- Tipranavir in treatment experienced patients: results from RESIST-1
- Simon Collins, HIV i-Base
- One on the most anticipated studies at ICAAC was the 24-week results from tipranavir RESIST-1 study: Randomised Evaluation of Strategic Intervention in Multi-Drug Resistant Patients with Tipranavir, presented by Charles Hicks from Duke University, North Carolina. RESIST-2, the European sister study in slightly more experienced and resistant patients will be presented a month later at Glasgow.
- Reverset: first data in patients with nucleoside resistance
- Simon Collins, HIV i-Base
- d-d4FC (Reverset) is a cytidine analogue reverse transcriptase inhibitor that has shown in vitro activity to HIV resistant to 3TC, AZT, tenofovir and other RTIs. First in vivo data, from exposure to 10 days monotherapy in treatment naïve patients, achieved mean viral load reductions of –1.77 log after 10 days exposure to 200mg dose, and was presented at the 2004 retrovirus conference.
- BHIVA audit on management of hepatitis coinfection
Further reports from the XV Intl AIDS Conference - Simon Collins, HIV i-Base
- Each year BHIVA audit an aspect of HIV management and the degree to which recommendations included in UK guidelines are being followed in practice. The 2004 audit assessed the impact of last years BHIVA guidelines for management of patients coinfected HIV and hepatitis B (HBV) or hepatitis C (HCV). Preliminary results were presented at the 10th BHIVA Autumn Conference on Friday 8th October by Dr Shamela de Silva from St Mary’s Hospital, London.
- The X4 Files: sampling the science on HIV co-receptors in Bangkok
- Bob Huff, GMHC
- It has become conventional wisdom that the International AIDS Conference (IAC) is no longer the place to find cutting-edge research on HIV science. And although Track A, the basic science track at the conference, had fewer posters and presentations than the tracks for clinical research, prevention, social issues and policy, a respectable 618 basic science presentations were submitted and 439 accepted to the 2004 IAC in Bangkok. Here’s a selection of abstracts covering one aspect of HIV basic research of emerging importance.
- Women and HIV: research directions
- The symposium, a follow-up to the 2002 “Sex & Gender in the Management of HIV Disease Care, Prevention and Research workshop was designed to focus attention on research needs specific to women and HIV. Three themes from the frontlines of HIV care and prevention research were chosen for discussion: new approaches to prevention, addressing underlying social needs, and special needs of women in conflict and post-conflict settings.
- A round-up of news about access to treatments with links to sources: Britain, Ukraine, Thailand, Europe, South Africa
- Graham McKerrow, HIV i-Base
- The UK is giving US$ 5.3 million (£ 3 million) to the Global Fund to Fight AIDS, Tuberculosis and Malaria - money that has been brought forward from the UK pledge for 2005.
- Body Mass Index at diagnosis is independent predictor of survival
- HIVandHepatits.com
- Identification of basic prognostic indicators of HIV infection is essential before widespread antiretroviral therapy can be implemented in low-technology settings. This study assessed how well body mass index (BMI:kg/m2) predicts survival.
- Six generics compare well with US-made ARVs
- Graham McKerrow, HIV i-Base
- A comparison between several generic antiretrovirals and the brand name formulations, carried out by researchers in Channai, India, and Boston, USA, shows that the drug content of the generics compared well. All the formulations were within the 5% range of the stated contents compared with the proprietary drugs, except for two.
- Viral load response at 4 weeks predicts treatment success
- Laurence Gibson, HIV i-Base
- To prevent the development of drug resistance, it is useful to be able to predict at an early stage whether or not a treatment-naïve patient’s viral load will become undetectable (VL <50) after 24 weeks.
- Resistance mutations in patients with persistent viraemia show need to improve clinical assays
- Graham McKerrow, HIV i-Base
- Richard Nettles and colleagues at Johns Hopkins University and the Howard Hughes Medical centre, Maryland, USA, conclude from a study of 21 patients who had persistent, detectable, low level viraemia while on highly active antiretroviral therapy, that there is a need to improve the sensitivity of clinical assays for the detection of drug resistance.
- Researchers call for new approach to assessing pipeline drugs for salvage patients
- Graham McKerrow, HIV i-Base
- Researchers from four countries have written to the Lancet calling on the pharmaceutical industry, the US Food and Drug Administration (FDA), researchers and the patient community to work together to assess the use of more than one new drug simultaneously to provide more effective so-called salvage therapy.
- Vancouver researchers urge caution with combinations of lipid drugs
- Sean R. Hosein, catie.org
- As people age there is a trend to gradually develop abnormal levels of sugar and lipids (cholesterol, triglycerides) in their blood. People with HIV/AIDS (PHAs) who use highly active antiretroviral therapy (HAART) can also develop high levels of these substances. If left untreated, this increases the risk of developing diabetes and cardiovascular disease.
- 3TC-resistance leads to hepatitis B flare
- Graham McKerrow, HIV i-Base
- Doctors in Melbourne, Australia, report a severe and prolonged flare of hepatitis B in an HIV-HBV co-infected patient, which they believe was caused by the emergence of 3TC-resistant HBV together with a strong and prolonged HBV-specific CD8 T cell response.
- Sight changes reported with PEG-interferon
- Sean Hosein, CATIE News
- Hepatitis C virus (HCV) infects the liver and over the long-term can cause serious damage to this vital organ. Some people with HIV/AIDS (PHAs) are co-infected with hepatitis C. Treatment for HCV infection is a combination of a long-lasting form of interferon, peginterferon (Pegetron, Pegasys), together with the drug ribavirin.
- BMS submits marketing applications for entecavir to treat HBV in US and Europe
- Bristol-Myers Squibb Company has announced the submission of a New Drug Application to the US Food and Drug Administration for entecavir, an investigational antiviral agent under development for the treatment of chronic Hepatitis B. The company also submitted a marketing authorisation application for entecavir to the European Medicines Evaluation Agency.
- Study raises questions about cost effectiveness of nevirapine regimen
- Polly Clayden, HIV i-Base
- A cost effectiveness analysis published in the 20 August 2004 edition of AIDS reports that the efficacy of the nevirapine regimen for reducing mother-to child transmission in a field setting is much lower than desired and despite the low cost of the drug itself requires significant financial resources to implement successfully.
- Low efficacy of nevirapine to reduce MTCT in real life situation
- Polly Clayden, HIV i-Base
- A research letter in the 3 September edition of AIDS discusses the effectiveness of nevirapine in reducing mother to child transmission in a field setting in Mombasa, in which mother to child transmission rates were similar to those found using no intervention. The authors point out that although the HIVNET012 regimen has been widely recommended, data to validate the effectiveness of this strategy outside a research setting are lacking.
- Use of T-20 at the end of pregnancy to a multi-treated HIV-infected woman with virological breakthrough
- Polly Clayden, HIV i-Base
- A research letter in the 24 September edition of AIDS describes a French case of a treatment experienced pregnant woman with virological breakthrough treated with enfuvirtide during the last three weeks of her pregnancy.
- CHIPS data finds response to HAART varies with age in children
- Polly Clayden, HIV i-Base
- The Collaborative HIV Paediatric Study (CHIPS) is a multicentre cohort of children in the UK and Ireland participating in PENTA trials since 1996. A study reported in the 24 September issue of AIDS evaluates the effect of age, pre-HAART CD4 percentage (CD4%) and plasma HIV-1 RNA on response to highly active antiretroviral therapy (HAART) in treatment naïve children.
- HAART is effective in African children in a resource-limited setting
- Graham McKerrow, HIV i-Base
- Researchers in Abidjan, Cote D’Ivoire, and in Paris, France, conclude from a study of the effects ofHAART in an observational cohort of 159 HIV-1-infected children in Cote d’Ivoire, that it is possible to treat African children in a resource-limited setting and that this treatment appears to be as effective as in developed countries.
- Predictive factors of virologic success in HIV positive children treated with lopinavir/ritonavir
- HIVandHepatitis.com
- Predictive factors of the virologic success of the use of the protease inhibitor lopinavir/r (Kaletra) in HIV-infected children are unknown, especially in children who have been pretreated with protease inhibitors (PIs).
- Clinical features and predictors of survival in patients with AIDS-related non-Hodgkin’s lymphoma
- HIVandHepatitis.com
- n this study, Australian researchers analysed the clinical features and predictors of survival for AIDS-related non-Hodgkin’s lymphoma (NHL) in the era of HAART, compared to earlier in the HIV epidemic.
