Antiretroviral Treatment (antiretroviral + treatment)

Distribution by Scientific Domains

Selected Abstracts

What Determines Cross-Country Access to Antiretroviral Treatment?

Nicoli Nattrass
Despite the recent international effort to expand access to highly active antiretroviral therapy (HAART) in developing countries, its coverage still varies significantly from country to country and is strongly correlated with per capita income. However, regional and political variables are also important. Cross-country regressions indicate that, controlling for political and economic characteristics and the scale of the HIV epidemic, Latin American and African countries have better coverage than predicted. Whereas the level of HIV prevalence was a significantly (negative) factor when accounting for HAART coverage in June 2004, this effect had disappeared by December 2004. The improvement appears to have benefited democratic countries in particular. [source]

Predicting short-term disease progression among HIV-infected patients in Asia and the Pacific region: preliminary results from the TREAT Asia HIV Observational Database (TAHOD)

HIV MEDICINE, Issue 3 2005
J Zhou
Objectives HIV disease progression has been well documented in Western populations. This study aimed to estimate the short-term risk of AIDS and death from the TREAT Asia HIV Observational Database (TAHOD), a prospective, multicentre cohort study in Asia and the Pacific region. Methods Prospective data were analysed to estimate short-term disease progression. Endpoints were defined as the time from study entry to diagnosis with AIDS or death. Antiretroviral treatment was fitted as a time-dependent variable. Predictors of disease progression were assessed using Cox proportional hazards models, and prognostic models were developed using Weibull models. Results A total of 1260 patients with prospective follow-up data contributed 477 person-years of follow-up, during which 18 patients died and 34 were diagnosed with AIDS, a combined rate of 10.1 per 100 person-years. Compared with patients receiving antiretroviral treatment, patients not on treatment had a higher rate of disease progression (17.6 vs. 8.1 per 100 person-years, respectively). Baseline CD4 count was the strongest predictor of disease progression. Prognostic models, using either a baseline CD4 count as the sole marker or markers including baseline haemoglobin, AIDS-related symptoms and previous or current antiretroviral treatment, were successful at identifying patients at high risk of short-term disease progression. Conclusions Similar to the situation in Western countries, baseline CD4 count was the strongest predictor of short-term disease progression. Prognostic models based on readily available clinical data and haemoglobin level should be useful in estimating short-term clinical risk in HIV-infected patients in Asia and the Pacific region. [source]

Intracellular and cell-free (infectious) HIV-1 in rectal mucosa

Mariantonietta Di Stefano
Abstract The intestinal mucosa contains most of the total lymphocyte pool and plays an important role in viral transmission, but only slight attention has been given to the immunological and virological aspects of human immunodeficiency virus-1 (HIV-1) infection at this site. In this study, before initiating or changing antiretroviral therapy, paired blood samples and rectal biopsies (RB) were obtained from 26 consecutive HIV-infected subjects. HIV-1 isolation and biological characterization, DNA, and HIV-1 RNA titration were assessed, as were in vitro tumor necrosis factor-alpha (TNF-,) and interleukin-, (IL-1,) spontaneous production. The rate of HIV-1 isolation from peripheral blood mononuclear cells (PBMCs) and RBs was 75% and 58%, respectively. All RB-derived isolates were nonsyncytium inducing (NSI), independent of the phenotype of blood-derived isolates. Proviral DNA and detectable HIV-1 RNA levels were measured in 100% and 77% of RBs, respectively. A statistical correlation was observed between HIV-1 DNA and HIV-1 RNA levels in rectal mucosa (P,=,0.0075), whereas no correlation was found between these levels in blood samples (P,>,0.05). Antiretroviral treatment did not seem to influence HIV-1 detection in RBs. Higher levels of in vitro proinflammmatory cytokine production were found in the RBs of most infected patients when compared with healthy controls. Therefore, the rectal mucosa is an important HIV-1 reservoir that demonstrates a discordant viral evolution with respect to blood. Both the virus type and the mucosa pathway of immunoactive substances might have important implications for therapeutic decision-making and monitoring and could influence the bidirectional transmission of HIV-1 in mucosal surfaces. J. Med. Virol. 65:637,643, 2001. 2001 Wiley-Liss, Inc. [source]

