Plasma HIV-1 RNA Viral Load Research Articles

Immune reconstitution inflammatory syndrome

To describe incidence of immune reconstitution inflammatory syndrome (IRIS) and its association with mortality in a large multisite US HIV-infected cohort applying an objective, comprehensive definition. We studied 2,610 patients seen during 1996-2007 who initiated or resumed highly active combination antiretroviral therapy (cART) and, during the next 6 months, demonstrated a decline in plasma HIV-RNA viral load of at least 0.5 log(10) copies/ml or an increase of at least 50% in CD4 cell count per microliter. We defined IRIS as the diagnosis of a type B or C condition [as per the Centers for Disease Control and Prevention (CDC) 1993 AIDS case definition] or any new mucocutaneous disorder during this same 6-month period. We assessed the incidence of IRIS and evaluated risk factors for IRIS using conditional logistic regression and for all-cause mortality using proportional hazards models. We identified 370 cases of IRIS (in 276 patients). Median and nadir CD4 cell counts at cART initiation were 90 and 43 cells/μl, respectively; median viral load was 2.7 log(10) copies/ml. The most common IRIS-defining diagnoses were candidiasis (all forms), cytomegalovirus infection, disseminated Mycobacterium avium intracellulare, Pneumocystis pneumonia, varicella zoster, Kaposi's sarcoma and non-Hodgkin lymphoma. Only one case of Mycobacterium tuberculosis was observed. IRIS was independently associated with CD4 cell count less than 50 cells/μl vs. at least 200 cells/μl [odds ratio (OR) 5.0] and a viral load of at least 5.0 log(10) copies vs. less than 4.0 log(10) copies (OR 2.3). IRIS with a type B-defining or type C-defining diagnosis approximately doubled the risk for all-cause mortality. In this large US-based HIV-infected cohort, IRIS occurred in 10.6% of patients who responded to effective ART and contributed to increased mortality.

Discordance inMycobacterium tuberculosisRifampin Susceptibility

Discordance in<i>Mycobacterium tuberculosis</i>Rifampin Susceptibility

Pharmacokinetics and short-term safety and tolerability of etravirine in treatment-experienced HIV-1-infected children and adolescents

To evaluate the pharmacokinetics, weight-based dose selection and short-term safety and tolerability of etravirine in HIV-1-infected children and adolescents. Phase I, nonrandomized, open-label study in two stages. Children and adolescents aged at least 6 years to 17 years or less on a stable lopinavir/ritonavir-based antiretroviral regimen with HIV-1 RNA plasma viral load less than 50 copies/ml were enrolled. In both stages, etravirine (4 mg/kg twice daily in stage I, 5.2 mg/kg twice daily in stage II), added to the existing antiretroviral regimen, was administered for 7 days followed by a morning dose and 12-h pharmacokinetic assessment on day 8. Pharmacokinetic parameters were determined using noncompartmental analysis. Data were compared with those previously established in HIV-1-infected adults on a similar etravirine (200 mg twice daily) combination antiretroviral regimen. Twenty-one patients were recruited to each stage; 19 and 20 had evaluable pharmacokinetics in stages I and II, respectively. Mean (SD) maximum plasma concentrations in stages I and II were 495 (453) and 757 ng/ml (680), respectively; area under the plasma concentration-time curve over 12 h was 4050 (3602) and 6141 ng h/ml (5586), respectively. Statistical/qualitative comparisons showed comparable exposures with adults in stage II; however, the upper 90% confidence interval fell outside the predefined range. Plasma viral load remained undetectable on day 8 in all patients, and etravirine was well tolerated at both doses. Etravirine 5.2 mg/kg was well tolerated in this study and this dose was selected for further investigation in clinical trials.