- Dispersal of HIV-positive asylum seekers: national survey of UK healthcare providers
- Beginning April 2000, the UK National Asylum Support Service initiated a policy of dispersing asylum seekers from London and southeast England to locations around the United Kingdom in an effort to diffuse health care costs. More than 100,000 asylum seekers to date have been dispersed, many of whom are from regions with HIV epidemics. It is not known how many HIV- positive seekers have been affected by the policy. Asylum seekers may receive only 48 hours notice, and they face immediate cessation of income, housing and legal benefits if they decline dispersal.
- Medical journals require pre-trial registration in public database as criteria for submission for publication
- Conference abstracts and reports
- Hepatitis coinfection
- Several articles and papers have been published online over the last month that address liver transplantation in HIV-positive patients.
- EDITORIAL
- This double issue of HTB features reports and research presented at the XV International AIDS Conference held in Bangkok in July. There is always far more to report at every meeting that we can cover in this journal and we also include links to other sites, including those with webcasts of some of the sessions.
- XV International World AIDS Conference - 11-16 July 2004, Bangkok
- The biennial World AIDS Conference, which alternates hosting by countries in the Northern and Southern hemispheres, is the largest and broadest focused of the international HIV meetings. At this year"s event close to 20,000 delegates met at a conference centre on the outskirts of Bangkok. Although basic and clinical science tracks are still important, they are now outnumbered by combined studies on social, prevention, community and access.
- Dollars, commerce, politics and prejudice all present obstacles to scaling up access to treatment in resource poor countries
- Graham McKerrow, HIV i-Base
- The question of how to scale up access to treatments in poor countries dominated the XV International AIDS Conference in Bangkok and it quickly became clear that different regions, different countries and different organisations would be pursuing their own ways of trying to treat as many people as possible. There is no one-size-fits-all solution to this enormous task because funding sources, local conditions, infrastructure, culture and needs all vary widely. What suits a middle-income democracy with a free-at-the-point-of-delivery public health service, like Brazil, would not suit a poor but stable country like Uganda, or a country like Cambodia, with political conflict and widespread corruption which make greater government involvement as undesirable as it would be ineffective.
- MTCT programmes in South Africa: nevirapine and the minister
- Jonathan Berger and Nathan Geffen for HIV i-Base
- Never one for passing up the opportunity to score a few cheap points, South Africa’s Minister of Health used the opening of the South African Department of Health’s exhibition at the XV International AIDS Conference in Bangkok on Sunday, 11 July 2004 to launch yet another unjustified attack on her most vocal and organised critic, the Treatment Action Campaign (TAC). Claiming that new scientific evidence “vindicated” her original position on the use of nevirapine for the prevention of motherto- child transmission of HIV (MTCT), Dr Manto Tshabala-Msimang sneeringly referred to the “pressure from some civil society organisations” that had caused the South African Constitutional Court to force the
extension of the MTCT prevention “research programme”.
- Urgency of global access to ARV treatment for IV drug users
- Mauro Guarinieri, for HIV i-Base
- A week-long conference is definitely a good thing in the fight against AIDS but it will count for almost nothing if it is not followed up by concrete measures and action. Since the last global AIDS gathering in Barcelona in 2002 6 million people have died and 10 million have been newly infected, so the question now is: "What will the follow up be?"
- Replace myths with evidence–based policies on IV drug use
- Paisan Suwannawong, Director of the Thai AIDS Treatment Action Group
- I would like to tell you a little bit about myself. I grew up in one of Bangkok"s biggest slums, not far from here. I saw many people using drugs, but never imagined that I would become a drug user myself. The first time I smoked marijuana, it felt like a challenge because all the public campaigns said drugs were “bad” and “dangerous.” I found it wasn"t true, so I continued to smoke it. Then I started smoking heroin, and became addicted without realising it. I didn"t have any money, I was feeling withdrawal symptoms, and my friend offered to share his heroin and inject me. Yes, it was scary the first time.
- Adding Combivir to single dose nevirapine for reduction of MTCT significantly reduces resistance
- Polly Clayden, HIV i-Base
- Perhaps the most important data from this meeting was an interim analysis from the currently ongoing TOPS (Treatment Options Preservation Study, aka BI 1100.1413) presented as a late breaker by James McIntyre from the University of Witwatersrand, Johannesburg, South Africa. McIntyre described these preliminary findings as “causing quite a stir, certainly among the Africans.”
- Lopinavir/r levels reduced during pregnancy
- Polly Clayden, HIV i-Base
- Pregnancy can alter the pharmacokinetics (PK) of antiretrovirals and it is well known that optimal exposure during pregnancy is essential both for maternal health and preventing mother to child transmission. In an oral late breaker, Alice Stek presented preliminary findings from a small sub study of PACTG 1026 – an ongoing study of PK in HIV-infected women.
- Another chance for 3TC in patients with M184V mutation?
- Simon Collins, HIV i-Base
- The continued use of 3TC to maintain 3TC-associated M184V mutation because of the theoretical impact on viral fitness is supported by several early and persuasive studies. However, no clinical benefit was found in the long-enrolling Colate study when results were eventually presented earlier this year at CROI. [1] Colate had randomised patients on failing 3TC-containing treatment to either stop or maintain 3TC in their subsequent regimen.
- Kaletra monotherapy: small studies and early data
- Simon Collins, HIV i-Base
- At last year’s IAS conference in Paris, several studies reported on ritonavir boosted PI monotherapy using either indinavir or lopinavir/r both as maintenance therapy and first-line therapy.
- Lowering dose of d4T can maintain efficacy and reduce side effects
- Simon Collins, HIV i-Base
- As ARV programmes slowly increase access to treatment in resource-poor countries, it is important not to repeat the same mistakes made in patient management in the West. Prolonged use of d4T, in particular, left many patients with permanent and debilitating peripheral neuropathy or substantial lipoatrophy. The incidence of both these side effects is higher when treatment is started in more advanced disease, and this is often the case in access programmes.
- Three-year renal safety with tenofovir; cystatin may be a useful marker
- Simon Collins, HIV i-Base
- Tenofovir is now widely used in treatment naïve patents and 3-year data presented at the conference showed in several analysis from the 903 Study and numerous smaller studies continued to support its improved lipid profile and reduced peripheral lipoatrophy and neuropathy, when used with 3TC and efavirenz, and compared to d4T.
- Fluconazole increases nevirapine levels and risk of serious hepatotoxicity
- Simon Collins, HIV i-Base
- A South African study from Geel and colleagues reported the new data on the potential effect of fluconazole to increase nevirapine plasma levels. In a single-centre, open-label, single-arm trial the pharmacokinetic parameters of fluconazole were measured alone and in combination with nevirapine in 24 patients on a stable regimen of three nucleoside analogue antiretrovirals.
- Efavirenz interaction with rifampin may not require dose adjustment in patients with low body weight
- Simon Collins, HIV i-Base
- Treatment guidelines for patient requiring treatment for both HIV and TB currently recommend increasing the dose of efavirenz from 600mg to 800mg daily in patients using rifampin-based TB regimens. This has difficult logistic and cost implications especially for treatment in patients using WHO-recommended fixed-dose combinations that include efavirenz. These recommendations are based on pharmacokinetic interaction studies.
- Tipranavir significantly lowers doses of saquinavir, amprenavir and lopinavir/r
- Simon Collins, HIV i-Base
- Interaction data were presented again from the BI 1182.51 study using tipranavir with additional protease inhibitors in extensively PI-experienced patients. Although management of treatment-experienced patients has often included multiple-PI and boosted-PI regimens, the negative interaction of tipranavir in reducing levels of saquinavir, amprenavir and lopinavir/r must be remembered.
- Responses to hepatitis vaccinations: an optimum window for protection?
- Simon Collins, HIV i-Base
- HIV-positive people often belong to groups associated with high risk for hepatitis infection, and guidelines therefore recommend screening HIV patients for hepatitis A, B and C when diagnosed with HIV, and subsequent vaccination for hepatitis A and B when antibodies for either virus is not present.
- HBV vaccine, CD4 count and increasing response with double-dose
- Simon Collins, HIV i-Base
- Veiga and colleagues from Brazil reported response rate by CD4 count to hepatitis B vaccination in 55 HIV-positive patients and 20 HIV-negative controls, who had received 3 doses (0, 30 and 180 days) of recombinant DNA hepatitis B vaccine.
- Response to Hepatitis A (HAV) vaccine determined by CD4 count
- Simon Collins, HIV i-Base
- Rimland and colleagues from the VA Medical Center, Atlanta, Georgia analysed responses to hepatitis A vaccine in 214 patients who were vaccinated between 1996 and 2003 (standard dose and schedule). Overall, 130 of 214 vaccinated individuals developed HAV antibody (61%). Response rate by CD4 count at time of vaccination were 83%, 62%, 39%, 27% and 8% in patients with CD4 >500, 201-500, 101-200, 51-100 and <50 cells/mm3 respectively (p<0.0001).
