Purpose
To provide information about main pregnancy outcomes in HIV–HCV coinfected women and about the possible interactions between HIV and HCV in this particular population.
Methods
Data from a ...multicenter observational study of pregnant women with HIV, conducted in Italian University and Hospital Clinics between 2001 and 2015, were used. Eligibility criteria for analysis were HCV coinfection and at least one detectable plasma HCV-RNA viral load measured during pregnancy. Qualitative variables were compared using the Chi-square or the Fisher test and quantitative variables using the Mann–Whitney
U
test. The Spearman’s coefficient was used to evaluate correlations between quantitative variables.
Results
Among 105 women with positive HCV-RNA, median HCV viral load was substantially identical at the three trimesters (5.68, 5.45, and 5.86 log IU/ml, respectively), and 85.7 % of the women had at least one HCV-RNA value >5 log IU/ml. Rate of preterm delivery was 28.6 % with HCV-RNA <5 log IU/ml and 43.2 % with HCV-RNA >5log (
p
= 0.309). Compared to women with term delivery, women with preterm delivery had higher median HCV-RNA levels (third trimester: 6.00 vs. 5.62 log IU/ml,
p
= 0.037). Third trimester HIV-RNA levels were below 50 copies/ml in 47.7 % of the cases. No cases of vertical HIV transmission occurred. Rate of HCV transmission was 9.0 % and occurred only with HCV-RNA levels >5 log IU/ml.
Conclusions
Coinfection with HIV and HCV has relevant consequences in pregnancy: HIV coinfection is associated with high HCV-RNA levels that might favour HCV transmission, and HCV infection might further increase the risk of preterm delivery in women with HIV. HCV/HIV coinfected women should be considered a population at high risk of adverse outcomes.
The purpose of this investigation was to determine the impact on human immunodeficiency virus (HIV) tropism of uncontrolled virus exposure during 2 years of intermittent highly active antiretroviral ...therapy (HAART). The Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) randomized study compared the outcome of 2 years of structured treatment interruptions (STIs) versus standard continuous treatment in first-line HAART responder subjects. The STI schedule consisted of five STIs of 1, 1, 2, 2, and 3 months, respectively, separated by four periods of 3-month therapy. In the present study, coreceptor tropism was assessed in 12 patients of the STI arm at different time points over a period of 2 years. Tropism was determined on DNA and RNA by V3 loop region sequencing. The Geno2pheno algorithm (false-positive rate, FPR: 20 %) was used for data interpretation. At baseline, 9/12 subjects (75.0 %) had CCR5-tropic viruses in their HIV. Three had a CXCR4-tropic virus. Ten patients maintained the same coreceptor in DNA after 2 years, whereas in two patients, a shift occurred (one R5–X4, one X4–R5). In a patient with an R5 virus at baseline, a transient change to X4 tropism was seen in the rebounding virus during STI. Changes in tropism were not associated with the amplitude and duration of virus exposure during STIs, residual viremia at baseline, or the development of resistance mutations in the RT region. Our preliminary results suggest that viral replication, observed after short periods of treatment interruption, is not enough to drive the evolution of HIV tropism.
We evaluated rates and determinants of virological failure in triple-class experienced patients receiving raltegravir-based regimens from a national observational study over 48 weeks, defined by any ...one of the following: (1) no HIV-RNA suppression to undetectable levels (<50 copies/mL) during follow-up; (2) detectable viral load after obtaining undetectable levels; and (3) leaving the study before 48 weeks. Among 101 eligible patients, 26 (25.7%; 95% CI 17.2-34.2) had virological failure. No significant differences between patients with and without virological failure were observed for gender, age, route of transmission, baseline CD4/HIV-RNA, CDC group, hepatitis B or C co-infections, resistance (based on the last genotype available), type and number of concomitant drug classes, concomitant use of darunavir, atazanavir, etravirine, enfuvirtide or maraviroc, and health-related quality-of-life measures. A high rate of treatment response was observed. The analyses did not identify any baseline factor associated with failure, including resistance status. Even if we cannot exclude the presence of pre-existing minority resistant variants not captured by genotypic tests, the lack of baseline predictors of failure suggests the need to monitor patients closely during follow up for other factors, such as potential drug interactions and reduced levels of adherence, which may favour virological failure.
Simian-human immunodeficiency virus (SHIV) 89.6P is considered to be one of the most pathogenic chimeric viruses in rhesus macaques. However, when crossing from one to another species of monkeys the ...pathogenicity of this virus may be affected. By using SHIV-89.6Pcy₂₄₃, a virus obtained by passaging SHIV-89.6P in cynomolgus macaques, we investigated the dynamics of viral replication and the impact of the inoculum size (from 10 up to 50 monkey infectious dose) on the progression of the infection in 22 cynomolgus macaques. SHIV-89.6Pcy₂₄₃ caused massive depletion of CD4+ T-cells within 4 weeks of the inoculum, followed by an irreversible immune deficiency in a high proportion of the infected monkeys. This study demonstrates that SHIV-89.6Pcy₂₄₃ is pathogenic in cynomolgus macaques and that the dynamics of the viral replication and the rate of clinical progression depend on the size of the inoculum. Our findings provide unique and relevant data, particularly with regard to the value of the in vivo titration used to select the most appropriate infectious dose to study the “virus-host” interplay.
Background: No data are available on the use of atazanavir (ATV) in patients with end-stage liver disease (ESLD), and guidelines discourage its use in this setting. The objective of our study was to ...evaluate the efficacy and safety of unboosted ATV in patients infected with HIV and suffering from ESLD who had been screened for orthotopic liver transplantation (OLTx). Patients and Methods: This was a single-arm, 24-week pilot study. Atazanavir-naïve patients undergoing a highly active antiretroviral therapy were switched to ATV 400 mg daily plus two non-thymidine nucleoside reverse transcriptase inhibitors. Results: Fifteen patients (ten males and five females, age range 36-59 years) were enrolled in the study. Of these, 11 (73%) had a baseline CD4 cell count > 200 μl⁻¹, and 12 had undetectable plasma HIV-RNA. 12 subjects (80%) were able to remain on ATV until week 24 (n = 10) or transplantation (n = 2). At the end of the study, the median CD4 cell count was 340 μl⁻¹ , and nine of the ten patients had undetectable RNA. During the study period, two patients received a transplant, two died of intracerebral hemorrhage and lactic acidosis, respectively, and one discontinued ATV. Among the ten patients completing the 24-week study, no significant changes from baseline were observed for most of the liver function markers, with the exception of unconjugated bilirubin (from 1.15 mg/dl to 1.32 mg/dl, p = 0.047). Conclusions: Unboosted ATV treatment did not worsen liver disease and was able to maintain or gain immunovirological eligibility for OLTx in all patients, with a limited effect on unconjugated bilirubin. These results suggest that ATV is an easy-to-use drug in patients with ESLD.
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