A survey of hepatitis B and C virus prevalence in human immunodeficiency virus positive patients in a tertiary health institution in North Eastern Nigeria

Co-infection of hepatotropic virus(es), with HIV has been associated with a reduced survival rate, an increased risk of progression to severe liver disease, and an increased risk of hepatotoxicity associated with active antiretroviral therapy. Information regarding prevalence of HBV and HCV co-infection with HIV in Nigeria is limited. This study was designed to determine the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV), and the impact of co-infection on baseline serum alanine transaminase (ALT), CD4+ T lymphocyte (CD4) count, and plasma HIV-RNA (viral load) in a cohort of HIV-infected Nigerians. Patients confirmed to be positive for HIV infection by Western blot analysis were consecutively recruited into the study from Infectious Disease Clinic, General Out-patient Department and Medical Wards of University of Maiduguri Teaching Hospital, Nigeria. Demographic data and pre-treatment laboratory results (hepatitis B surface antigen (HBsAg), and HCV antibodies (anti-HCV), ALT, CD4 count and viral load) were analysed. A total of 569 HIV-infected patients (male: female ratio, 1:1.4) were consecutively recruited. HBsAg was present in 12.3%; anti- HCV in 0.5% and both markers was not present in any patients. HBsAg prevalence was 12.3% in both male and females, while anti-HCV was detected in 0.8% in males and 0.3% females. HIV-infected patients alone had a higher mean baseline CD4 count compared to those without anti- HCV or HBsAg (181 vs. 117 cells/mm 3 , respectively; p = 0.01). Serum ALT was higher among patients co-infected with HBsAg or anti-HCV than only HIV infected (37 vs. 34 International Units (IU), respectively p = 0.1). The high frequency of HBsAg confirms the need for routine screening for these markers in HIV-infected patients in our setting. CD4 count was significantly lower, in patients with prior exposure to hepatitis B or C, while ALT was slightly higher among those positive for HBV or C infection. These findings are pointer to the importance of testing for HBV and HCV in all HIV-infected persons in our setting.

Short- and long-term outcomes of HIV-infected patients admitted to the intensive care unit: impact of antiretroviral therapy and immunovirological status

BackgroundThe purpose of this study was to assess the short- and long-term outcomes of HIV-infected patients admitted to intensive care units (ICU) according to immunovirological status at admission and highly active antiretroviral therapy (HAART) use in ICU.MethodsRetrospective study of 98 HIV-infected patients hospitalized between 1997 and 2008 in two medical ICU in Montpellier, France. The primary outcome was mortality in ICU. The secondary end point was probability of survival in the year following ICU admission.ResultsEighty-two (83.6%) admissions in ICU were related to HIV infection and 45% of patients had received HAART before admission. Sixty-two patients (63.3%) were discharged from ICU, and 34 (34.7%) were alive at 1 year. Plasma HIV RNA viral load (VL) and CD4+ cell count separately were not associated with outcome. Independent predictors of ICU mortality were the use of vasopressive agents (odds ratio (OR), 3.779; 95% confidence interval (CI), 1.11–12.861; p = 0.0334) and SAPS II score (OR, 1.04; 95% CI, 1.003-1.077; p = 0.0319), whereas introducing or continuing HAART in ICU was protective (OR, 0.278; 95% CI, 0.082-0.939; p = 0.0393). Factors independently associated with 1-year mortality were immunovirological status with high VL (>3 log10/ml) and low CD4 (<200/mm3; hazard ratio (HR), 5.19; 95% CI, 1.328-20.279; p = 0.0179) or low VL (<3 log10/ml) and low CD4 (HR, 4.714; 95% CI, 1.178-18.867; p = 0.0284) vs. high CD4 and low VL, coinfection with C hepatitis virus (HR, 3.268; 95% CI, 1.29-8.278; p = 0.0125), the use of vasopressive agents (HR, 3.68; 95% CI, 1.394-9.716; p = 0.0085), and SAPS II score (HR, 1.09; 95% CI, 1.057-1.124; p <0.0001). Introducing HAART in a patient with no HAART at admission was associated with a better long-term outcome (HR, 0.166; 95% CI, 0.043-0.642; p = 0.0093).ConclusionsIn a population of HIV-infected patients admitted to ICU, short- and long-term outcomes are related to acute illness severity and immunovirological status at admission. Complementary studies are necessary to identify HIV-infected patients who benefit from HAART use in ICU according to immunovirological status and the reasons of ICU admission.