- Inventive ways to explain HAART and adherence to children
- Simon Collins, HIV i-Base
- Inventive ways to explain complicated ideas behind HAART allow people of any age to have greater understanding and control over their treatment. Most healthcare workers and advocates have probably developed their own examples, but amid 100s of adherence-related posters one study from South Africa shared several creative ways to explain the importance of continued treatment and maintaining viral suppressions to children.
- Isoniazid has early and unexpected benefit in reducing childhood mortality
- Polly Clayden, HIV i-Base
- This prospective double blind study conducted at two centres in Cape Town compared INH to placebo given in addition to co-trimoxazole (TMP-SMX) - either daily or three times a week - to a group of 278 HIV positive children with a median age of 23.5 months (range 3 to 123 months). Children in Cape Town have a 4% chance of developing active TB. The study was powered to look at the effect of isoniazid primarily on mortality and secondly on developing active TB.
- Lack of keratin overlaying inner foreskin may explain lower HIV infection rates in circumcised men
- Simon Collins, HIV i-Base
- McCoombe and colleagues from University of Melbourne presented results of a study designed to determine where HIV enters the penis, hoping to understand the reported lower incidence of circumcised men in many African countries. They studied the distribution of target cells in the glans penis, frenulum, foreskin and urethral meatus from five uncircumcised penises obtained at autopsy and measured the thickness of the overlying layer of keratin. Keratin potentially prevents HIV gaining access to these penile receptors.
- A round-up of news about access to treatments with links to sources
- Graham McKerrow, HIV i-Base
- A clinical trial in field conditions of a fixed dose combination (FDC) of generic versions of nevirapine, stavudine and lamivudine – called Triomune and increasingly commonly prescribed in the developing world – shows that its effectiveness and tolerability are similar to that reported with other HAART regimens in patients with comparable baseline HIV disease status.
- US FDA approves Glaxo and Gilead drug combinations
- The US Food and Drug Administration has approved two antiretroviral drug combinations made by GlaxoSmithKline and Gilead Sciences for use in the United States and in developing countries. Truvada, the Gilead medicine, contains emtricitabine and tenofovir. Epzicom, the Glaxo combination, contains lamivudine and abacavir.
- Abbott applies for once-daily license for lopinavir/r
- Abbott Laboratories has submitted a supplemental New Drug Application to both the US Food and Drug Administration (FDA) and a Marketing Authorisation variation to the European Medicines Agency (EMA), seeking approval of once-daily dosing for its protease inhibitor (PI) Kaletra (lopinavir/ritonavir).
- AIDS activists respond to NIH decision on overriding HIV drug patent
- AIDS activists in the US expressed disappointment with a recent decision of the National Institutes of Health (NIH) regarding the patent for ritonavir (Norvir®), made by Abbott Laboratories. In an official statement released yesterday, Dr Elias A Zerhouni, NIH Director, stated the NIH’s official decision not to override the patent on ritonavir. The NIH held a public hearing on 25 May as a result of a petition claiming that a 400% increase in the drug’s price in December 2003, which was developed in part with government funding, adversely affected reasonable consumer access to the drug.
- Efficacy of acetyl-l-carnitine for antiretroviral toxic neuropathy
- Leighton Davies MD, for HIV i-Base
- The results of a recently published trial by Andrew Hart and colleagues from Blond McIndoe Centre, Manchester, and the Royal Free Hospital in London, provide confirmatory evidence for the use of acetyl-l-carnitine as a pathogenesis-based treatment for antiretroviral-associated toxic neuropathy (ATN). ATN is the commonest cause of distal symmetrical neuropathy affecting between 11% and 66 % of individuals on antiretroviral therapy and is usually associated with the dideoxynucleoside analogue drugs ddC, d4Tand ddI (the "d-drugs").
- Chiron relaxes patent licenses for hepatitis C
- Chiron Corp plans a change in the licensing policy on its patents covering the genetic makeup of the hepatitis C virus, a move that they say could lead to the development of new drugs to fight the disease.
- Activists arrested in Nepal in homophobic atmosphere
- Graham McKerrow, HIV i-Base
- On the night of 9 August at about 10.30pm, 39 members of Blue Diamond Society (BDS), a gay rights and HIV prevention organisation in Nepal, were arrested and taken to Hanuman Dhoka Police Station in the centre of Kathmandu. First reports as HTB went to press said they were being detained without food and had been treated inhumanly. Sunil Pant, Director of BDS issued a statement saying: "We are very concerned."
- SMART study examines the long term benefit risk of interruptions versus continued use of ART
- In the July issue of HTB, Simon Collins raised concerns regarding the potential of emergence of resistance in patients discontinuing an NNRTI-based ART regimen, and he was asking for guidelines for how to diminish the risk of this in the SMART study.
- IAPAC conference in London
- The International Association of Physician in AIDS Care (IAPAC) announces the first-ever IAPAC Sessions—Europe,23-24 September 2004 at London’s Royal College of Physicians. Accommodation and most meals in London will be provided by IAPAC. For the past three years, IAPAC-hosted symposia in the United States have provided HIV-treating physicians an opportunity to discuss and debate the latest issues of HIV clinical management.
- Three-day course on methodological and statistical issues in clinical HIV research
- This three day workshop will be run by the HIV Epidemiology and Statistics Group, Royal Free Centre for HIV Medicine, Royal Free and University College Medical School. The course is for healthcare professionals and those working in the pharmaceutical industry who have an interest in HIV.
- EDITORIAL
- This issue includes reports from the recent resistance meeting in Tenerife – in which we include reviews of the research with the relevance to clinical practice – and Gareth Hardy provides an overview of the highly specialised Keystone meeting that took place in April.
- Risk of NNRTI-resistance during STI: implications for SMART and other STI studies
- Simon Collins, HIV i-Base
- The potential for NNRTI-resistance due to monotherapy when these drugs are discontinued is now widely recognised. Although many doctors already advise discontinuing the NNRTI one week earlier than their nucleosides, this may still not be sufficient as recent studies showed some patients can maintain therapeutic levels for several weeks after stopping treatment.
- Persistent nevirapine resistance following mother to child transmission interventions
- Polly Clayden, HIV i-Base
- Three studies presented at this meeting evaluated resistance in women having received single dose nevirapine to reduce mother to child transmission.
- Tipranavir resistance and viral response: L90M did not reduce response, recommendation to use with T-20
- Simon Collins, HIV I-Base
- Virological efficacy in the study was clearly driven by tipranavir with patients in all groups achieving median change of >1log reductions by week 4, once tipranavir was included in the combination. In this highly experienced group, this unfortunately only provided a short-term effect and by week 8 median viral load was rebounding to approximately -0.5 log below.
- Resistance in the UK: new approach to epidemiological studies
- Simon Collins, HIV I-Base
- Incidence of resistance is frequently presented from an analysis of single time point data from specific populations such as new infections, primary infection and national or local cohorts. This is often used to interpret prevalence and trends in resistance to specific drugs and drug classes.
- Low AZT activity against HIV-2 infection
- Simon Collins, HIV I-Base
- Although AZT is widely used to treat HIV-2 infection recent studies showing difference in response compared to patients with HIV-1. This prompted Garcia-Lerma and colleagues from CDC Atlanta USA to evaluate in vitro selection experiments with strains of each virus.
- No evidence for cross resistance between nevirapine and d4T
- Simon Collins, HIV I-Base
- The study therefore failed to find an association between Y181C and d4T sensitivity and concluded that d4T should not be avoided as a treatment option on the basis of this genotypic mutation.
- Experimental compounds to target viral expression in latent cells
- Simon Collins, HIV I-Base
- Earlier studies were have investigated the use of IL-7 to stimulate latently infected CD4 cells to express HIV and therefore render them susceptible to effect of antiretroviral treatment. If this response was sufficiently extensive and robust, this would re-open discussions on possibilities of HIV eradication.
- Case of MDR reinfection with MDR virus
- Simon Collins, HIV I-Base
- Incidents of HIV reinfection or superinfection are generally difficult to isolate and report as the structure for patient management are not geared to be able to look for this. When cases are identified (see report on last years meeting in HTB 4/7, Aug/Sep 2003) they tend to be picked up by clinicians who notice unexpected virological rebound or increases, that are linked to a personal patient history, and then confirmed by technology that is not generally easily accessible to practicing clinicians.
- Keystone HIV Pathogenesis and Vaccine Report
- Gareth Hardy PhD, for HIV i-Base
- This highly specialised and relatively small annual meeting is often not attended by community activists or press. The focus on basic science means that much of what is presented and discussed has little, if any, direct implications for clinical practice. However, the meeting attracts some of the world"s experts on HIV immunology and pathogenesis as a forum to exchange and discuss ideas and data. Collaborations were also as likely to be forged between sessions as on-piste on The Cougar and The Harmony Ridge slopes on the heights of the Whistler and Blackcomb Mountains.
