2006

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8th International Congress on Drug Therapy in HIV Infection, 12—16 November 2006, Glasgow

• Introduction
• Drug-drug interactions
• Pharmacokinetic data with existing antiretrovirals
• Antiretroviral pharmacokinetics in special patient populations
• Pharmacology of investigational drugs
• d4T associated with significantly increased risk of type-2 diabetes mellitus
• Saquinavir/r vs lopinavir/r: interim results from the Gemini study
• Explanation for failure of TMC-125 (etravirine) in TMC227 study
• Wide disparity in switch to second-line therapy among children in CHIPS cohort
• Multi-drug resistance in vertically infected children
• Viral load blips in children from the CHIPS cohort
• Switching from PIs to NNRTIs has similar effect on TC/HDL ratio as use of lipid lowering drugs in the management of dyslipidaemia
• Higher doses of ribavirin increases response rate to HCV treatment in coinfected patients: results from PRESCO study
• NNRTI levels high in HCV co-Infected patients with cirrhosis
• Drug interactions with darunavir (TMC-114)
• Drug interactions with etravirine (TMC-125)
• Community meeting on criminalisation of HIV transmission: jailing people for passing on HIV may threaten public health

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8th International Workshop on Adverse Drug Effects and Lipodystrophy in HIV Infection (IWADELHI), 23-26 September 2006, San Francisco.

• Introduction
• The role of the metabolic syndrome in HIV
• Effect of lifestyle modification on risk factors for cardiovascular disease and metabolic syndrome
• Pioglitazone reduces peripheral lipoatrophy and improves adipokines without reducing visceral fat
• Leptin reduces visceral abdominal tissue (VAT) without reducing limb fat
• Adipose tissue morphology improved after treatment discontinuation
• Incidence of lipodystrophy in Rwanda

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46th Interscience Conference on Antiretroviral Agents and Chemotherapy (ICAAC), 27-30 September 2006, San Francisco.

• Introduction
• MK-0518 demonstrates potent efficacy in patients with triple-class resistant virus: 24 week results
• Lipid profile of integrase inhibitor MK-0518: 24 week results compared to efavirenz in treatment naive patients
• Cell studies predict cross-resistance among integrase inhibitors
• HIV may use different coreceptors in blood and brain
• Critical interactions between darunavir (TMC114), lopinavir, Viagra, and oral contraceptives
• NRTI elvucitabine active against HIV in a 7-day monotherapy study
• Efavirenz/tenofovir fails as 2-drug maintenance regimen
• Nucleoside inhibitor MK-0608 mediates suppression of HCV replication for >30 days in chronically infected chimpanzees

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Report from the 10th Annual UK Resistance Meeting, 21 September 2006, London

• Introduction

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Further reports from XVI International AIDS Conference, 13-18 August 2006, Toronto, Canada.

• Introduction
• Prevalence and predictors of squamous intraepithelial lesions of the cervix in HIV positive women in Lusaka, Zambia
• Effect of herpes simplex therapy on genital and plasma HIV viral load
• Maternal health and prevention of mother to child transmission
• 18-month effectiveness of short-course perinatal antiretroviral regimens combined to infant-feeding interventions for PMTCT in DITRAME PLUS ANRS 1201/1202 2001-2005
• HIV prevalence rates amongst 6 week old infants in South Africa: the case for universal screening at immunisation clinics
• Maternal illness during pregnancy is associated with in utero mother to child transmission
• Extensively drug resistant TB (XTB) in South Africa

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16th International AIDS Conference, 13-18 August 2006, Toronto, Canada