Manejo clínico de la infección aguda y crónica por el virus de la inmunodeficiencia humana antes del inicio del tratamiento antirretroviral

The evaluation of new cases of HIV infection is relatively common in Spain, where several thousands of patients with new infections are diagnosed each year. Eighty per cent of them have a chronic HIV infection at the first clinical evaluation, which is symptomatic (late presenters) in up to 30% of patients. The initial evaluation of HIV infection is not only directed at determining the clinical, virological (plasma HIV RNA viral load, resistance test and viral tropism) and immunological (CD4+ T-cell cell count) situation of the patients, but must also address the study of their co-infections (hepatitis, tuberculosis) and comorbidities (cardiovascular, hepatic, renal and bone) and the risk of HIV transmission. This is needed in order to decide, whether or not to start antiretroviral treatment, and with which combined antiretroviral treatment to start with, the prophylaxis of opportunistic infections, and the treatment of coinfections and comorbidities. The past and current medical history, the physical examination and laboratory tests will help us decide if the patient is to receive therapeutic intervention. The level of CD4+ T-cell lymphocytes is the best marker to suggest when to start combined antiretroviral treatment, indicating whether or not to start prophylaxis against opportunistic infections (if patients have a CD4+ T-cell count below 200 cells/mm(3)), and in advanced patients should make us suspect the presence of active opportunistic diseases in symptomatic cases. The management of patients with HIV infection must also include appropriate health education on the modes of transmission and prevention of HIV infection, and also to explain its natural history and how it can be modified with proper antiretroviral treatment, as well as to promote a healthy life. No less important is the psychological support, as these patients must learn to live with a chronic infection, which managed properly can ensure a very good long-term prognosis and quality of life.

Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial

Dolutegravir (S/GSK1349572) is a new HIV-1 integrase inhibitor that has antiviral activity with once daily, unboosted dosing. SPRING-1 is an ongoing study designed to select a dose for phase 3 assessment. We present data from preplanned primary and interim analyses. In a phase 2b, multicentre, dose-ranging study, treatment-naive adults were randomly assigned (1:1:1:1) to receive 10 mg, 25 mg, or 50 mg dolutegravir or 600 mg efavirenz. Dose but not drug allocation was masked. Randomisation was by a central integrated voice-response system according to a computer-generated code. Study drugs were given with either tenofovir plus emtricitabine or abacavir plus lamivudine. Our study was done at 34 sites in France, Germany, Italy, Russia, Spain, and the USA beginning on July 9, 2009. Eligible participants were seropositive for HIV-1, aged 18 years or older, and had plasma HIV RNA viral loads of at least 1000 copies per mL and CD4 counts of at least 200 cells per μL. Our primary endpoint was the proportion of participants with viral load of less than 50 copies per mL at week 16 and we present data to week 48. Analyses were done on the basis of allocation group and included all participants who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00951015. 205 patients were randomly allocated and received at least one dose of study drug: 53, 51, and 51 to receive 10 mg, 25 mg, and 50 mg dolutegravir, respectively, and 50 to receive efavirenz. Week 16 response rates to viral loads of at most 50 copies per mL were 93% (144 of 155 participants) for all doses of dolutegravir (with little difference between dose groups) and 60% (30 of 50) for efavirenz; week 48 response rates were 87% (139 of 155) for all doses of dolutegravir and 82% (41 of 50) for efavirenz. Response rates between nucleoside reverse transcriptase inhibitor subgroups were similar. We identified three virological failures in the dolutegravir groups and one in the efavirenz group-we did not identify any integrase inhibitor mutations. We did not identify any dose-related clinical or laboratory toxic effects, with more drug-related adverse events of moderate-or-higher intensity in the efavirenz group (20%) than the dolutegravir group (8%). We did not judge that any serious adverse events were related to dolutegravir. Dolutegravir was effective when given once daily without a pharmacokinetic booster and was well tolerated at all assessed doses. Our findings support the assessment of once daily 50 mg dolutegravir in phase 3 trials.