Ophthalmic microsporidiosis: the Manchester experience

Purpose We report cases of ocular and adnexal microsporidiosis diagnosed in Manchester, UK, and review the literature. Methods The archives of the National Specialist Ophthalmic Pathology (NSOPS) Manchester Laboratory and Health Protection Agency Laboratory (HPA)at Manchester Royal Infirmary were reviewed for cases of microsporidiosis between 1990 and 2009. Results 8 cases of ocular and adnexal microsporidiosis were identified. Organisms were Encephalitozoon hellem, Encephalitozoon sp., Vittaforma corneae, Trachipleistophora hominis, Nosema sp. with infection of ocular surface, cornea, nasolacrimal apparatus and nasal sinuses, and eyelid; a historical case of Microsporidium ceylonensis keratitis, first reported by Norman Ashton in 1973 was also reviewed. Ages ranged from 11 years (Ashton's case) to 50 years. One case was from an HIV +ve patient, the others were immunocompetent. At least 4 infections were contracted whilst the patient was outside the UK. Conclusion Microsporidia, minute obligate intracellular parasites related to fungi, infect via a polar tube housed within a highly resistant spore. Microsporidial infection in HIV/AIDS, usually entereic, is the most reported. Antiretroviral treatment has lowered the incidence of enteric microsporidiosis and ocular infection is increasingly prevalent and often not HIV-related. In our cases the majority were immunocompetent individuals. LM can be diagnostic if characteristic refractile ZN-positive spores are seen, but LM does not permit speciation, which usually requires EM. Diligent searching for organisms may be necessary as distribution may be focal. Insufficient data exist for PCR-based diagnosis of most microsporidial species.Sources and mechanisms of microsporidial infection remain speculative. [source]

Scaling Up AIDS Treatment in Developing Countries: A Review of Current and Future Arguments

Jens Kovsted
Until recently, antiretroviral treatment against AIDS was perceived to be beyond the reach of the majority of patients in developing countries. This situation has changed drastically as international funding for AIDS treatment has swelled to several billion dollars a year. What has brought about this change? Analysis of the merit of six arguments often put forward against scaling up AIDS treatment in developing countries makes it clear that the most significant (and perhaps only) real change has been the large reduction in the price of the drugs. Although affordability is obviously a central issue, it is noticeable that most of the remaining arguments continue to be unresolved. This underlines the dangers of proceeding too fast towards treatment goals. [source]

Alcohol use and non-adherence to antiretroviral therapy in HIV-infected patients in West Africa

ADDICTION, Issue 8 2010
Antoine Jaquet
ABSTRACT Aim To investigate the association between alcohol use and adherence to highly active antiretroviral treatment (HAART) among human immunodeficiency virus (HIV)-infected patients in subSaharan Africa. Design and setting Cross-sectional survey conducted in eight adult HIV treatment centres from Benin, Cte d'Ivoire and Mali. Participants and measurements During a 4-week period, health workers administered the Alcohol Use Disorders Identification Test to HAART-treated patients and assessed treatment adherence using the AIDS Clinical Trials Group follow-up questionnaire. Findings A total of 2920 patients were enrolled with a median age of 38 years [interquartile range (IQR) 32,45 years] and a median duration on HAART of 3 years (IQR 1,4 years). Overall, 91.8% of patients were identified as adherent to HAART. Non-adherence was associated with current drinking [odds ratio (OR) 1.4; 95% confidence interval (CI) 1.1,2.0], hazardous drinking (OR 4.7; 95% CI 2.6,8.6) and was associated inversely with a history of counselling on adherence (OR 0.7; 95% CI 0.5,0.9). Conclusions Alcohol consumption and hazardous drinking is associated with non-adherence to HAART among HIV-infected patients from West Africa. Adult HIV care programmes should integrate programmes to reduce hazardous and harmful drinking. [source]

Response to first-line antiretroviral treatment among human immunodeficiency virus-infected patients with and without a history of injecting drug use in Indonesia

ADDICTION, Issue 6 2010
Rudi Wisaksana
ABSTRACT Background There is a common belief that injecting drug use (IDU) is associated with lower uptake, retention and success of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected patients. We examined this in an Indonesian setting, where IDU is the main risk factor for HIV infection. Methods Patient characteristics and response to ART were recorded for all patients diagnosed with HIV infection in the referral hospital for West Java (40 million people). Kaplan,Meier estimates and Cox's regression were used to compare mortality, loss to follow-up and virological failure between patients with and without a history of IDU. Result A total of 773 adult HIV patients (81.9% IDUs) presented between January 1996 and April 2008. IDUs had a median CD4 cell count of 33 [interquartile ratio (IQR), 12,111] cells/mm3 compared to 84 (IQR, 28,224) cells/mm3 in non-IDUs. Among patients with a history of IDU, 87.7% were coinfected with hepatitis C (HCV). Mortality was associated strongly with CD4 count; after 6 months of ART, 18.3, 20.3, 7.1 and 0.7% of patients with CD4 cell counts <25, 25,99, 100,199, respectively, ,200/mm3 had died (P < 0.0001). Mortality [adjusted for CD4; hazard ratio (HR) = 0.65; 95% confidence interval (CI) 0.35,1.23], loss to follow-up (HR = 0.85, 95% CI 0.51,1.41) and virological failure (HR = 0.47, 95% CI 0.19,1.13) were not significantly different in IDUs and non-IDUs. Conclusion Intravenous drug users (IDUs) in Indonesia with HIV/acquired immune deficiency syndrome tend to have more advanced disease but respond similarly to non-IDUs to antiretroviral therapy. [source]