• Introduction
• Enough is enough: South African activists demand “fire Manto”
• Treatment access: more optimistic results from scale up programmes
• Integrase inhibitor MK-0518: early results show greater early potency than efavirenz
• Maraviroc results in R5/X4 mixed/dual tropic patients: unexpected safety data shows possible immunolocical effect
• Vicriviroc 24-week results in triple-class experienced R5-tropic patients
• Etravirine (TMC-125) associated with -1log viral load reduction at 48-weeks results in treatment experienced patients
• Three-class experienced patients experience 1 log viral load reduction using monoclonal antibody TNX-355
• New data on darunavir (TMC-114)
• Lopinavir/r monotherapy: less potent than triple therapy with higher risk of resistance
• Atazanavir/r monotherapy and CNS penetration
• Fosamprenavir/r is non-inferior to lopinavir/r in treatment naïve patients
• Tenofovir/FTC maintains greater virological response and reduced lipoatrophy compared to AZT/3TC after 96 weeks
• Paediatric studies in Toronto: Children face a serious service delivery gap; Accumulating data shows children from resource limited settings benefit from antiretroviral treatment (ART)
• Bioavailability study results for new paediatric tablets for oral suspension, and caution against splitting adult doses
• Pharmacokinetic and virological evaluations after stopping NNRTIs in children: a substudy of the PENTA 11 (TICCH) Trial
• 3TC /abacavir maintains virological superiority over AZT/3TC and AZT/abacavir beyond 5 years in children
• French study raises importance of early screening for anal cancer in HIV-positive people
• Prognostic index for risk of progression of Kaposi’s Sarcoma
• Tenofovir did not increase the incidence nephrotoxicity in limited numbers of HIV-positive patients using chemotherapy or HCV-coinfeced patients using ribavirin
• Selected abstracts from Track A presentations at Toronto
• Use of complementary alternative medicine that could interact with ARV treatment reported by 20% patients in the UK
• Poor scientific or medical knowledge is a factor in increase in criminal charges for HIV transmission in the UK
• Online webcasts and debates

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XV International Drug Resistance Workshop, 13-17 June 2006, Sitges, Spain

• Introduction
• Resistance implications of monotherapy with lopinavir/r (Kaletra)
• Ritonavir reduces virological failure and resistance in treatment naïve patients treated with atazanavir
• Resistance to darunavir (TMC-114): predicting responses for treatment experienced patients
• Epidemiological studies and transmission of resistance: evidence for optimism – or issues with interpretation?
• Overview of epidemology studies
• Methamphetamine use linked to transmission of drug resistance
• Transmission of resistance to T-20
• K103N containing variants persist longer in women with subtype D and with higher viral loads
• No subtype-based differences in baseline levels of K103N-containing variants in women receiving single dose nevirapine
• Phenotypic NNRTI resistance and genetic diversity in antiretroviral naïve women
• High prevalence of the K65R mutation in Botswana patients treated with ddI/d4T-based regimens
• Potential for easier selection of K65R mutation with tenofovir pressure in subtype C HIV-1 isolates
• Limitations in online tools to identify HIV-1 subtypes
• Categorisation of transmitted HIV drug resistance using the WHO/CDC HIV drug resistance threshold survey method may be useful in resource limited settings
• Resistance implications from PrEP and microbicide studies in macaques
• Low-level resistance linked to treatment failure: a role for more sensitive testing for naïve patients
• Testing for resistance after starting treatment

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7th International Workshop on Clinical Pharmacology of HIV Therapy, 20-22 April 2006, Lisbon

• Introduction
• Efavirenz levels above recommended upper target in 20% of African patients in Senegal
• Lower dose of AZT provides adequate exposure in patients with low body weight
• Pharmacokinetics for generic fixed dose combinations for children are comparable to the branded products
• Caution against dividing adult FDCs (Triomune) for young children
• University of Liverpool audit of paediatric TDM
• Age-dependent pharmacokinetics of 3TC in children
• Use of small sample drug level monitoring for paediatric PI concentrations
• Intracellular and plasma measurements of AZT and 3TC and their metabolites in neonates
• Effect of pregnancy on PK of protease inhibitors
• Using enzyme inducers to reduce the half-life of nevirapine
• Relationship between nevirapine concentrations and virological failure in a clinical setting
• Summary of drug interaction studies
• Effects of ketoconazole and rifampin on TMC278
• Brecanavir interaction study with ritonavir and atazanavir
• Fixed-dose formulation of efavirenz/tenofovir/FTC bioequivalent to separate dosing
• Saquinavir/r (1000/100mg) levels reduced when taken fasted and should be taken with food
• Lack of food effect with Meltrex formulation of lopinavir/r
• Food interaction reduces ddI intracellular absorption and supports requirement to take fasted
• Conflicting results on how T-20 affects tipranavir