Antiretroviral therapy alone resulted in successful resolution of large idiopathic esophageal ulcers in a patient with acute retroviral syndrome

Antiretroviral therapy alone resulted in successful resolution of large idiopathic esophageal ulcers in a patient with acute retroviral syndrome

Pilot, randomized study assessing safety, tolerability and efficacy of simplified LPV/r maintenance therapy in HIV patients on the 1 PI-based regimen.

ObjectivesTo compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART) with a ritonavir-boosted protease inhibitor (PI/r) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs) to lopinavir/ritonavir (LPV/r) monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART.MethodsThis is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL), time-to-virologic rebound, patient-reported outcomes (PROs) and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE).ResultsForty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/r;32:HAART) patients completed treatment, while 9(2:LPV/r;7:HAART) discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98%) patients on LPV/r and 37(95%) on HAART had VL<200copies/mL (P = 0.61). Time-to-virologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%), headache (18%) and influenza (16%). Four (10%) patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/r;3:HAART) patients.ConclusionAt day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re-introduction upon viral rebound, in virologically-suppressed patients merits further prospective long-term evaluation.Trial RegistrationClinicalTrials.gov NCT00159224

Impact of Cerebrovascular Disease on Cognitive Function in HIV-Infected Patients

Impact of Cerebrovascular Disease on Cognitive Function in HIV-Infected Patients

Meta-analysis of randomized trials on the association of prophylactic acyclovir and HIV-1 viral load in individuals coinfected with herpes simplex virus-2

To summarize the randomized evidence regarding the association between acyclovir use and HIV-1 replication as measured by plasma HIV-1 RNA viral load among individuals coinfected with herpes simplex virus (HSV)-2. Meta-analysis of seven randomized trials conducted between 2000 and 2009. Inclusion criteria composed of acyclovir or valacyclovir use as prophylaxis among individuals coinfected with HIV-1 and HSV-2 who were ineligible for highly active antiretroviral therapy. HIV-1 viral load was the outcome. Random-effects summarization was used to combine treatment effect estimates. Stratified and meta-regression analyses were used to compare estimated treatment effects by characteristics of trials and participants. The summary treatment effect estimate was -0.33 (95% confidence interval: -0.56, -0.10, 95% population effects interval: -0.74, 0.08) log(10) copies, an approximate halving of plasma viral load. However, there was marked heterogeneity (P < 0.001). Older median age, valacyclovir, higher compliance, earlier publication, and shorter study length were associated with a larger decrease in viral load as compared with their counterparts. Current evidence suggests a range of favorable effects of acyclovir on plasma HIV-1 viral load among persons coinfected with HSV-2.

Bevacizumab reverts serous retinal detachment caused by tuberculosis-associated immune reconstitution inflammatory syndrome

Bevacizumab reverts serous retinal detachment caused by tuberculosis-associated immune reconstitution inflammatory syndrome

Quality of Life Among Individuals with HIV Starting Antiretroviral Therapy in Diverse Resource-Limited Areas of the World

