New Publications in HIV : Archive

20 April 2009

Immune senescence, activation, and abnormal T Cell homeostasis despite effective HAART, a hallmark of early aging in HIV disease.

Desai S et al. CROI 2009;Abstract 381. Feb Naïve, memory, and effector T cell subsets were evaluated in 10 HIV-1-infected, HAART-suppressed subjects (median 56 years) and 10 older HIV-negative subjects (median age 88 years).

Age-dependent changes in HIV-infected compared to young HIV-negative controls are more pronounced in CD8+ T-cells, which exhibit higher immune activation and senescence levels and reduced naïve and central memory subsets.

Conclusions: HIV-infected subjects with good immune reconstitution and viral suppression had immune changes comparable to older HIV-negative subjects.
Link 23 April 2009

Benefits and risks of stavudine therapy for HIV-associated neurologic complications in Uganda.

Sacktor N et al. Neurology 2009;72:165–70. • This study investigated the risk/benefit of stavudine-based HAART for HIV-associated cognitive impairment and distal sensory neuropathy.
• Conclusion: Treatment was associated with improvement in verbal memory, motor and psychomotor speed, executive thinking, and verbal fluency. However, neuropathy symptoms developed in 38% of previously asymptomatic HIV+ patients.
Link 23 April 2009

Immune senescence, activation, and abnormal T Cell homeostasis despite effective HAART, a hallmark of early aging in HIV disease.

Desai S et al. CROI 2009;Abstract 381. • Naïve, memory, and effector T cell subsets were evaluated in 10 HIV-1-infected, HAART-suppressed subjects (median 56 years) and 10 older HIV-negative subjects (median age 88 years).
• Age-dependent changes in HIV-infected compared to young HIV-negative controls are more pronounced in CD8+ T-cells, which exhibit higher immune activation and senescence levels and reduced naïve and central memory subsets.
• Conclusions: HIV-infected subjects with good immune reconstitution and viral suppression had immune changes comparable to older HIV-negative subjects.
Link 28 April 2009

Hepatotoxicity associated with long versus short-course HIV-prophylactic nevirapine use. A systematic review and meta-analysis from the research on Adverse Drug events And Reports (RADAR) Project.

McKoy JM et al. Drug Saf 2009;32:147–58. Feb • A review of hepatotoxicity cases among HIV-negative individuals and HIV-positive pregnant women and their offspring receiving short- (≤4 days) versus long-course (≥5 days) NVP prophylaxis.
• Long-course NVP was associated with a greater incidence of hepatotoxicity then short-course NVP in all the patient groups studied.
• Conclusions: The duration of NVP therapy appears to significantly predict hepatotoxicity.
Link 29 April 2009

Assessment of liver fibrosis by transient elastography in persons with hepatitis C virus infection or HIV-hepatitis C virus coinfection.

Kirk GD et al. Clin Infect Dis 2009;48:963–72. • This study compared elastography with histology to stage liver fibrosis among HCV-infected and HIV/HCV-co-infected individuals in an urban, primarily black population.
• Elastography correctly staged liver fibrosis in 79–83% of participants compared with histology.
• Conclusions: Elastography was similar to histology in predicting fibrosis stage in most individuals. Elastography is a promising technique to expand liver disease screening and monitoring.
Link 06 May 2009

Association of non-cirrhotic portal hypertension in HIV-infected persons and ART with didanosine.

Kovari H et al. CROI 2009;Abstract 751. • This nested case-control study investigated possible risk factors for cryptogenic non-cirrhotic portal hypertension (NCPH).
• In bi-variable models, only the association of NCPH with ddI exposure was robust; other co-variables, particularly low CD4 cell count, were not independent risk factors.
• Conclusion: There was a strong association with prolonged exposure to ddI and the development of NCPH.
Link 07 May 2009

Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir.

Labarga P et al. AIDS 2009;23:689–96. • This study investigated plasma and 24-hour urine markers of kidney tubulopathy in patients on TDF-containing HAART, patients on non-TDF HAART and ARV-naïve individuals.
• There were no significant differences in creatinine clearance between the three groups. The only independent predictors of tubular dysfunction were TDF use (p<0.001) and older age (p= 0.01).
• Conclusions: TDF is associated with an increased risk of kidney tubular abnormalities in the absence of significant impaired glomerular function. The long-term consequences of this tubulopathy are unknown.
Link 14 May 2009

Bone pain due to fractures revealing osteomalacia related to tenofovir-induced proximal renal tubular dysfunction in a human immunodeficiency virus-infected patient.

