70 subjects with HIV/HCV co-infection, and 48 subjects with HIV infection alone were enrolled. Serum samples were tested for detectable cryoglobulins, liver enzymes, HCV viral load and HCV genotypes. Plasma HIV-RNA levels and CD4
+ cell count were also evaluated in HIV-positive subjects.
Cryoglobulinemia was detected in 24.1% HCV mono-infected, 14.2% HCV/HIV co-infected and 6% HIV mono-infected patients. A significant statistical correlation was found between the presence of cryoglobulins and HCV infection (
P=0.03), while cryoglobulins were unrelated to HIV mono-infection (
P=0.16) and HCV/HIV co-infection (
P=0.7). No significant correlation was observed between the presence of cryoglobulinemia and alanine transaminase (ALT) levels, HCV viremia and duration of HCV infection. Circulating cryoglobulins in HIV patients were not correlated with plasma HIV viral load, CD4
+ cell count or duration of HIV infection. Only two HCV mono-infected patients complained of arthralgia.
A similar rate of cryoglobulinemia prevalence was detected in the patient groups with an HCV-related infection. HIV infection does not appear to play a significant role in cryoglobulin production.
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