To define the impact of coinfection with hepatitis B virus (HBV) or hepatitis C virus (HCV) on viroimmunological response to raltegravir-based salvage regimens that also include new HIV inhibitors ...such as maraviroc, darunavir and etravirine.
We used data from a national observational study of patients starting raltegravir-based regimens to compare virological suppression and CD4 cell change from baseline in patients with and without concomitant HBV or HCV infection.
Overall, 275 patients (107 coinfected and 168 non-coinfected) were evaluated. Coinfected patients were more commonly former intravenous drug users and had a longer history of HIV infection and higher baseline aminotransferase levels. Both HIV-RNA and CD4 response were similar in the two groups. Mean time to first HIV-RNA copy number <50 copies/mL was 4.1 months (95% CI 3.5-4.6) in non-coinfected patients and 3.9 months (95% CI 3.3-4.5) in coinfected patients (hazard ratio 1.039, 95% CI 0.761-1.418, P = 0.766, log-rank test). The risk of developing new grade 3-4 hepatic adverse events was significantly higher in coinfected patients (hazard ratio 1.779, 95% CI 1.123-2.817, P = 0.009). The two groups of coinfected and non-coinfected patients had similar rates of interruption of any baseline drug (hazard ratio 1.075, 95% CI 0.649-1.781, P = 0.776) and of raltegravir (hazard ratio 1.520, 95% CI 0.671-3.447, P = 0.311). Few AIDS-defining events and deaths occurred.
Viroimmunological response to regimens based on raltegravir and other recent anti-HIV inhibitors is not negatively affected by coinfection with HBV or HCV. Liver toxicity, either pre-existing or new, is more common in coinfected patients, but with no increased risk of treatment interruption.
Few data have been reported on the dynamics of HIV-1 DNA during intermittent highly active antiretroviral therapy (HAART). In this study, we measured cell-associated HIV-1 DNA and provirus-infected ...cells during the Istituto Superiore di Sanità-Pulsed Antiretroviral Therapy (ISS-PART) clinical trial.
HIV-1 DNA was measured by real-time polymerase chain reaction (PCR) in the peripheral blood mononuclear cells (PBMCs) of 37 subjects enrolled in the ISS-PART, a randomized clinical trial comparing 24 months of intermittent (arm B) versus continuous (arm A) HAART in chronic HIV infection. In 14 subjects, the number of provirus-infected cells was also measured at baseline and at month 24.
At baseline, the number of HIV-1 DNA copies/10(6) PBMCs was similar in arm B (mean +/- SD: 121 +/- 172, median = 35) and arm A (mean +/- SD: 107 +/- 153, median = 10) (P = not significant n.s.). No significant variations occurred over time; at 24 months, the HIV-1 DNA level was 77 +/- 28 (median = 30) copies/10(6) PBMCs in arm B and 166 +/- 321 copies/10(6) PBMCs (median = 10) in arm A (P = n.s.). At baseline, the provirus-infected cell counts were 85 +/- 98 (median = 50) cells/10(6) PBMCs in arm B and 92 +/- 113 (median = 50) cells/10(6) PBMCs in arm A (P = n.s.), with no variations at 24 months.
These findings suggest that the intermittent schedule of the ISS-PART has no major impact on viral reservoirs, at least in a midterm follow-up.
There is limited information on pregnancy loss in women with HIV, and it is still debated whether HIV-related markers may play a role.Objectives: To explore potential risk factors for pregnancy loss ...in women with HIV, with particular reference to modifiable risk factors and markers of HIV disease.
Multicenter observational study of HIV-positive pregnant women. The main outcome measure was pregnancy loss, including both miscarriage (<22 weeks) and stillbirth (≥22 weeks). Possible associations of pregnancy loss were evaluated in univariate and multivariate analyses.
Among 2696 eligible pregnancies reported between 2001 and 2018, 226 (8.4%) ended in pregnancy loss (miscarriage 198, 7.3%; stillbirth 28, 1.0%). In multivariate analyses, only older age (adjusted odds ratio AOR per additional year of age: 1.079, 95% confidence interval CI 1.046-1.113), HIV diagnosis before pregnancy (AOR: 2.533, 95%CI 1.407-4.561) and history of pregnancy loss (AOR: 1.625, 95%CI 1.178-2.243) were significantly associated with pregnancy loss. No significant association with pregnancy loss was found for parity, coinfections, sexually transmitted diseases, hypertension, smoking, alcohol and substance use, CD4 cell count, HIV-RNA viral load, and CDC HIV stage.
