Decrease In HIV-1 RNA Research Articles

Comparison of Metabolic Effects of Three Different Treatment Combinations with Retrospective Real-life Data in People Living with HIV.

Comorbidities are increasing in people living with HIV (PLHIV), and different treatment options have advantages and disadvantages. It is important to compare information from real-life treated cases. The aim of this study was to retrospectively evaluate the data on efficacy and clinical and laboratory findings during different antiretroviral therapies. Retrospective file data of 47 PLHIV using Dolutegravir and Lamivudine (3TC/DTG), Tenofovir Alafenamide Emtricitabine and Elvitegravir Cobicistat (EVG/c/TAF/FTC) and Tenofovir Disoproxil Fumarate and Emtricitabine and Efavirenz (EFV/FTC/TDF) were analyzed. Data of the patients at baseline and 12 months after antiretroviral therapy (ART) were compared. About 47 PLHIV were included in the study. Of the patients, 22 (46.8%) were in the 3TC/DTG group, 19 (40.4%) in the EVG/c/TAF/FTC, and 6 (12.8%) in the EFV/FTC/TDF group. After 12 months of treatment, BMI, HIV-RNA, CD4, WBC, hemoglobin, MCV, PDW, RDW, platelet count, creatinine, eGFR, HDL, AST, glucose values of the 3TC/DTG group were significantly different (p<0.05). After 12 months of treatment, BMI, HIV-RNA, CD4 count, MCV, creatinine, eGFR, HDL, LDL, TG, TC, AST, and HOMA-IR values of the EVG/c/TAF/FTC treatment group were significantly different (p<0.05). After 12 months of treatment, HIV RNA, total bilirubin, and LDL values in the EFV/FTC/TDF treatment group were statistically different (p<0.05). All treatment groups showed a decrease in HIV-RNA and an increase in CD4 at the end of one year. While CD4 elevation is lower in EFV recipients than in integrase inhibitor (INSTI) recipients, weight gain is higher in INSTI recipients. While the lipid profile was more positively affected in the 3TC/DTG group, lipid profiles were more negatively affected in the EVG/c/TAF/FTC group, although liver and kidney functions were preserved.

A Review on Therapeutic Application of CRISPR/Cas9 for HIV

Despite the significant progress that has been made in the battle against HIV-1, the virus remains a major threat to global health. Since it can only be suppressed with the utilization of highly active antiretroviral therapy, it remains a challenge to prevent the flow of the infection. According to UNAIDS, only 70% of individuals with HIV are diagnosed and only 53% are treated. This means that 44% of the tainted people have undetectable viral load. Despite the efforts made by various governments and private organizations, the battle against HIV infection remains a challenge that requires a comprehensive approach. The fast rise and evolution of technologies that enable the modification of qualities at the DNA level has raised hopes for an end to the epidemic. Through the employment of endonucleases, we've been able to build exact changes in DNA of being cells. The capacity to alter the outflow of the HIV gene by replicating the LTR promoter played vital role. If the promoter is edited, then the impact of viral transcription might be suppressed. Using aa more limited form of the nuclease Cas9, the evacuation of crucial parts of the infective agent ordering was with success performed in HIV transgenic mice. The outcomes showed that the decrease of HIV-RNA was significant in all examined tissues and circulating lymphocytes. (Kaminski et al. Gene Ther2016; 23:690-5). This review objective is to summarise the work of eminent researcher on the utilization of CRISPR-Cas’squality treatment for the treatment of HIV-1.

Terapi &lt;i&gt;Doxycycline &lt;/i&gt;pada Laki-laki Homoseksual dengan Sifilis Sekunder dan Infeksi &lt;i&gt;Human Immunodeficiency Virus&lt;/i&gt;

