2009

Vol. 10 No. 9/10 September-October 2009

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EDITORIAL: Welcome to the September/October issue of HTB. This issue includes further coverage from the 5th IAS Conference in CapeTown. We review antiretroviral , pregnancy and PMTCT, HSV and TB research presented at this conference.

CONFERENCE REPORTS
5th IAS Conference on HIV Pathogenesis, Treatment and Prevention
19-23 July 2009, Cape Town

Introduction: We continue with further reports from this important conference with an overview of ARV studies at IAS
Overview of ARV studies at IAS: Simon Collins, HIV i-Base; The conference included a broad range of important studies that could inform use of currently approved drugs, and first results of a new integrase inhibitor.

Vol. 10 No. 7/8 July-August 2009

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EDITORIAL: Welcome to the July/August 2009 issue of HTB that includes our first coverage from the IAS conference held in Cape Town in July.

Swine Flu

Swine Flu Epidemic: The following resource was developed by Birmingham Heartlands Hospital and is to be used with flow diagram ‘HIV and Influenza H1N1v‘. This is an empirical protocol drawn up by individuals with some experience in the recent UK swine flu outbreak. Modifications have been made following a meeting at the HIV/ IAS conference 2009 in July. This is just one suggested clinical approach.
HIV and swine flu – patient leaflet: HIV patients may come into contact with hospital services in various ways. Flow diagram A outlines a suggested protocol for 2 of a common scenarios: telephone contact to members of the HIV team or unplanned presentation to HIV/ID/GUM outpatient clinics.

CONFERENCE REPORTS: 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention. 19-23 July 2009, Cape Town

Introduction: As we went to press with this issue of HTB just as this important conference was concluding, we only include a brief overview of some of the most important studies. Further coverage will be included in the next issue.
Five-year survival rates of 87% without routine CD4 or laboratory monitoring in DART study demonstrate an important model for ARV access programmes: Simon Collins, HIV i-Base; These results strongly support expanding access to treatment to wider populations independent of access to routine laboratory monitoring and that delaying treatment access while waiting for laboratory infrastructure to be developed is resulting in extensive mortality and morbidity.
Biomarkers associated with mortality: long-term follow up from SMART: Nathan Geffen, i-Base and TAC; The association between mortality and hs-CRP, IL-6 and D-dimer is significant, even after long-term follow-up and the termination of the structured treatment interruption arm. This highlights the importance of further research on whether anti-inflammatory medicines will have an additional role in HIV management of high-risk patients.

Vol. 10 No. 5/6 May-June 2009

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EDITORIAL: Welcome to the May/June 2009 issue of HTB.

CONFERENCE REPORTS: 15th Annual Conference of the British HIV Association (BHIVA)
1-3 April 2009, Liverpool

Introduction: The annual BHIVA conferences consistently provide an opportunity to understand important aspects of HIV care, including the first presentations of results from national audits, lectures from international experts on emerging concerns and a wealth of studies from junior researchers.
Superinfection identified in 2 out of 8 patients with unexpected viral load increases: Simon Collins, HIV i-Base; While the study conclusion is that targeted screening based upon sexual history and viral load can achieve a high detection rate and is important in the context of transmitted resistance, it is not appropriate to conclude that early HAART should be used as a public health measure between consenting HIV-positive adults who choose to use neither condoms nor treatment.
Peripheral DEXA scans to identify rates of reduced bone mineral density: Simon Collins, HIV i-Base; Short and colleagues presented results from using a portable DEXA scanner to identify high rates of reduced bone mineral density and relationship to ARV use in 168 HIV-positive men (median age 45) treated in Brighton.
Vitamin D deficiency, supplementation and tenofovir: Simon Collins, HIV i-base; The researchers concluded that VD3/calcium supplements increased serum 25(OH)D and decreased PTH and are a safe and effective treatment for HAART-associated hyperparathyroidism.
High rate of lost and untested TB biopsy samples and low screening for latent TB: Simon Collins, HIV i-Base; This study highlighted both the sub-optimal screening in a high-risk patient group, together with the cost effectiveness of treating latent TB and using the immune-based interferon-γ (TB Quantiferon Gold) testing for diagnosis.

CONFERENCE REPORTS: 16th Conference on Retroviruses and Opportunistic Infections (CROI) 8-11 February 2009, Montreal

Introduction: In depth reporting on the 16th CROI conference.

