CDC Issues Interim Guidance for Clinicians Considering the Use of Preexposure Prophylaxis for the Prevention of HIV Infection in Heterosexually Active Adults

via Morbidity and Mortality Weekly Report

In the United States, an estimated 48,100 new human immunodeficiency virus (HIV) infections occurred in 2009 (1). Of these, 27% were in heterosexual men and women who did not inject drugs, and 64% were in men who have sex with men (MSM), including 3% in MSM who inject drugs. In January 2011, following publication of evidence of safety and efficacy of daily oral tenofovir disoproxil fumarate 300 mg (TDF)/emtricitabine 200 mg (FTC) (Truvada, Gilead Sciences) as antiretroviral preexposure prophylaxis (PrEP) to reduce the risk for HIV acquisition among MSM in the iPrEx trial, CDC issued interim guidance to make available information and important initial cautions on the use of PrEP in this population.

Those recommendations remain valid for MSM, including MSM who also have sex with women (2). Since January 2011, data from studies of PrEP among heterosexual men and women have become available, and on July 16, 2012, the Food and Drug Administration (FDA) approved a label indication for reduction of risk for sexual acquisition of HIV infection among adults, including both heterosexuals and MSM.* This interim guidance includes consideration of the new information and addresses pregnancy and safety issues for heterosexually active adults at very high risk for sexual HIV acquisition that were not discussed in the previous interim guidance for the use of PrEP in MSM.

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

HIV/AIDS: WHO issues guidelines on PrEP

via PlusNews

NAIROBI/KAMPALA, 20 July 2012 (PlusNews) - Days after US officials gave unprecedented approval for the use of an antiretroviral drug by HIV-negative people to reduce the risk of their acquiring the HI virus, the World Health Organization (WHO) has issued guidance to governments on so-called pre-exposure prophylaxis (PrEP).

WHO's guidelines, which call for a cautious and gradual roll-out, will likely see many countries begin to add PrEP to the growing arsenal of tools in the fight against HIV.

The guidance is based on evidence from clinical trials on the daily use of ARVs for HIV prevention among high-risk HIV-negative people. A 2010 study - Iniciativa Profilaxis Preexposicion, or Prexposure Prophylaxis Initiative (iPrEX) - among men who have sex with men (MSM) and transgender people, found that a daily dose of the ARV, Truvada - a combination of emtricitabine and tenofovir disoproxil fumarate - reduced HIV infection risk by about 42 percent.

The 2011 Partners PrEP study in Kenya and Uganda concluded that a daily dose of Truvada, taken by the HIV-negative partner in a heterosexual HIV-discordant relationship - where one sexual partner is infected and the other is not - could reduce the risk of HIV transmission by up to 75 percent.

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

SA docs welcome US approval of ARV as a prevention tool

via health-e news, by Anso Thom

South African HIV Clinicians have welcomed an announcement that the Food and Drug Administration (FDA) in the United States has approved the use of an antiretroviral by sexually active HIV-negative men and women as a method of reducing the risk HIV infection in adults.

The debate around the use of ARVs as prevention surfaced several years ago with a number of studies showing it to be effective and safe. In what has been described a possibly a major turning point, the FDA announced this week that it had approved the use of tenofovir disproxil fumarate/emtricibatine (TDF/FTC), also known as Truvada, in HIV prevention.

TDF/FTC has been used to treat HIV infection since 2004, in combination with other antiretroviral drugs.

The FDA announcement means the pill can be taken by uninfected men and women a day before and after exposure (know as pre-exposure prophylaxis or PrEP).

Dr Francesca Conradie, president of the Southern African HIV Clinicians Society welcomed the announcement.

She said there was no one single answer to the prevention of HIV infection, no “one size fits all”.

 Read the rest.



[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

A Qualitative Study of Provider Thoughts on Implementing Pre-Exposure Prophylaxis (PrEP) in Clinical Settings to Prevent HIV Infection

via PLoS ONE, by Emily A. Arnold, Patrick Hazelton, Tim Lane, Katerina A. Christopoulos, Gabriel R. Galindo, Wayne T. Steward, Stephen F. Morin

ABSTRAST

Background

A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States.

Methods

Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time.

Results

Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations.

Conclusions

While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP in their practice.

Read the full text here.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

The road to PrEP: trials, regulation and roll-out

via aidsmap.com, by Gus Cairns

Within the next three years, up to 33,000 people may take part in 22 different studies worldwide to demonstrate the feasibility, or otherwise, of pre-exposure prophylaxis (PrEP) to prevent HIV, the IAPAC evidence summit, Controlling the HIV epidemic with antiretrovirals, was told on 12 June.Some of these studies are underway but others are still in the design stage or in need of funding.