Background: Re-emergence of syphilis is increasing especially among MSM (men who have sex with men) patients. Syphilis in HIV-infected patients is reported to show faster and higher risk for progression to neurosyphilis. Co-infection of syphilis and human immunodeficiency virus (HIV) is correlated with decrease in CD4 and increase in HIV-RNA. Doxycycline has an antiinflammatory effect associated with decrease of HIV-RNA and increase of CD4 in HIV patients. Case: A 20 years old foreigner MSM man complained about non-itchy red spots throughout his body for 2 days with slight fever. He has a history of more than 10 sexual partners and rarely use condom. Physical examination revealed various sizes of erythematous macules and papules on his trunk and extremities. We found erythematous plaques with regular border but no ulcer on his scrotum and no secrete from his urethra. There was enlargement in the inguinal lymph node. VDRL and TPHA examinations were 1:32 and 1:640, respectively. HIV test was reactive with CD4 value 558 cells/ml. Treatment consists of doxycycline 2x100 mg for 14 days and also ARV (nevirapine, lamivudine and zidovudine). His symptoms were improved after a month accompanied with decreased VDRL to 1:2 and slightly increased CD4 to 570 cells/ml. Discussion: Doxycycline is a second line treatment for syphilis that is known to help decreasing the viral load and increasing CD4 level in syphilis with HIV. A significant decrease in VDRL titer in this patient indicates a successful therapy.

Safety, Immune, and Antiviral Effects of Pegylated Interferon Alpha 2b Administration in Antiretroviral Therapy-Suppressed Individuals: Results of Pilot Clinical Trial

In the pilot NCT01935089 trial, we tested whether pegylated interferon alpha2b (Peg-IFN-α2b) with antiretroviral therapy (ART) was safe and could impact HIV and immune measures in blood and in gut-associated lymphoid tissue (GALT). Twenty HIV-1+ ART-suppressed individuals received 1 μg/kg/week Peg-IFN-α2b with ART for 20 weeks, with intermediate 4-week analytical ART interruption (ATI). Safety, immune activation, HIV viral load and integrated HIV DNA in blood, and HIV RNA and DNA in gut biopsies were measured. A total of 7/20 participants experienced grade 3-4 adverse events, while 17/20 participants completed the study. Of the 17 participants who completed the study, 8 remained suppressed during ATI, while all 17 were suppressed at end of treatment (EoT). As expected, treatment increased activation of T and natural killer (NK) cells and IFN-stimulated molecule expression on monocytes in periphery. While circulating CD4+ T cells showed a trend for a decrease in integrated HIV DNA, GALT showed a significant decrease in HIV-1 RNA+ cells as measured by in situ hybridization along with a reduction in total HIV DNA and cell-associated RNA by EoT. The observed decrease in HIV-1 RNA+ cells in GALT was positively associated with the decrease in activated NK cells and macrophages. This study documents for the first time that 20 weeks of immunotherapy with Peg-IFN-α2b+ART (inclusive of a 4-week ATI) is safe and results in an increase in blood and GALT immune activation and in a significant decrease in HIV-1 RNA+ cells in GALT in association with changes in innate cell activation.

Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection.

Across many settings, lack of virologic control remains common in people with HIV (PWH) because of late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remains prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH). We recruited PWH initiating antiretroviral therapy and PWOH at 2 sites in the United States. One hundred eight adults were enrolled (56 PWOH and 52 PWH), most of whom had a second assessment at least 24 weeks later (193 total assessments). Tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), neopterin, soluble CD14, and neurofilament light chain protein (NFL) were measured in plasma and cerebrospinal fluid (CSF). Using multivariate models including Bayesian model averaging, we analyzed factors associated with global neuropsychological performance (NPT-9) and CSF NFL at baseline and over time. At baseline, higher CSF MCP-1 and plasma sCD14 were associated with worse NPT-9 in PWH, while CSF HIV RNA decrease was the only marker associated with improved NPT-9 over time. Among PWH, higher CSF neopterin was most closely associated with higher NFL. Among PWOH, higher CSF MCP-1 was most closely associated with higher NFL. After antiretroviral therapy initiation, decrease in CSF MCP-1 was most closely associated with NFL decrease. Monocyte-associated CSF biomarkers are highly associated with neuronal damage in both PWH and PWOH. More research is needed to evaluate whether therapies targeting monocyte-associated inflammation may ameliorate HIV-associated neurobehavioral diseases.

Early Progression and Immune Reconstitution Inflammatory Syndrome During Treatment of Mild-To-Moderate Kaposi Sarcoma in Sub-Saharan Africa and South America: Incidence, Long-Term Outcomes, and Effects of Early Chemotherapy.