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12TH Annual Conference of the British HIV Association, 29 March-1 April 2006,Brighton

• Introduction
• One in five patients with CD4 <200 are not on treatment;
• Growing viral diversity with non-B subtype reported in gay men;
• Viral rebound ­ stability of treatment and viral blips
• Primary care practice still fails to diagnose HIV patients from high-risk groups or with symptomatic acute infection
• Use of HLA B5701 genetic testing to reduce abacavir hypersensitivity reactions
• Dosing rifabutin and lopinavir/r – sub-optimal rifabutin levels reported in five patients dosed according to current guidelines
• Fatal seronegative visceral leishmaniasis in a Portuguese patient
• Awareness in HIV-positive and HIV-negative men of PEP after sexual exposure (PEPSE)

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13th Conference on Retroviruses and Opportunistic Infections (CROI), 5-8 February 2006, Denver

• Introduction
• Regimen durability and toxicity in 36-month follow up on ART in Khayelitsha, South Africa
• Adults in resource-limited settings are most likely to experience an HIV-associated Illness in the first three months from initiating therapy
• Causes of death in adults receiving ARV therapy in Senegal
• Rapid scale-up of treatment in Zambia delivered at primary health level
• The effect of HIV subtype on disease progression in Rakai, Uganda
• Pharmacokinetics of antiretrovirals in pregnancy: tenofovir, nelfinavir, lopinavir/r
• Risk of central nervous system birth defects associated with ART exposure during pregnancy
• No increase in adverse pregnancy outcomes in Thai women receiving nevirapine-containing HAART
• Treatment following singe dose nevirapine exposure
• Association of HIV replication capacity with mother to child transmission
• Association between HIV subtype and detection of K103N
• Other new antiretrovirals at Denver: ‘the future seems bright’
• Origins of HIV traced to chimps in Cameroon
• HSV-2 suppression reduces HIV and HSV shedding
• Pharmacology and drug interaction studies in adults: summary table from CROI, ICAAC and EACS conferences
• Early integrase inhibitor studies in treatment experienced patients raise hopes for new drugs in a new class
• Atazanavir in treatment naïve patients, with and without ritonavir boosting
• Simplification to atazanavir/ritonavir monotherapy
• Summary of STI studies: SMART shows clear increased risk from interrupting treatment at any CD4 count
• The effect of repeated single-dose nevirapine for PMTCT in a second pregnancy
• Should the criteria for initiation of HAART be revisited in pregnant women?
• Cotrimoxazole prophylaxis in pregnancy
• Treatment during primary HIV infection: reports from CROI
• CNS penetration of ARV drugs is associated with lower CSF viral load
• Sexually transmission of hepatitis C in HIV-positive men in the UK
• D:A:D study shows that PIs rather than NNRTIs drive the previously reported cardiovascular risk of combination antiretroviral therapy
• Interventions for the management of lipodystrophy and metabolic complications

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2005

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10th European AIDS Conference (EACS), Dublin Ireland.17-20 November 2005

• Introduction
• Rifaximin cure reported for cryptosporidium in advanced HIV
• Analysis of hepatic events in 2NN study by CD4 entry criteria, levels differences between nevirapine and efavirenz; excess hepatic events in once-daily nevirapine arm linked to single site in Thailand
• FTC studies at EACS: reduced incidence of M184V compared to 3TC; side effect profile in clinical practice
• Paediatric studies at EACS: Trends in antiretroviral use in the Madrid Cohort; Life expectancy significantly increased HIV/HCV co-infected children since HAART; Use of tenofovir in treatment experienced children; Switching to lopinavir/r from double protease inhibitor regimen; Once daily lopinavir/r, 3TC and abacavir; Planned treatment interruptions in children
• Efficacy of lopinavir/r in patients with advanced HIV (CD4 <25 cells/mL)
• Potential barriers to use of T-20: results from patient and physician interviews
• Factors associated with sexual dysfunction in HIV patients
• Decreased varicella zoster immunity in migrants from sub-Saharan Africa
• Clinical experience of switching to atazanavir in the UK’s largest clinic
• Replacing a PI with atazanavir: separating swans from ducklings?
• TMC 125: some good and bad news
• When to change a failing regimen: Second-line and salvage strategies
• Antiretrovirals and other stuff!
• Heart disease in people with HIV
• Mortality trends: why people with HIV die (or don’t) today
• Pregnancy studies at EACS