16th CROI: SIDE EFFECTS

Assessing the cardiovascular impact of HIV, abacavir, and new signals for lopinavir/r: Nathan Geffen, TAC and Simon Collins, HIV i-Base; While consensus on the use of abacavir in patients at high cardiovascular risk appears to be following Peter Reiss’s summary statement, the new data on individual PI effect are new, linked to lopinavir and not apparently related to the boosting effect of ritonavir. Lower use of both indinavir and ddI should make those data largely of historical interest.
Intensive smoking cessation programme reports limited success at 6 months: Simon Collins, HIV i-Base; Patients did not have to express an interest in trying to quit and the financial reimbursement may have encourged particpants with a low motivation. This intervention may have looked more impressive if patients had been selected more appropriately.
HDL particle concentration predicts cardiovascular disease in SMART: Nathan Geffen, TAC; This study improves our understanding of the role of various lipid particles in CVD events in HIV-positive people, and further research on the relationships between lipoproteins, HIV, ARVs and CVD is warranted.

16th CROI: WOMEN'S HEALTH

No effect of hormonal contraception on HIV disease progression in large multi-country cohort: Polly Clayden, HIV i-Base; Finally, when they looked at the hazard of disease progression by site, neither progesterone only nor combined progesterone- oestrogen contraception use appeared to have an impact.
Pregnancy, family planning, and HIV acquisition in HPTN 039: Polly Clayden, HIV i-Base; Previous studies have suggested that pregnancy may increase the risk of HIV transmission and that this is due to the biological state of pregnancy rather than any behavioral factors. This study shows no increased risk with pregnancy. These conflicting findings need to be explored.
Progression and regression of pre-malignant cervical lesions in HIV-positive women from Soweto: Polly Clayden, HIV i-Base; It is hard to develop recommendations for a package of services that are evidence based for use in this setting.
CD4 count >250 not predictive of rash-associated hepatoxicity among women initiating nevirapine-based ART in Zambia, Thailand, and Kenya: Polly Clayden, HIV i-Base; In 2004 Boehringer-Ingelheim, manufacturers of nevirapine (Viramune) performed a retrospective analysis of hepatoxicity events among 633 women receiving NVP within the company’s trials. This analysis revealed 11% women having hepatoxicity with pre-treatment CD4 count >250 cells/mm3 vs 0.9% with CD4 <250 cells/mm3. Following these results the company changed the Summary of Product Characteristics to include a caution that women with higher CD4 counts are at increased risk of hepatic toxicity.

16th CROI: PAEDIATRICS

HIV testing of infants at immunisation clinics in Kwazulu-Natal: Polly Clayden, HIV i-Base; Since estimations suggest that as many as 89% of HIV-infected children will have died before they are 5 years old in sub-Saharan African, currently the overwhelming majority of children who could benefit from WHO recommendations are neither being tested nor treated.
Rapid HIV disease progression in South African infants co-infected with cytomegalovirus (CMV): Polly Clayden, HIV i-Base; A number of studies (including one from Jane Deayton at the Royal Free published in the Lancet) have previously reported that CMV viraemia is a risk factor for disease progression, even in the HAART era. Whilst CMV prophylaxis is not routinely used in adults, pre- emptive therapy is certainly used in transplant recipients, and some groups do believe that CMV prophylaxis should be considered in high-risk groups. So, this is an issue of debate at the moment. Several trials are underway (including one at the RF) of potential CMV vaccines. This may be particularly helpful for pregnant women as CMV during pregnancy is associated with a large proportion of birth abnormalities.
Pharmacokinetic studies in very young infants: Polly Clayden, HIV i-Base; Nevirapine (NVP)-based ART is recommended for infants with no perinatal NVP exposure from mother-to-child transmission prophylaxis or NNRTI-based maternal ART. Protease inhibitor-based ART, usually lopinavir/ritonavir (LPV/r), is recommended for NNRTI-exposed infants.
Double-dose lopinavir/ritonavir provides insufficient lopinavir exposure in children receiving rifampicin: Polly Clayden HIV i-Base; Rifampicin-based TB treatment is recommended for children (there is no formulation of rifabutin for young children nor is it widely available). In South Africa children with HIV who are <3 years old receive lopinavir/ritonavir-based antiretroviral 1st line regimens. Rifampicin reduces trough concentrations of lopinavir by more than 90%. Additional boosting with ritonavir to a 1:1 ratio during TB treatment provides adequate concentrations in adults and children but this strategy is complex with oral solutions and not always feasible.
PI-based ART in HIV-infected and HIV/TB coinfected children in South Africa: Polly Clayden, HIV i-Base; South African HIV guidelines recommend PI-based regimens for children <3 years old. Young children mostly receive lopinavir/ritonavir (LPV/r) but in some cases full-dose ritonavir (RTV) is used if a child is also being treated for TB.
Etravirine dose selection in children aged 6 to 17: Polly Clayden, HIV i-Base; All children had a viral load <50 copies/mL on day 8. The majority of side effects were grade 1 or 2, most commonly rhinitis or headache. Two children in stage 1 had a mild to moderate rash on day 8. No child discontinued treatment due to toxicity.
Preliminary results from first paediatric raltegravir study: Polly Clayden, HIV i-Base; The study demographics included: 47% male, 67% black, and 25% white. Median baseline viral load was 4.4 log (range 3.1 to 5.9) copies/mL and were similar between the cohorts. Median CD4 percentage was 22 (range 0 to 42%).