Early progression of AIDS-associated Kaposi sarcoma (KS-PD) and immune reconstitution inflammatory syndrome (KS-IRIS) sometimes occur after the initiation of antiretroviral therapy (ART). Early KS-PD and KS-IRIS were assessed in the A5264/AMC-067 trial in which participants with mild-to-moderate AIDS-KS were randomized to initiate ART with either immediate or as-needed oral etoposide. Early KS-PD was defined as tumor progression within 12 weeks of ART initiation. When investigators had concern that early KS-PD was KS-IRIS, additional evaluations were performed. Suspected KS-IRIS was defined as early KS-PD accompanied by a CD4 count increase of ≥50 cells per cubic millimeter or plasma HIV-1 RNA decrease of ≥0.5 log10 copies/mL. Clinical outcome was a composite end point categorized as failure, stable, and response at 48 and 96 weeks compared with baseline. Fifty of 190 participants had early KS-PD (27%): 28 had KS-IRIS and 22 were not evaluated for KS-IRIS. Early KS-PD and KS-IRIS incidences with immediate etoposide versus ART alone were 16% versus 39%, and 7% versus 21%, respectively. Week 48 clinical outcome was 45% failure, 18% stable, and 37% response for no early KS-PD; 82% failure, 2% stable, and 16% response for early KS-PD; and 88% failure, 0% stable, and 12% response for KS-IRIS. Cumulative incidence of KS tumor response by week 96 was 64% for no early KS-PD, 22% with early KS-PD, and 18% with KS-IRIS. Early KS-PD, including suspected KS-IRIS, was common after starting ART for AIDS-KS and was associated with worse long-term clinical outcomes. Starting ART concurrently with etoposide reduced the incidence of both early KS-PD and KS-IRIS compared with ART alone.

Effect of mobile text messages on antiretroviral medication adherence and patient retention in early HIV care: an open-label, randomized, single center study in south Florida

BackgroundPeople with HIV (PHIV) with limited access to health services often experience suboptimal antiretroviral therapy (ART) adherence. We investigated whether a daily text messaging intervention improves ART adherence and retention in early HIV care in PHIV in a south Florida hospital-based clinic.MethodsART-naïve PHIV receiving care through the clinic’s Ryan White HIV/AIDS Program were enrolled and randomly assigned to the intervention or control groups with a 1:1 ratio. The intervention group received a 1-way text message daily and the control group received standard care without receiving text message reminders for 6 months. HIV RNA and CD4 cell count were measured at baseline and post-intervention. Adherence to ART was defined as a visual analog scale of ≥ 90%. Retention in care was defined as continued engagement at study end.Results94 ART-naïve patients were randomized and 83 (85.6%) completed the study, of which 44 were in the intervention group and 39 were in the control group. At the end of the 6-month study period, adherence to ART was 84.4% in the intervention group versus 73.5% in the control group (OR, 1.9; 95% CI 0.7–5.0; p = 0.194). Retention in care significantly improved in the intervention group compared to the control group with the odds of retention increasing by 20% (OR, 1.2; 95% CI 1.1–1.5; p = 0.006). Undetectable HIV RNA (< 50 copies/mL) was 86.7% in the intervention group versus 73.5% in the control group (OR, 2.3; 95% CI 0.8–6.9; p = 0.112). A significant increase in CD4 cell count and a decrease in HIV RNA were found at study end, with no differences between the two groups.ConclusionsIn this pilot study, a one-way daily text messaging intervention did not improve ART adherence over a 6-month study period, but significantly enhanced patient retention in early HIV care. Implementation of interventions to improve adherence in this population is required.

Reduction of HIV-1 Reservoir Size and Diversity After 1 Year of cART Among Brazilian Individuals Starting Treatment During Early Stages of Acute Infection.