Effect of simplification from protease inhibitors to boosted atazanavir-based regimens in real-life conditions

HIV MEDICINE, Issue 9 2010
R Rubio
Background Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well-tolerated, once-daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs. Objective The aim of the study was to determine the effectiveness and safety of ATV-containing regimens in patients who have simplified their antiretroviral treatment. Methods SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI-containing therapy and who were switched to an ATV/r-based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction. Results A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/,L. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low-density lipoprotein cholesterol were ,13 mg/dL (,7%; P<0.0001), ,19 mg/dL (,13%; P<0.0001) and ,7 mg/dL (,6%; P=0.021), respectively. Conclusions In a real-world setting, switching from other PIs to ATV/r is a well-tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients. [source]

Analysis of serious non-AIDS events among HIV-infected adults at Latin American sites

HIV MEDICINE, Issue 9 2010
WH Belloso
Objective Acquired immune deficiency appears to be associated with serious non-AIDS (SNA)-defining conditions such as cardiovascular disease, liver and renal insufficiency and non-AIDS-related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort. Materials and methods Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV-associated factors on non-AIDS-defining conditions. Results Among 6007 patients in follow-up, 130 had an SNA event (0.86 events/100 person-years of follow-up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non-AIDS-defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T-cell count prior to index date (P=0.0056, with an average difference of more than 100 cells/,L) and area under the CD4 cell curve in the year previous to index date (P=0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors. Conclusions The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment. [source]

Prevalence of drug resistance and importance of viral load measurements in Honduran HIV-infected patients failing antiretroviral treatment

HIV MEDICINE, Issue 2 2010
W Murillo
Objective The Honduran HIV/AIDS Program began to scale up access to HIV therapy in 2002. Up to May 2008, more than 6000 patients received combination antiretroviral therapy (cART). As HIV drug resistance is the major obstacle for effective treatment, the purpose of this study was to assess the prevalence of antiretroviral drug resistance in Honduran HIV-1-infected individuals. Methods We collected samples from 138 individuals (97 adults and 41 children) on cART with virological, immunological or clinical signs of treatment failure. HIV-1 pol sequences were obtained using an in-house method. Resistance mutations were identified according to the 2007 International AIDS Society (IAS)-USA list and predicted susceptibility to cART was scored using the anrs algorithm. Results Resistance mutations were detected in 112 patients (81%), 74% in adults and 98% in children. Triple-, dual- and single-class drug resistance was documented in 27%, 43% and 11% of the study subjects, respectively. Multiple logistic regression showed that resistance was independently associated with type of treatment failure [virological failure (odds ratio (OR)=1) vs. immunological failure (OR=0.11; 95% confidence interval (CI) 0.030,0.43) vs. clinical failure (OR=0.037; 95% CI 0.0063,0.22)], route of transmission (OR=42.8; 95% CI 3.73,491), and years on therapy (OR=1.81; 95% CI 1.11,2.93). Conclusion The prevalence of antiretroviral resistance was high in Honduran HIV-infected patients with signs of treatment failure. A majority of study subjects showed dual- or triple-class resistance to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors. Virologically defined treatment failure was a strong predictor of resistance, indicating that viral load testing is needed to correctly identify patients with treatment failure attributable to resistance. [source]

Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy,

HIV MEDICINE, Issue 4 2008
S Grabar
Objectives To analyse the impact of combined antiretroviral treatment (cART) on survival with AIDS, according to the nature of the first AIDS-defining clinical illness (ADI); to examine trends in AIDS-defining causes (ADC) and non-AIDS-defining causes (non-ADC) of death. Methods From the French Hospital Database on HIV, we studied trends in the nature of the first ADI and subsequent survival in France during three calendar periods: the pre-cART period (1993,1995; 8027 patients), the early cART period (1998,2000; 3504 patients) and the late cART period (2001,2003; 2936 patients). Results The three most frequent initial ADIs were Pneumocystis carinii (jirovecii) pneumonia (PCP) (15.6%), oesophageal candidiasis (14.3%) and Kaposi's sarcoma (13.9%) in the pre-cART period. In the late cART period, the most frequent ADIs were tuberculosis (22.7%), PCP (19.1%) and oesophageal candidiasis (16.2%). The risk of death after a first ADI fell significantly after the arrival of cART. Lower declines were observed for progressive multifocal leukoencephalopathy, lymphoma and Mycobacterium avium complex infection. After an ADI, the 3-year risk of death from an ADC fell fivefold between the pre-cART and late cART periods (39%vs. 8%), and fell twofold for non-ADCs (17%vs. 9%). Conclusions The relative frequencies of initial ADI have changed since the advent of cART. Tuberculosis is now the most frequent initial ADI in France; this is probably the result of the increasing proportion of migrants from sub-Saharan Africa. After a first ADI, cART has a major impact on ADCs and a smaller impact on deaths from other causes. The risk of death from AIDS and from other causes is now similar. [source]