Dr Jim Rooney of Gilead Sciences, the manufacturer of tenofovir (Viread) and Truvada (tenofovir and FTC), the products being tested in the vast majority of these studies, told the meeting that up to 13,000 men who have sex with men (MSM) could end up being involved in 14 different studies and up to 19,500 heterosexual men and women in eight studies. These studies were particularly crucial in establishing whether PrEP might be less, or more, effective in open-label settings than in randomised placebo-controlled trials.

Some of these are ongoing or open-label extensions of studies such as Partners PrEP in 4758 sero-different couples in Kenya and Uganda, or iPrEx OLE (Open Label Extension) in 1500 MSM in six countries.  

Others are just beginning, such as the IPERGAY study of intermittent PrEP in gay men in France. While it is planned that this could eventually include 1900 men, researcher Bruno Spire told the IAPAC meeting that 300 participants had to be enrolled by February 2013 if the next phase of the study was to be funded, and that recruitment had been rather slow so far, partly because of "ideological obstacles" to there being a placebo arm.

Similarly, Dr Sheena McCormack of the UK's Medical Research Council told the meeting that, while the planned UK PROUD study of immediate versus delayed PrEP could eventually include 5000 MSM, only a pilot project in 300 MSM has so far been proposed, with a tentative start date (if the protocol is agreed) in October 2012. 

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

Tenofovir Shortage Exposes Problems in Health Management in South Africa

via allafrica.com, by Khopotso Bodibe

The recent shortage of a crucial antiretroviral drug, Tenofovir, is but just a symptom of an underlying general problem of health management in South Africa. Part of this is the lack of oversight on drug supplies and availability by the national Health Department.

At the heart of the seven months' long shortage of Tenofovir, which started running out in October last year is nothing else, but poor planning. For the whole of last year, the Health Department had a donated stock of the drug from the United States' government and retained two pharmaceutical companies, Aspen Pharmacare and Sonke Pharmaceuticals to produce a tiny fraction of the supply.

It was only when small quantities of the donated stock of Tenofovir were left that the Health Department urgently requested the two drug manufacturers in November to increase their production and supply 100 % of the stock, with Aspen Pharmacare responsible for producing 70% and Sonke Pharmaceuticals 30% of the required Tenofovir packs for an estimated 1.2 million patients. But the two failed to meet the demand at short notice, leaving patients in dire straits. Director of Section 27 and executive member of the Treatment Action Campaign, Mark Heywood, says this demonstrates a general lack of planning by the Health Department to address drug shortages in the country.

"Planning is absolutely crucial. If I was the Minister of Health, then I would instruct that the relevant official in the Department of Health has a monthly meeting with the pharmaceutical companies, with key people in some of the provinces just to assess on an on-going basis, not necessarily because there's a crisis, but just to make sure that they are looking at what are the drugs are the drugs in the system, are the drugs in the pipeline, are we getting to people, where is the weak point in the chain? If you put that type of system in place, then we wouldn't be facing what we are facing now", according to Heywood.

The recent shortages of Tenofovir, for example, occurred as a result of the Health Department not informing the contracted drug manufacturers in good time that a shortage was looming. Thus, they were not able to produce the required amounts. In addition, Aspen Pharmacare and Sonke Pharmaceuticals neglected to inform the Health Department that producing 1.2 million packs of Tenofovir within the required time would not be possible.

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

HIV Drug Trial in South Africa Draws Concerns

via allafrica.com, by Anso Thom

AIDS activists and researchers are at loggerheads over the planned South African trial of a lower dose version of the controversial antiretroviral stavudine, which has in the past been responsible for debilitating side-effects in HIV patients.

The main adverse effect is peripheral neuropathy, which can be corrected by reducing dosage.

The symptoms of peripheral neuropathy include burning, stiffness, prickling, tingling, and numbness or a loss of feeling in the toes and soles of the feet. Sometimes the nerves in the fingers, hands, and wrists are also affected.

Stavudine is also one of the most likely ARVs to cause lipodystrophy, and for this reason it is no longer considered an appropriate treatment for most patients in developed countries and is no longer recommended by the World Health Organisation.

However, due to its low price, it is still widely used in the developing world.

Lipodystrophy is the redistribution of fat in the body, which manifests as excess, or lack of, fat in various regions of the body. People can have sunken cheeks and/or "humps" on the back or back of the neck (also referred to as buffalo hump).

In the one camp, the Treatment Action Campaign, Medecins Sans Frontieres (Doctors without borders) and the Treatment Action Group have serious concerns about the proposed trial.

