ABSTRACT
Despite the huge advance that antiretroviral therapy represents for the prognosis of infection by the human immunodeficiency virus (HIV), opportunistic infections (OIs) continue to be a cause of morbidity and mortality in HIV-infected patients. OIs often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an OI. The present article updates our previous guidelines on the prevention and treatment of various OIs in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome.
Subject(s)
HIV Infections/complications , Opportunistic Infections/drug therapy , Opportunistic Infections/prevention & control , AIDS-Related Opportunistic Infections/drug therapy , AIDS-Related Opportunistic Infections/prevention & control , Antiretroviral Therapy, Highly Active , Bacterial Infections/drug therapy , Coinfection , Humans , Immune Reconstitution Inflammatory Syndrome/drug therapy , Immune Reconstitution Inflammatory Syndrome/prevention & control , Mycobacterium Infections/drug therapy , Mycobacterium Infections/prevention & control , Mycoses/drug therapy , Mycoses/prevention & control , Opportunistic Infections/etiology , Parasitic Diseases/drug therapy , Parasitic Diseases/prevention & control , Virus Diseases/drug therapy , Virus Diseases/prevention & controlABSTRACT
Opportunistic infections continue to be a cause of morbidity and mortality in HIV-infected patients. They often arise because of severe immunosuppression resulting from poor adherence to antiretroviral therapy, failure of antiretroviral therapy, or unawareness of HIV infection by patients whose first clinical manifestation of AIDS is an opportunistic infection. The present article is an executive summary of the document that updates the previous recommendations on the prevention and treatment of opportunistic infections in HIV-infected patients, namely, infections by parasites, fungi, viruses, mycobacteria, and bacteria, as well as imported infections. The article also addresses immune reconstitution inflammatory syndrome. This document is intended for all professionals who work in clinical practice in the field of HIV infection.
Subject(s)
HIV Infections/complications , Opportunistic Infections/drug therapy , Opportunistic Infections/prevention & control , AIDS-Related Opportunistic Infections/prevention & control , Bacterial Infections/drug therapy , Bacterial Infections/prevention & control , Coinfection/drug therapy , Coinfection/prevention & control , Humans , Immune Reconstitution Inflammatory Syndrome/diagnosis , Immune Reconstitution Inflammatory Syndrome/drug therapy , Immune Reconstitution Inflammatory Syndrome/prevention & control , Mycoses/drug therapy , Mycoses/prevention & control , Parasitic Diseases/drug therapy , Parasitic Diseases/prevention & control , Virus Diseases/drug therapy , Virus Diseases/prevention & controlABSTRACT
OBJECTIVES: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based regimens on renal function of human immunodeficiency virus (HIV) naïve patients >50 years old who started combination antiretroviral therapy (cART). DESIGN: National, retrospective cohort analysis of patients >50 years old when they started cART (January 1, 2006-December 31, 2009). METHODS: We compared renal safety (changes in estimated glomerular filtration rate [eGFR] during the first year, and time to renal events during 4 years of follow-up) in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitors vs non-nucleoside reverse transcriptase inhibitors and Lopinavir/ritonavir vs Efavirenz. RESULTS: We included 103 patients: median age: 54.9 years, 84% males, median CD4 count 247âcells/µl, median viral load 4.7 log; median follow up 18 months (max: 48 months); 73 started with FTC/TDF and 30 with other NRTIs. Change in eGFR was significantly worse for ritonavir-boosted lopinavir (LPV/r) vs efavirenz (EFV) users in the FTC/TDF group (71.2 vs 98.9âml/min/1.73âm(2) at month 12, P < 0.05). The risk of renal events (progression to an Chronic Kidney Disease Epidemiology Collaboration value < 60âml/min/1.73âm(2) in subjects with baseline values >60) was comparable for FTC/TDF users and non users, but was higher and almost significant for LPV/r as compared to EFV users in the FTC/TDF group (adjusted hazard ratio 6.1, 95% CI 0.8-45.5). CONCLUSIONS: In our study with a population of HIV infected subjects ≥ 50 years old, renal safety was similar for FTC/TDF and other NRTI-based regimens, but worse for LPV/r as compared to other regimens.