Osteoprotegerin and bone turnover markers in heavily pretreated HIV-infected patients

HIV MEDICINE, Issue 3 2005
E Seminari
Objectives To characterize osteoprotegerin (OPG) levels, bone remodelling and bone mineral density (BMD) in heavily pretreated HIV-infected patients on antiretroviral therapy, and to evaluate the clinical factors associated with bone density decline. Methods Heavily pretreated (>5 years) HIV-positive patients were enrolled in this cross-sectional, observational study, which was based on a total body bone densitometry examination and a comprehensive evaluation of bone and mineral parameters. Results Sixty-eight patients (55 male and 13 female) with a median age of 41 years (range 25,60 years) were included in the study. Their antiretroviral treatment lasted for 82 months. On the basis of the World Health Organization criteria, nine patients (13.2%) were osteoporotic [T-score<,2.5 standard deviation (SD)] and 19 patients (27.9%) were osteopenic (T-score between,1 and,2.5). The principal outcomes associated with the presence of a low BMD were high OPG and lysylpyridinoline/creatinine ratio (Dpd) values. Most of the patients (39 of 48; 81.25%) showed vitamin D insufficiency [Vitamin D (25(OH)D)<18 ng/mL] with secondary hyperparathyroidism (13 of 50 patients: 26%), which proved to be correlated to osteocalcin (BGP) levels [parathyroid hormone (PTH) vs. BGP: r=0.34; P<0.01]. There was an inverse correlation between T-scores and serum osteocalcin and alkaline phosphatase (AP) levels, on one hand, and Dpd, on the other. High AP and Dpd values were associated with relative risks of 4.1 [95% confidence interval (CI)=1.01,17.6] and 7.2 (95% CI=1.67,31.03), respectively, of a pathological T-score. Multivariate analysis revealed that the factors associated with the presence of osteopenia or osteoporosis were older age and lower body mass index. Conclusions About 40% of our heavily pretreated subjects with advanced HIV infection had a low BMD, and 56% (24 of 44 patients) showed a high bone turnover rate with marked osteoclast activation. High OPG levels may protect against bone resorption. [source]

Predicting short-term disease progression among HIV-infected patients in Asia and the Pacific region: preliminary results from the TREAT Asia HIV Observational Database (TAHOD)

HIV MEDICINE, Issue 3 2005
J Zhou
Objectives HIV disease progression has been well documented in Western populations. This study aimed to estimate the short-term risk of AIDS and death from the TREAT Asia HIV Observational Database (TAHOD), a prospective, multicentre cohort study in Asia and the Pacific region. Methods Prospective data were analysed to estimate short-term disease progression. Endpoints were defined as the time from study entry to diagnosis with AIDS or death. Antiretroviral treatment was fitted as a time-dependent variable. Predictors of disease progression were assessed using Cox proportional hazards models, and prognostic models were developed using Weibull models. Results A total of 1260 patients with prospective follow-up data contributed 477 person-years of follow-up, during which 18 patients died and 34 were diagnosed with AIDS, a combined rate of 10.1 per 100 person-years. Compared with patients receiving antiretroviral treatment, patients not on treatment had a higher rate of disease progression (17.6 vs. 8.1 per 100 person-years, respectively). Baseline CD4 count was the strongest predictor of disease progression. Prognostic models, using either a baseline CD4 count as the sole marker or markers including baseline haemoglobin, AIDS-related symptoms and previous or current antiretroviral treatment, were successful at identifying patients at high risk of short-term disease progression. Conclusions Similar to the situation in Western countries, baseline CD4 count was the strongest predictor of short-term disease progression. Prognostic models based on readily available clinical data and haemoglobin level should be useful in estimating short-term clinical risk in HIV-infected patients in Asia and the Pacific region. [source]

Non-nucleoside reverse transcriptase inhibitors: a review

L. Waters
Summary Non-nucleoside reverse transcriptase inhibitors form the backbone of antiretroviral treatment for many HIV-infected individuals. The tolerability, pill burden and efficacy associated with this class of agents make them a frequent choice for first-line therapy. Here we review nevirapine and efavirenz in terms of efficacy, resistance and toxicity, focusing particularly on the use of nevirapine to prevent mother-to-child transmission in developing countries. [source]