They are concerned that stavudine is more toxic than tenofovir (the drug which replaced stavudine in the government treatment programme), making it an inferior treatment.

Patients' poor tolerance means that they are more likely to not adhere to treatment and will have to be switched to more expensive second-line treatment when they fail first line treatment.

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

Improving the Production of Tenofovir

via AllAfrica.com, by Khopotso Bodibe

The national health department has contracted additional pharmaceutical manufacturers to make up the critical shortage of the antiretroviral tenofovir across the country.

HIV clinicians and doctors warned last week that the continued stock out of tenofovir and the failure to advise health workers on how to deal with it was a looming disaster.

Reports of stock outs go as far back as October last year with the explanation given that the drug suppliers Aspen Pharmacare and Sonke Pharmaceuticals were not able to meet the demand once they were awarded the tender.

It emerged this week that the national health department had directed provinces to order tenofovir from two additional suppliers.

Dr Anban Pillay, Cluster Manager for Financial Planning and Health Economics in the national health department, confirmed that Adcock Ingram Pharmaceuticals as well as Cipla Medpro Pharmaceuticals were now also supplying tenofovir to provinces.

"The procurement rules allow that. Obviously, there's a good reason for it. The current suppliers are not able to keep up with the total need. So, for the balance they are allowed to go out and get it from other suppliers," Pillay explained.

Aspen Pharmacare and Sonke Pharmaceuticals were initially contracted to supply tenofovir to the public sector antiretroviral programme, but they have struggled to meet the demand.

"The split between Aspen Pharmacare and Sonke is a 70 30 split, meaning that 70% of the volume goes to Aspen and 30% to Sonke. Unfortunately, Sonke hasn't been able to ramp up its production to the level that is required to meet the demand," said Pillay.

The national health department estimates that tenofovir is dispensed to about 1.2 million patients every month.

Aspen Pharmacare was only able to increase its production to the 70 per cent tender requirement in recent weeks. With Sonke Pharmaceuticals not being able to supply its quota of the tender, the supplies from Aspen Pharmacare were not sufficient to serve all patients on tenofovir, resulting in the shortage.

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

AIDSmeds: Adherence Challenges in Intermittent HIV PrEP Study

via AIDSmeds.com

Intermittent use of Truvada (tenofovir plus emtricitabine) as pre-exposure prophylaxis was associated with poor adherence, compared with daily use of the tablet to prevent HIV infection, according to results of a small clinical trial published in the online scientific journal PLoS ONE.

Using electronic pill caps, the Kenyan study found that the adherence rate associated with daily PrEP use was 83 percent. Among those using intermittent therapy—Truvada taken on Monday, Friday and within two hours following sexual intercourse—the adherence rate was 55 percent. Among those who only took Truvada within two hours following sexual intercourse, the post-coital adherence rate was only 26 percent.

Truvada as PrEP was recently recommended for U.S. Food and Drug Administration (FDA) approval by the Antiviral Drugs Advisory Committee. The recommendation is based on data from several clinical trials, all exploring the safety and efficacy of Truvada PrEP used daily.

There has been interest in exploring alternative dosing strategies, notably scheduled and as-needed intermittent use of the drug. Experts hypothesize less frequent dosing may reduce the risk of side effects and prove easier for people to use, in light of the poor adherence that has been noted in clinical trials evaluating daily use of Truvada.

Read the Rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

FDA Hearing on Truvada as PrEP - Watch the Webcast!

On May 10, 2012 the FDA Antiviral Drug Advisory Committee strongly recommended that emtricitabine/tenofovir disoproxil fumarate (TDF/FTC or Truvada) be approved for use as pre-exposure prophylaxis (PrEP) among sexually active adult men and women – particularly gay men and other MSM, serodiscordant heterosexual couples, and other individuals at high risk. It is likely the FDA will follow the committee’s recommendations and issue a new prevention indication for the use of Truvada by mid June.

Watch the recorded webcast here.

Check out the slide presentations here.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position. Please look for us on Facebook here www.facebook.com/MappingPathways and you can follow us on Twitter @mappingpathways as well.]

New Project Initiative Involving PrEP Research Throughout California

via California HIV/AIDS Research Program

In April 2012, the California HIV/AIDS Research Program (CHRP) of the University of California awarded grants totaling $11.8 million to three collaborative teams of investigators to test a potential HIV prevention medication among high-risk HIV-uninfected persons in several communities throughout California. The studies also will examine new strategies to engage and retain HIV-infected persons in care and treatment. Both of these strategies are expected to help curb the HIV epidemic in California.