Perrot S, Aslangul E, Szwebel T et al. J Clin Rheumatol 2009;15:72–4. • This study reports a case of chronic metabolic complications with bone fractures related to TDF.
• Several factors increased the renal toxicity of TDF including low BMI, concomitant use of NSAIDs, and other ARVs, including RTV.
Link 15 May 2009

Kidney tubular abnormalities in the absence of impaired glomerular function in HIV patients treated with tenofovir.

Labarga P, Barreiro P, Martin-Carbonero L et al. AIDS 2009;23:689–96. • This study investigated renal function in three patient groups: TDF-containing HAART (1); HAART never exposed to TDF (2); and ARV-naïve (3).
• No significant differences in CrCl were observed between the groups. The proportion of patients with tubular damage in groups 1, 2 and 3 was 22%, 6% and 12%, respectively. In a multivariate analysis, the only independent predictors of tubular dysfunction were TDF use (OR: 21.6; 95% CI: 4.1–113; p<0.001) and older age (OR: 1.1 per year; 95% CI: 1.0–1.1; p=0.01).
• Conclusions: TDF is associated with an increased risk over time of kidney tubular abnormalities in the absence of significant impaired glomerular function. Periodic screening of tubular function parameters should be recommended to patients receiving TDF.
Link 15 May 2009

A delayed hypersensitivity reaction to enfuvirtide after rechallenge.

Emerson CR, Post JJ, Workman C. Int J STD AIDS 2009;20:288–9. • This is the first case report of a delayed hypersensitivity reaction to ENF.
• A highly ARV-experienced man was started on a new ENF-containing regimen together with TMP-STX prophylaxis for Pneumocystis jirovecii pneumonia. A maculopapular rash on the chest and abdomen without any systemic features developed 10 days later. Both ENF and TMP-STX were discontinued and re-introduction of ENF occurred in a hospital setting. The rash re-appeared involving the whole body 5 hours post-dose and was associated with fever, nausea and a presyncopal episode.
Link 05 June 2009

Changes in body composition with ritonavir-boosted and unboosted atazanavir treatment in combination with lamivudine and stavudine: a 96-week randomized, controlled study.

McComsey G, Rightmire A, Wirtz V et al. Clin Infect Dis 2009;48:1323–6. • This open-label, randomized study investigated changes in body composition in treatment-naïve patients treated with either ATV or RTV-boosted ATV in combination with d4T and 3TC.
• Both groups had similar increases in trunk fat but there was a significantly lower incidence of lipoatrophy in patients treated with RTV-boosted ATV.
Link 08 June 2009

HIV-related lipodystrophy in Africa and Asia.

Womack J. AIDS Read 2009;19:131–9, 148–52. • This article reviews the literature on lipodystrophy in Africa and Asia.
• Lipodystrophy in resource-constrained settings has significant implications for patient health, QoL and long-term adherence.
• Lipoatrophy may be an important adverse effect of ART in Africa and Asia.
• Although a causative link has not been identified from the literature, the consistent evidence from the West means that it is reasonable to support the WHO’s effort to remove d4T from first-line therapy options.
• Affordability and access to alternative NRTIs and the newer ARV classes are key issues.
Link 25 June 2009

Predictors of kidney tubular dysfunction in HIV-infected patients treated with tenofovir: a pharmacogenetic study.

Rodríguez-Nóvoa S, Labarga P, Soriano V et al. Clin Infect Dis 2009;48:e108–16. • This study investigated the association between kidney tubular dysfunction due to TDF and polymorphisms in genes encoding drug transporters.
• Kidney tubular dysfunction was higher among patients with genotype CC at position -24 of ABCC2 than among those with genotypes CT and TT (24% [16/68 patients] versus 6% [3/47 patients]; p=0.020). In a multivariate analysis, older age (OR: 1.1; 95% CI: 1.0–1.2; p=0.024), lower body weight (OR: 0.9; 95% CI: 0.8–0.9; p=0.048) and genotype CC at ABCC2 position -24 (OR 5; 95% CI: 1.2–21; p=0.027) were independently associated with kidney tubular dysfunction.
• Conclusions: Homozygosity for the C allele at position -24 of the ABCC2 gene was strongly associated with kidney tubular dysfunction. This polymorphism may help to identify patients at greater risk for developing TDF-associated tubulopathy. These patients should be closely monitored for renal function.
Link 16 September 2009