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45th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Washington USA. 16-19 December 2005.

• Introduction
• One third of HIV/HCV coinfected patients with normal ALT have advanced fibrosis in Spanish cohort
• New antiretroviral compounds at ICAAC: New PI from GSK: brecanavir; Maturation inhibitor PA-457: safety and efficacy during 10-day; Antiviral activity of monoclonal antibody TNX-355 in treatment experienced patients
• Understanding TMC114 power against resistant HIV
• Comparison of pharmacokinetics of originator and generic liquid formulations and split tablets in Malawian children
• African-Americans in ACTG 5095 had shorter time to virologic failure and grade 3/4 side effects
• Predictors of insulin resistance in first year of therapy
• Three measures confirm 144-week renal record of tenofovir
• Low rash risk with efavirenz after nevirapine rash

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7th Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, Dublin Ireland. 13-16 November 2005.

• Introduction
• Monitoring side effects in resource limited countries
• Uridine supplement reverses thymidine-induced lipoatrophy
• Pravastatin increases limb fat in HIV-positive patients with hypercholesterolaemia
• Evidence that facial fat can return after switching d4T or AZT, to either abacavir or tenofovir
• Niacin has beneficial effect on lipids but no reduction in abdominal fat
• Gluteal implants used to replace lost buttock fat

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3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro Brasil. 24-27July 2005.

• Introduction
• Further Reports from 3rd IAS Conference on AIDS Pathogenesis and Treatment. Rio de Janeiro, Brazil, 24-27 July, 2005
• Management of hepatitis C and B in HIV-coinfected individuals: an overview of studies presented at the 3rd IAS conference
• Highlights of HIV drug resistance studies presented at the 3rd IAS conference
• Adult male circumcision reduces transmission rates over 18 months comparable to a vaccine with 65% efficacy
• Benefits of adding 4 or 7 days of AZT/3TC to single-dose nevirapine to prevent MTCT: further analysis from TOPS
• New drugs in pregnancy: atazanavir; T20
• Lopinavir/r use in children less than two years old – promising results despite low plasma levels
• Favourable outcomes in children treated with HAART in the MSF programmes
• Encouraging results with cut up generic fixed dose combination tablets in Uganda
• Predictors of survival at three years follow up for HIV-infected children in Cote D’Ivoire
• Benefit of maintaining M184V with 3TC monotherapy: final 48-week results
• T20 (enfuvirtide) studies presented at Rio
• Strategies for salvage therapy
• Antiviral activity of foscarnet in salvage patients
• Novel strategies with existing drugs: Reduced PI combination of indinavir/ritonavir 400/100 in Mali; 5 Days On HAART, 2 Days off; Kaletra monotherapy
• Antiretroviral activity of new and novel agents
• Overview of pharmacology studies
• Tenofovir interactions and renal toxicity
• Atazanavir inter-patient variability and drug interactions
• Interactions between proton pump inhibitors and PIs
• PK in pregnancy and liver impairment
• Drug interactions with new and existing drugs
• PK in paediatric patients
• Incidence of TB infection despite HAART and treatment in coinfected patients
• Evaluation of ESAT-6 and CFP-10 as markers for response to TB treatment in HIV/TB coinfected patients
• Does WHO clinical stage reliably predict who should receive ARV treatment?
• Continuous vs intermittent treatment with triple nuke combination of AZT/3TC/tenofovir in Africa: early results from DART study

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Keystone Vaccine Workshop on Vaccines and Pathogenesis 2005: vaccines, pathogenesis, snow and a couple of elk, Banff Alberta Canada. 9-15 April 2005.