Subject(s)
Anti-HIV Agents/therapeutic use , Emtricitabine/therapeutic use , HIV Infections/drug therapy , Reverse Transcriptase Inhibitors/therapeutic use , Tenofovir/therapeutic use , CD4 Lymphocyte Count , Drug Therapy, Combination , Female , Follow-Up Studies , HIV Infections/epidemiology , Humans , Male , Middle Aged , Retrospective Studies , Spain/epidemiology , Treatment Outcome , Viral Load/drug effectsABSTRACT
In this update, antiretroviral therapy (ART) is recommended for all patients infected by type 1 human immunodeficiency virus (HIV-1). The strength and grade of the recommendation vary depending on the CD4+ T-lymphocyte count, the presence of opportunistic infections or comorbid conditions, age, and the efforts to prevent the transmission of HIV. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should comprise three drugs, namely, two nucleoside reverse transcriptase inhibitors (NRTI) and one drug from another family. Three of the recommended regimens, all of which have an integrase strand transfer inhibitor (INSTI) as the third drug, are considered a preferred regimen; a further seven regimens, which are based on an INSTI, an non-nucleoside reverse transcriptase inhibitor (NNRTI), or a protease inhibitor boosted with ritonavir (PI/r), are considered alternatives. The reasons and criteria for switching ART are presented both for patients with an undetectable PVL and for patients who experience virological failure, in which case the rescue regimen should include three (or at least two) drugs that are fully active against HIV. The specific criteria for ART in special situations (acute infection, HIV-2 infection, pregnancy) and comorbid conditions (tuberculosis and other opportunistic infections, kidney disease, liver disease, and cancer) are updated.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1 , AIDS-Related Opportunistic Infections , Adult , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active , Breast Feeding , CD4 Lymphocyte Count , Comorbidity , Contraindications , Drug Resistance, Viral , Drug Substitution , Drug Therapy, Combination , Female , HIV Infections/immunology , HIV-1/drug effects , HIV-2 , Humans , Pregnancy , Pregnancy Complications, Infectious/drug therapy , Viral Load , Viremia/drug therapyABSTRACT
Combination antiretroviral therapy (ART) has increased patient survival, which is currently similar to that of the general population in western countries. However, ART is unable to completely restore normal health, given the persistence of chronic immune activation. Human immunodeficiency virus (HIV) infection has become a chronic disease and 50% of patients will soon be older than 50 years. Currently, there is a debate on the possibility of accelerated aging in the HIV-infected population. An overlap has been observed between chronic inflammation, age-related comorbidities, lifestyle, and the long-term toxicity of ART. ART-related toxicity can encourage the development of comorbidities, especially cardiovascular and renal complications, while toxicity-especially that of thymidine analogs-can also contribute to inflammation and aging. Evidence is available on simplification strategies with boosted protease inhibitor monotherapy aiming to avoid or reduce potential or demonstrated toxicity. Currently, studies are underway of dual therapy strategies with lopinavir/ritonavir (LPV/r) with distinct antiretroviral agents. The studies with the largest samples are those with raltegravir and lamivudine. The GARDEL trial has demonstrated that dual therapy with LPV/r plus a generic drug such as lamivudine is non-inferior to triple therapy in treatment- naïve patients. All of the above indicates the response to the challenge posed to LPV/r by the chronic phase of the disease and by the need to reduce costs.
Subject(s)
HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , Aging , Anti-HIV Agents/adverse effects , Anti-HIV Agents/economics , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , Chronic Disease , Comorbidity , Drug Combinations , Drug Costs , HIV Infections/economics , HIV Integrase Inhibitors/therapeutic use , HIV Protease Inhibitors/adverse effects , HIV Protease Inhibitors/economics , Humans , Lopinavir/adverse effects , Medication Adherence , Meta-Analysis as Topic , Multicenter Studies as Topic , Practice Guidelines as Topic , Randomized Controlled Trials as Topic , Reverse Transcriptase Inhibitors/adverse effects , Reverse Transcriptase Inhibitors/economics , Reverse Transcriptase Inhibitors/therapeutic use , Ritonavir/adverse effectsABSTRACT
OBJECTIVES: Current antiretroviral guidelines state that being older than 50 to 55 years of age is an indication to start antiretroviral therapy (ART), regardless of CD4 status. However, no references to the preferred combination ART (cART) for these patients have been described. Our study compares emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) versus other nucleoside reverse transcriptase inhibitor (NNRTI) regimens in HIV ART-naïve patients who are ≥50 years. DESIGN: National, retrospective cohort analysis of patients who were ≥50 years old when they began the first cART (January 1, 2006 to December 31, 2009). METHODS: We compared safety, effectiveness, and persistence of treatment in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitor (PI) versus NNRTI users and lopinavir/r versus efavirenz users. RESULTS: We included 161 patients: median age was 54.6 years, 83% were men, median CD4 count was 191 cells/µL, median viral load was 4.7 log, and median follow-up was 19 months (maximum, 48 months). Of these participants, 112 started with FTC/TDF and 49 with other nucleotide reverse transcriptase inhibitors (NRTIs). During follow-up, 21.9% of subjects developed at least one laboratory event ≥grade 3, 5.6% interrupted cART due to adverse events,19.3% had virologic failure, and 49.1% modified cART. There were no statistically significant differences between FTC/TDF and non-FTC/TDF users for any output except for persistence: The proportion of subjects who changed cART was 71.4% for non-FTC/TDF users and 38.6% for FTC/TDF users (log rank 0.001; adjusted hazard ratio, 2.10; 95% CI, 1.34-3.29). CONCLUSIONS: In a population of HIV-infected subjects who were ≥50 years old, our study suggests that the use of FTC/TDF is generally safe and effective, with a longer persistence as compared to other regimens.
Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/therapeutic use , Deoxycytidine/analogs & derivatives , HIV Infections/drug therapy , Organophosphonates/therapeutic use , Adenine/administration & dosage , Adenine/adverse effects , Adenine/therapeutic use , Aging , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Drug Therapy, Combination , Emtricitabine , Female , Humans , Male , Middle Aged , Organophosphonates/administration & dosage , Organophosphonates/adverse effects , TenofovirABSTRACT
BACKGROUND: Ribavirin (RBV) exposure seems to be critical to maximize treatment response in human immunodeficiency virus (HIV)-positive patients with chronic hepatitis C virus (HCV) infection. METHODS: HIV/HCV-coinfected individuals naive to interferon were prospectively randomized to receive peginterferon-α-2a (180 µg/d) plus either RBV standard dosing (1000 or 1200 mg/d if <75 or ≥ 75 kg, respectively) or RBV induction (2000 mg/d) along with subcutaneous erythropoietin ß (450 IU/kg/wk), both during the first 4 weeks, followed by standard RBV dosing until completion of therapy. Early stopping rules at weeks 12 and 24 were applied in patients with suboptimal virological response. RESULTS: A total of 357 patients received ≥ 1 dose of the study medication. No differences in main baseline characteristics were found when comparing treatment arms. Sustained virological response (SVR) was attained by 160 (45%) patients, with no significant differences between RBV induction and standard treatment arms (SVR in 72 of 169 patients [43%] vs 88 of 188 [47%], respectively). At week 4, undetectable HCV RNA (29% vs 25%) and mean RBV trough concentration (2.48 vs 2.14 µg/mL) were comparable in both arms, whereas mean hemoglobin decay was less pronounced in the RBV induction plus erythropoietin arm than in the RBV standard dosing arm (-1.7 vs -2.3 mg/dL; P < .005). Treatment discontinuation occurred in 91 (25%) patients owing to nonresponse and in 29 (8%) owing to adverse events. HCV relapse occurred in 34 patients (10%). Univariate and multivariate analyses identified HCV genotype 2 or 3 (odds ratio [OR], 10.3; 95% confidence interval [CI], 2.08-50.2; P = .004), IL28B CC variants (OR, 2.92; 95% CI, 1.33-6.41; P = .007), nonadvanced liver fibrosis (OR, 2.27; 95% CI, 1.06-5.01; P = .03), and rapid virological response (OR, 40.3; 95% CI, 5.1-314.1; P < .001) as predictors of SVR. CONCLUSIONS: A 4-week course of induction therapy with high RBV dosing along with erythropoietin does not improve SVR rates in HIV/HCV-coinfected patients. Preemptive erythropoietin might blunt the benefit of RBV overdosing by enhancing erythrocyte uptake of plasma RBV.
Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/complications , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Adult , Antiretroviral Therapy, Highly Active , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Hepacivirus/genetics , Hepatitis C, Chronic/complications , Humans , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Male , Middle Aged , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/adverse effects , RNA, Viral/blood , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use , Ribavirin/administration & dosage , Ribavirin/adverse effectsABSTRACT
The role of rs1127354/rs7270101 alleles at the inosine triphosphatase (ITPA) gene on ribavirin-induced anemia was assessed in 74 patients with hepatitis C virus and human immunodeficiency virus coinfection. Anemia developed in 80% of patients with normal ITPA activity compared with 33% of those with reduced ITPA activity. In contrast, ITPA variants did not influence sustained virological response.
