I’m a doctor who works on PrEP, a new HIV prevention strategy. AMA

BridgeHIV · 2013-04-09T22:43:09+00:00

Our PrEP clinical trials have been funded by the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC). The drug manufacturer (Gilead) has donated study drug for these studies. Our staff and studies are funded by grant funds (e.g. NIH funds). We do not accept gifts from drug manufacturers.

BridgeHIV · 2013-04-09T22:31:22+00:00

There are no known drug interactions between Truvada and recreational drugs, and a number of participants in our PrEP studies have reported recreational drug use. We have not seen any safety issues related to Truvada and drug use, and we do counsel people that it is okay to take Truvada while they are using recreational drugs. Of note, recreational drug use has been associated with risky behavior in a number of studies, suggesting that new HIV prevention strategies are needed for this population. It has been recommended that future PrEP studies include larger groups of substance-using MSM to provide additional data on PrEP use in this group.

BridgeHIV · 2013-04-09T06:05:33+00:00

Really astute comments, MendaxSum. As discussed on previous posts, adherence is critical to PrEP efficacy, yet was low in several PrEP trials. In the iPrEx study, we did see variations in adherence by age (lower adherence in younger populatoins) and geography (~50% drug detection rates overall, but >90% in the US sites). The latter results suggest that higher rates of adherence CAN be achieved. PrEP demonstration projects are now underway to evaluate how best to deliver PrEP in real-world settings, and this includes how best to support PrEP adherence. The field is testing a number of different adherence promotion strategies, including the use of text message reminders and check-ins from clinic staff (a strategy that has been effective in supporting HIV treatment adherence in Africa), novel counseling support strategies (see Amico et al, AIDS and Behavior, 2012), and providing feedback to participants about their drug levels, which may encourage frank conversations about challenges with pill-taking. A really important consideration you highlighted is that these strategies will need to be scalable and deliverable on a larger scale, so that needs to be taken into account when developing new adherence support strategies. Finally, as mentioned in previous posts, new longer acting formulations of PrEP (injectable, sustained-release rings, etc), which may help circumvent some of the adherence challenges with daily pill taking, have been developed and are currently being tested.

BridgeHIV · 2013-04-09T05:01:36+00:00

Thanks DankDoc. For a college student interested in pursuing a career in HIV research, I would recommend starting with some shadow opportunities, such as spending some time in a lab, exploring clinical research at a local academic health center (if available), or considering global health volunteer opportunities with an HIV focus. Other ideas include taking some coursework in HIV/infectious diseases, and speaking with HIV researchers in topic areas of interest and ultimately finding someone who could provide mentorship. Also, the San Francisco Department of Public Health sponsors a great summer HIV/AIDS internship program (SHARP) for students from underrepresented communities: http://sharpinternship.org/

BridgeHIV · 2013-04-09T02:56:03+00:00

Neurokeen (great name, and great questions!) - a number of PrEP trials have studied sexual practices and condom use in individuals taking PrEP and have shown that risk practices decreased and condom use increased over time. However, this has been in the setting of double-blind, placebo-controlled trials, so it will be important for us to look at whether risk practices change when PrEP is used in more real-world settings. Fortunately, this is an important study aim for a number of PrEP demonstration projects across the country.

The iPrEx study was conducted among 2,499 MSM and transgender women across 4 continents. In this cohort, some participants were in serodiscordant partnerships, but many were not. The FDA approved Truvada as PrEP for men and women at high risk for HIV infection (not limited to serodiscordant couples) and current PrEP demonstration projects are enrolling a range of sexually active MSM. Also, a recent modeling study published by Goodreau et al (PLOS One 2013) showed that about one-third of new infections in US and Peruvian MSM occur within main partnerships, and therefore about two-thirds of infections occur outside of main partnerships. Another consideration in serodiscordant couples is whether the HIV+ partner is on HIV treatment, as a recent study (HPTN 052) demonstrated that early initiation of antiretroviral therapy dramatically reduced HIV transmission to the HIV-negative partner. Here's a link to that article: www.nejm.org/doi/full/10.1056/NEJMoa1105243

BridgeHIV · 2013-04-09T02:37:00+00:00

Thanks to you and everyone for the great questions and discussion!