Two of the collaborative teams of investigators will offer PrEP (pre-exposure prophylaxis with antiretroviral drugs) to high-risk uninfected men who have sex with men (MSM) and to transgender women (male to female transgendered persons) located in Los Angeles, San Diego, and Long Beach over the next four years. These investigators also will assess the implementation of TLC+ (testing and linkage to care plus treatment), a strategy to locate, engage, and retain HIV-infected persons in care and start them on life-saving treatment for their HIV infection

A third grantee consortium will not fully implement PrEP or TLC+ at the present time, but will instead plan and pilot PrEP/TLC+ implementation strategies for young MSM of color located in Oakland, Richmond, Berkeley, and other East Bay Area locations.

PrEP involves the provision of antiretroviral drugs and risk reduction counseling to high risk uninfected persons to prevent future HIV infection among those who potentially may be exposed to the virus. Previous international research trials have shown that PrEP has been very effective in preventing new HIV infections among MSM and selected other risk populations, but only when taken as prescribed in addition to ongoing risk reduction counseling. Recent studies have suggested that the mixed results found for some populations may be due to a lack of consistent adherence to the medication, leading to suboptimal or ineffective levels of drug in the body. In addition, other studies have suggested that identification and rapid institution of antiretroviral therapy for people infected with HIV not only improves survival of those treated, but also lowers the level of HIV virus in the community and might ultimately reduce HIV transmission rates.

This will be the largest PrEP/TLC+ demonstration project initiative in the U.S., and will be the first to test PrEP in several communities throughout California. In these demonstration projects in California, PrEP will be delivered as part of a comprehensive prevention package including risk reduction counseling, sexually transmitted infection screening, and other components. Daily Tenofovir/FTC (Truvada®, a tenofovir/emtricitabine two-drug combination pill manufactured and distributed by Gilead Sciences, Inc. of Foster City, CA) based PrEP will be offered to eligible uninfected high-risk men who have sex with men, as well as to transgender women. Gilead Sciences will provide the drug product (brand name Truvada®) to support these studies. The studies will adhere to safety and implementation guidelines issued by the Centers for Disease Control and Prevention.

Read the Rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Researchers Explain the Role of Adherence in PrEP Trials at CROI 2012

via AidsMap.com, by Gus Cairns

Adherence makes all the difference to the efficacy of pre-exposure prophylaxis (PrEP), the 19th Conference on Retroviruses and Opportunistic Infections (CROI) heard today.

Further data were presented from two trials of PrEP (giving anti-HIV drugs to HIV-negative people to prevent infection), which announced dramatically different results last year.

In April 2011, the FEM-PrEP study found that giving HIV-negative women tenofovir/FTC (Truvada) pills to prevent their acquiring HIV was totally ineffective: there was no difference in HIV incidence between women taking Truvada and women taking placebo.

In July 2011, however, the Partners PrEP study found that Truvada was 73% effective in preventing HIV transmission between heterosexual partners of different HIV status.

How do we explain why giving HIV-negative women antiretroviral pills made no difference to the HIV infection rate in one trial, but prevented at least two in every three infections in the other? The difference, it appears, is that in the Partners PrEP trial, adherence to the study medication was very high, whereas in FEM-PrEP, despite counselling and support, less than half the women took their PrEP pills regularly.    

The Partners PrEP study

The Partners PrEP study enrolled 4758 serodiscordant couples in Kenya and Uganda; the HIV-negative partner was female in 38% of couples. This study had three arms: a daily tenofovir pill, a daily Truvada pill, or placebo.

There were 17 infections in participants on tenofovir, 13 on Truvada and 52 on placebo. Efficacy overall was 75% in those assigned Truvada and 67% in those assigned tenofovir, though confidence intervals (44% to 81% in tenofovir and 55% to 87% for Truvada) overlapped, so the efficacy of the two regimens was the same statistically. The same was true of efficacy observed in women (65%) and men (70.5%).     

Adherence according to pill counts of unused medication was 97%. A substudy (Donnell) compared tenofovir levels in the blood of 29 out of the 30 people who became infected in the two PrEP arms with levels in a random selection of 198 people who did not become infected.

Tenofovir was undetectable in the blood of 70% of the people who became infected but only 18% of the people who did not, indicating a ‘true’ adherence level of about 80% – and having a detectable level of tenofovir in the blood was associated with an 86% reduction in HIV risk in those taking tenofovir and a 90% reduction in those on Truvada.  