As Antiretroviral Therapy (ART) is scaled up in low- and middle-income countries, it is important to understand Quality of Life (QOL) correlates including disease severity and person characteristics and to determine the extent of between-country differences among those with HIV. QOL and medical data were collected from 1,563 of the 1,571 participants at entry into a randomized clinical trial of ART conducted in the U.S. (n = 203) and 8 resource-limited countries (n = 1,360) in the Caribbean, South America, Asia, and Africa. Participants were interviewed prior to initiation of ART using a modified version of the ACTG SF-21, a health-related QOL measure including 8 subscales: general health perception, physical functioning, role functioning, social functioning, cognitive functioning, pain, mental health, and energy/fatigue. Other measures included demographics, CD4+ lymphocyte count, plasma HIV-1 RNA viral load. Higher quality of life in each of the 8 QOL subscales was associated with higher CD4+ lymphocyte category. General health perception, physical functioning, role functioning, and energy/fatigue varied by plasma HIV-1 RNA viral load categories. Each QOL subscale included significant variation by country. Only the social functioning subscale varied by sex, with men having greater impairments than women, and only the physical functioning subscale varied by age category. This was the first large-scale international ART trial to conduct a standardized assessment of QOL in diverse international settings, thus demonstrating that implementation of the behavioral assessment was feasible. QOL indicators at study entry varied with disease severity, demographics, and country. The relationship of these measures to treatment outcomes can and should be examined in clinical trials of ART in resource-limited settings using similar methodologies.

Are HIV-Infected Donors Suitable for Renal Transplantation?

Recent studies confirm that outcome of renal transplantation (RT) in adequately selected HIV-infected patients receiving kidneys from HIV-negative donors is similar to that of HIV-negative RT recipients (1). Main challenges in the clinical management of HIV-infected RT recipients are the pharmacologic interactions between immunosuppressive agents and some classes of antiretroviral drugs and a higher rate of acute rejection in comparison with HIV-negative RT recipients. Currently, organ transplantation from HIV-infected donors is an absolute contraindication in Western countries (2,3), but its potential utility is under consideration (4). Recently, Muller et al. (5) reported the outcome of four HIV- infected RT recipients who received their grafts from two HIV-infected donors in South Africa, being the first clinical experience published involving this type of transplants. After 12 months of follow-up, all recipients had a functioning renal allograft with a good renal function, and HIV infection was controlled under different antiretroviral regimens. South Africa is a country with a high HIV prevalence in the general population, and HIV infection is an absolute exclusion criterion for access to dialysis or RT. Muller et al. (5) suggested that the use of HIV-infected donors would increase the donor pool, providing renal allografts to HIV-infected patients otherwise sentenced to death as a consequence of end-stage renal disease. It is likely that organ transplantation from HIV-infected donors will generate considerable controversy. The situation is similar to what occurred a decade ago in relation to hepatitis C virus RNA-positive donors, who are now accepted for hepatitis C virus-positive recipients in international guidelines (2,3). The strategy under consideration is bold and implies difficult decisions. Nonetheless, it must be evaluated with caution and based on several considerations. First, there are ethical implications stemming from the lack of long-term safety data. In countries with a resource-limited health system, HIV infection is an exclusion criterion for access to dialysis or RT. We agree that in these cases, the balance between justice and equity is more difficult. Second, recipients might acquire a more aggressive HIV strain from the donor (e.g., different clade or recombinant virus, or X4 tropism), including drug- resistant strains, which could lead to superinfection, virologic failure, and HIV progression to death. Previous reported experiences do not provide donor's virologic information (5), which, moreover, is difficult to obtain during organ procurement (3). Third, HIV-infected donors are at high risk for transmitting other infections that could increase morbidity and reduce recipient survival. Finally, there are nephrologic issues that must also be considered. HIV-associated nephropathy is the leading cause of end-stage renal disease in HIV-infected patients in South Africa; it is caused by direct viral infection of kidney cells (particularly the visceral epithelial cells of the glomerulus and the tubular epithelial cells), and it is more common in patients with high plasma HIV-RNA viral load (6). Moreover, HIV is associated with other renal diseases: immune-mediated glomerulonephritis, postinfectious glomerulonephritis, and thrombotic microangiopathies. Muller et al. (5) reported that the two HIV-infected donors had normal kidney biopsies, and no proteinuria was observed. However, technical limitations of renal allograft biopsy during procurement may misdiagnose subclinical renal disease, which could have a negative impact on allograft survival. To accelerate acquisition of evidence enabling resolution of these considerations, we suggest evaluating this approach in a prospective, controlled, pilot clinical trial of RT in HIV-infected recipients, containing two arms (HIV-positive and -negative donors) with virologic and histologic (protocolled renal biopsy) assessment and biochemical markers of renal injury and clinical outcome. Thus, the effectiveness and safety of this type of transplantation can be established. We believe that this strategy must initiate an intense scientific debate because of different ethical, nephrologic, virologic, and clinical considerations, and an international consensus conference could be of interest to analyze the controversies of this interesting and emerging issue. Federico Cofan1 Joan-Carles Trullas2 Carlos Cervera3 Federico Oppenheimer1 Asuncion Moreno3 Josep-Maria Campistol1 Jose-Maria Miró3 1 Renal Transplant Unit Nephrology Department Hospital Clinic–IDIBAPS University of Barcelona Barcelona, Spain 2 Internal Medicine Service Hospital Sant Jaume Olot, Universitat de Girona, Girona, Spain 3 Infectious Diseases Service Hospital Clinic–IDIBAPS University of Barcelona Barcelona, Spain