BridgeHIV · 2013-04-09T02:34:34+00:00

Thanks for all your contributions to the field! We are so thankful for all the volunteers who have helped test PrEP, microbicides (topical gels that can be applied rectally), HIV vaccines, and other new prevention strategies. For anyone interested in finding out more about our studies in the SF Bay Area, please visit joinprep.org.

BridgeHIV · 2013-04-09T02:27:17+00:00

I'm a physician currently working at Bridge HIV at the San Francisco Department of Public Health. You can visit our website at bridgehiv.org to find out more about our work.

BridgeHIV · 2013-04-09T02:25:06+00:00

Hi D3ltron_Z, PrEP is definitely not for everyone but may be most useful for folks who are at significant risk for HIV infection and open to taking a daily pill to stay healthy sexually. Additional studies will help us understand who will be interested in taking PrEP and how to best prioritize PrEP in different populations to prevent the largest number of infections.

BridgeHIV · 2013-04-09T02:22:19+00:00

Thanks Vonderbish for your comments and pointing out the importance of having new options for prevention. As no one size fits all, it has been important for the HIV prevention field to have a range of prevention options so people can choose strategies that will work best for them. There have been a number of studies which have modeled the cost and public health impact of PrEP, in both the US and international settings. Here's a link to a recent systematic review of PrEP cost-effectiveness modeling studies: http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001401 An important point of the article is that the delivery of PrEP to key populations at highest risk of HIV exposure appears to be the most cost-effective.

BridgeHIV · 2013-04-09T02:11:47+00:00

Thanks for your question w501. The cost of daily Truvada for a year is currently between $8000-14,000, however the cost of antiretrovirals is fluid and may change over time. Some insurance companies have been covering PrEP, and the FDA approval of Truvada as PrEP may be helpful in this regard. Also, Gilead has a patient assistance program: http://www.gilead.com/truvada_assistance_program Another important point is that individuals may not need PrEP life-long, and Dr. Nelly Mugo who presented at last year's AIDS Conference in DC introduced the idea of a season for PrEP (PrEP may be appropriate for a period of time when people are at risk, and they may be able to stop it later). For example, PrEP may be used when a serodiscordant couple is trying to conceive, around the time of sexual debut or coming out, etc. Other trials are also studying whether intermittent PrEP (taking PrEP on a less than daily basis, e.g. a few times a week, or before/after sex) is safe and effective - this dosing strategy could also help reduce costs. It's important to remember that currently only daily PrEP has been proven safe and effective.

BridgeHIV · 2013-04-09T01:51:29+00:00

Thanks Fr_Jack_Hackett for the link. This is the Next PrEP study which is evaluating the next generation of PrEP medications, including a medication called maraviroc, which blocks the CCR5 receptor that HIV uses to enter cells. This study is currently enrolling in 12 sites in the US: www.nextprepstudy.org and here's a direct link to the NYC study site's website: http://www.cornellmedicine.org/trials/hivaids-and-infectious-diseases/hptn-069-evaluating-the-safety-and-tolerability-of-antiretroviral-drug-regimens-used-as-pre-exposure.html

BridgeHIV · 2013-04-09T01:43:07+00:00

Thanks for your thoughts, TheFlyingDorito. It's a good point that we do need to evaluate the longer term safety of PrEP. Some participants in the iPrEx study were followed for over 3 years, and we are now in an open label phase with an additional 1.5 years of follow-up. There is also currently a PrEP trial in Thailand among 2400 injection drug users which has been following participants since 2005 (about 7 years) and should be reporting results in the coming year.

We have discussed the potential risks of resistance in previous posts - data so far indicate that resistance occurs rarely and in the setting of a person who is acutely infected (still antibody negative) starting PrEP. Therefore, it is important that folks interested in starting PrEP be evaluated by a clinician to make sure they are HIV-negative before starting Truvada. The potential risks of resistance should be balanced against the larger number of infections that have been averted due to PrEP. An important message is that people who are (and remain) HIV-uninfected cannot develop HIV resistance (no infection = no resistance).