Continuous antiretroviral therapy decreases bone mineral density

Grund B, Peng G, Gibert CL et al. AIDS 2009;23:1519–29. • This study reports the effects of continuous versus intermittent ART on bone mineral density in 214 patients in the Strategies for Management of Antiretroviral Therapy (SMART) Body Composition substudy.
• The annual decline in bone mineral density was 0.8% (hip), 0.4% (spine by dual-energy radiographic absorptiometry) and 2.4% (spine by quantitative computed tomography) with continuous ART.
• The decline in bone mineral density was significantly less with intermittent ART.
• Estimated intermittent minus continuous group differences in mean change in bone mineral density were: 1.4% (hip; 95% CI: 0.6–2.3; p=0.002), 1.3% (spine; 95% CI: 0.1–2.4; p=0.03) and 3.0% (spine; 95% CI: 0.8–5.2; p=0.007).
• There was no consistent drug-specific association with bone mineral density decline.
• In the parent study, 10 of 2753 patients in the continuous ART group and two of 2720 in the intermittent group reported serious fractures (HR: 4.9; 95% CI: 1.1–22.5; p=0.04).
• Conclusion: Continuous ART is associated with a greater decline in bone mineral density and possibly more fractures than intermittent ART.
Link 16 September 2009

Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure.

Ouyang et al. AIDS 2009;23:2425–30. • This study investigated whether the association between (NVP) and hepatotoxicity differs according to pregnancy status in HIV-infected women.
• Two outcomes were assessed: any liver enzyme elevation (grade 1–4) and severe liver enzyme elevation (grade 3–4).
• Data on 2050 HIV-infected women taking ART were included: 1229 (60%) were pregnant and 821 (40%) were not.
• Among pregnant women, 174 (14.2%) developed any liver enzyme elevation and 15 (1.2%) developed severe liver enzyme elevation compared with 75 (9.1%) and 5 (0.6%), respectively, of the non-pregnant women.
• In multivariate adjusted models, NVP was not significantly associated with a risk of liver enzyme elevation, regardless of pregnancy status.
• However, pregnancy was associated with an increased risk of any liver enzyme elevation (RR: 4.7; CI: 3.4–6.5) and severe liver enzyme elevation (RR: 3.8; CI: 1.3–11.1).
• The association of pregnancy and liver enzyme elevation was seen, regardless of prior ART and NVP exposure history.
• Conclusions: No significant association between NVP and liver enzyme elevation was observed, regardless of pregnancy status, but pregnancy was significantly associated with increased hepatotoxicity in HIV-infected women.
Link 16 November 2009

Reporting of adverse events in randomized controlled trials of highly active antiretroviral therapy: systematic review.

Chowers MY, Gottesman BS, Leibovici L et al. J Antimicrob Chemother 2009;64:239–50. Reporting of adverse events in randomized controlled trials of highly active antiretroviral therapy: systematic review (JAC 2009) Reporting of adverse events in randomized controlled trials of highly active antiretroviral therapy: systematic review.
Chowers MY, Gottesman BS, Leibovici L et al.
J Antimicrob Chemother 2009;64:239–50.

Aug

Yes http://jac.oxfordjournals.org/cgi/content/abstract/64/2/239

Link to abstract
Full article requires payment
Adverse events – Other • This review assessed the quality of adverse-event reporting in publications of randomized HAART trials and examined whether reporting quality affects the effect estimates reported for adverse events.
• Forty-nine randomized controlled trials (published 2000–2008) assessing HAART for treatment-naïve HIV+ adults with 48 weeks' follow-up were included.
• The quality of adverse-event reporting was extracted according to CONSORT guidelines.
• Only one trial reported the method of collecting adverse events. Twenty-six trials reported only adverse events attributed to drugs, 17 of which did not refer to the attribution methods.
• Adverse-event reporting was nearly always selective and selection criteria were highly variable, based on severity grading or occurrence threshold.
• Presentation of adverse events above an occurrence threshold was more common in studies sponsored by industry (30/31) than in studies sponsored by non-profit organisations (3/18).
• Differences in the methods of adverse-event reporting may affect the results reported for adverse events. There was no significant improvement in adverse-event reporting over this period.
• Conclusions: There was substantial variability in adverse-event reporting, which was influenced by sponsor identity and affected outcomes.

Link 18 December 2009

Long-term evolution and determinants of renal function in HIV-infected patients who began receiving combination antiretroviral therapy in 1997-1999, ANRS CO8 APROCO-COPILOTE.

Leport C et al. Clin Infect Dis 2009;49:1950–4. • This study investigated the long-term evolution and determinants of renal function in HIV+ patients who began receiving combination ART in 1997–1999
• Among 1,121 HIV+ patients (90% caucasian), the glomerular filtration rate increased (+0.72 mL/minute/1.73 m2/month) from treatment initiation to month 16.
• The rate increase was lower among men and those with a low BMI, AIDS, or treatment with IDV, then remained stable up to 7 years.
• Conclusions: Kidney function should be monitored in patients previously exposed to IDV.
Link 27 January 2010

Incidence and risk factors for chronic elevation of alanine aminotransferase levels in HIV-infected persons without hepatitis B or C virus co-infection.