Older women and those with a previous history of pregnancy loss should be considered at higher risk of pregnancy loss. The severity of HIV disease and potentially modifiable risk factors did not increase the risk of pregnancy loss.
Some studies on untreated patients have shown a general correlation between plasma HIV copy number and plasma infectivity in in vitro models. Recent observations also indicate that HIV-RNA level is ...an important predictor of perinatal transmission and may also have a role in heterosexual transmission. To further analyse the correlation between HIV viral load and plasma infectivity, we studied the relationship between HIV-1 plasma copy number and plasma infectivity prior to and during treatment with antiretroviral combination regimens in HIV-1 infected adults. Plasma infectivity was assessed in vitro by coculture of plasma from HIV-positive patients with PHA-stimulated fresh PBMC from uninfected donors. A positive plasma isolation, in almost all cases (43/45) and irrespective of treatment status, was associated with an HIV viral load higher than 100 000 copies per ml, with higher plasma HIV-1 RNA values in isolation-positive samples compared with isolation-negative samples (median values, 710 000 vs. 37 500 copies per ml, respectively). SI and NSI strains had similarly high viral load values (470 000 vs. 790 000 copies per ml), but CD4 counts were lower in the SI phenotype group. Our data indicate that low levels of viral load are only exceptionally associated with isolation from plasma in the in vitro model we used. This observation confirms indirectly the presence of an association between viral load and infectivity. The requisite of a high plasma viral load in order to obtain infectivity (i.e. positivity of HIV isolation from plasma) also seems maintained under antiretroviral treatment, adding confidence in the conclusion that reductions in viral load translate into reduction of plasma infectivity. Due to the extreme complexity of factors determining transmission, a very prudent interpretation of the results is essential when information from experimental studies has to be transferred to clinical situations requiring assessment of risks or clinical decisions.
To evaluate the quality of life outcomes in antiretroviral-naive patients randomized to zidovudine plus didanosine versus zidovudine plus didanosine plus nevirapine for treatment of advanced HIV ...disease (the Istituto Superiore di Sanità 047 trial).
A 48-week randomized, double-blind trial.
Sixty patients were enrolled and evaluated over 24 weeks. Quality of life was assessed using a modified version of the Medical Outcomes Study-HIV Health Survey. For analysis, we calculated two summary scores reflecting the physical (PHS) and the mental (MHS) components of health.
Although the three-drug combination was superior at inducing immunologic and virologic responses, the two-drug regimen was superior for both PHS and MHS, especially at week 8 where differences were both statistically and clinically significant (5.8 and 9.2 points, respectively, P< 0.02 for both). Quality of life changes paralleled trends in body weight and Karnofsky performance status score.
Although a three-drug antiretroviral therapy regimen was superior in terms of short term virologic/immunologic response, the two-drug regimen was better in terms of quality of life. In general, triple therapy remains the most effective treatment option. However, quality of life assessments can yield results that may be discordant with and complementary to those obtained using conventional endpoints. Comparative trials should collect a comprehensive range of outcome measures, including patient-reported quality of life, in order to provide clinicians and patients with additional information that may influence treatment decisions.
Dyes are organic compounds used in textile, food and drug industries, and their abatement represents one of the main problems in the treatment processes because generally they are very stable toxic ...compounds. In this work, two commercial azo-dyes, i.e. Congo Red (C
32H
22N
6Na
2O
6S
2) and Patent Blue (C
27H
31N
2NaO
6S
2), in aqueous solution were degraded in a photocatalytic membrane reactor by using TiO
2 Degussa P25 as the catalyst. Different system configurations and irradiating sources were studied, and the influence of some operational parameters such as the pressure in the membrane cell and the initial concentration of the substrates was determined. A comparison between suspended and entrapped TiO
2 was also done. The experimental results showed a satisfactory degradation efficiency of the photocatalytic membrane process. The influence of various parameters (e.g. feed concentration, recirculation rate) has been discussed to obtain high reaction rates, operating stability and high membrane rejection, both for substrates and by-products. Congo Red was photodegraded with higher rate under the same experimental conditions probably due to its higher adsorption onto the catalyst surface. It was possible to treat successfully highly concentrated solutions (500
mg/L) of both dyes by means of a continuous process obtaining good values of permeate fluxes (30–70
L/m
2
h); this could be interesting for industrial applications. The reactor containing the suspended photocatalyst was significantly more efficient than the reactor containing the catalyst entrapped into the membrane.
Background
Most of the studies evaluating rash in HIV‐positive patients have focused on nonnucleoside reverse transcriptase inhibitors (NNRTI), particularly nevirapine, and little is known about the ...occurrence of rash and the risk factors for its development in patients receiving regimens not based on NNRTI.