- A round-up of news about access to treatments, with links to sources
- Graham McKerrow, HIV i-Base
- Trade deals being negotiated between the United States and individual countries or regional groups could severely restrict access to essential medicines for millions of people around the world according to the international medical humanitarian organisation Medecins Sans Frontieres (MSF). MSF warns that the negotiations are part of a US strategy to build a network of agreements that undermine international consensus reached at the World Trade Organization (WTO) about the appropriate balance between the protection of private intellectual property and the protection of public health.
- CD4 entry criteria dropped for UK tipranavir named-patient access
- Polly Clayden, HIV I-Base
- From June 14 the entry criteria for the Named Patient Supply of the investigational protease inhibitor tipranavir have broadened. There are now no restrictions on the basis of CD4 count or viral load. Inclusion criteria that remain include being triple-class experienced with at least two previous PI based regimens. Women need to have a negative pregnancy test if they are of childbearing potential and be willing to use effective barrier method of contraception.
- Tenofovir/FTC co-formulation expected in US by September
- Gilead Sciences announced on May 17 that the US Food and Drug Administration (FDA) had granted priority review status to the New Drug Application (NDA) for the fixed dose co-formulation of the company"s anti-HIV medications tenofovir (Viread) and FTC (emtricitabine, Emtriva). Gilead submitted its application to the FDA on March 12, 2004 and had anticipated a decision by January 12, 2005 based on a 10-month traditional review. Under priority review, the NDA will be reviewed with in six months and the action date by which the FDA will make a decision is September 12, 2004.
- Guidelines for T-20 (Fuzeon)
- The full guidelines are only available online to subscribers or as a pay-to-view article but reprint copies are available free from the Roche Drug Information Department on 0800 328 1629.
- Persistent HIV viraemia fosters immunologic harm and viral evolution
- David Douglas, HIVandHepatitis.com
- "Although our study focused on HIV pathogenesis in the setting of highly effective antiretroviral therapy, we believe that our data have direct clinical implications," Dr Deeks said. "For example, low level viral replication-as defined by persistent levels of detectable HIV RNA-is associated with immunologic harm and ongoing viral evolution. Such individuals may require a treatment modification." "Also, our data suggest that specific immunomodulators during incompletely suppressive therapy may prove to be very useful," Dr. Deeks said. "My hope is to see such drugs developed for this purpose."
- Latent drug-resistant HIV harboured for years
- David Douglas, HIVandHepatitis.com
- “These findings indicate that once resistance arises against an antiretroviral, the activity of this drug will remain reduced for several years and possibly life-long, even after a withdrawal period of years,” said Verhofstede. “Recycling drugs is therefore not an advisable option if other alternatives are available.” He further noted that the results “argue against a possible benefit of therapy interruptions as a way to improve the effect of a subsequently introduced salvage regimen containing recycled drugs.”
- Non-prescription simvastatin in the UK: contraindicated with many HIV medications
- Simon Collins, HIV i-Base
- Simvastatin (Zocor) is contraindicated for HIV patients who are on treatment because of significant interactions with indinavir, lopinavir, nelfinavir, ritonavir and saquinavir. There are also potential interactions with amprenavir, nevirapine, efavirenz and delavirdine.
- Label changes for indinavir warn of several interactions including atazanavir and PDE5 inhibitors
- Graham McKerrow, HIV i-Base
- Several changes have been made to the product label for indinavir (Crixivan) to warn of interactions with a number of drugs and to say that it should not be coadministered with atazanavir and that patients and doctors should be alert to interactions with the phosphodiesterase type 5 (PDE5) inhibitors sildenafil (Viagra), tadalafil (Cialis) or vardenafil (Levitra).
- Smoking during HIV infection may alter the natural history of HPV infection and increase the risk of cervical disease
- HIVandHepatitis.com
- Among HIV-infected women, smoking is associated with a significantly higher prevalence and incidence of HPV infection. Smoking during HIV infection may alter the natural history of HPV infection and increase the risk of cervical disease.
- Sexual transmission of HIV by acutely infected individuals has a disproportionate effect on the spread of HIV and may explain the current pandemic
- HIVandHepatitis.com
- The present study provides empirical evidence that men with acute HIV infection are biologically hyper-infectious because of increased genital shedding of HIV. In addition, the present study has provided evidence that, during acute infection, HIV load increases and decreases in semen in approximate parallel with changes occurring in blood, which have been well described. The present model of viral dynamics in semen suggests that, on average, individuals are hyper-infectious beginning before the onset of the acute retroviral syndrome and continuing for approximately 6 weeks thereafter.
- Online medical resources
- Meeting announcements
- Conference abstracts on AEGiS
- Treatment Access
- MSF's 'Untangling the web'; Botswana Generic report
- Journal articles
- AIDS, the official journal of the International AIDS Society, is now free after one year. Articles older than 12 months will be freely accessible through the journal website
- EDITORIAL
- This issue of HTB includes reports from the recent BHIVA meeting in Cardiff. Data were presented from the BHIVA pregnancy audit and provides a fascinating insight into current practice in this country and will inform the revised BHIVA pregnancy guidelines.
- Pregnancy 2003-4 audit
- Polly Clayden, HIV i-Base
- The investigators described these findings as “broadly positive” but cited areas in which they felt stronger guidance to be needed. In particular: appropriate use and stopping of nevirapine; avoidance of ddI and d4T together; appropriate use of planned vaginal delivery; timing of elective caesarean section; management of women who wish to breast rather than formula feed and management of subsequent pregnancies.
- More positive children are surviving into adult life and require tailored services
- Graham McKerrow, HIV i-Base
- Addressing the needs of vertically infected adolescents has implications for both paediatric and adult HIV services. Transition should be viewed as a process throughout the adolescent years rather than a one off transfer of care.
- Other news from the BHIVA conference
- Simon Collins, HIV i-Base
- Atazanavir switch appears tolerable and effective; Therapeutic drug levels can continue three weeks after stopping efavirenz; Use of detuned HIV test to establish recent infection; Tenofovir for treatment of HBV in coinfected patients; Sub-type-B infection in UK traced to 1975-1982; HIV still missed by GPs.
- Antiviral activity of foscarnet in salvage therapy
- Graham McKerrow, HIV i-Base
- Foscarnet toxicity and the risk of severe infections related to intravenous administration represent a major limitation in clinical practice. Therefore, regardless of the promising antiretroviral properties, treatment with foscarnet should be instituted with great caution and restricted to patients with severely deteriorated immunology and no other treatment options left. The objective of therapy should be to identify tolerable maintenance doses that provide a reasonable improvement in the CD4 cell count.
- Kaletra therapy fails woman with subtype C virus with multiple mutations
- Graham McKerrow, HIV i-Base
- Mutations in the protease gene that are known polymorphisms but are also secondary mutations associated with PI resistance were present before starting treatment and may have made the accumulation of additional mutations more likely. In addition, poor adherence with suboptimal lopinavir levels may have contributed to the development of resistance. This observation supports the hypothesis that resistance to lopinavir requires the accumulation of a series of mutations, and demonstrates that well-described PI resistance mutations can accumulate when on lopinavir-ritonavir therapy and can contribute to virological failure. A signature mutation for lopinavir resistance was not identified.
- Oral uridine treats mitochondrial toxicity
- Graham McKerrow, HIV i-Base
- Several investigators have found beneficial effects of uridine in vitro and in animals, but Ulrich Walker and colleagues report in the 30 April issue of AIDS the case of a man who has been on antiretroviral medication since being diagnosed with HIV-1/AIDS four years ago.
- Phase II results show ThGRF could be safe, effective treatment for lipodystrophy, says company
- Graham McKerrow, HIV i-Base
- The preliminary results suggest that ThGRF is safe and effective, concentrating its effect on reducing visceral fat while preserving subcutaneous fat. This would make it particularly useful in treating people with an accumulation of visceral fat (lipohypertrophy) together with a loss of subcutaneous fat (lipoatrophy). It demonstrated good glycaemic control, even among glucose intolerant and diabetic patients. About 40% of HIV-associated lipodystrophy patients are either glucose intolerant or diabetic.
- Reversibility of lipoatrophy in HIV patients 2 years after switching from a thymidine analogue to abacavir
- From HIVandHepatitis.com
- The authors conclude: “In patients with moderate-to-severe lipodystrophy, significant improvements in subcutaneous fat continued over 104 weeks after switching from a thymidine analogue to ABC. Nevertheless, the lipodystrophy syndrome was still evident, indicating additional strategies need evaluating.”