Kovari H et al. Clin Infect Dis 2010;50:502–11 • This study investigated the incidence of and risk factors for chronic elevation of alanine aminotransferase (ALT) levels in 2,365 patients participating in the Swiss HIV Cohort Study without HBV or HCV infection.
• Chronic elevated ALT levels developed in 385 patients (16%), with an incidence of 3.9 cases per 100 person-years (95% CI: 3.5–4.3).
• Chronic elevated ALT levels were associated with an HIV RNA level of >100,000 copies/mL (incidence rate ratio [IRR]: 2.23; 95% CI: 1.45–3.43), increased BMI (BMI 25–29.9 IRR: 1.56; 95% CI: 1.24–1.96; BMI 30 IRR: 1.70; 95% CI: 1.16–2.51), severe alcohol use (IRR: 1.83; 95% CI: 1.19–2.80), exposure to stavudine (IRR per year exposure: 1.12; 95% CI: 1.07–1.17) and zidovudine (IRR per year exposure: 1.04; 95% CI: 1.00–1.08]). Black ethnicity was inversely correlated (IRR: 0.52; 95% CI: 0.33–0.82).
• Treatment outcome and mortality did not differ between groups with and groups without elevated ALT levels.
• Conclusions: Chronic elevated ALT levels had an incidence of 3.9 cases per 100 person-years among patients without HBV or HCV co-infection and were associated with high HIV RNA levels, increased BMI, severe alcohol use and prolonged stavudine and zidovudine exposure. Long-term follow-up is needed to assess whether chronic elevation of ALT levels will result in increased morbidity or mortality.
Link 02 March 2010

Impact of tenofovir on renal function in HIV-infected, antiretroviral-naive patients.

Horberg M et al. J Acquir Immune Defic Syndr 2010;53:62–9. • This retrospective cohort study compared renal function among ARV-naïve patients starting a TDF-containing (964 patients) or TDF-sparing regimen (683 patients).
• Glomerular filtration rate (GFR), serum creatinine and the development of renal proximal tubular dysfunction were evaluated.
• TDF was associated with a larger relative decline in GFR over 104 weeks (–7.6 mL/min/1.73 m2 versus a TDF-sparing regimen (p< 0.001); the relative difference varied by baseline GFR, with the greatest effect seen in patients with a GFR >80 mL/min/1.73 m2.
• TDF was also associated with a higher rate of proximal tubular dysfunction over time (HR[adjusted]:1.95; p=0.01 at 52 weeks and 5.23; p=0.0004 at 104 weeks) and an increased risk of discontinuation (HR(adjusted): 1.21; p=0.02), particularly as renal function deteriorated.
• Conclusions: TDF was associated with a greater effect on renal function and a higher risk of proximal tubular dysfunction in ARV-naïve patients starting ARV treatment.
Link 02 March 2010

Substitution of nevirapine because of efavirenz toxicity in AIDS clinical trials group A5095.

Schouten JT et al. Clin Infect Dis 2010;50:787–91. • In the AIDS Clinical Trials Group study A5095, 9% of patients who experienced an EFV-related adverse event substituted NVP.
• Most adverse events resolved but 15 patients discontinued NVP.
• Grade 3/4 hepatotoxicity was observed in 14% of patients who substituted NVP versus 6% who continued EFV.
• Conclusion: Substitution of NVP because of EFV toxicity was generally safe and effective.
Link 22 March 2010

Relationship between HIV/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome and stavudine-triphosphate intracellular levels in patients with stavudine-based antiretroviral regimens.

Domingo P et al. Infect Dis 2010;50:1033–40. • This study investigated whether there is a link between intracellular levels of d4T and HAART-associated lipodystrophy syndrome (HALS) by measuring intracellular levels of d4T-triphosphate (TP) in peripheral blood mononuclear cells in 17 patients with and 16 patients without HALS.
• The median concentration of d4T-TP was 20.60 femtomoles (fmol)/1 x 106 cells (interquartile range [IQR]: 14.90–26.92) for patients with HALS and 13.85 fmol/1 x 106 cells (IQR: 8.65–20.15) for patients without HALS.
• d4T-TP levels were correlated with cumulative d4T exposure by time and dose. d4T-TP intracellular levels were independently associated with HALS (OR: 1.58; 95% CI: 1.08–2.32).
• Conclusions: Intracellular levels of d4T-TP were strongly associated with the development of HALS.
Link 22 March 2010

Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy.