The FEM-PrEP study

In the FEM-PrEP study, 2056 HIV-negative women in South Africa, Kenya and Tanzania were randomised to take a daily Truvada pill or a placebo. The trial was stopped when an interim analysis found near-identical HIV infection rates in both trial arms. There were 33 HIV infections in women taking Truvada and 35 in women taking placebo; this translates into annual incidence rates of 4.7% and 5.0% respectively. This 0.3% difference is no difference at all, statistically speaking (hazard ratio 0.94, 95% confidence interval 0.59 to 1.52, p = 0.81). 

Participants in the study said they took their pills 95% of the time and adherence as measured by pill count was 85%. However when drug levels of tenofovir and FTC were measured in the blood of women assigned to Truvada, the investigators found that less than 50% of the women who should have been taking the drug had actually done so in the last 12 days, and less than 40% within the last 48 hours.

In infected participants, 26% had detectable levels of tenofovir in their blood in the last visit before they tested HIV positive, 21% at the visit they tested positive, and 15% at both visits; in non-infected participants whose samples were taken at the same visits they were 35%, 38% and 26% respectively.

Read the Rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

CROI 2012: Results of iPrEx Trial Show Effective Dosage of PrEP

via AidsMap.com, by Gus Cairnes

Further testing of drug levels in the blood and immune cells of gay men participating in the iPrEx trial of tenofovir/FTC (Truvada) pre-exposure prophylaxis (PrEP) has found that HIV infection in men assigned to Truvada was associated with a lapse in taking the drug after initially adhering reasonably well, rather than never having taken it at all, which was what the researchers originally thought. The research was presented at the 19th Conference on Retroviruses and Opportunistic Infections (CROI), in Seattle.

The testing also found that only a minority of participants appeared to be taking their drugs as prescribed, seven days a week, but that protection levels were very high – in the order of 96% of infections prevented – as long as participants took four or more doses a week.

Drug levels plummet three months before infection

 The results of iPrEx, a large multi-country study of PrEP in gay men, were announced in 2010 and showed an overall efficacy of 42% – in the trial subjects as a whole, four out of ten HIV infections that would otherwise have happened were prevented if subjects were given Truvada pills to take daily rather than placebo pills. When drug levels were tested in the 48 participants who became HIV-infected on Truvada, and a random sample of uninfected participants, it was found, perhaps not surprisingly, that drug was detectable in only 10% of the infected participants but also, perhaps more surprisingly, in only 50% of the uninfected ones.

New measurements have now looked back at drug levels in stored samples in the months prior to infection and compared with drug levels in the same time period in uninfected participants. In the uninfected participants, consistently 45% or so had detectable drug in their samples across the whole length of the study – confirming that at least half of the participants simply never took their pills. In the infected participants average adherence rates started off the same as in the uninfected. They showed a slight decline in the first year of the trial but then declined to 10% in the three months preceding infection. This suggests a role for quarterly adherence reinforcement.

What levels of tenofovir are protective?

 The researchers also wished to find out what levels of tenofovir in the blood were associated with protection against HIV. They did this by comparing drug levels in iPrEx participants with drug levels in a small study called STRAND, presented at last year’s conference (Liu),which gave participants directly-observed doses of tenofovir twice, four time or seven times a week and then measured drug levels in their hair. By then comparing the levels of protection seen in participants with specific drug levels in iPrEx, the researchers were able to compute what drug level was protective.

In iPrEx the average drug levels seen in infected people were consistent with less than one dose of tenofovir a week, but drug levels in those who were not infected were consistent with only about three doses a week. Only 18% of iPrEx participants had drug levels consistent with taking seven doses a week. The investigators used very sensitive tests to look at levels of metabolised tenofovir inside cells and found that a reduction of 90% in the risk of HIV infection correlated with a drug level of 16 femtomols per mol (fm/M – 16 in every million billion molecules by weight). The average level associated with seven doses a week in STRAND was about 38 fm/M and with four doses a week about 32 fm/M.

This enabled them to calculate that the protection offered by taking four doses of tenofovir a week was high, and more or less the same as taking seven doses – that is, in the order of 96%, with a minimum likely protectiveness of 90%. They also calculated that absolutely perfect adherence would offer 99% protection. Taking two doses a week (consistently) would still offer 72% protection, though within wide confidence intervals (56% to 96%) while the 42% level of protection actually seen in iPrEx was consistent with participants taking, on average, one dose a week.

This study has important limitations. STRAND did not measure FTC levels so the iPrEx researchers could not calculate what extra protection was offered by that drug. They also could not measure drug levels at the actual moment of exposure – they were measured at anything between 15 and 90 days after infection. And of course the ‘number of doses a week’ measure is purely an average – most participants probably had much more irregular patterns of taking their pills, with (amongst the 50% who took it at all) periods of good adherence interspersed by periods off drug, maybe correlated with times on and off sex. But it does give a guide to the likely minimum levels of tenofovir that people need to maintain in order to be protected from HIV.