A service evaluation to determine the effectiveness of current dietary advice in treating human immunodeficiency virus-associated weight loss and to highlight potential service improvements

C.A. Hunt
Background:, Weight loss and muscle wasting are experienced by many patients with human immunodeficiency virus (HIV) (Grinspoon et al., 2003). Malnutrition is an important predicator of morbidity and mortality; people who are malnourished who received antiretroviral treatment are six times more likely to die than those who are adequately nourished (Paton et al., 2006). The physical manifestations of muscle wasting can have significant psychosocial implications for HIV patients (Power et al., 2003; Sattler, 2003). The aim of this study to evaluate provision of dietetic care to patients referred for acute weight loss advice and identify areas for potential service improvement. Methods:, The data were gathered from the departmental dietetic activity statistics in 2007, diagnosis code ,HIV , acute weight loss'. Fifty-nine cards were located and baseline weight, height and body mass index (BMI) were recorded (two female, 57 male). Qualitative data on dietetic intervention were extracted from record cards , little and often eating approach, food fortification (FF), high energy high protein oral nutritional supplement (ONS) prescribed. Data were collected on body image, exercise and weight at follow-up visits during 2007. Results:, Forty-three percent of the patients referred for ,HIV-acute weight loss' were lost to follow-up. Forty-seven percent of the remaining patients had a BMI <20 kg m,2. Following their initial dietetic intervention, 81% of these patients had gained weight at the first follow-up. All had received nutritional counselling on little and often eating approach and FF; 75% had ONS prescribed. Average weight gain with nutritional counselling alone was 1.3 kg (2.1 kg) and for nutritional counselling plus supplementation was 2.1 kg (1.8 kg). This represented 2.5% (4.1%) and 3.9% (3.4%) weight gain, respectively. Discussion:, This evaluation has highlighted that patient follow-up frequency is an area for service improvement. Fifty-three per cent of patients (excluding those lost to follow up) had a BMI ,20 kg m,2 and were inaccurately recorded in the statistics as being referred for ,HIV-acute weight loss'. Fifty-two percent of these patients reported lipodystrophy and body image concerns, similar to findings of other studies. Fifty-six percent reported weight improvements following dietetic consultation. Body image is a frequent referral trigger, therefore improvements should be made to identify and treat patients with body shape issues. Conclusions:, Dietitians are effective at achieving weight gain in HIV positive patients with a BMI <20 kg m,2 using nutritional counselling methods with or without oral nutritional supplementation; these patients experienced a 3.3% weight gain. Strategies need to be implemented to reduce the number of patients lost to follow-up, as weight loss is a key morbidity and mortality indicator in HIV. References, Grinspoon, S. & Mulligan, K. (2003) Weight loss and wasting in patients infected with HIV. Clin. Infect. Dis.36 (Suppl. 2): 69,78. Nerad, J., Romeyn, M., Silverman, E., Allen-Reid, J., Dieterich, D., Merchant, J., Pelletier, V., Tinnerello, D. & Fenton, M. (2003) General nutritional management in patients infected with HIV. Clin. Infect. Dis.36 (Suppl. 2): 52,62. Ockenga, J., Grimble, R., Jonkers-Schuitema, C., Macallan, D., Melchior, J.C., Sauerwein, H.P., Schwenk, A. & Suttmann, U. (2006) ESPEN guidelines on enteral nutrition: wasting in HIV and other chronic infectious diseases. Clin. Nutr.25, 319,329. Paton, N.I., Sangeetha, S., Earnest, A. & Bellamy, R. (2006) The impact of malnutrition on survival and the CD4 count response in HIV-infected patients starting antiretroviral therapy. HIV Med.7, 232,330. Power, R., Tate, H.L., McGill, S.M. & Taylor, C. (2003) A qualitative study of the psychosocial implications of lipodystrophy syndrome on HIV positive individuals. Sex. Transm. Infect.79, 137,141. Sattler, F. (2003) Body habitus changes related to lipodystrophy. Clin. Infect. Dis36 (Suppl. 2): 84,90. [source]

Prognostic factors of long-term CD4+count-guided interruption of antiretroviral treatment