Canestri A et al. Clin Infect Dis 2010;50:773–8. • This retrospective study reports data from 11 patients with neurological symptoms and HIV CSF viremia but suppressed plasma HIV RNA during ART.
• All but one patient had CSF pleocytosis and/or elevated protein levels. The median CSF HIV RNA level was 880 copies/mL (range: 558–12,885 mL). Eight patients had a plasma HIV RNA level <50 copies/mL and three had plasma HIV RNA blips with their CSF HIV RNA level >1 log higher than their plasma HIV RNA level.
• Resistance-associated mutations were detected in seven of eight CSF HIV RNA genotypic strains. After ART optimization, all patients clinically improved, with normalization of CSF.
• Conclusions: HIV may replicate in the CSF despite successful suppression of plasma viremia with ART, with the development of CSF HIV resistance resulting in acute or subacute neurological complications.
Link 25 June 2010

Cognitive dysfunction in HIV patients despite long-standing suppression of viremia.

Simioni S et al. AIDS 2010;24:1243–50. • This study investigated the prevalence of cognitive complaints and HIV-associated neurocognitive disorders (HANDs) in a cohort of aviremic HIV+ patients to evaluate the relevance of the HIV dementia scale to detect HANDs.
• The prevalence of cognitive complaints was 27%. The prevalence of HANDs was 84% among patients with cognitive complaints and 64% among non-complainers (p<0.001).
• A score of ≤14 points on the HIV dementia scale yielded a positive predictive value of HANDs of 92% in complainers and 82% in non-complainers.
• Conclusions: The prevalence of HANDs is high even in long-standing aviremic HIV+ patients. The HIV dementia scale with a cut-off of ≤14 points appears to be a useful tool to screen for HANDs.
Link 25 June 2010

HIV-associated neurocognitive disorders: is there a hidden epidemic?

McArthur JC, Brew BJ. AIDS 2010;24:1367–70. • This study investigated the prevalence of cognitive complaints and HIV-associated neurocognitive disorders (HANDs) in a cohort of aviremic HIV+ patients to evaluate the relevance of the HIV dementia scale to detect HANDs.
• The prevalence of cognitive complaints was 27%. The prevalence of HANDs was 84% among patients with cognitive complaints and 64% among non-complainers (p<0.001).
• A score of ≤14 points on the HIV dementia scale yielded a positive predictive value of HANDs of 92% in complainers and 82% in non-complainers.
• Conclusions: The prevalence of HANDs is high even in long-standing aviremic HIV+ patients. The HIV dementia scale with a cut-off of ≤14 points appears to be a useful tool to screen for HANDs.
Link 25 June 2010

Comparison of 2 doses of liposomal amphotericin B and conventional amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis: a randomized, double-blind clinical trial of efficacy and safety.

Hamill RJ et al. Clin Infect Dis 2010;51:225–32. • This study compared the efficacy and safety of liposomal amphotericin B (3 or 6mg/kg/day) with that of conventional amphotericin deoxycholate in patients with AIDS and acute cryptococcal meningitis.
• Efficacy was similar for all three treatments.
• The overall incidence of infusion-related reactions was significantly lower for both liposomal doses compared with conventional amphotericin B (p<0.001).
• The 3 mg/kg/day liposomal amphotericin B dose was associated with significantly less nephrotoxicity than conventional amphotericin B (p=0.004).
• Conclusions: Liposomal amphotericin B provides an equally effective alternative to conventional amphotericin B deoxycholate in patients with AIDS and acute cryptococcal meningitis.
Link 05 July 2010

Nevirapine-associated early hepatotoxicity: incidence, risk factors, and associated mortality in a primary care ART programme in South Africa.

Chu KM et al. PLoS One 2010;5:e9183. • This study investigated NVP-associated hepatotoxicity among 1,809 HIV+ ARV-naïve adults starting NVP-based therapy.
• The cumulative proportion of early hepatotoxicity was 1–2%, giving an incidence rate at 102 days of 3.6–7.6 per 100 person-years. The median time to hepatotoxicity was 32 days (IQR 28–58 days).
• No association was found between age, gender, baseline CD4 count, concurrent TB infection, prior participation in a programme to prevent mother-to-child-transmission, or baseline weight and early hepatotoxicity.
• Hepatotoxicity was not associated with mortality.
• Conclusions: The cumulative proportion of early hepatotoxicity with NVP-based ART was low in this resource-constrained setting.
Link