Treatment Change in Pregnancy Is a Significant Risk Factor for Detectable HIV-1 RNA in Plasma at End of Pregnancy

Purpose: To investigate the risk factors for an HIV-1 RNA plasma viral load above 400 copies/mL in the third trimester of pregnancy. Methods: Data from a large national study were used. The possible determinants were assessed in univariate analyses and in a multivariate logistic regression model in order to adjust for possible confounders. Results: Among 662 pregnancies followed between 2001 and 2008, 131 (19.8%) had an HIV-1 plasma copy number above 400/mL at the third trimester of pregnancy. In the multivariate analysis, the variables significantly associated with this occurrence were earlier calendar year (adjusted odds ratio [AOR] per additional calendar year, 0.70; 95% CI, 0.63–0.77; P < .001), lower CD4 count at enrollment (AOR per 100 cells lower, 1.18; 95% CI, 1.09–1.27; P < .001), HIV-1 RNA levels above 400 copies per mL at enrollment (AOR, 2.23; 95% CI, 1.50–3.33; P < .001), and treatment modification during pregnancy (AOR, 1.66; 95% CI, 1.07–2.57; P = .024). Conclusions: Treatment changes in pregnancy significantly increase the risk of an incomplete viral suppression at the end of pregnancy. In HIV-infected women of childbearing age, proper preconception care, which includes the preferential prescription of regimens with the best safety profile in pregnancy, is likely to prevent an incomplete viral suppression at the end of pregnancy.

Genotypic Impact of Prolonged Detectable HIV Type 1 RNA Viral Load after HAART Failure in a CRF01_AE-Infected Cohort

HIV subtype-specific data on mutation type, rate, and accumulation following HAART treatment failure are limited. We studied patterns and accrual of drug resistance mutations in a Cambodian CRF01_AE-infected cohort continuing a virologically failing first-line, nonnucleoside reverse transcriptase inhibitor- (NNRTI-) based, HAART. Between 2005 and 2007, 837 adult HIV-infected patients had regular plasma HIV-1 RNA viral load measurements at Sihanouk Hospital Centre of Hope (SHCH), Cambodia. Drug resistance testing was performed in all patients with HIV-1 RNA >1000 copies/ml after at least 6 months of HAART. Seventy-one patients with a mean age of 34 years, of whom 68% were male, were retrospectively assessed at virological failure. The median duration of antiretroviral therapy was 12.3 (IQR 7.1-18.23) months, the median CD4 cell count was 173 (IQR 118-256) cells/mm(3), and the mean plasma HIV-1 RNA viral load was 3.9 log (SD 0.72) at failure. NNRTI mutations, M184I/V mutation, thymidine analogue mutations, and K65R were observed in 78.9%, 69%, 20%, and 12.7% of patients, respectively. For 33 patients, genotypic testing was carried out on at least two occasions before the switch to second-line HAART after a median duration of 5.8 (IQR 4.3-6.1) months of virological failure: 54.5% of patients accumulated new mutations with a rate of 1.6 mutations per person-year. Accumulation was seen both for nucleoside and nonnucleoside reverse transcriptase inhibitors, and also in patients with low-level viremia. Subtype-specific data on mutation type, rate, and accumulation after HAART failure are urgently needed to optimize treatment strategies in resource-limited settings.