- Rapid clearance of HIV-1 is associated with decreased risk of AIDS
- Graham McKerrow, HIV i-Base
- Multivariate analysis showed that a rapid rate of initial clearance was the sole independent predictor of subsequent progression to AIDS and was associated with a 92% reduction in the risk of AIDS. The rate of initial clearance was inversely correlated with the number of early symptoms (r = -0.66; P = .0008). However, symptoms did not predict subsequent risk of AIDS.
- HIV patients get long-term boost with short, intermittent drug regimen
- NIAID Press Release
- US National Institutes of Health (NIH) scientists report that brief, widely-spaced courses of the experimental immune-boosting drug interleukin-2 (IL-2) allow people with HIV to maintain near normal levels of a key immune system cell for long periods. The researchers, from NIH"s National Institute of Allergy and Infectious Diseases (NIAID) and the Warren G. Magnuson Clinical Centre, describe their findings in the 1 May issue of the journal Blood.
- 39th Annual Meeting of the European Association for the Study of the Liver (39th EASL) 14-18 April 2004, Berlin, Germany.
- Although coinfection with HIV only covered a minority of the studies presented at the 39th EASL, reports on new drugs to treat HBV or HCV monoinfection indicate the most hopeful pipeline for coinfected patients. Full abstracts from the meetings are not available on the conference website, but coverage of many of the HIV and hepatitis coinfection and new agent studies have been grouped by subject and are reported or included as abstracts on the HIVandHepatitis.com and NATAP websites
- Tenofovir blocks viral replication in HBV monoinfected and in HIV-HBV coinfected patients with lamivudine resistance
- From HIVandHepeatitis.com
- The authors conclude: “These data show that tenofovir is capable of blocking viral replication in patients with lamivudine induced mutant viruses in HBV patients as well as in HBV/HIV co-infected patients.”
- Compared to Caucasians, Africans have significantly higher rates of fibrosis and cirrhosis despite lower levels of HBV replication
- From HIVandHepeatitis.com
- The authors conclude: “A significant proportion of patients with chronic hepatitis B have advanced fibrosis despite a low level of HBV replication. Differences between Af and As patients suggest a considerable clinical impact of different HBV genotypes.”
- Undetectable HIV viral load in HIV-HCV coinfected patients slows liver fibrosis progression rate
- From HIVandHepeatitis.com
- In the pre-HAART era, HIV-HCV-coinfected patients were reported to have a faster fibrosis progression rate (FPR) than HCV-monoinfected patients. One preliminary study suggested that HAART might slow down FPR. The study was conducted in New York City and at four sites in Puerto Rico.
- US government stops scientists attending International AIDS Conference
- Graham McKerrow, HIV i-Base
- A spokeswoman for CDC told the journal Science that the agency would select scientists according to “which [talks] are most important”. NIH refused to comment.
- EMEA releases recommendations for better information for patients
- The European Medicines Evaluation Agency (EMEA) has released recommendations on improving information for patients. Drawn up in collaboration with patients" organisations, the recommendations fall into three main areas; providing information adapted to patients" needs, developing appropriate communication tools, and increasing public awareness on the use of drugs and EMEA activities.
- Response to report from 11th CROI on treatment in primary infection
- Dr Sarah Fidler
- The clinicians" dilemma as to whether to offer ART intervention in patients presenting with acute HIV infection remains unanswered. The only way to address this is with a large-scale randomised clinical trial appropriately powered to definitively answer this question.
- Conference abstracts
- The ongoing project by AEGiS to archive important HIV/AIDS conference abstracts in a single online database resource continues to add conferences monthly.
- Treatment Access
- MSF"s 'Untangling the web'; Botswana Generic report
- Journal articles
- AIDS, the official journal of the International AIDS Society, is now free after one year.
- Online medical resources
- Online publications
- IAVI Report online; New PRN Reports on line; GMHC Treatment Issues - March/April 2004; TAGline – May 2004
- EDITORIAL
- This issue has reports from the recent 2nd European HIV Drug Resistance Workshop and 5th International Workshop on Clinical Pharmacology of HIV Therapy conferences plus two final Retrovirus reports. One of the most import presentations from the PK meeting was the analysis of tipranavir interactions with other protease inhibitors.
- Large reductions in plasma PK levels of saquinavir, amprenavir and lopinavir/r levels when given with tipranavir/ritonavir
- Simon Collins, HIV i-Base
- One of the most important studies presented at the workshop was the first analysis of interaction between tipranavir and other protease inhibitors, from the BI 1182.51 trial. The results have important implications for people currently using tipranavir in regimens that also contain saquinavir, amprenavir or lopinavir/r.
- Good generic drugs and good adherence in Rwanda
- Polly Clayden, HIV i-Base
- A report from the ESTHER treatment programme - a collaboration between Rwanda and Luxembourg - described good quality generic drugs and good adherence in 70 Rwandan patients at the Centre Hopital de Kigali. The study performed an analysis of antiretroviral generic drugs (tablets, capsules and syrups) available in Rwanda. Zidovir, Nevimune and Lamivir are manufactured by Cipla, and Avolam, Coviro and Triviro by Ranbaxy.
- Steady state PK of nelfinavir and M8 in pregnancy
- Polly Clayden, HIV i-Base
- A study from Rolf van Heeswijk and colleagues from the Ottawa Health Research Institute in Canada evaluated the pharmacokinetics and its active metabolite M8 during pregnancy and post partum.
- Higher nelfinavir concentrations improve response in children
- Polly Clayden, HIV i-Base
- David Burger from the University Medical Centre in Nijmegen, Holland, presented data from a pharmacokinetic substudy of the PENTA 5 trial, in which naïve children received nelfinavir plus two nucleosides. All participating children received NFV 25-30 mg/kg TID or 45-55 mg/kg BID with food. Trough samples were taken between week 20 and 80. NFV troughs <0.8 mg/L were considered subtherapeutic. Viral load <50 copies/mL was measured at week 24 and 48.
- PK of once daily lopinavir/r in children
- Polly Clayden, HIV i-Base
- A report from Glenda Verweel et al from University Medical Centre in Rotterdam evaluated the pharmacokinetics of children on a QD dosing schedule of lopinavir/ritonavir. A group of 14 children on stable antiretroviral therapy with HIV-1 RNA below 50 copies for at least six months were switched to receive LPV/r 460/115 mg/m2 QD with zidovudine and lamivudine BID as part of the RONDO trial. The LPV/r dose was given with food.
- Understanding developments in HIV drug resistance for new drugs and targets — atazanavir, fusion (T-20) and receptor inhibitors
- Mike Youle, for NATAP
- The annual European gathering of resistance aficionados took place recently on a hill above the Vatican and conformed to the best of Italian characteristics: good food, exquisite style and a complete disregard for time-keeping. I chaired a session that started 90 minutes late but since the presentations and discussion were so engrossing no one but the most anally retentive cared a jot.
- HIV-associated dementia and cognitive dysfunction
- Paul Blanchard, HIV i-Base
- Further reports from 11th Conference on Retroviruses and Opportunistic Infections (CROI)
- Diabetes and HIV and HCV; aging/HIV and diabetes
- Judith A Aberg and Jules Levin, NATAP
- This article reports on studies presented at the 11th Retrovirus Conference held in February 2004 and highlights the concern that persons with HIV can be at greater risk for developing diabetes. This report also highlights research findings that diabetes may be more prevalent in older HIV-positive individuals and may lead to cognitive impairment, thus identifying a new risk factor associated with aging and HIV.
- Outcomes after two years of providing antiretrovirals in Khayelitsha, South Africa
- Polly Clayden, HIV i-Base
- The results of this programme are comparable with data from observational settings in both developed and developing countries…These findings provide encouragement to those seeking to provide similar services in poor communities where HIV mortality and morbidity are high.
- A round-up of news on access to treatments
- Graham McKerrow, HIV i-Base
- Bill Clinton brokers deal on lower prices; UN welcomes 'Clinton deal'; Pharmacos 'aim to discredit WHO procedures and control $10b US spending' 381 NGOs call on US to accept the standards of the WHO"s prequalification programme; Pressure mounts on Bush to allow US dollars to buy generic drugs; MSF attacks Bush for rejecting generics; MSF says US should accept FDCs; US plan to fight AIDS is foundering; 3x5 is failing, says Joepe Lange; BMS overturns AIDS patent in Thailand
- US treatment guidelines updated – March 2004
- The US Department of Health and Human Services updated its adult antiretroviral treatment guidelines on 23 March 2004
- Atazanavir launched in UK
- Simon Collins, HIV i-Base
- On 10 March, atazanavir (Reyataz®), the once-daily protease inhibitor from Bristol-Myers Squibb, was approved as a ritonavir-boosted treatment in Europe for patients who have already used one previous treatment. Approval was not granted for treatment naïve patients, although in practice many doctors will be interested in this option. Atazanavir was approved in the US in June 2003 for both first-line and salvage therapy.