The aim of early combined antiretroviral therapy (cART) of HIV is to limit the seeding of the viral reservoir during the initial phase of infection and, consequently, decrease intrahost viral diversity. Here, we assessed the effect of early cART on size and complexity of the proviral reservoir. Peripheral blood mononuclear cell (PBMC) and plasma samples were obtained from ten HIV-infected Brazilian individuals diagnosed at the acute phase of infection, before (PREART) and 12 months (M12ART) after suppressive cART. HIV proviral reservoir size was determined by quantitative real-time PCR; intrahost viral diversity of the env C2-V3 region was assessed by single genome amplification or next-generation sequencing in PBMC and plasma, respectively. Mean nucleotide diversity (π) and normalized Shannon entropy (HSN) were used to infer the complexity of the viral population. Compared to PREART, M12ART saw an immunological recovery with a gain of ∼200 CD4+ T cells (P = 0.008) and a normalization of the CD4/CD8 ratio [1.0 (IQR: 0.88–1.18), P = 0.016], as well as a significant decrease in HIV-1 RNA (∼4 log, P = 0.004) and DNA (∼1 log, P = 0.002) levels. The median time to achieve viral suppression was 3 months (IQR: 2.8–5.8 months). The high intermixing between sequences from both visits suggests that the HIV-1 DNA reservoir remained remarkably stable under cART. After 1 year of cART, there was a minor reduction in proviral π (PreART = 0.20 vs. M12ART = 0.10; P = 0.156) but a significant decrease in HSN (PreART = 0.41 vs. M12ART = 0.25; P = 0.019). We found no correlation between π or HSN at PreART and the rate of HIV DNA decay, T CD4+ counts, or CD4/CD8 ratio at M12ART. Based on a small cohort of Brazilian infected individuals under early cART and analyses of the env region, 1 year of follow-up suggested a reservoir size reduction, allowed a significant decrease of HIV-1 complexity, and achieved immunological restoration regardless of the initial HIV-1 plasma viral load, CD4+ T cell counts, or HIV-1 subtype. However, further studies in the Brazilian setting aiming a longer follow-up and larger cohort are required in this field.

Effectiveness, safety, durability and immune recovery in a retrospective, multicentre, observational cohort of ART-experienced, HIV-1-infected patients receiving maraviroc.

The aim of this retrospective, multicentre, observational study was to assess the durability, safety, immune recovery and effectiveness on viral suppression of antiretroviral therapy (ART) in a maraviroc (MVC)-based cohort. We collected clinical, demographical, immunological and virological parameters of adult HIV patients who were infected by CCR5-tropic virus and started an ART regimen containing MVC from 2005 to 2012. We created a longitudinal mixed model to assess the change over time of data. We enrolled 126 drug-experienced patients; the median duration of MVC treatment was 25 months. The probability of stopping ART at one year was 13.3%, and at three years was 27.3%. Statistically significant changes were observed for CD4+ cell count increase ( p < 0.001), HIV-RNA decrease ( p < 0.001) and total cholesterol decrease ( p = 0.005). Ninety-four patients (79.7%) had CD4 ≥ 200 cells/mm3 at baseline while nine of them reached this threshold at nine months (7.6%), 17 (13%) after nine months and six (5%) remained below 200 cells/mm3 at the end of the study. Overall, 114 patients (90.5%) achieved an HIV-RNA ≤ 50 cp/ml. A majority of patients maintained CD4 cell counts of ≥ 200 cells/mm3 and achieved an undetectable HIV viral load within three months. MVC-containing regimens are safe and appear to be a feasible therapeutic option for ART.

Soluble endothelial protein C receptor (sEPCR) as an inflammatory biomarker in naive HIV-infected patients during ART.

After the advent of ART, non-AIDS-related comorbidities are the main causes of death in HIV patients. Multiple biomarkers have been studied as markers of disease. We wanted to test soluble endothelial protein C receptor (sEPCR) in an HIV setting. The primary objective was to determine whether sEPCR decreases after 48 weeks of ART in naive HIV patients. Secondary objectives were to compare sEPCR levels between patients with chronic HIV infection (CHI) and primary HIV infection (PHI) and to analyse if there is a correlation between sEPCR and both immunovirological parameters and different markers of inflammation. We analysed sEPCR in 33 patients with CHI and 19 patients with PHI naive to ART. sEPCR was compared together with immunovirological parameters (HIV RNA and CD4 cell count) and IL-6 or D-dimer (DD). After 48 weeks of ART, in CHI, the sEPCR decrease was significant (P = 0.0006) and sEPCR at baseline was correlated with both CD4 cell increase (r = +0.463, P = 0.007) and HIV RNA decrease (r = -0.363, P = 0.038). In PHI, sEPCR was stable (P = 0.35); there was a correlation between 48 week DD change and IL-6 change (r = +0.696, P = 0.0009) and also between 48 week DD change and sEPCR change (r = +0.553, P = 0.014). Despite the small sample size, we hypothesize that sEPCR levels reflect coagulant pathway activation caused by the endothelial damage during chronic infection more than a marker of the cytokine storm that occurs during PHI. Alternatively, in PHI, the link found between sEPCR and DD secondary to IL-6 suggests sEPCR is an indirect marker of inflammation.