[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

British HIV Association: Revised Guidelines for Antiretroviral Therapy

viaHivandHepatitis.com, by Liz Highleyman 

The British HIV Association (BHIVA) has issued revised guidelines for antiretroviral therapy (ART) for adults and for pregnant women and prevention of mother-to-child HIV prevention. Comments are currently being accepted.

ART for Adults

 

The draft for adults includes guidance on starting ART in treatment-naive patients, supporting people on treatment, and managing people who experience virological failure. The guidelines also cover special considerations for specific patient populations.

The guidelines are available on the BHIVA website, which features an online form for comments, and published in the January 2012 issue of HIV Medicine. The deadline for feedback is March 5, 2012.

As described in an overview by Aidsmap, the revised guidelines recommend that clinicians should discuss with all HIV positive patients the growing evidence that effective ART reduces the likelihood of HIV transmission to sexual partners. However, evidence to date -- for example, recent findings from study HPTN 052 showing a 96% risk reduction -- mainly concerns heterosexual couples having vaginal sex.

Patients should be informed of the prevention benefits of ART even if they do not yet need treatment for their own health because their CD4 T-cell count has not fallen below 350 cells/mm^3.

Unlike the latest U.S. guidelines -- which raised the treatment initiation level to 500 cells/mm^3 -- BHIVA kept the 350 cells/mm3 threshold for most patients, though people with certain coinfections and other risk factors (e.g., hepatitis B or C, HIV-related kidney disease or neurocognitive impairment) may benefit from starting sooner.

BHIVA came down in favor of tenofovir/emtricitabine (the drugs in the Truvada combination pill) as the favored dual nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) component of ART. U.S. guidelines also deem tenofovir/emtricitabine as the "preferred" NRTI combo, although the new European AIDS Clinical Society (EACS) guidelines rank tenofovir/emtricitabine and abacavir/lamivudine (the drugs in Epzicom) as equals.

BHIVA and the U.S. panel both demoted abacavir due to concerns about lower effectiveness for people with high viral load and elevated cardiovascular risk; tenofovir, however, has been linked to kidney impairment. All guidelines authorities agree that individual risk factors should be taken into account when selecting antiretroviral drugs.

BHIVA lists drugs in 3 classes as preferred third agents: the NNRTI efavirenz (Sustiva), the boosted protease inhibitors atazanavir (Reyataz) or darunavir (Prezista), and the integrase inhibitor raltegravir (Isentress).

Read the Rest.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

HIV Treatment's Effect on Fractures

viaAidsmap, by Michael Carter

Treatment with antiretroviral drugs reduces the risk of low-impact fractures, according to a case-controlled study published in the on-line edition of AIDS. Investigators compared fracture incidence between patients taking HIV therapy and non-treated individuals.

Despite the overall beneficial effect of treatment, the investigators found a complex relationship between drug class and duration of therapy and fracture risk.

Although there are concerns that tenofovir (Viread, also in the combination pills Truvada and Atripla) causes reductions in bone mineral density, the investigators found no robust evidence that the drug was associated with an increased risk of fracture.

“Our study identified an overall reduced risk for fracture in persons treated versus not treated with antiretroviral drugs for HIV infection,” write the authors.

With the right treatment and care, the prognosis of many HIV-positive patients is excellent. However, there is an increased prevalence of low bone mineral density in patients with HIV. The exact causes are uncertain, but may include HIV infection itself, the ageing of the HIV-infected population, and the side-effects of antiretroviral therapy. Nor are the clinical consequences clear. Some studies have shown that patients taking HIV treatment have an increased risk of fragility fractures, but such findings have been contradicted by other research.

Because of this continuing uncertainty, investigators in the US designed a case-controlled study involving patients who received HIV care between 1997 and 2008. The incidence of  low impact fragility fractures was compared between patients who received HIV therapy lasting at least twelve months and individuals with no history of antiretroviral treatment. The relationship between specific classes of antiretrovirals, individual drugs and duration of therapy and fracture risk was also examined. Finally, because of tenofovir’s association with low bone mineral density, the investigators compared fracture incidence between patients taking this drug and that seen among individuals taking abacavir (Ziagen, also in the combination pills Kivexa and Trizivir).

Read the Rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Tenofovir linked with risk of kidney damage

via UCSF, by Steve Tokar

Tenofovir, one of the most effective and commonly prescribed antiretroviral medications for HIV/AIDS, is associated with a significant risk of kidney damage and chronic kidney disease that increases over time, according to a study of more than 10,000 patients led by researchers at the San Francisco VA Medical Center (SFVAMC) and the University of California, San Francisco (UCSF).