The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010

BackgroundIn France, it is estimated that 24% of HIV-infected patients are also infected with HCV. Longitudinal studies addressing clinical and public health questions related to HIV-HCV co-infection (HIV-HCV clinical progression and its determinants including genetic dimension, patients' experience with these two diseases and their treatments) are limited. The ANRS CO 13 HEPAVIH cohort was set up to explore these critical questions.To describe the cohort aims and organization, monitoring and data collection procedures, baseline characteristics, as well as follow-up findings to date.MethodsInclusion criteria in the cohort were: age > 18 years, HIV-1 infection, chronic hepatitis C virus (HCV) infection or sustained response to HCV treatment. A standardized medical questionnaire collecting socio-demographic, clinical, biological, therapeutic, histological, ultrasound and endoscopic data is administered at enrolment, then every six months for cirrhotic patients or yearly for non-cirrhotic patients. Also, a self-administered questionnaire documenting socio-behavioral data and adherence to HIV and/or HCV treatments is administered at enrolment and yearly thereafter.ResultsA total of 1,175 patients were included from January 2006 to December 2008. Their median age at enrolment was 45 years and 70.2% were male. The median CD4 cell count was 442 (IQR: 304-633) cells/μl and HIV RNA plasma viral load was undetectable in 68.8%. Most participants (71.6%) were on HAART. Among the 1,048 HIV-HCV chronically co-infected patients, HCV genotype 1 was predominant (56%) and cirrhosis was present in 25%. As of January, 2010, after a median follow-up of 16.7 months (IQR: 11.3-25.3), 13 new cases of decompensated cirrhosis, nine hepatocellular carcinomas and 20 HCV-related deaths were reported, resulting in a cumulative HCV-related severe event rate of 1.9/100 person-years (95% CI: 1.3-2.5). The rate of HCV-related severe events was higher in cirrhotic patients and those with a low CD4 cells count, but did not differ according to sex, age, alcohol consumption, CDC clinical stage or HCV status.ConclusionThe ANRS CO 13 HEPAVIH is a nation-wide cohort using a large network of HIV treatment, infectious diseases and internal medicine clinics in France, and thus is highly representative of the French population living with these two viruses and in care.

Liver transplantation in HIV-1-infected patients

With the advent of highly active antiretroviral therapy in 1996, patients infected with HIV are now living longer and dying from illnesses other than acquired immunodeficiency syndrome (AIDS). Liver disease due to chronic hepatitis B and C is now a leading cause of mortality among HIV-infected patients in the developed world. For these patients, liver transplantation (OLT) is the only therapeutic option and HIV infection alone is not a contraindication. The current HIV selection criteria for HIV-infected OLT candidates are as follows: 1) ideally no history of opportunistic infections or HIV-related cancer, although some treatable and preventable opportunistic infections are not exclusion criteria; 2) CD4 cell count >100 cells/mm3; and, 3) plasma HIV RNA viral load that is undetectable or can be suppressed with antiretroviral treatment. Drug users must abstain from heroin and cocaine, although patients can be in a methadone programme. Accumulated experience in North America and Europe in the last few years indicates that five-year survival in liver recipients coinfected with HIV and HCV is lower than that of HCV-monoinfected recipients, being the five-year survival of around 50%. Conversely, 3-5--year survival of non-HCV-HIV-coinfected liver recipients is very good and it was similar to that of HIV-negative patients. Pharmacokinetic (PK) and pharmacodynamic interactions between NNRTI- or protease-inhibitor based regimens and immunosuppressors have been one of the most important problems in the post-trasplant period, although with the new NNRTI- and protease inhibitor-sparing raltegravir-based regimens we can avoid them. Other problems in the post-transplant period are the high rates of acute rejection, and the HCV re-infection in HIV-infected liver recipients, that is the main cause of mortality. Better anti-HCV management and therapy could improve the long-term outcome of OLT recipients coinfected with HIV and HCV.