L. Sarmati
Abstract Aim of the study was to determine predictors of the duration of antiretroviral treatment interruption in patients infected with HIV. This pilot prospective, open-label, multicenter trial comprised 62 HIV-seropositive subjects who decided voluntarily to interrupt therapy after two or more years of successful HAART. The primary end-point was the time to patients being free of therapy before reaching a CD4+ cell count ,350/l. Fifteen of 62 patients remained in treatment interruption for more than 180 days. Patients restarting therapy had higher HIV-DNA levels (P,=,0.05), were treated more frequently with NNRTI-drugs (P,=,0.02), had a shorter period of HAART (P,=,0.046), and lower CD4+ cell counts after day 14 of interruption of treatment (P,=,0.04). Multivariate regression analysis showed that less than 323 baseline proviral HIV-DNA cp/106 PBMCs and more than 564 CD4 cells/l at day 14 after interruption were associated independently with a reduced risk of restarting treatment (P,=,0.041 and P,=,0.012, respectively). A score based on CD4+ cell counts at nadir, at baseline, at week 2 of treatment interruption, and on baseline HIV-DNA values can identify patients with a prolonged period free safely of treatment. J. Med. Virol. 81:481,487, 2009. 2009 Wiley-Liss, Inc. [source]

Intrahepatic HCV RNA loads in 37 HIV-HCV co-infected patients with controlled HIV infection

P. Trimoulet
Abstract Serum and intrahepatic hepatitis C virus (HCV) RNA were measured in 37 HIV-HCV co-infected patients with controlled human immunodeficiency virus (HIV) infection and correlated with clinical, biological, and histological parameters. Thirty-seven interferon-naive patients underwent liver biopsy. HCV-induced activity (A) and fibrosis (F) were evaluated with METAVIR score. The 37 patients included had HIV plasma loads,<,10,000 copies/ml, CD4+ count,>,250/,l. All the patients but two were receiving antiretroviral treatment. Liver tissue and sera were used for measurement of HCV RNA by the Cobas Amplicor HCV Monitor. All patients had serum and liver HCV RNA, and both levels were correlated (r,=,0.47; P,=,0.003). Intrahepatic HCV load did not depend on age, sex, duration of HCV infection, CD4+, HCV genotype, or fibrosis. AST levels correlated with intrahepatic HCV load (r,=,0.52; P,=,0.001). Patients with METAVIR A1/A2 had significantly lower levels of liver HCV-RNA than were found in patients with METAVIR A3 (P,=,0.026). Highly active antiretroviral therapy (HAART) including protease inhibitors(PI)-treated patients had significantly lower intrahepatic HCV load (P,=,0.04). A weak but significant correlation between serum and liver HCV RNA was found. The amount of hepatic HCV RNA was correlated with AST levels, histological activity, but not with HCV genotype or fibrosis. The immune improvement associated with PI regimens could help reduce HCV load, supporting a protective effect of PI-induced immune restoration. J. Med. Virol. 67:143,151, 2002. 2002 Wiley-Liss, Inc. [source]


A. Sghirlanzoni
Unlike peripheral motor disorders, sensory disturbances are rarely diagnosed by the probable site of pathology. This approach is useful in the differential diagnosis between chronic sensory axonal neuropathies and ganglionopathies, in which routine clinical and neurophysiological evaluation alone often do not provide definite clues. Methods: Thirty patients with peripheral sensory disturbances were investigated. MRI was performed at cervical level in all cases. Four patients also underwent thoracic and lumbar MRI. Seventeen patients underwent skin biopsy at the proximal thigh and the distal leg. In 4 of them, further skin biopsies were taken at C5 dermatome and at the hand. Density of intra-epidermal nerve fibers (IENF) was quantified. Results: In 22 patients, sensory ganglionopathy was suspected. Disease was idiopathic in 7 cases; paraneoplastic in 3 cases; and associated with Sjgren, AIDS, autoimmune chronic hepatitis, and cisplatin neurotoxicity in 4 cases. One patient had a hereditary sensory autonomic neuropathy. Four patients had vitamin E deficiency and 3 patients a spinocerebellar syndrome. In 8 patients, sensory axonal neuropathy related to diabetes, alcoholism, and AIDS on antiretroviral treatment, and monoclonal gammopathy of undetermined significance was diagnosed. MRI findings: All ganglionopathy patients showed posterior columns hyperintensity on T2-weighted MRI. Conversely, MRI was negative in all axonal sensory neuropathy patients. Skin biopsy findings: In neuropathies, IENF density was significantly lower at the distal leg than at the proximal thigh, while ganglionopathies did not show any change with respect to the rostral:caudal orientation. A similar pattern of epidermal denervation was observed in the arm. Discussion: The degeneration of both central and peripheral sensory pathway in a fashion that is not length-dependent localizes the disease to T-shaped sensory neurons Early ataxia and cutaneous sensory symptoms involving the proximal regions of the body reflect this pattern of denervation and should prompt the diagnosis of ganglionopathy. This can be confirmed by T2-weighted hyperintensity in the posterior columns and a distinct pattern of IENF loss. [source]