Subject(s)
Anemia/chemically induced , Antiviral Agents/adverse effects , HIV Infections/drug therapy , Hepatitis C, Chronic/drug therapy , Polymorphism, Genetic , Pyrophosphatases/genetics , Ribavirin/adverse effects , Adult , Anemia/epidemiology , Antiviral Agents/administration & dosage , Female , HIV Infections/complications , Hepatitis C, Chronic/complications , Humans , Incidence , Male , Middle Aged , Pyrophosphatases/metabolism , Ribavirin/administration & dosage , Risk Assessment , Inosine TriphosphataseABSTRACT
BACKGROUND: Previous studies have suggested that hepatocellular carcinoma (HCC) has an aggressive presentation and a shorter survival in people with HIV (PWH). This could be due to later diagnosis or lower rates of HCC treatment, and not to HIV infection itself. AIM: :: To assess the impact of HIV on HCC survival in hepatitis C virus (HCV)-infected patients. METHODS: Multicenter cohort study (1999-2018) of 342 and 135 HCC cases diagnosed in HIV/HCV-infected and HCV-monoinfected patients. Survival after HCC diagnosis and its predictors were assessed. RESULTS: HCC was at Barcelona-Clinic Liver-Cancer (BCLC) stage 0/A in 114 (33%) HIV/HCV-coinfected and in 76 (56%) HCV-monoinfected individuals (Pâ<â0.001). Of them, 97 (85%) and 50 (68%) underwent curative therapies (Pâ=â0.001). After a median (Q1-Q3) follow-up of 11 (3-31) months, 334 (70%) patients died. Overall 1 and 3-year survival was 50 and 31% in PWH and 69 and 34% in those without HIV (Pâ=â0.16). Among those diagnosed at BCLC stage 0/A, 1 and 3-year survival was 94 and 66% in PWH whereas it was 90 and 54% in HIV-negative patients (Pâ=â0.006). Independent predictors of mortality were age, BCLC stage and α-fetoprotein levels. HIV infection was not independently associated with mortality [adjusted hazard ratio (AHR) 1.57; 95% confidence interval: 0.88-2.78; Pâ=â0.12]. CONCLUSION: HIV coinfection has no impact on the survival after the diagnosis of HCC in HCV-infected patients. Although overall mortality is higher in HIV/HCV-coinfected patients, this seem to be related with lower rates of early diagnosis HCC in HIV-infected patients and not with HIV infection itself or a lower access to HCC therapy.
Subject(s)
Carcinoma, Hepatocellular/mortality , Coinfection , HIV Infections , Hepatitis C, Chronic , Liver Neoplasms/mortality , Cohort Studies , HIV Infections/complications , Hepacivirus , Hepatitis C, Chronic/complications , Humans , Liver Neoplasms/virology , Survival RateABSTRACT
OBJECTIVE: To assess the performance of ultrasound surveillance for the diagnosis of hepatocellular carcinoma (HCC) in HIV-infected patients. METHODS: The GEHEP-002 cohort recruits HCC cases diagnosed in HIV-infected patients from 32 centers across Spain. The proportion of 'ultrasound lack of detection', defined as HCC diagnosed within the first 3 months after a normal surveillance ultrasound, and the proportion of 'surveillance failure', defined as cases in which surveillance failed to detect HCC at early stage, were assessed. To assess the impact of HIV, a control population of 104 HCC cases diagnosed in hepatitis C virus-monoinfected patients during the study period was used. RESULTS: A total of 186 (54%) out of 346 HCC cases in HIV-infected patients were diagnosed within an ultrasound surveillance program. Ultrasound lack of detection occurred in 16 (8.6%) of them. Ultrasound surveillance failure occurred in 107 (57%) out of 186 cases diagnosed by screening, whereas this occurred in 18 (29%) out of 62 diagnosed in the control group (Pâ<â0.0001). HCC cases after ultrasound surveillance failure showed a lower frequency of undetectable HIV viral load at diagnosis. The probability of 1-year and 2-year survival after HCC diagnosis among those diagnosed by screening was 56 and 45% in HIV-infected patients, whereas it was 79 and 64% in HIV-negative patients (Pâ=â0.038). CONCLUSION: The performance of ultrasound surveillance of HCC in HIV-infected patients is very poor and worse than that shown outside HIV infection. A HCC surveillance policy based on ultrasound examinations every 6 months might be insufficient in HIV-infected patients with cirrhosis.
Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , HIV Infections/complications , Liver Neoplasms/diagnostic imaging , Ultrasonography/methods , Aged , Carcinoma, Hepatocellular/epidemiology , Epidemiological Monitoring , Female , Humans , Liver Neoplasms/epidemiology , Male , Middle Aged , Retrospective Studies , Sensitivity and Specificity , Spain/epidemiologyABSTRACT
The efficacy of voriconazole in 107 patients with scedosporiosis was analyzed. Principal infection sites were the lungs/sinuses (24%), central nervous system (CNS) (20%), and bone (18%), while 21% of patients had disseminated infection. Solid organ transplantation (22%), hematological malignancy (21%), and surgery/trauma (15%) were the predominant underlying conditions. A successful therapeutic response was achieved in 57% of patients (median, 103 therapy days), with > 98% of those responding receiving > or = 28 days of therapy. Patients receiving primary therapy showed a 61% response versus 56% for the others. The best therapeutic responses were seen for skin/subcutaneous (91%) or bone (79%) infections, and the lowest for CNS infections (43%). Patients without major immune suppression (72%) or those with solid organ transplantation (63%) or various hematological conditions (60%) showed the best responses by underlying condition. Median known survival time was 133 days (therapy successes, 252 days; failures, 21 days). In all, 43 (40%) patients died, 73% due to scedosporiosis. Patients with Scedosporium prolificans infection had significantly reduced survival times (P = 0.0259) and were more likely to die from fungal infection (P = 0.002) than were Scedosporium apiospermum-infected patients. In a subset of 43 patients where voriconazole baseline MICs were available, response to voriconazole was higher for S. apiospermum-infected patients (54% response; MIC(50), 0.25 microg/ml) than for S. prolificans-infected patients (40% response; MIC(50), 4.0 microg/ml). Voriconazole demonstrated clinically useful activity in the treatment of both S. apiospermum and S. prolificans infections and was well tolerated.
Subject(s)
Aspergillosis/drug therapy , Pyrimidines/therapeutic use , Scedosporium/drug effects , Triazoles/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Antifungal Agents/therapeutic use , Aspergillosis/microbiology , Aspergillosis/pathology , Child , Child, Preschool , Clinical Trials as Topic/statistics & numerical data , Female , Health Surveys , Humans , Infant , Male , Middle Aged , Treatment Outcome , VoriconazoleABSTRACT
INTRODUCTION: We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality. METHODS: All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected. RESULTS: Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7,067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1,000 people-year. In addition to aging and smoking, time on ART (OR 1.11; 95% CI 1.05-1.17) and PI use (OR 1.72; 95% CI 1.0-2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99-1.0; P=.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08-3.92) were associated with higher mortality. CONCLUSIONS: Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS.
Subject(s)
HIV Infections/complications , Neoplasms/complications , Neoplasms/epidemiology , Adult , Case-Control Studies , Female , Humans , Incidence , Male , Middle Aged , Prognosis , Prospective Studies , Risk Factors , Survival RateABSTRACT
TRIAL DESIGN: The QoLKAMON study evaluated quality of life, efficacy and treatment safety in HIV patients receiving lopinavir/ritonavir in monotherapy (MT) versus continuing combined antiretroviral triple treatment with a boosted protease inhibitor (TT). METHODS: This was a 24-week, open-label, multicentre study in virologically-suppressed HIV-infected participants (N = 225) with a 2:1 randomization: 146 patients who switched to MT were compared with 79 patients who remained on a TT regimen. The primary endpoint was change in patient-reported outcomes in quality of life as measured by the MOS-HIV and EQ-5D questionnaires. Secondary endpoints included treatment adherence, patient satisfaction, incidence of adverse events and differences in plasma HIV-1 RNA viral load (VL) and CD4 cell counts. RESULTS: Baseline quality of life, measured with the MOS-HIV score, was very good (overall score of 83 ± 10.5 in the MT arm and 82.3 ± 11.3 in the TT arm) and suffered no change during the study in any of the arms (at week 24, 83.5 ± 12.2 in MT arm and 81.9 ± 12.7 in TT arm), without statistically significant differences when compared. In regards to adherence to therapy and patient satisfaction, some aspects (number of doses forgotten in the last week and satisfaction of treatment measured with the CESTA score, dimension 1) improved significantly with MT. There were also no differences in the incidence and severity of adverse events, even though 22.8% of those in the MT arm switched their treatment when they were included in the study. Moreover, there was also no significant difference between the immunological and virological evolution of MT and TT. In the MT arm, the VL was always undetectable in 83% of patients (vs 90.7% in the TT arm) and there were only 6.7% of virological failures with VL > 50 copies/mL (vs 2.3% in the TT arm), without resistance mutations and with resuppression of VL after switching back to TT. CONCLUSIONS: In a new clinical trial, monotherapy as a treatment simplification strategy in HIV-1 infected patients with sustained viral suppression has demonstrated quality of life, safety and efficacy profiles comparable to those of conventional triple therapy regimens.