- Tenofovir/FTC co-formulation application made to EMEA
- Application for marketing approval for a new dual-nucleoside formulation of tenofovir and the recently approved FTC (emtricitabine) was made to the US and European regulatory authorities by Gilead on 15 March 2004. Simultaneous submissions to each agency are likely to result in a decision on approval in six to nine months in both Europe and the US. Each drug is already approved as once-daily treatment.
- Abacavir/3TC co-formulation available in expanded access
- The once-daily coformulation of abacavir/3TC from GlaxoSmithKline is also progressing through the regulatory pipeline. Although expanded-access programmes are driven by medical urgency for a new compound prior to marketing approval, a programme is now available in the UK for patients who are in such a situation.
- Eating grapefruit triggers statin-related rhabdomyolysis
- Graham McKerrow, HIV i-Base
- Grapefruit consumption appears to have triggered a recent case of statin-associated rhabdomyolysis, doctors in Berlin report in Neurology. The case involved simvastatin but Dr Jens Dreier and colleagues at the Charite Hospital say that other statins could also be affected by eating grapefruit.
- FDA panel recommends approval of New-Fill
- Simon Collins, HIV i-Base
- On 25 March, the US Food and Drug Administration (FDA) convened a panel to review study results for accelerated approval of New-Fill (Sculptra). The studies that were reviewed included the early Vega Study from Paris and the study from the Chelsea and Westminster Hospital in London. New-Fill is now owned by Aventis/Dermik. The meeting also included public testimony from patients on how lipoatrophy made it difficult to lead a normal life and that treatment had changed their personal and professional lives.
- Lipodystrophy regresses in three patients switched to atazanavir
- Graham McKerrow, HIV i-Base
- Switching to atazanavir (ATV, Reyataz) 400 mg once a day from other PI-containing antiretroviral regimens resulted in decreases in total cholesterol and fasting triglyceride levels and in a regression of body fat accumulations in three patients in Germany, according to case reports outlined in a research letter published in 9 April issue of AIDS
- Post partum complications in HIV-positive women
- Polly Clayden, HIV i-Base
- The authors report a five-fold higher overall prevalence of post partum complications in the elective caesarean section group compared to the vaginal delivery group in both HIV positive and HIV negative women. They explain however that most complications were minor, anaemia and fever, and that serious complications occurred only in women delivering by elective caesarean section. They also reported an increased risk of minor complications following elective caesarean section and a smaller increased risk in complications following vaginal delivery in HIV-positive compared to HIV-negative women.
- Children"s HIV National Network (CHINN) Review
- Following on from the 2004 report: Developing Paediatric HIV Clinical Services in London (available at www.bhiva.org/chiva) - which outlines aims to provide high quality specialist paediatric services local to children with HIV - the Department of Health in association with the Royal College of Paediatrics and Child Health and CHIVA are conducting a review of clinical services throughout the UK.
- FDA approves new paediatric dose of nelfinavir
- Based on five clinical paediatric studies, the US Food and Drug Administration (FDA) has approved new dosing recommendations in patients two years of age and older who are receiving nelfinavir. In patients less than two years of age, nelfinavir was found to be safe at the doses studied, but a reliably effective dose could not be established.
- Surgery and HAART are an effective combination for treating HPV-associated lesions
- Graham McKerrow HIV, i-Base
- The authors write: "Our data indicate that patients with HIV infection benefit from surgical therapy when performed in conjunction with any antiretroviral therapy regimen.” They say their findings suggest that lesion excision in conjunction with an effective antiretroviral therapy achieves a good response in the majority of cases. And they add: “Moreover, early intervention also appears determinant in avoiding more extensive surgery such as abdominal hysterectomy, that involves an increased risk of complications in HIV-infected women."
- The end of the financial year is upon us!
- HIV i-Base receives no statutory funding and yet we provide all our publications free of charge and delivery to individuals and NHS clinics all over the country. If your organisation has any spare funds in its coffers that it needs to spend before the end of the financial year, then please think of making a donation to HIV i-Base so that we can continue providing all our services free of charge.
- Risk factors for severe, life-threatening and fatal hepatotoxicity with nevirapine
- Recent research by Boehringer Ingelheim into risk factors for liver toxicity in patients using nevirapine found that women with a baseline CD4 count >250cells/mm3 and men with a count >400 cells/mm3 were at a significantly increased risk of rashassociated liver toxicity compared with patients who started treatment with lower CD4 counts. These data were reviewed and approved by both the European and US regulatory agencies, and finally letters have been released in Europe and the US to clarify this issue for doctors.
- 11th Conference on Retroviruses and Opportunistic Infections (CROI)
8-11 February 2004, San Francisco - About 3,500 doctors, researchers, healthcare workers, journalists and community advocates attended the 11th Conference on Retroviruses and Opportunistic Infections held in San Francisco from 8-11 February, 2004. This meeting is one of the most important annual meetings, and is prioritised by many researchers as the first choice platform for their research.
- Treatment with generics: tolerability, safety and resistance
- Simon Collins, HIV i-Base
- As antiretroviral treatment becomes more widely available, through reduced prices and generic combinations, it is important that lessons learned in the first countries to use treatments are not ignored for patients in resource poor countries.
- Drug levels can persist for more than two weeks after stopping efavirenz
- Simon Collins, HIV i-Base
- How to stop treatment safely is arguably as important a management issue as how to correctly initiate treatment, but it has been the focus of far less research. As antiretroviral drugs have different plasma and intracellular half-lives, a strategy to safely discontinue treatment may be essential in order to avoid resistance.
- Race affects absorption and clearance of efavirenz
- Simon Collins, HIV i-Base
- Heather Ribaudo followed the UK efavirenz study with particularly supportive results from a sub-study from ACTG 5095 that randomised patients in a double-blind placebo controlled trial to either efavirenz (EFV, Sustiva, Stocrin) + Trizivir (AZT+3TC+abacavir) or to Trizivir alone. This sub-study looked at efavirenz-related toxicity over the first 24 weeks of treatment. Plasma levels of efavirenz at 1, 4, 12 and 24 weeks obtained from 190 patients (36 women and 154 men) were analysed in relation to toxicity and virological response.
- Triple PI interactions: atazanavir increases saquinavir levels in ritonavir-boosted once-daily combination
- Simon Collins, HIV i-Base
- Marta Boffito and colleagues from the Chelsea and Westminster Hospital in London reported a synergistic boosting interaction between 300mg atazanavir (ATV, Reyataz) and 1600mg saquinavir hard gel capsule (SQV, Invirase) when both boosted by 100mg ritonavir (RTV, Norvir) in a once daily combination.
- Ribavirin (RBV) does not alter intracellular levels of AZT, 3TC or d4T
- Simon Collins, HIV i-Base
- In a late-breaker oral presentation, Gries and colleagues presented results from a PK sub-study of the APRICOT trial. This study randomised more than 800 patients coinfected with HIV and HCV to either standard interferon-alfa + ribavirin, pegylated interferon (Pegasys) + placebo or Pegasys + ribavirin. Results from the full APRICOT study are reported in detail later in this issue of HTB.
- COLATE study shows no clinical benefit from continuing 3TC to maintain M184V mutation
- Simon Collins, HIV i-Base
- This is the first randomised study looking at clinical results from maintaining M184V. It is disappointing that this easy to use strategy resulted in no apparent clinical differences. Viral fitness remains an intriguing and plausible factor in response to therapy that is proving difficult to link to practical benefit.
- Studies of new pipeline drugs
- Mike Youle, NATAP.org
- The Retroviruses Conference this year appeared to have a greater than usual emphasis on basic science and the clinicians were left feeling that a lot was in the pipeline but not much new around the corner. This was certainly true of new antiretroviral agents where exciting data were shown on a range of novel agents especially targeting the various steps required for attachment of HIV to the cell, a potentially very attractive proposition since the likelihood of toxicity from these compounds is low.
- Little benefit seen for treatment during acute infection
- Keith Henry, thebody.com
- Bruce Walker walked across the hall from the immune response session (featuring four Walker-linked studies) to present an update on his highly visible and often-presented small study of patients treated during primary infection who subsequently underwent several sequential treatment interruptions (STIs). The initial results from the study (3/8 maintained <5,000 copies HIV RNA after the first STI and 5/8 maintained <5,000 copies/mL after the second STI) suggested that very early antiretroviral therapy during primary infection, followed by a series of brief treatment interruptions, could lead to improved immune control of HIV off therapy. Those results have stimulated the practice of treating primary infection and spawned enthusiasm that
immunologic interventions (such as therapeutic vaccination) could also be utilised in chronic infection.