Unique Clinical Implications of HIV-Related Lymphoma

Since the introduction of combination antiretroviral therapy (cART) almost two decades ago, a number of changes have taken place in the spectrum of cancer affecting HIV-infected individuals. Although the incidence and proportion of deaths related to non-AIDS-defining malignancies, mostly infection-related cancers, are increasing, lymphoma is still a major complication of HIV-infection and is the most frequent neoplastic cause of death among HIV-infected individuals [1,2]. A decline in the incidence of lymphoma has been observed in the cART era, along with a concomitant increase in CD4 counts and a decrease of HIV RNA at lymphoma diagnosis. In general, the incidence of non-Hodgkin lymphoma (NHL) initially declined but has eventually stabilized. Nevertheless, the changes in the incidence of AIDS-related lymphoma (ARL) have been heterogeneous among the different lymphoma types. Cases of diffuse large B-cell lymphoma (DLBCL), especially primary CNS lymphoma, have decreased, while the proportion of Burkitt’s lymphoma (BL) cases have increased [3–5]. The incidence of Hodgkin’s lymphoma (HL) has remained stable and even increased in some cohorts [6,7]. This heterogeneity could be explained by the fact that the use of cART has decreased the proportion of HIV-infected individuals with low CD4 counts and, as a consequence, lymphomas that typically presented in severe immunosuppressed patients have diminished as well. This is the case of primary effusion lymphomas, plasmablastic lymphomas and primary CNS lymphoma, all having a higher incidence among patients with severe immunosuppression and poor HIV control. On the other hand, cART would act by increasing CD4 counts thereby facilitating the development of lymphomas with favorable biology and more likely to be cured, such as BL and HL [8]. Some changes have been observed in the presentation of HIV-associated lymphoma in the cART era. Regarding the transmission risk factor, there seems to have been an increase in the proportion of men who have sex with men and a decrease of intravenous drug users [5], probably due to the changes in the spectrum of HIV infection transmission in the population. Patients are older at lymphoma diagnosis, with higher

Virological response to short-course maraviroc monotherapy does not predict viral tropism in HIV-1-infected treatment-naive patients

We aimed to evaluate whether virological response to a short course of maraviroc monotherapy could predict HIV-1 tropism. A clinical trial was performed in HIV-1 treatment-naive patients infected with R5- or non-R5-tropic virus determined using the Trofile(®) assay, with >1000 HIV-1 RNA copies/mL. Maraviroc was administered for 10 days. Viral load was measured at baseline and days 4, 7, 10 and 28. The main outcome measurement was the decline in HIV-1 RNA at day 10. The trial was registered in the ClinicalTrials.gov database (NCT01060618; TROPISMVC). Forty patients [30 R5 and 10 dual/mixed (D/M)] were recruited. There was a significant decrease in HIV-1 RNA after 10 days of maraviroc treatment in patients with R5-tropic virus (median 1.52 log10 RNA copies/mL; 95% CI 1.23-1.63; P < 0.0001), but also in patients with D/M-tropic virus (median 1.62 log(10) RNA copies/mL; 95% CI 0.33-1.88; P = 0.00024). The difference in the HIV-1 RNA decrease (-0.16 log(10) RNA copies/mL; 95% CI -0.53 to 0.22) was not significant (P = 0.410). A decrease >0.5 log(10) RNA copies/mL was found in 96.3% of patients with R5-tropic virus and in 70% of patients with D/M-tropic virus (P = 0.052). The differences were not significant when a decline of 1 log(10) RNA copies/mL was considered (92.6% versus 70%; P = 0.11). Treatment-naive patients infected with R5- or D/M-tropic virus have similar virological responses to a short course of maraviroc monotherapy. This clinical test thus cannot be used as a surrogate marker of viral tropism in this population.