Predictors of Immune Reconstitution Inflammatory Syndrome–Associated With Kaposi Sarcoma in Mozambique: A Prospective Study

The impact and relevance of immune reconstitution inflammatory syndrome-associated with Kaposi sarcoma (IRIS-KS) has not been assessed in sub-Saharan African countries, where the bulk of HIV-1 and KS-associated herpesvirus (KSHV) coinfection occurs. Understanding the risk factors for developing IRIS-KS would aid in the identification and in the improvement of clinical management for high-risk patients. Sixty-nine consecutive HIV-1 and KSHV coinfected Mozambican adults initiating cART were prospectively followed for development of IRIS-KS over 10 months as part of a larger prospective observational study. Plasma HIV RNA, CD4 counts, anti-KSHV lytic antibodies, and plasma KSHV DNA viral load were assessed at the pre-cART visit and at 4 and 10 months after cART initiation. A survival analysis was performed to assess potential risk factors for developing IRIS-KS. During the first 10 months of combined antiretroviral therapy (cART), 8 patients (8/69, 11.6%) experienced IRIS-KS at a median time of 13.8 weeks after cART initiation. Multivariate analysis identified 4 independent IRIS-KS predictors: clinical pretreatment KS [hazard ratio (HR) 91.7], detectable plasma KSHV DNA (HR 24.4), hematocrit <30% (HR 26.5), and plasma HIV-1 RNA viral load (HR 34.6 per log viral load increase). Treatment with either cART alone or with a combination of cART and systemic chemotherapy led to partial or complete clinical response in 62.5% (5/8) of IRIS-KS cases. This study identified 4 independent predictors of IRIS-KS, which may help to develop screening tools aiding in the identification of patients at high risk of IRIS-KS for whom close clinical supervision is warranted.

Risk factors for perinatal HIV-1 transmission in pregnant women requiring lifelong antiretroviral therapy: a longitudinal study at a tertiary hospital in South Africa.

Objectives. To estimate the infant HIV-1 transmission rate and to evaluate risk factors for transmission in pregnant women at an Eastern Cape tertiary hospital requiring lifelong antiretroviral therapy (ART). Methods. Pregnant women who initiated lifelong ART during pregnancy and others who conceived on lifelong ART were followed up antenatally, through delivery, until 6 weeks postpartum. A qualitative HIV-1 DNA polymerase chain reaction (PCR) was done on the infants at 6 weeks. Risk factors evaluated for perinatal HIV transmission included CD4 count, duration of ART, plasma HIV-1 RNA viral load (VL) at delivery, preterm birth, and mode of delivery. Results. Data on 838 women with 858 live births are presented. The median CD4 count was 192 cells/μl, and the median duration of ART was 12 weeks. Of 618 women (73.7%) with VL results at delivery, 555 women (89.8%) had a VL <1 000 copies/ml. HIV-1 DNA PCR was performed on 665 out of 831 infants (80%) from 6 weeks onwards. Transmission occurred in 16 infants (2.4%; 95% confidence interval (CI) 1.4 - 4.0). The transmission rate was 7.8% with maternal plasma VL ≥1 000 copies/ml ( p =0.018), 4.2% with duration of ART <10 weeks ( p =0.010), and 8.6% with preterm birth ( p =0.046). On multivariable regression analysis VL ≥1 000 copies/ml (adjusted odds ratio (AOR) 12.82; 95% CI 1.72 - 95.53) and duration of ART <10 weeks (AOR 4.91; 95% CI 1.40 - 17.18) remained significant predictors of transmission. Conclusions. Maternal plasma VL at delivery and duration of ART are significant independent predictors of perinatal HIV-1 transmission, but transmission can occur with undetectable plasma VL at delivery.