CONFERENCE REPORTS: 10th Intl Workshop on Clinical Pharmacology of HIV Therapy
15-17 April 2009, Amsterdam

Introduction
Genetic markers linked to early discontinuation of three antiretrovirals: Mark Mascolini, natap.org; Gender had a big impact on genetic risk for efavirenz-related central nervous system toxicity. Among women, 80% of those with a risk marker versus 42.5% of those without a risk marker stopped efavirenz. Respective rates for men were 50% and 24.3%. The SHCS investigators noted that certain genetic markers they analysed are more common in nonwhites and that most of the nonwhites in this group were women.
Efavirenz lowers levels of darunavir given as 900/100 mg once daily with ritonavir: Mark Mascolini, natap.org; In a study reported separately by NATAP, this same once-daily dose of darunavir/ritonavir controlled HIV well in 25 people with moderate protease inhibitor (PI) experience and no mutations that make HIV resistant to darunavir. [2] But these researchers did not specify whether anyone took efavirenz with darunavir/ritonavir.
How much (or how little) ritonavir do you need to boost another PI?: Mark Mascolini, natap.org; Whether lower ritonavir-boosting doses might be equally effective has been a long-standing question raised by community advocates since the first days of PI-boosting. Studies have been limited by the only formulation being the 100mg capsule. However, the availability of the new non-refrigerated meltrex tablet formulation of ritonavir, hopefully in 100mg and 50mg tablets will broaden these options.

CONFERENCE REPORTS: 4th South African AIDS Conference
31 March – 3 April 2009, Durban, South Africa

HAART coverage and unmet need in South Africa: Nathan Geffen, TAC; Despite the actions of the Mbeki regime, particularly former Health Minister Tshabalala-Msimang, South Africa has rapidly scaled up its HAART rollout. This has been achieved because of the efforts of health workers, researchers activists and some civil servants. Nevertheless, as Johnson has demonstrated, the unmet need is substantial and growing. It will be challenging to meet the prevention and treatment targets of the National Strategic Plan.

Vol. 10 No. 3/4 March-April 2009

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EDITORIAL: Welcome to the March/April 2009 issue of HTB.

i-Base Funding Update

London Commissioners disregard costs in 2008 tender: Last year, i-Base funding was withdrawn by the London HIV Commissioners as part of their re-structuring of services for HIV-positive people. They have since refused to review the process or the final outcome, despite extensive letters of support from patients, doctors and other healthcare professionals, detailing the importance of the services we provide.

CONFERENCE REPORTS
16th Conference on Retroviruses and Opportunistic Infections (CROI)
8-11 February 2009, Montreal

Introduction: The following reports from the conference are included in this issue of HTB

Vol. 10 No. 1/2 January-February 2009

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EDITORIAL: Welcome to the January/February 2009 issue of HTB, the first issue in our tenth volume. It is both somewhat sobering to find ourselves the most widely distributed HIV-specific print journal for healthcare professionals in the UK, and also something of an achievement for this to be provided free.

CONFERENCE REPORTS
9th International Congress on Drug Therapy in HIV Infection, 9-13 November 2009, Glasgow

Introduction: The Glasgow conference, held every two years, has now produced webcasts from many of the lectures and these are online together with the conference abstracts.

CONFERENCE REPORTS
10th Intl Workshop on Adverse Drug Reactions and Lipodystrophy in HIV (IWADRLH), 6-8 November 2009, London

Introduction: This annual workshop continues to retain its importanceas an important focus for researchand discussions between scientists, researchers, clinicians and patient advocates, and expert in a wide range of comorbidities from outside the HIV field.

TREATMENT ACCESS

FDA approval of generic ARVs: Since the last issue of HTB, the US Food and Drug Administration (FDA) has granted tentative approval for the following new generic ARV products.
Lost benefit of ARVs in South Africa: Nathan Geffen, Treatment Action Campaign; Two studies have calculated the number of excess AIDS deaths due to the South African government's delayed rollout of highly active ARV treatment (HAART) and prevention of mother-to-child transmission (PMTCT).