Correlation of selenium and zinc levels to antiretroviral treatment outcomes in Thai HIV-infected children without severe HIV symptoms

BackgroundDeficiencies in antioxidants contribute to immune dysregulation and viral replication.ObjectiveTo evaluate the correlation of selenium (Se) and zinc (Zn) levels on the treatment outcomes in HIV-infected children.DesignHIV-infected Thai children 1–12 years old, CD4 15–24%, without severe HIV symptoms were included. Se and Zn levels were measured by graphite furnace atomic absorption spectrometry at baseline and 48 weeks. Deficiency cut-offs were Se<0.1 μmol/L and Zn<9.9 μmol/L. Serum ferritin and C-reactive protein (CRP) were performed every 24 weeks. No micronutrient supplement was prescribed.Results141 children (38.3% male) with a median (IQR) age of 7.3 (4.2–9.0) years, were enrolled. Median baseline CD4% was 20%, HIV-RNA was 4.6 log10copies/mL. At baseline, median (IQR) Se and Zn levels were 0.9 (0.7–1.0) μmol/L and 5.9 (4.8–6.9) μmol/L, respectively. None had Se deficiency while all had Zn deficiency.Over 48 weeks, 97 initiated antiretroviral therapy (ART) and 81% achieved HIV-RNA <50 copies/mL with 11% median CD4 gain. The mean change of Se was 0.06 μmol/L (p = 0.003) and Zn was 0.42 μmol/L (p=0.003), respectively. By multivariate analysis in children who received ART, predictors for greater increase of CD4% from baseline were lower baseline CD4% (p<0.01) and higher baseline Zn level (p=0.02). The predictors for greater decrease of HIV-RNA from baseline were higher baseline HIV-RNA and higher ferritin (both p<0.01). No association of CRP to the changes from baseline of CD4% or HIV-RNA was found.ConclusionIn HIV-infected Thai children without severe immune deficiency who commenced ART, no correlation between selenium and ART treatment outcomes were found. Higher pre-ART Zn levels were associated with significant increases in CD4 percent at 48 weeks.

Mean Corpuscular Volume as a Marker for Adherence to Zidovudine-Containing Therapy in HIV-Infected Adults

Objectives:To assess whether mean corpuscular volume (MCV) is useful in detecting non-adherence to AZTcontaining therapy.Design:Observational study within randomised controlled trial.Methods:We combined data from two treatment arms in SPARTAC, an RCT of short-course cART in primary HIV infection, classifying participants as responders (HIV-RNA decrease ≥1 log10 or reaching <400copies/ml) or nonresponders following cART initiation. We assessed the sensitivity and specificity of using different percentage increases in MCV for accurately differentiating between responders and non-responders. We further examined changes in MCV levels up to 24 weeks after protocol-indicated cART cessation.Results:Of 119 participants included in this analysis, 73 (61%) were women, 71 of whom were randomised in Africa. Ninety-eight (88%) and 84 (85%) were classified as responders at 4 and 12 weeks respectively following cART initiation. MCV increased by a mean 3% and 1% at week 4, and 14% and <1% at 12 weeks for responders and non-responders. A 2% MCV increase at 4 weeks had 62% sensitivity and specificity for identifying virological response. At 12 weeks, an 8% increase had 89% sensitivity and specificity. In responders, MCV remained lower for individuals in African compared to non-African sites throughout and rose from 85 vs 90 fL at cART start to 96 vs 103 fL at 12 weeks post-initiation then fell to 88 vs 93 fL and 86 vs 89 fL at 12 and 48 weeks post-cessation.Conclusion:In low-income countries, where HIV RNA may be unavailable, 12-weekly MCV measurements may be useful in monitoring adherence to AZT-containing regimens.