- Summary of resistance studies at Retrovirus
- Many of the oral presentations provided a higher profile for research than was first presented at the XII International HIV Drug Resistance Workshop, Los Cabos, Mexico, held in June 2003.
- Update on peripheral neuropathy in HIV-infection
- Paul Blanchard, HIV i-Base
- A major plenary session at this year"s CROI was devoted to the important issue of distal symmetrical polyneuropathy (DSPN) in HIV-infection [1]. This formed part of an oral session devoted to neuropathogenic manifestations of HIV-1 infection, which together with additional poster sessions provided a useful forum for presenting advances in the field.
- Smoking marijuana provides analgesic effect on HIV neuropathy
- Graham McKerrow, HIV i-Base
- A nine-day pilot study of 16 patients carried out by researchers at the University of California, San Francisco, found that smoking marjuana had an analgesic effect on HIV neuropathy.
- Two D:A:D updates: cardiovascular risk from HAART, and predictors of hypertension and changes in blood pressure
- Simon Collins, HIV i-Base
- The D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) study is the largest cohort study initiated to investigate whether HAART was linked to increased risk of cardiovascular disease (CVD). At the 2003 Retrovirus conference an analysis from the first 123 incidents of myocardial infarction (MI) predicted a cumulative relative rate of 1.26 with every year of HAART. While the absolute risk remained low, and was still clearly outweighed by the benefits of HAART, it was clear that health advice given to the general population was equally if not more important for HIV-positive patients.
- Low-dose rHGH maintains reductions in abdominal fat for 60 weeks
- Simon Collins, HIV i-Base
- Although several studies have shown that recombinant Human Growth Hormone (rHGH) can reduce abdominal fat accumulation and buffalo hump, the benefits have been reported to be transitory, and to reverse when treatment is discontinued. In an oral presentation, Donald Kotler presented results from using a maintenance dose of rHGH in patients who had previously responded to rHGH in the earlier STARS trial.
- Rosiglitazone shows no benefit for lipoatrophy
- Simon Collins, HIV i-Base
- Several research groups have already reported that rosiglitazone (RSG) is not an effective agent to treat lipoatrophy,2,3 and this was confirmed in an oral presentation of a new study from Andrew Carr. This study randomised 108 patients with lipoatrophy to either 4 mg rosiglitazone twice-daily (n =53) or placebo (n =55) for 48 weeks. The study was powered to detect a 0.5kg difference in limb fat by DEXA scan.
- Hypertension related to HAART in HIV-positive women
- Polly Clayden, HIV i-Base
- A poster reporting data from the US Women"s interagency HIV study (WIHS), an ongoing, prospective, multi site cohort study of HIV positive and at risk HIV negative women, evaluated the occurrence of hypertension and its association with HAART.
- Testosterone therapy for women with low androgen levels or body weight
- Polly Clayden, HIV i-Base
- Dr Dolan from the Massachusetts General Hospital, Boston, USA, presented findings from a double blind, placebo controlled study to evaluate the safety, efficacy and tolerability of testosterone administered to women with reduced androgen levels and low body weight.
- Nevirapine, pregnancy and adverse events
- Polly Clayden, HIV i-Base
- The findings of Kramer et al mirrors the published experience of nevirapine use in pregnancy in London (Edwards et al, HIV Medicine 2001) in which 4/30 women (13.3%) starting nevirapine during pregnancy experienced rash (2 women) or biochemical hepatitis (2 women) but otherwise nevirapine was well tolerated. It is also very encouraging to see no transmissions among the group of 125 pregnant women in this study.
- Prior nevirapine exposure for pregnant women can contribute to treatment failure
- Polly Clayden, HIV i-Base
- These studies confirm the efficacy of nevirapine to reduce mother-to-child transmission and to rapidly select resistance mutations. The novel finding that single dose nevirapine exposure can impact future outcome to such a dramatic extent must lead to a rapid change in policy especially in those countries rolling out combination therapy. The potential of NNRTIs as subsequent therapy for the mother must be protected with their use restricted to effective combinations only and with due consideration to their prolonged clearance which varies considerably between individuals.
- Conflicting findings with HAART use in pregnancy and prematurity
- Polly Clayden, HIV i-Base
- The data from the ECS, which overstate the risk of pre-term delivery by excluding deliveries by pre-labour Caesarean section, need to be re-evaluated with all deliveries included (with the understanding that elective pre-term Caesarian sections will also bias the data). Conversely the data from the Anti-retroviral Pregnancy Register may underestimate any effect, as only women exposed to any antiretroviral therapy are included.
- Antiretrovirals, mode of delivery and transmission risk
- Polly Clayden, HIV i-Base
- In an oral abstract presentation Dr David Shapiro presented data from the PACTG study looking at mother to child transmission rates among pregnant women with low viral loads. Data were collected from 3,081 women at 72 US centres between 1998 and 2002 and use of antiretrovirals, mode of delivery and viral load were evaluated in association with transmission risk.
- Tenofovir studies in children
- Simon Collins, HIV i-Base
- The authors concluded that TDF-containing combination antiretroviral therapy is virologically active for at least 48 weeks in heavily treatment-experienced children, but can be associated with decreased bone mineral density. Further efficacy, toxicity, and tolerability studies are ongoing. The relationship between lower BMD and virologic response should also be studied. Substantially reduced BMD in children has already been reported (Vignano et al) and been linked to HAART therapy and should be taken very seriously.
- Increase of non-AIDS defining cancers in HOPS cohort
- Simon Collins, HIV i-Base
- Screening availability is general by specialist referral in HIV clinics in the UK. However, cost effectiveness should be higher than for cervical screening as the population at risk is easily defined. Although the natural history can lead to regression, this is only in younger men and rarely in men over 30 years old.
- HIV/HCV coinfection: superiority of pegylated interferon plus ribavirin, but lower response rate compared to mono-infected patients, especially for genotype-1
- Simon Collins, HIV i-Base
- Although HCV-monoinfected patients with an HCV genotype of 1 can expect a 40–45% chance of an SVR using pegylated interferon/ribavirin, HIV/HCV-coinfected patients with genotype-1 are looking at an SVR of 14% (ACTG) to 29% (Apricot). The results in co-infected patients with genotypes 2/3 infections were encouraging with 45% (Ribavic) to 62% (Apricot) SVRs. However, it is important to note that all patients received 48 weeks of therapy. It is likely that, in order to achieve an optimal response, all genotype 2/3 HIV/HCV co-infected patients should receive 48 weeks of treatment with pegylated interferon/ribavirin.
- EDITORIAL
- The big story over the last month has been the ritonavir 400% "price hike" from Abbott in the US, which has provoked fury from activists and doctors alike. Although current prices will not increase for the moment in Europe the longer term implications are unclear at this stage, and it"s feared that things do not bode well for the cost of treatment and therefore treatment options.
- Abbott raises price of ritonavir in the US by over 400%
- Simon Collins, HIV i-Base
- The increase is seen as an attempt to regain a higher percentage of the limited budget available for HIV drugs in the US and may be one of the largest price increases announced for any medication in recent years. A spokesperson for Abbott could not say whether the company had recently increased the price of any of its other drugs so substantially in the last few years.
- Development of T-1249 put on hold
- Simon Collins, HIV i-Base
- On 5 January 2004, Roche and Trimeris, the companies that are jointly responsible for developing the fusion inhibitor T-20 (enfuvirtide, Fuzeon) announced that they have put on hold the development programme of the pipeline compound T-1249. T-1249 is a second fusion inhibitor in development, and in early studies had shown the potential for greater potency, once-daily rather than twice-daily dosing and activity over T-20 resistant virus. As with other HIV drugs, resistance to T-20 develops unless it is used in a combination with other active drugs.
- Tenofovir/abacavir/3TC triple-nuke fails as maintenance regimen
- Simon Collins, HIV i-Base
- A research letter in the 13 December issue of the Lancet further highlighted the risk of using the triple nucleoside combination of abacavir/3TC/tenofovir, even as a as maintenance therapy. Serious concern over the potency of this combination led to the issuing of safety warning letters from Gilead and the EMEA last year, following significantly lower rates of viral suppression and higher rates of viral rebound in several studies.
- New data on viral load 'blips' and the link to replication
- Bob Huff, GMHC Treatment Issues
- You can be a "blipper" and still be chipper, suggests a study in the November 2003 issue of the Journal of Virology by Michele Di Mascio and her colleagues from the Los Alamos National Laboratory and the Aaron Diamond AIDS Research Centre in New York. Blips are usually thought of as occasional, transient episodes of low-level HIV RNA viraemia in someone who is adherent to their antiretroviral therapy and otherwise enjoys a well-suppressed viral load.