Subject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/drug therapy , Lopinavir/administration & dosage , Quality of Life , Ritonavir/administration & dosage , Adult , CD4 Lymphocyte Count , Female , HIV Protease Inhibitors/administration & dosage , HIV Protease Inhibitors/therapeutic use , HIV-1/genetics , Humans , Male , Middle Aged , Reproducibility of Results , Spain , Surveys and Questionnaires , Treatment Outcome , Viral Load/drug effectsABSTRACT
OBJECTIVE: To assess the possible association between the use of direct antiviral agents (DAA) and the risk of hepatocellular carcinoma (HCC) in HIV/hepatitis C virus (HCV)-coinfected patients. METHODS: The GEHEP-002 cohort recruits HCC cases in HIV-infected patients from 32 centers from Spain. Three analyses were performed: the proportion of HCC cases after sustained virological response (SVR) and the evolution of this proportion over time, the frequency of HCC after SVR in HIV/HCV-coinfected patients with cirrhosis, and the probability of HCC recurrence after curative therapies among those undergoing HCV therapy. RESULTS: Forty-two (13%) out of 322 HCC cases in HIV/HCV-coinfected patients occurred after SVR. Twenty-eight (10%) out of 279 HCC cases diagnosed during the years of use of IFN-based regimens occurred after SVR whereas this occurred in 14 (32.6%) out of the 43 HCC cases diagnosed in the all-oral DAA period (Pâ<â0.0001). One thousand, three hundred and thirty-seven HIV/HCV-coinfected patients with cirrhosis achieved SVR in the cohort. The frequency of HCC after SVR declined from 15% among those cured with pegylated-IFN with ribavirin to 1.62 and 0.87% among those cured with DAA with and without IFN, respectively. In patients with previous HCC treated with curative therapies, HCC recurrence occurred in two (25%) out of eight patients treated with IFN-based regimens and four (21%) out of 19 treated with DAA-IFN-free regimens (Pâ=â1.0). CONCLUSION: The frequency of HCC emergence after SVR has not increased after widespread use of DAA in HIV/HCV-coinfected patients. DAA do not seem to impact on HCC recurrence in the short-term among those with previously treated HCC.
Subject(s)
Antiviral Agents/administration & dosage , Carcinoma, Hepatocellular/epidemiology , Coinfection/complications , Coinfection/drug therapy , HIV Infections/complications , Hepatitis C, Chronic/drug therapy , Sustained Virologic Response , Female , Hepatitis C, Chronic/complications , Humans , Male , Middle Aged , Prevalence , Risk Assessment , Spain/epidemiologyABSTRACT
BACKGROUND: Chronic hepatitis C therapy in HIV patients is often penalized by more frequent premature treatment discontinuations. It is unclear what the relative contribution of more adverse events and/or early virological failures are. METHODS: PRESCO was a prospective, multicentre, comparative trial, in which 389 HIV/HCV-coinfected patients with CD4+ T-cell counts >300 cells/ml and elevated aminotransferases received pegylated interferon-alpha2a (peg IFN-alpha2a) 180 mg per week plus ribavirin (RBV) 1,000-1,200 mg daily. Patients with HCV genotypes 1 or 4 were treated for 48 or 72 weeks while HCV genotypes 2 or 3 carriers were treated for 24 or 48 weeks. Use of didanosine was not allowed. RESULTS: Sustained virological response (SVR) was achieved by 193 (49.6%), and was significantly greater in HCV-2/3 than in HCV-1/4 patients (72.4% versus 35%; P<0.0001). Premature treatment discontinuations occurred in 174 patients (44.7%). This was due to early virological failure in 66 (17%), serious adverse events in 32 (8.2%), loss-to-follow-up in 12 (3.1%) and voluntary withdrawal in 64 (16.4%). Only 10 patients (2.6%) stopped HCV therapy due to severe anaemia. Two patients stopped HCV medication due to symptomatic mitochondrial toxicity. There were no episodes of hepatic decompensation. CONCLUSIONS: Treatment with RBV 1,000-1,200 mg/day plus peg IFN-alpha2a is relatively safe and provided SVR in nearly half of the HIV/HCV-coinfected patients, twice as many amongst the HCV-2/3 than HCV-1/4 carriers. Avoidance of didanosine, limited use of zidovudine and therapy restricted to patients with CD4+ T-cell counts >300 cells/ml most probably explains the lower and different spectrum of serious adverse events in PRESCO compared with prior trials conducted in coinfected patients.