The researchers call for increased screening for kidney damage in patients taking the drug, especially those with other risk factors for kidney disease.

In their analysis of comprehensive VA electronic health records, the study authors found that for each year of exposure to tenofovir, risk of protein in urine – a marker of kidney damage – rose 34 percent, risk of rapid decline in kidney function rose 11 percent and risk of developing chronic kidney disease (CKD) rose 33 percent. The risks remained after the researchers controlled for other kidney disease risk factors such as age, race, diabetes, hypertension, smoking and HIV-related factors.

For individual patients, the differences in risk between users and non-users of tenofovir for each year of use were 13 percent vs. 8 percent for protein in urine, 9 percent vs. 5 percent for rapidly declining kidney function and 2 percent vs. 1 percent for CKD. “However, these numbers are based on the average risks in our study population, and patients with more risk factors for kidney disease would be put at proportionately higher risk,” said principal investigator Michael G. Shlipak, MD, MPH, chief of general internal medicine at SFVAMC and professor of medicine and epidemiology and biostatistics at UCSF.

Patients were tracked for an average of 1.2 years after they stopped taking tenofovir. They remained at elevated risk for at least six months to one year compared with those who never took the drug, suggesting that the damage is not quickly reversible, said Shlipak. “We do not know the long-term prognosis for these patients who stop tenofovir after developing kidney disease,” he cautioned.

The implications for patients already on or starting antiretroviral therapy are “mixed,” said Shlipak. “The best strategy right now is to work with your health care provider to continually monitor for kidney damage. Early detection is the best way to determine when the risks of tenofovir begin to outweigh the benefits.”

Shlipak noted that HIV, itself, increases the risk of kidney damage, while modern antiretroviral treatments clearly reduce that overall risk. “Patients need to be aware of their kidney disease risks before they start therapy, and this should influence the medications that they choose in consultation with their doctor,” he said. “For an otherwise healthy patient, the benefits of tenofovir are likely to exceed the risks, but for a patient with a combination of risk factors for kidney disease, tenofovir may not be the right medication.”

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

FDA Priority Review of HIV-fighting drug by Gilead

viaSan Francisco Business Times, by Ron Leuty

A plan to use an approved HIV-fighting drug from Gilead Sciences Inc. as prevention to the AIDS virus will get priority review by the Food and Drug Administration, the agency said Monday.

The move means that the use of Truvada as a way to reduce HIV risk could be approved by June 15, rather than face a standard 10-month agency review.

If approved, Truvada would be the first drug for uninfected people to reduce the risk of acquiring HIV.

But Foster City-based Gilead faces a rough road on its way to winning approval of Truvada as a preventative treatment.

At least one AIDS patient advocacy group has opposed the plan. The Los Angeles-based AIDS Healthcare Foundation has argued that a study of 2,499 gay men showed that Truvada was effective as a preventative 44 percent of the time — not enough to warrant approval by the FDA, it claims — and that men might believe taking the drug is a fail-safe measure and will stop using condoms.

The group has set up a web page, called nomagicpills.org, created mailers and taken out ad space in newspapers to spread its message.

What's more, the FDA news closely follows a finding by researchers at the University of California, San Francisco, and the San Francisco Veterans Administration Medical Center that found that one of Truvada's ingredients, tenofovir, is associated with a significant risk of kidney damage and chronic kidney disease that increases over time.

The study of 10,000 patients used VA electronic health records to find that for each year of exposure to tenofovir, the risk of protein in urine rose 34 percent and the risk of developing chronic kidney disease increased 33 percent.

Protein in urine is a marker of kidney damage.

The study's principal investigator was Dr. Michael Shlipak, chief of general internal medicine at the VA Medical Center and a professor of medicine and epidemiology and biostatistics at UCSF.

Truvada faces a May meeting in front of the FDA’s antiviral drugs advisory committee, Gilead said in a press release. That panel will give a non-binding recommendation to the agency.

A once-a-day pill that combines two AIDS-fighting drugs, Truvada originally was approved by the FDA in 2004 for patients who already have HIV.

The drug, which costs $12,000 a year, registered sales of $1.4 billion in 2011.

Read the Rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Epidemiological impact of tenofovir gel on the HIV epidemic in South Africa

via pubmed.gov, by Williams BG, Abdool Karim SS, Karim QA, Gouws E.

Background

Tenofovir gel, an antiretroviral-based vaginal microbicide, reduced HIV acquisition by 39% in women in a recent randomized controlled clinical trial in South Africa.