ANTIRETROVIRALS

Increased atazanavir dose recommended when used in combination with efavirenz or Atripla in naïve patients: In December 2008, BMS changed their package insert to indicate that treatment-naïve patients taking efavirenz (Sustiva or Atripla) with atazanavir (Reyataz) in their first combination, should increase the atazanavir dose from 300mg to 400mg and take this with 100mg of ritonavir (Norvir) and food.
EMEA approves once-daily darunavir/ritonavir (800mg/100mg) for treatment-naïve patients in Europe: On 3 February 2009, the European Commission approved once-daily dosing of 800 mg darunavir (Prezista),, with low-dose ritonavir as part of combination therapy in treatment-naïve adults.
Maraviroc safety label changes included with US traditional approval: On 25 November 2008, the FDA granted full, traditional approval for the use of maraviroc in treatment-experienced patients infected with CCR5-tropic HIV-1 and approved new information to be included in the label. Some of the major changes associated with the approval are included here.
US approval of paediatric abacavir: On 19 December 2008, FDA approved abacavir (Ziagen) 300 mg scored tablets with corresponding dosing information for paediatric patients weighing 14 kg or more using the scored tablet.
EMEA supports extension of D:A:D study until at least 2012 and the new remit to include non-AIDS cancers and kidney disease: The European Medicines Agency (EMEA) has welcomed the commitment of the sponsors to continue the D:A:D study at least until 2012. This ensures that the study, which was started on the initiative of the EMEA in 1999, will remain one of the most powerful pharmacovigilance tools to monitor the long-term safety of antiretroviral medicines.
Applications to approve non-refrigerated ritonavir submitted to EMEA and FDA: On 21 January 2009, Abbott announced that it has submitted applications seeking registration for a new tablet formulation of the protease inhibitor ritonavir (Norvir) with the European and US regulatory authorities. This new formulation will not require refrigeration.

DRUG INTERACTIONS

A selection of the latest news and reviews from the Liverpool University pharmacology team at http://www.hiv-druginteractions.org are included below.

Drug interactions with integrase inhibitors: This is an outstanding review on the pharmacology of integrase inhibitors with a substantial section on raltegravir drug-drug interactions and elvitegravir drug-drug interactions. There are four tables summarising all known interactions to date. The authors conclude that overall raltegravir has a low propensity for clinically meaningful drug interactions, whereas elvitegravir (with the presence of ritonavir) has modest potential for interactions.
Serum bilirubin increases when PEG-interferon and ribavirinare used with atazanavir: The elevation in serum bilirubin levels is directly related to the haemoglobin decline as a result of ribavirin use and haemolysis. The clearance of the increased bilirubin is compromised by atazanavir.
Drug interactions between efavirenz and itraconazole: This is a case report of the interaction between itraconazole and efavirenz in a woman with disseminated histoplasmosis and HIV-1 infection. Previous data in healthy volunteers have shown a decrease of about 40% in exposure of itraconazole and its active metabolite (hydroxyitraconazole) and a recommendation to consider alternative antifungal treatment.
Effect on tacrolimus when switching from nelfinavir to fosamprenavir: This case report outlines the change in tacrolimus trough blood concentrations when 4 HIV-infected orthotopic liver transplant patients were switched from nelfinavir (1250 mg twice daily) to fosamprenavir (1400 mg twice daily without ritonavir) due to the EMEA ruling on nelfinavir in June 2007.
Elvitegravir with tipranavir/ritonavir or darunavir/ritonavir: In the tipranavir study healthy volunteers received elvitegravir/ritonavir (200/100 mg once daily) alone, or tipranavir/ritonavir (500/200 mg twice daily) alone, or elvitegravir (200 mg once daily) in combination with tipranavir/ritonavir (500/200 mg twice daily).

BASIC SCIENCE & VACCINE RESEARCH

Cause for caution on HIV cure report: Richard Jefferys, TAG; An avalanche of media coverage has been loosed by the recently announced case of an individual who may have been “functionally cured” of HIV infection.
Low-level HIV replication versus latency: identifying the source of viral rebounds during treatment interruptions: Richard Jefferys, TAG; In HIV research, there is a persistent and vigorous debate around the question of whether or not viral replication persists in the face of successful antiretroviral therapy. During a plenary session at the International AIDS Conference in Mexico City back in August, Bob Siliciano made a compelling argument that, in most cases, antiretroviral therapy completely shuts down virus production.

OTHER NEWS

Martin Delaney, leading treatment activist and founder of Project Inform, dies at 63: It is with great sadness that we report that Marty Delaney, one of the most outspoken and respected American treatment activists, died on 23 January 2009.
Report refutes HIV denialist claims on children's HIV trials: Simon Collins, HIV i-Base; Several years ago, allegations from a fringe group of HIV denialists who claiming that foster children in New York were used as guinea pigs for adult HIV drug trials, gained media publicity when used as a basis for a BBC documentary. It is important that these have been quashed following a lengthy investigation, detailed in a recent article in the New York Times.

This information is designed to support, not replace, the relationship that exists between you and your doctor.
©1980-2009, AEGiS.