Epidermoid anal cancer prognosis comparison among HIV+ and HIV, patients

Summary Background, Previous studies suggest a poor prognosis of epidermoid anal cancer in HIV+ patients. Aim, To investigate the long-term outcome of epidermoid anal cancer in HIV+ and HIV, patients in the highly active antiretroviral treatment (HAART) era. Methods, We included all patients with epidermoid anal cancer referred to six hospitals from 1998 to 2004. Results, In all, 151 patients (44 HIV+, 107 HIV,) were reviewed retrospectively for 27 (median of 16,44) months. HIV+ patients were male (100% vs. 27%, P < 0.001) and younger (45 vs. 62 years old, P < 0.001) than HIV, patients. No significant differences were observed in the tumour stage, pelvic radiotherapy dose or concomitant chemotherapy, according to the HIV status. After chemoradiotherapy, similar numbers of HIV+ and HIV, patients had grade III-IV toxicity. A complete response was obtained in 82% and 75% (N.S.) of cases, respectively. The disease-free survival rates were 77% and 67% (N.S.) and the overall survival rates were 85% and 84% (N.S.), respectively, after 3 years of follow-up. Duration of HIV infection, viral load and CD4 count had no effect on the survival rate of HIV+ patients with EAC. Conclusions, The clinical outcome of HIV+ patients with epidermoid anal cancer is similar to that of HIV, patients. Therefore, the same therapeutic guidelines should be applied to both populations. [source]

Recent strategies in the development of new human cytomegalovirus inhibitors

Ana Martinez
Abstract Human cytomegalovirus (HCMV) is one of the most common opportunistic infections in immunucompromised individuals, such as AIDS patients and organ transplant recipients, and is the most frequent congenital viral infection in humans. Despite a reduction of the incidence of AIDS-related opportunistic infections in patients under highly active antiretroviral treatment, attention should be paid to the HCMV risk factor in these individuals. Furthermore, HCMV may have an important role in atherosclerosis. Existing antiviral treatments for the HCMV infection suffer from poor bioavailability, toxicity, and limited effectiveness, mainly due to the development of drug resistance. Fortunately there are novel and potentially very effective new compounds undergoing pre-clinical and clinical evaluation. This review provides an overview in the last five years of new HCMV inhibitors (chemical structures, SAR, and new mechanisms of action) with the aim to provide new clues for the development of future drugs against this opportunistic virus. 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 3, 227,244, 2001 [source]

Psychosocial issues in antiretroviral treatment

Marshall Forstein M.D.
The advent of effective treatments for HIV has begun a new era in the worldwide HIV epidemic. Many new political, social, economic, medical, and psychological issues arise in the struggle to contain this epidemic. Mental health providers must understand the context in which people with HIV find themselves making decisions about their health care and the future directions of their lives. [source]

Declined neural efficiency in cognitively stable human immunodeficiency virus patients,

Thomas Ernst PhD
Objective To determine whether brain activation changes in clinically and neurocognitively normal human immunodeficiency virus (HIV),infected and in HIV-seronegative control (SN) participants over a 1-year period. Methods Functional magnetic resonance imaging (fMRI) was performed in 32 SN and 31 HIV patients (all with stable combination antiretroviral treatment) at baseline and after 1 year. Each participant performed a set of visual attention tasks with increasing attentional load (from tracking two, three, or four balls). All HIV and SN participants had normal neuropsychological function at both examinations. Results Over 1 year, HIV patients showed no change in their neurocognitive status or in task performance during fMRI. However, HIV patients showed significant 1-year increases in fMRI signals in the prefrontal and posterior parietal cortices for the more difficult tasks, whereas SN control participants showed only decreases in brain activation in these regions. This resulted in significant interactions between HIV status and time of study in left insula, left parietal, left temporal, and several frontal regions (left and right middle frontal gyrus, and anterior cingulate). Interpretation Because fMRI task performance remained unchanged in both groups, the HIV patients appeared to maintain performance by increasing usage of the attention network, whereas the control participants reduced usage of the attention network after 1 year. These findings suggest improved efficiency or a practice effect in the SN participants but declined efficiency of the neural substrate in HIV patients, possibly because of ongoing brain injury associated with the HIV infection, despite their apparent stable clinical course. Ann Neurol 2009;65:316,325 [source]

Preventing mother-to-child transmission of HIV

CN Mnyani
HIV transmission from mother-to-child remains a major cause of infant morbidity and mortality in resource-poor settings. There is consensus that women who need antiretroviral treatment should receive this during pregnancy and beyond, and that an appropriate antiretroviral prophylactic regimen should be given to those who do not yet need ongoing therapy. Infant feeding remains a major source of infection and new antiretroviral strategies, for mothers or children, are emerging with the potential to control this. Access to HIV testing and antiretroviral treatment or prophylaxis remain very limited in low resource settings and needs to be expanded. [source]