Methods

To inform policy, we used a dynamical model of HIV transmission, calibrated to the epidemic in South Africa, to determine the population-level impact of this microbicide on HIV incidence, prevalence, and deaths and to evaluate its cost-effectiveness.

Results

If women use tenofovir gel in 80% or more of sexual encounters (high coverage), it could avert 2.33 (0.12 to 4.63) million new infections and save 1.30 (0.07 to 2.42) million lives and if used in 25% of sexual encounters (low coverage), it could avert 0.50 (0.04 to 0.77) million new infections and save 0.29 (0.02 to 0.44) million deaths, over the next 20 years. At US $0.50 per application, the cost per infection averted at low coverage is US $2392 (US $562 to US $4222) and the cost per disability-adjusted life year saved is US $104 (US $27 to US $181); at high coverage the costs are about 30% less.

Conclusions

Over 20 years, the use of tenofovir gel in South Africa could avert up to 2 million new infections and 1 million AIDS deaths. Even with low rates of gel use, it is highly cost-effective and compares favorably with other control methods. This female-controlled prevention method could have a significant impact on the epidemic of HIV in South Africa. Programs should aim to achieve gel use in more than 25% of sexual encounters to significantly alter the course of the epidemic.

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

Medicines Control Council Delays HIV Drug Trials in South Africa

via allAfrica.com, by Marian Shinn of the Democratic Alliance

For the past year two applications for field trials have been awaiting approval by the MCC. One is from the Centre for the Aids Programme of Research in South Africa (CAPRISA) for the second field trial of its world-acclaimed antiretroviral vaginal gel.

The second is from the University of the Western Cape-based International Centre for Innovation Partnerships for a field trial of a drug that could delay the onset of AIDS in HIV positive people. This drug is a breakthrough in the use of active extracts from the Sutherlandia indigenous plant.

Both these drug developments are funded, in part, by the Department of Science and Technology (DST).

A year ago CAPRISA's Tenofovir gel received world-wide scientific recognition based on the results of the successful pioneering field trial held in KwaZulu-Natal. In November 2010 the developers of this microbicide gel applied to the MCC for permission to launch a second field trial that would include women attending family planning clinics in KwaZulu-Natal.

Many of these women took part in the first trial and, since that first ended in March 2010, have been prevented from continuing to use the preventative gel because CAPRISA cannot obtain permission to start its new trial, for which about R28 million in funding from UNAids and the DST has been secured.

Read the rest.


[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]

HIV researcher plans new PrEP study

Via Now Chelsea, by Sam Spokony.

Few methods of HIV prevention have been as promising, or as controversial, as pre-exposure prophylaxis (PrEP). After a history of underground practice and off-label prescriptions, the approach has recently begun to receive serious attention from researchers, policy makers and health care advocates.

An outgrowth of post-exposure prophylaxis (or PEP, a short-term antiretroviral treatment that has been used since the early 90s to decrease the likelihood of HIV infection after exposure to the virus, either occupationally or through sex), PrEP is a similar antiretroviral that can be taken by HIV-negative individuals in order to help prevent them from seroconverting (being infected).

The results of a Phase III clinical study known as iPrEx were published in the New England Journal of Medicine on November 23, 2010. The study showed that, in a group of 2,499 gay men, PrEP — in the form of a combination of drugs under the brand name Truvada — was 44 percent effective in preventing HIV seroconversion.

Under the guidance of Dr. Roy Gulick (director of the Weill Cornell Medical College HIV Clinical Trials Unit), a new experiment called the NEXT (Novel Explorations of Therapeutics) PrEP Study will begin this fall. It will include 400 at-risk, HIV-negative gay men, and will take place over 48 weeks at 12 sites across the U.S. and Puerto Rico.

The NEXT PrEP Study will differ from iPrEx in that its primary experimental group will receive a daily regimen of the drug maraviroc (brand name Selzentry). The control group will receive Truvada, and two other experimental groups will receive combinations of maraviroc and either tenofovir or FTC (the two individual drugs that make up Truvada). A major goal of the study, along with testing the HIV-prevention efficacy of maraviroc, will be to gauge the side effects of the drug on participants.

“The longest any HIV-negative person has taken PrEP in a clinical study is 12 weeks,” Gulick told Chelsea Now in a July 23 phone interview. [This is inaccurate. The participants in iPrEx, for instance, were followed about 14 months - MP] “Now, since this is a drug we’re giving to healthy people, the next step is exploring further to prove that it is both safe and tolerable for them.”

Read the rest here.

[Content that is linked from other sources is for informational purposes and should not construe a Mapping Pathways position.]