Dynamics of HIV-1 DNA level in highly antiretroviral-experienced patients receiving raltegravir-based therapy

To assess dynamics of HIV-1 DNA in highly antiretroviral (ARV)-experienced HIV-infected patients successfully treated with raltegravir (RAL)-containing therapy. Nineteen patients with virological failure whose ARV treatment was switched to a RAL-based salvage regimen with virological success were included (Group I). Ten patients in virological failure and responding to ARV salvage therapy not containing RAL were also included (Group II). The HIV-1 DNA level in peripheral blood mononuclear cells (PBMC) was assessed by real-time PCR at baseline, W12, W24, W36 or W48. In group I, a marked decrease in the HIV-1 DNA level was observed at W12 both in PBMC (median decrease = 0.38 log(10)copies/10(6)PBMC; P < 0.001) and in CD4 T cells (0.85 log(10)copies/10(6)CD4 T cells; P < 0.001). Plasma HIV-1 RNA decrease was correlated with HIV-1 DNA decrease expressed as copies/10(6)CD4 T cells (r = 0.55, P = 0.03). HIV-1 DNA level reached a steady state by W24. Thus, RAL-containing treatment in highly ARV-experienced patients was associated with a rapid HIV-1 DNA decrease, mainly in the circulating CD4 T cells compartment. Group II patients showed an early decrease in the HIV-1 DNA load until W12, which was 2.5-fold less pronounced in the CD4 T cells compartment than in the RAL-treated patients. The potent action of RAL-containing treatment observed in the CD4 T cells compartment may suggest a pronounced reduced inhibition in the pool of regenerating CD4 T cells on a RAL-based therapy.

The basal activation state of DC subsets correlates with anti-HCV treatment outcome in HCV/HIV co-infected patients

In this work we evaluated plasmacytoid (pDC) and myeloid dendritic (mDC) cells activation before and during anti-HCV treatment in HCV+/HIV+ individuals. HCV+/HIV+ patients received Peg-IFN-α2b subcutaneously for 28 days, followed by oral weight-based ribavirin. DCs activation was evaluated by flow cytometry. Baseline pDC CD80 and CD86 expression was correlated with HIV, but not with HCV viral load. A transient decrease of HIV RNA was found not associated with DC activation. When patients were grouped according to early/sustained virological response (EVR/SVR) to anti-HCV treatment, baseline pDC CD80 and CD86 expression was higher in non-EVR and non-SVR compared to EVR and SVR. Moreover, in responder patients CD80 and CD86 were upregulated by IFN-α. Our data suggest a correlation between DCs activation and response to therapy. These findings could be helpful to better understand the mediators of IFN-α action in HCV+/HIV+ patients and to explore possible exploitation of this knowledge to improve therapeutic response.

Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy.

To determine whether raltegravir-containing antiretroviral therapy (ART) intensification reduces HIV levels in the gut. Open-label study in HIV-positive adults on ART with plasma HIV RNA below 40 copies/ml. Seven HIV-positive adults received 12 weeks of ART intensification with raltegravir alone or in combination with efavirenz or darunavir. Gut cells were obtained by upper and lower endoscopy with biopsies from duodenum, ileum, colon, and rectum at baseline and 12 weeks. Study outcomes included plasma HIV RNA, HIV DNA and RNA from peripheral blood mononuclear cells (PBMC) and four gut sites, T-cell subsets, and activation markers. Intensification produced no consistent decrease in HIV RNA in the plasma, PBMC, duodenum, colon, or rectum. However, five of seven participants had a decrease in unspliced HIV RNA per 10 CD4(+) T cells in the ileum. There was a trend towards decreased T-cell activation in all sites, which was greatest for CD8(+) T cells in the ileum and PBMC, and a trend towards increased CD4(+) T cells in the ileum. Most HIV RNA and DNA in the blood and gut is not the result of ongoing replication that can be impacted by short-term intensification with raltegravir. However, the ileum may support ongoing productive infection in some patients on ART, even if the contribution to plasma RNA is not discernible.

Successful HCV eradication and inhibition of HIV replication by intravenous silibinin in an HIV–HCV coinfected patient