Subject(s)
Antiviral Agents/administration & dosage , HIV Infections/complications , Hepatitis C, Chronic/complications , Interferon-alpha/administration & dosage , Polyethylene Glycols/administration & dosage , Ribavirin/administration & dosage , Adult , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV Infections/drug therapy , HIV-1/drug effects , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Interferon-alpha/therapeutic use , Male , Polyethylene Glycols/adverse effects , Polyethylene Glycols/therapeutic use , Recombinant Proteins , Ribavirin/adverse effects , Ribavirin/therapeutic use , Treatment OutcomeABSTRACT
The response to pegylated interferon (pegIFN) plus ribavirin (RBV) as treatment of chronic hepatitis C virus (HCV) infection is lower in HIV-coinfected than in HCV-monoinfected patients and could be due to suboptimal RBV dosing and/or insufficient duration of therapy in prior trials. In a prospective, multicenter, open, comparative trial, HCV/HIV-coinfected patients received pegIFN plus weight-based RBV for 48 or 72 weeks (HCV genotypes 1 and 4) and 24 or 48 weeks (HCV genotypes 2 and 3). Use of didanosine was not allowed. Out of 389 patients included in the trial, 61% were infected by HCV-1/4 and 67% had serum HCV-RNA >500,000 IU/ml. Sustained virological response (SVR) was achieved by 49.6%, significantly higher in HCV-2/3 than HCV-1/4 (72.4% vs. 35%; p < 0.0001). A high drop-out rate in the longer treatment arms precluded obtaining definitive conclusions about the efficacy of prolonging therapy. Premature treatment discontinuations due to serious adverse events occurred in 8.2%. Infection with HCV-2/3, lower baseline HCV-RNA, and negative HCV-RNA at week 12 were all independent predictors of SVR in the multivariate analysis. The use of RBV 1000-1200 mg/day plus pegIFN is relatively safe and provides SVR in nearly half of coinfected patients, twice as high in HCV-2/3 than HCV-1/4.
Subject(s)
Antiviral Agents/therapeutic use , HIV Infections/complications , HIV , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Adult , CD4 Lymphocyte Count , Female , HIV Infections/drug therapy , HIV Infections/virology , Hepacivirus/drug effects , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Male , Prospective Studies , Recombinant Proteins , Ribavirin/administration & dosageABSTRACT
OBJECTIVE: To evaluate the effectiveness and tolerability of a simplification regimen with tenofovir DF (TDF), lamivudine (3TC), and efavirenz (EFV) in HAART-experienced HIV-1-infected subjects with sustained viral suppression. METHOD: Patients with HIV-1 RNA <200 copies/mL during the previous 6 months and who switched their current twice-daily or three-times-daily HAART to a simplified once-daily regimen of TDF (300 mg), 3TC (300 mg), and EFV (600 mg) were included. RESULTS: 154 patients (70% males, mean age 42 years) were included. Previous HAART included a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in 55% of the patients and a thymidine analog in 87%. The percentage of patients with viral load <200 copies/mL in the intent-to-treat (ITT) data set was 83% at 6 months and 75% at 12 months (98% and 96%, respectively, in the on-treatment [OT] analysis). Five patients (3%) were identified as virologic failures according to the study protocol. The mean CD4 T-cell count increased significantly 12 months after simplification (from 570 to 632 cells/mm3; p < .01). At 12 months, mean triglyceride levels decreased from 233 to 170 mg/dL (p < .01) and mean cholesterol levels decreased from 205 to 189 mg/dL (p < .01). Thirty-three patients (21%) discontinued the study treatment prior to completing the 12-month follow-up. CONCLUSION: Simplification to a once-daily regimen containing TDF, 3TC, and EFV is virologically and immunologically effective, well-tolerated, and safe with benefits in the lipid profile in the majority of patients.
Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/administration & dosage , Benzoxazines/administration & dosage , HIV Infections/drug therapy , Lamivudine/administration & dosage , Organophosphonates/administration & dosage , Viral Load , Adenine/administration & dosage , Adenine/adverse effects , Adult , Alkynes , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active , Benzoxazines/adverse effects , CD4 Lymphocyte Count , Cholesterol/blood , Cyclopropanes , Female , HIV Infections/immunology , HIV Infections/virology , Humans , Lamivudine/adverse effects , Male , Middle Aged , Organophosphonates/adverse effects , Patient Acceptance of Health Care , RNA, Viral/blood , Tenofovir , Treatment Outcome , Treatment Refusal , Triglycerides/bloodABSTRACT
Antiretroviral treatment has modified the course of human immunodeficiency virus (HIV) infection transforming it into a chronic disease. However, as treatment is conceived "for life", more effective and safety drugs, overcoming the growing resistance of the virus are required. New molecules may block the known viral targets or other new ones. The mechanism of the virus union and entrance to the cell includes the new therapeutic targets that are studied more frequently. Although studies with substances that efficiently block the virus-CD4 receptors union are in very early phases, other studies of molecules capable to block the entrance co-receptors are in more advanced phases (II or III), and enfuvirtide, a substance that blocks membrane fusion, the last phase of virus entrance, has been recently marketed. Another very promising pharmacological target is the integration of the proviral DNA as we know some substances that in vitro block HIV integrase. Besides this, new drugs are increasing the three classic antiretroviral families. Among nucleoside analogs emtricitabine (recently marketed) and amdoxovir are the more prominent. Capravirine and TMC-125 are the non-nucleoside analogs whose studies are more advanced. And atazanavir, fos-amprenavir, tipranavir and TMC-114 are the new protease inhibitors recently marketed or near to be.
Subject(s)
Anti-HIV Agents/therapeutic use , Drugs, Investigational/therapeutic use , HIV Infections/drug therapy , Anti-HIV Agents/pharmacology , Clinical Trials as Topic , Drug Delivery Systems , Drug Design , Drug Evaluation, Preclinical , HIV Fusion Inhibitors/pharmacology , HIV Fusion Inhibitors/therapeutic use , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/therapeutic use , HIV Protease Inhibitors/pharmacology , HIV Protease Inhibitors/therapeutic use , HIV Reverse Transcriptase/antagonists & inhibitors , HIV-1/drug effects , Humans , Receptors, Virus/drug effects , Reverse Transcriptase Inhibitors/pharmacology , Reverse Transcriptase Inhibitors/therapeutic use , Virus Physiological Phenomena/drug effectsABSTRACT
OBJECTIVE: To describe the frequency and the characteristics of hepatocellular carcinoma (HCC) cases that appeared in HIV/hepatitis C virus (HCV)-coinfected patients with previous sustained virological response (SVR) and to compare these cases to those diagnosed in patients without SVR. METHODS: All HIV/HCV-coinfected patients diagnosed with HCC in 26 hospitals in Spain before 31 December 2012 were analyzed. Comparisons between cases diagnosed in patients with and without previous SVR were made. RESULTS: One hundred and sixty-seven HIV/HCV-coinfected patients were diagnosed with HCC in the participant hospitals. Sixty-five (39%) of them had been previously treated against HCV. In 13 cases, HCC was diagnosed after achieving consecution of SVR, accounting for 7.8% of the overall cases. The median (Q1-Q3) elapsed time from SVR to diagnosis of HCC was 28 (20-39) months. HCC was multicentric and was complicated with portal thrombosis in nine and six patients, respectively. Comparisons with HCC cases diagnosed in patients without previous SVR only yielded a significantly higher proportion of genotype 3 infection [10 (83%) out of 13 cases versus 34 (32%) out of 107; Pâ=â0.001)]. The median (Q1-Q3) survival of HCC was 3 (1-39) months among cases developed in patients with previous SVR, whereas it was 6 (2-20) months in the remaining individuals (Pâ=â0.7). CONCLUSION: HIV/HCV-coinfected patients with previous SVR may develop HCC in the mid term and long term. These cases account for a significant proportion of the total cases of HCC in this setting. Our findings reinforce the need to continue surveillance of HCC with ultrasound examinations in patients with cirrhosis who respond to anti-HCV therapy.