- Invirase and Fortovase: new dosing regimens approved by FDA
- The FDA approved, on 24 December 2003, new dosing regimens for the two available formulations of saquinavir, Invirase (hard gel capsule) and Fortovase (soft gel capsule). The newly approved dosing regimen for both Invirase and Fortovase is 1000 mg BID (twice a day) co-administered with ritonavir 100 mg BID.
- UK named-patient access to tipranavir
- The named-patient access to tipranavir that started in Autumn 2003 is still continuing.
- FDA labelling changes for indinavir (Crixivan)
- The following revisions to the package insert in the US were approved by the FDA in January 2004.
- Global Fund awards bring total to $2.1bn and supply ARVs to 700,000 people
- Graham McKerrow, HIV i-Base
- The third round of awards granted by the Global Fund to Fight AIDS, TB and Malaria amounted to another $623 million, bringing the total given and promised by the Fund to $2.1 billion over two years. The latest money given by the Fund is less than in the previous round, and less than was originally projected by the Fund.
- COMMENTARY: The Global Fund and treatment access in Latin America – a critical view
- Richard Stern, Agua Buena Human Rights Association
- The Global Fund to Fight AIDS, TB and Malaria offers promises and hope for many, but a view from the field in Latin America and the Caribbean indicates that when it comes to antiretroviral treatment access, the complications are many and the promises offered by the Fund are slow to be fulfilled.
- COMMENTARY: China starts long march against HIV
- Bernard Rivers, Aidspan, Beijing, November 2003
- Until recently, there was little evidence that the government of China was serious about AIDS, despite its own forecast that today’s one million people with HIV could reach at least 10 million by 2010. However, the Ministry of Health now appears willing to take some hesitant steps forward – although there is, as yet, little evidence that other ministries, or local government outside Beijing, are ready to act decisively.
- WHO guidelines for use of ARVs in resource-poor settings
- On 1 December 2003, the World Health Organisation launched the 3 by 5 Initiative, a new effort to scale-up antiretroviral therapy in the developing world, with an initial target of reaching 3 million people by 2005. Guidelines for use of ARVs in resource-poor settings were also published.
- Millions will benefit after GSK and BI license generic manufacturers to produce AZT, lamivudine and nevirapine
- Graham McKerrow, HIV i-Base
- Two of the world’s biggest pharmaceutical companies have signed an agreement with a group of South African AIDS activists that will result in affordable medicines for millions of sub-Saharan Africans.
- Scaling up treatment access risks damaging national health systems, says WHO/UK report
- Graham McKerrow, HIV i-Base
- The HIV epidemic is increasing demands on already struggling health systems and undermining their capacity to provide services, says a review of the provision of antiretroviral therapy in poor countries, published in November 2003 by the World Health Organisation and the UK government. The problem is that the extra pressure leads to the breakdown of services because of “the attrition of health sector workers”.
- Importance of dietary management in treating lipid disorders: soy diets may offer comparable effect as statins
- Graham McKerrow, HIV i-Base
- Studies in the United States and Canada emphasise the importance of dietary management in the treatment of lipid disorders, which can be just as effective as the use of statins.
- Human histology and persistence of various injectable filler substances for soft tissue augmentation
- An increasing number of soft tissue filler substances have been introduced to the beauty market outside the US which lack experimental and clinical data in support of their claim. Ten commercially available filler substances were examined for biocompatibility and durability: 0.1 cc of each substance was injected deep intradermally into the volar forearm of one of the authors and observed for clinical reaction and permanence.
- Treating oral hairy leukoplakia with high dose valacyclovir
- Graham McKerrow, HIV i-Base
- A study of 19 people (73% on HAART) with HIV-associated oral hairy leukoplakia (OHL) and Epstein-Barr virus (EBV) replication found that treatment with high dose oral valacyclovir (Valtrex), one gram every eight hours for a month, could inhibit productive replication of EBV. Walling and colleagues at the University of Texas report that in the majority of cases OHL was resolved and EBV replication was halted.
- Should treatment be started in all HIV-infected newborns?
- Polly Clayden, HIV i-Base
- A report from the HIV Paediatric Prognostic Markers Collaborative Study Group, published in the 15 November 2003 issue of the Lancet, evaluated the risk of progression to AIDS - with regards to CD4% or viral load and age - of HIV-infected newborns in the first year of life.
Vol. 5, No. 9/10 - October/November 2004
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CONFERENCE REPORT:
10th BHIVA Autumn Conference
TREATMENT ACCESS
ANTIRETROVIRALS
METABOLIC CHANGES
HEPATITIS COINFECTION
PREGNANCY AND MTCT
PAEDIATRIC CARE
OPPORTUNISTIC INFECTIONS
OTHER NEWS
ON THE WEB
Vol. 5, No. 7/8 - August/September 2004
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CONFERENCE REPORT:
XV International World AIDS Conference,
11-16 July 2004, Bangkok.
BANGKOK: ACCESS TO TREATMENTS
BANGKOK: IVDU ISSUES
BANGKOK: PREGNANCY AND MTCT
BANGKOK: ANTIRETROVIRALS
BANGKOK: SIDE EFFECTS
BANGKOK: PK AND DRUG INTERACTIONS
BANGKOK: COINFECTION
BANGKOK: PAEDIATRICS
BANGKOK: TRANSMISSION
TREATMENT ACCESS
ANTIRETROVIRALS
PERIPHERAL NEUROPATHY
HEPATITIS COINFECTION
OTHER NEWS
CORRESPONDENCE
ON THE WEB
MEETINGS AND COURSES
PUBLICATIONS AND SERVICES FROM i-BASE
Vol. 5, No. 6 - July 2004
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CONFERENCE REPORTS
XIII International HIV Resistance Workshop,
8-12 June 2004, Tenerife, Canary Islands
CONFERENCE REPORT
Keystone HIV Pathogenesis and Vaccine Development Conference,
12-18 April 2004, British Columbia, Canada
TREATMENT ACCESS
ANTIRETROVIRALS
DRUG INTERACTIONS
WOMEN"S HEALTH
PAEDIATRIC CARE
PRIMARY INFECTION
ON THE WEB
Vol. 5, No. 5 - June 2004
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CONFERENCE REPORTS
10th Anniversary Conference of the British HIV Association (BHIVA) Cardiff, 15–17 April 2004
ANTIRETROVIRALS
RESISTANCE
SIDE EFFECTS
LIPODYSTROPHY
PRIMARY INFECTION
IMMUNE BASED TREATMENT
HEPATITIS COINFECTION
OTHER NEWS
CORRESPONDENCE
ON THE WEB
Vol. 5, No. 4 - May 2004
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CONFERENCE REPORTS
5th International Workshop on Clinical Pharmacology of HIV Therapy, 1-3 April 2004, Rome, Italy
This international meeting continues to provide a lively and important platform for a wide range of research.
Although not yet posted as HTB went to press, the programme and abstract book from this meeting are due to be posted to:
http://www.virology-education.comUnless otherwise stated all references are to the Programme and Abstracts for the 5th International Workshop on Clinical Pharmacology of HIV Therapy, Rome, March 2004.
2nd European HIV Drug Resistance Workshop, 11-13 March 2004, Rome, Italy
Further reports from 11th Retroviruses Conference, 8-11 February 2004
TREATMENT ACCESS
ANTIRETROVIRALS
DRUG INTERACTIONS
LIPODYSTROPHY
HIV AND PREGNANCY
PAEDIATRICS
OPPORTUNISTIC INFECTIONS
Vol. 5, No. 3 - April 2004
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EDITORIAL
TREATMENT ALERT
CONFERENCE REPORTS
CONFERENCE REPORTS
11th Conference on Retroviruses and Opportunistic Infections (CROI)
8-11 February 2004, San Francisco
CROI: ACCESS
CROI: PK AND DRUG INTERACTIONS
CROI: ANTIRETROVIRALS
CROI: RESISTANCE
CROI: SIDE EFFECTS
CROI: METABOLIC COMPLICATIONS
CROI: WOMEN"S HEALTH
CROI: PREGNANCY, MATERNAL HEALTH AND MTCT
CROI: PAEDIATRICS
CROI: OPPORTUNISTIC INFECTIONS
CROI: HEPATITIS COINFECTION
Vol. 5, No. 1/2 - January / February 2004
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ANTIRETROVIRALS
TREATMENT ACCESS
LIPODYSTROPHY AND METABOLIC COMPLICATIONS
OPPORTUNISTIC INFECTIONS
PAEDIATRICS