Introduction The efficacy of antiviral therapy with pegylated interferon (PEGIFN) plus ribavirin (RBV) in patients with HIV and hepatitis C virus (HCV) coinfection is limited. Intravenous silibinin (ivSIL), a milk thistle extract with proven antiviral effects represents a novel therapeutic strategy for virological nonresponders. Methods We report a case of an HIV–HCV coinfected patient, who has not responded to a prior course of PEGIFN-α2a (180 μg/week/s.c.) and RBV (1000 mg/day/p.o.). Testing for IL-28β small nucleotid polymorphism revealed the nonfavourable genotype T/T. Antiretroviral therapy was not prescribed because the patients presented with well-preserved CD4+ cell counts and low HIV-RNA levels. She received retreatment with ivSIL for two weeks followed by PEGIFN/RBV combination therapy starting at week 1. Results After 2 weeks of ivSIL therapy both HCV-RNA and HIV-RNA become undetectable. On ivSIL monotherapy we noticed a trend towards an increase of CD4+ cell counts and a decrease of HIV-RNA. After 16 weeks PEGIFN + RBV was discontinued due to patients wish because of adverse events. HCV-RNA was still negative 24 weeks after cessation of therapy, while HIV-RNA returned to baseline levels. Conclusion ivSIL may represent a potential treatment option for retreatment of HIV–HCV coinfected patients nonresponding to PEGIFN + RBV combination therapy. Further investigations on the possible beneficial effects of ivSIL on CD4+ cell counts and HIV-RNA levels are necessary.

Hospitalization risk following initiation of highly active antiretroviral therapy

While highly active antiretroviral therapy (HAART) decreases long-term morbidity and mortality, its short-term effect on hospitalization rates is unknown. The primary objective of this study was to determine hospitalization rates over time in the year after HAART initiation for virological responders and nonresponders. Hospitalizations among 1327 HAART-naïve subjects in an urban HIV clinic in 1997-2007 were examined before and after HAART initiation. Hospitalization rates were stratified by virological responders (> or =1 log(10) decrease in HIV-1 RNA within 6 months after HAART initiation) and nonresponders. Causes were determined through International Classification of Diseases, 9th Revision (ICD-9) codes and chart review. Multivariate negative binomial regression was used to assess factors associated with hospitalization. During the first 45 days after HAART initiation, the hospitalization rate of responders was similar to their pre-HAART baseline rate [75.1 vs. 78.8/100 person-years (PY)] and to the hospitalization rate of nonresponders during the first 45 days (79.4/100 PY). The hospitalization rate of responders fell significantly between 45 and 90 days after HAART initiation and reached a plateau at approximately 45/100 PY from 91 to 365 days after HAART initiation. Significant decreases were seen in hospitalizations for opportunistic and nonopportunistic infections. The first substantial clinical benefit from HAART may be realized by 90 days after HAART initiation; providers should keep close vigilance at least until this time.

Changes in Darunavir/r Resistance Score After Previous Failure to Tipranavir/r in HIV-1-Infected Multidrug-Resistant Patients

To evaluate changes in resistance to tipranavir/r (TPV/r) and darunavir/r (DRV/r) in patients who had failed a TPV/r-including regimen. HIV genotypes obtained both at baseline and at tipranavir/r failure (TPVF) were analyzed in 47 HIV-infected patients failing a TPV/r-including regimen. Genotypes were evaluated through the Stanford mutation score: patients were ranked for TPV/r and DRV/r resistance as susceptible (class 1), potential low-level (class 2), low-level (class 3), intermediate-level (class 4), and high-level resistance (class 5). Values are expressed as median (interquartile range) or as frequency (%). Forty-seven patients were eligible. At baseline (tipranavir initiation), the scoring for TPV/r was: class 3 = 4 (8.5%); class 4 = 31 (66%); and class 5 = 12 (25.5%). Corresponding scores for DRV/r were: class 2 = 1 (2%), class 3 = 12 (25.5%), class 4 = 32 (68%), and class 5 = 2 (4.5%). At TPVF, a shift toward a higher TPV/r scoring class was seen in 16 (34.1%) patients (P = 0.001), whereas a shift toward a higher DRV/r scoring class was observed in 9 (19.2%) patients (P = 0.2381). After TPVF, 25/47 patients (53%) were treated with a DRV/r-containing regimen. After 24 weeks (on-treatment analysis), the median HIV RNA decrease was 3.04 (2.13-3.45) log10 copies per milliliter in DRV/r group versus -0.04 (-0.44; 0.50) log10 copies per milliliter in patients not treated with a DRV/r-containing regimen (P < 0.0001); CD4 increase was 126 (70-169) cells per cubic millimeter in DRV/r group versus -42 (-121; 42) (P < 0.0001). Treatment with TPV/r did not significantly increase the resistance score to DRV/r and did not preclude the efficacy of subsequent treatment with DRV/r.