Pregnancy outcomes and antiretroviral treatment in a national cohort of pregnant women with HIV: overall rates and differences according to nationality

M Floridia
We used data from the main surveillance study of HIV and pregnancy in Italy to evaluate possible differences in pregnancy care and outcomes according to nationality. Among 960 women followed in 2001,06, 33.5% were of foreign nationality, mostly from African countries. Foreign women had lower rates of preconception counselling and planning of pregnancy. They had more frequently HIV diagnosed during pregnancy, with a later start of antiretroviral treatment and lower treatment rates at all trimesters but not when the entire pregnancy, including delivery, was considered. No differences were observed between the two groups in ultrasonography assessments, hospitalisations, AIDS events, intrauterine or neonatal deaths, and mode and complications of delivery. Foreign women had a slightly lower occurrence of preterm delivery and infants with low birthweight. The results indicate good standards of care and low rates of adverse outcomes in pregnant women with HIV in Italy, irrespective of nationality. Specific interventions, however, are needed to increase the rates of counselling and HIV testing before pregnancy in foreign women. [source]

Involvement of intraocular structures in disseminated histoplasmosis

Marianne Ala-Kauhaluoma
Abstract. Purpose:, To describe ocular involvement and response to treatment in a patient with human immunodeficiency virus (HIV) infection with severe progressive disseminated histoplasmosis (PDH). Methods:, We report a 35-year-old HIV-infected patient seen in our clinics over a period of 4 years. During antiretroviral treatment (ART), the HIV load became undetectable at 3 months; however, CD4 T-cell count increased slowly and rose to 100 cells/,l. Histoplasma capsulatum was cultured from skin pustules, cerebrospinal fluid (CF) and aqueous humour. Results:, The patient developed central nervous system (CNS) involvement 2 months and panuveitis in both eyes 4 months after the initiation of ART. With intravenous liposomal amphotericin B followed by oral voricanozole, the chorioretinal lesions of the right eye (RE) became inactivated and magnetic resonance imaging (MRI) lesions of CNS disappeared. Relapse of the inflammation in the anterior segment of the left eye (LE) resulted in a total closure of the chamber angle and severe glaucoma. Despite medical therapy, two cyclophotocoagulations, total vitrectomy and repeated intravitreal amphotericin B injections, LE became blind. Histoplasma capsulatum was cultured from the aqueous humour after antifungal therapy of 16 months' duration. Conclusion:, PDH with intraocular and CNS manifestations was probably manifested by an enhanced immune response against a previous subclinical disseminated infection. It seems difficult to eradicate H. capsulatum from the anterior segment of the eye in an immunocompromised patient. [source]

Nonconcordance between subclinical atherosclerosis and the calculated Framingham risk score in HIV-infected patients: relationships with serum markers of oxidation and inflammation

HIV MEDICINE, Issue 4 2010
S Parra
Objectives HIV-infected patients show an increased cardiovascular disease (CVD) risk resulting, essentially, from metabolic disturbances related to chronic infection and antiretroviral treatments. The aims of this study were: (1) to evaluate the agreement between the CVD risk estimated using the Framingham risk score (FRS) and the observed presence of subclinical atherosclerosis in HIV-infected patients; (2) to investigate the relationships between CVD and plasma biomarkers of oxidation and inflammation. Methods Atherosclerosis was evaluated in 187 HIV-infected patients by measuring the carotid intima-media thickness (CIMT). CVD risk was estimated using the FRS. We also measured the circulating levels of interleukin-6, monocyte chemoattractant protein-1 (MCP-1) and oxidized low-density lipoprotein (LDL), and paraoxonase-1 activity and concentration. Results There was a weak, albeit statistically significant, agreement between FRS and CIMT (,=0.229, P<0.001). A high proportion of patients with an estimated low risk had subclinical atherosclerosis (n=66; 56.4%). In a multivariate analysis, the presence of subclinical atherosclerosis in this subgroup of patients was associated with age [odds ratio (OR) 1.285; 95% confidence interval (CI) 1.084,1.524; P=0.004], body mass index (OR 0.799; 95% CI 0.642,0.994; P=0.044), MCP-1 (OR 1.027; 95% CI 1.004,1.050; P=0.020) and oxidized LDL (OR 1.026; 95% CI 1.001,1.051; P=0.041). Conclusion FRS underestimated the presence of subclinical atherosclerosis in HIV-infected patients. The increased CVD risk was related, in part, to the chronic oxidative stress and inflammatory status associated with this patient population. [source]