• Introduction

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14th International HIV Drug Resistance Workshop (14th IHDRW), Quebec City Canada. 7-11 June 2005.

• Introduction
• Genetic factors affecting HIV infection and progression rates: immunological factors relating to entry inhibitors
• Resistance during MTCT strategies:: new data on protective benefit of Combivir added to single-dose nevirapine, and impact of treatment and breastfeeding on the infant
• Short course of 3TC and AZT reduces the emergence of nevirapine resistance
• Higher rates of resistance in TOPS using more sensitive resistance tests
• Avoiding maternal nevirapine and adding AZT to infant prophylaxis
• Resistance patterns vary by subtype in infants in HIVNET 012 and NVAZ studies
• Mutations present in majority of women: early analysis suggests a similar rate of resistance in infants
• Patterns of viral load and resistance in breast milk vary by HIV sub-type
• Reduced replicative capacity of M184V explains benefit of 3TC monotherapy compared to stopping all drugs
• Interaction between tenofovir and ddI in triple-nucleoside combinations: role of M184V in explaining resistance on failure
• Predicting clinical responses to ddI from genotypic resistance
• Under-detection of transmission of transmitted resistance and impact on treatment response
• Risk of death in UK after diagnosis of 3-class resistance

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11th BHIVA and BASSH joint annual conference, Dublin Ireland. 22-25 April 2005.

• Introduction
• Long-awaited UK pregnancy guidelines now updated; pregnancy studies in Dublin
• Underdosing of ARVs in children: results from CHIPS cohort
• Sexual transmission and response to treatment in acute HCV infection in HIV-positive gay men coinfected with HIV
• Levels of efavirenz 10-fold above minimum target level despite coadministration with rifampicin
• Schistosomiasis after immune reconstitution: symptoms appear as HAART side effects

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6th International Workshop on Clinical Pharmacology of HIV Therapy, Québec Canada. 28-30 April 2005.

• Introduction
• Effect of age/menopause on lopinavir and efavirenz concentrations in women
• Effect of age on lopinavir concentrations
• Gender and pharmacokinetics of saquinavir
• Dosing nevirapine in children
• Intracellular NRTI-triphosphate levels in children are similar to adults
• Efavirenz and rifampicin during pregnancy: lower body weight associated with higher concentrations
• Summary of drug interaction studies
• Responses to atazanavir, Kaletra and side effects 

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Third European HIV Drug Resistance Workshop,Athens. 30 March – 1 April 2005.

• Introduction
• Tenofovir, nucleosides, and non-nucleosides
• Protease inhibitors
• CCR5 antagonists

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Paediatric reports from 12th Conference on Retrovirus and Opportunistic Infections (CROI), Boston MA. 22-25 February 2005.

• Introduction
• Once-daily lopinavir/ritonavir for children may offer advantages
• Lopinavir/ritonavir for young infants
• Paediatric dose finding studies of atazanavir and atazanavir/ritonavir
• Switching d4T to tenofovir and protease inhibitors to efavirenz in children

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40th Annual Meeting of the European Association for the Study of the Liver, Paris.13-17 April 2005

• Introduction

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12th Conference on Retrovirus and Opportunistic Infections (CROI), Boston MA. 22-25 February 2005.