Methods We evaluated all cases of rash observed during a 48‐week randomized multicentre trial in 1251 nucleoside‐experienced patients who started treatment with protease inhibitors (ritonavir or indinavir) at CD4 counts below 50 cells/μL. Incidence rates for rash were calculated according to gender, clinical status, age, use of highly active antiretroviral therapy (HAART), Pneumocystis carinii pneumonia (PCP) prophylaxis and use of individual antiretroviral drugs at enrolment. Differences between groups defined according to the above characteristics were tested for statistical significance using the log‐rank test in a Kaplan‐Meier survival analysis. All factors that gave results in the univariate analyses below the significance level of 0.05 were included in a multivariate analysis using a Cox regression model.
Results During a follow‐up period of 9690 person‐months, 66 patients (5.3%) developed rash (0.68 events/100 person‐months). In the univariate analyses, risk of rash did not differ with trial treatment (indinavir or ritonavir), clinical status, PCP prophylaxis, or age. During follow‐up, rash was observed in 7.5% of enrolled women and in 4.5% of enrolled men (P=0.03). Serious rash occurred in 4.5% of enrolled women and in 1.6% of enrolled men (P=0.003). Use of HAART (P<0.001) and inclusion of zidovudine and of zalcitabine in the prescribed regimen (P=0.02) appeared to be associated with a lower risk of rash. In the multivariate analysis, the variables that remained significantly predictive of rash were gender (risk for women compared to men: 1.65, 95% confidence interval (CI): 1.00–2.72, P=0.048) and use of a non‐HAART regimen (risk for non‐HAART patients compared to HAART: 2.73, 95% CI: 1.49–5.02, P=0.001).
Conclusions In our study, about 5% of HIV‐positive patients who started treatment with protease inhibitors at very low CD4 counts developed rash, generally in the first few weeks after treatment. Risk was significantly higher in women and in patients who did not receive a HAART regimen. Our data indicate that women have a higher risk of rash than men, also with regimens that do not include NNRTI.
Residual viraemia is detectable in the majority of human immunodeficiency virus (HIV)-infected subjects with plasma HIV-1 RNA <50 copies ml(-1). In the present study, the impact of repeated treatment ...interruptions on residual HIV-1 viraemia was investigated in 58 subjects enrolled in the ISS-PART, a multicentre, randomized clinical trial comparing 24 months of continuous (arm A) and intermittent (arm B) highly active antiretroviral therapy (HAART). Residual viraemia was measured by a modified Roche Amplicor HIV-1 RNA assay (limit of detection 2.5 copies ml(-1)). At baseline, the median value of residual viraemia was 2.5 copies ml(-1) in both arms; after 24 months, the median value was 2.5 in arm A and 8.3 in arm B. The median change from baseline to month 24 was significantly different between patients under continuous or intermittent HAART: 0 copies ml(-1) (range -125.2 to +82.7) of HIV-1 RNA in arm A versus 2.1 copies ml(-1) (range -80 to +46.8) in arm B (P=0.024). These results suggest that intermittent HAART tends to modify HIV-1 viraemia set point even if a virological response is achieved after HAART reinstitution.
Background
AIDS defining events occur infrequently in the presence of CD4 counts above 200 cells/µL. It is, however, uncertain for most of the AIDS defining conditions whether this threshold can be ...considered equally safe in patients with a previously very low CD4 nadir.
Methods
We evaluated in detail all the AIDS defining events observed during a 48‐week clinical trial in 1251 nucleoside reverse transcriptase inhibitor‐experienced patients who started protease inhibitors (PIs) at CD4 counts below 50 cells/µL. The type of event, immunological status at the moment of event and time between start of PI treatment and event occurrence were analysed cumulatively and by event type; event rates were calculated.
Results
Concomitant data on CD4 counts were available for 338 AIDS defining events (81% of total events). Median time between start of treatment with PI and event was 94.5 days and median absolute CD4 value at the occurrence of event was 20 per µL. Only 14 events (in 12 patients) were observed above the threshold of 200 CD4 cells/µL. An analysis of the 67 deaths with concomitantly available CD4 counts (57%) showed a median CD4 count of 10 cells/µL, with only four deaths occurring in the presence of a CD4 count above 100 cells/µL.
Conclusions
Very few clinical AIDS defining conditions were observed in patients who start PIs at very low CD4 counts and with treatment restore absolute values in CD4 counts above 200 cells/µL. This threshold can therefore be considered a clinically effective goal of treatment with respect to occurrence of all AIDS defining conditions in patients starting PIs in very advanced HIV disease.
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