• Introduction
• Developments in nevirapine use in MTCT reduction
• Mashi Study – late breakers on breastfeeding
• Maternal health and infant mortality
• Paediatric care in lower income settings
• Tenofovir not linked to bone toxicity in children followed for one year
• Gut memory CD4 T cells implicated in a central role for HIV disease pathology: dramatic impact prior to seroconversion
• Case of multi-drug resistant (MDR) rapid progressor
• Case report of antibody reversion and negative viral load four-years post treatment discontinuation
• 24-week efficacy of TMC114: dramatic early activity in heavily-experienced patients
• Maturation inhibitor shows anti-HIV activity in single dose pilot study
• New antiretrovirals at 12th CROI
• Absolute risk is modest, but cumulative cardiovascular risk of HAART over five years is similar to ‘ever smoked’: new data on gender and age
• Omega-3 supplement effective to reduce triglycerides
• Switch to tenofovir from AZT or d4T improves fat loss and improves lipid parameters compared to abacavir
• Continued use of a thymidine analogue may limit benefit from rosiglitazone when used to treat lipoatrophy
• Entecavir is effective against 3TC-resistant hepatitis B
• Tenofovir is ‘non-inferior’ to adefovir for the treatment of hepatitis B in HBV-HIV co-infected patients

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2004

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7th International Congress on Drug Therapy in HIV Infection (ICDTHI), Glasgow. 14-18 November 2004.

• Introduction
• Nandrolone decanoate combats HIV-related weight loss: results from three randomised studies.
• Atazanavir boosts intracellular saquinavir levels: data for important new dual-boosted regimen.
• Marked variability in plasma atazanavir levels: importance of ritonavir boosting and TDM.
• Effective switching to atazanavir/ritonavir in clinical practice.
• Ritonavir boosting may not overcome interaction between atazanavir and nevirapine.
• Nevirapine associated adverse events in a cohort of pregnant women.
• Higher nevirapine doses for children leads to better outcome.
• TDM in Ugandan study highlights importance of refridgerated ritonavir.
• Responses to TB treatment in HIV-positive and HIV-negative patients in the UK.
• 800mg efavirenz may not be needed with rifampicin-based TB regimens, especially in African patients.
• EuroSIDA shows HIV-HCV coinfected patients more likely to stop HAART because of side effects.
• Lower d4T dose maintains virologic suppression and CD4 increases.

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6th International Workshop on Adverse Drug Reactions & Lipodystrophy in HIV Washington. 26-28 October 2004.

• Introduction
• Nucleoside analogue-related mitochondrial toxicity and link to lipoatrophy: effect of non-thymidine analogues (abacavir and tenofovir)
• Nucleosides reduce PPAR-gamma: a role for rosiglitazone without thymidine analogues?
• Potential for uridine to treat mitochondrial toxicity: still only in vitro data
• 25% patients take Kaletra on an empty stomach: dietary advice often missed at ‘centre of excellence’
• rHGH reduces central fat accumulation in adolescent lipodystrophy
• Weight loss is associated with elevated PBMC proviral DNA levels
• Coronary artery bypass graft is safe in HIV-positive patients but higher risk of longer term events
• Endothelial dysfunction similar in ARV-experienced and -naïve patients
• Pravastatin improves lipid profiles but not endothelial function
• Indinavir impairs endothelial function without insulin resistance
• Treatment interruptions improve lipids within four weeks: IL-2 has no metabolic effect
• Improvement of lipids following switch to tenofovir
• HCV coinfection linked to discontinuing ART due to toxicity
• Restorative treatments for HIV-associated lipoatrophy

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44th Annual ICAAC Washington. 30 October – 2 November 2004.

• Introduction
• Tipranavir in treatment experienced patients: results from RESIST-1
• Reverset: first data in patients with nucleoside resistance
• Poor response with tenofovir and ddI backbone causes early study termination
• Paradoxical CD4 response with tenofovir and ddI backbone
• Tenofovir/FTC backbone outperforms AZT/3TC (Combivir) with efavirenz in treatment naïve patients; reduced toxicity drives ITT viral efficacy
• Limited stability of lopinavir/r (Kaletra) above 25°C
• PK and drug interaction studies:
• Atorvastatin requires dose reduction with tipranavir/r
• Once-daily T-20 is less effective than twice daily: lower potency is related to C trough
• Further genetic link to efavirenz absorption
• Long-term response to FTC in children Is similar to adults
• Side effect update: hypersensitivity, heart, bones

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55th Annual Meeting of the American Society for the Study of Liver Diseases (55th AASLD) Boston MA. 29 October – 2 November 2004.

• Introduction