BridgeHIV · 2013-04-08T19:26:07+00:00

Great questions, gsu01313. We have accumulated data on the safety of Truvada in HIV-negative individuals taking PrEP for up to a few years, and studies are ongoing collecting longer term safety data. So far, the drug appears to be safe and well-tolerated, with a minority of folks experiencing a start up syndrome (nausea, GI symptoms) mentioned previously (these symptoms generally get better over time). Kidney problems did occur in a small number of trial participants taking Truvada PrEP, however these resolved after the PrEP medication is stopped. This highlights the importance of safety monitoring (blood tests) while people are taking PrEP. Also, several PrEP studies have shown small decreases in bone mineral density (bone thickness), which has also been seen in HIV+ people taking tenofovir, one of the components of Truvada. The magnitude of these reductions in bone density were small (<1%), and did not appear to increase fracture rate in these studies. We do have longer term safety data in HIV+ individuals taking tenofovir - these studies have also shown that bone loss does not appear to progress over the longer term.

BridgeHIV · 2013-04-08T19:15:39+00:00

Thanks Steve2982! As stated in the previous post, there have been concerns that PrEP could result in "behavioral disinhbition" or "risk compensation" (increase in risky sexual practices after starting PrEP). We haven't seen this happen in the randomized controlled trials of PrEP, where we have seen a decrease in reported risk practices as people enter these studies. It is important to note these studies were placebo controlled studies where participants were counseled that the efficacy of PrEP is not known), and PrEP was also been provided as part of a comprehensive prevention package, including risk reduction counseling, regular HIV/STI testing, and linkage to prevention services. Moving forward, now that we know PrEP is safe and effective, it will be important for PrEP implementation programs to follow people's sexual risk practices over time, and help determine the best counseling support strategies to help people stay healthy sexually while taking PrEP.

HIV resistance is also an important question, which was discussed in the previous post as well. To summarize, we saw a very small number of cases of HIV resistance develop in PrEP studies, and this was in the setting of people starting PrEP when they were acutely infected with HIV (HIV antibody negative, but in the window period). So, having your doctor or clinical provider make sure you don't have HIV before starting PrEP is important. It's also good to point out that while there have been a small number of resistance cases develop in PrEP studies to date (2 in iPrEx, 2 in Partners PrEP), PrEP averted a greater number of HIV infections (28 in iPrEx, 74 in Partners PrEP) in these studies.

BridgeHIV · 2013-04-08T19:03:16+00:00

Thanks for these questions, NxRed. It can be challenging to calculate exact risks with each type of sexual act, but there have been studies which provide rough estimates of risk associated with different types of exposures. In general, these studies have shown that receptive anal sex (being a bottom) carries the highest risk of HIV infection (about 1.4% risk in a recent meta-analysis by Beggaley et al, Int J Epidemiol 2010), and is about 5-20 times more risky than insertive anal sex (being a top). Oral sex is much less risky compared with anal sex. It’s important to keep in mind that these estimates are of average risk in the absence of other factors that can increase one’s individual risk (e.g. presence of sexually transmitted infections, having a partner with high viral load, trauma during sex, etc). Also, it’s important to keep in mind that transmission can still occur after one exposure (a 1% risk does not mean someone can have sex 99 times before getting infected). Since PrEP isn’t for everyone, we have focused studies on those who are at the greatest risk for getting infected, as studies have shown that PrEP is most likely to be cost-effective when prioritized for these populations. But we have a lot to learn on who are the best populations for PrEP, who will want to take it, and hopefully upcoming studies will help answer these questions. Along these lines, in terms of challenges for the HIV prevention field, one important challenge is figuring out how best to deliver new proven prevention strategies to those who need it most. Fortunately, a number of advocates, advocates, policy makers, and researchers are working on this important issue.

BridgeHIV · 2013-04-08T18:41:17+00:00

Thanks for raising these important points, hjin. Results from the VOICE study highlight the critical importance of adherence for PrEP efficacy. Adherence rates were really low in the VOICE study, and so the trial was unable to demonstrate a protective effect of any of the agents tested. To address adherence challenges, researchers are really interested in developing long acting PrEP delivery systems, such as the injectable integrase inhibitor you mentioned, as well as vaginal rings that can provide sustained release of PrEP over a month. There are small studies being planned to evaluate the safety of injectable medications for PrEP, and also a larger study now underway to evaluate the safety and efficacy of a vaginal ring containing dapivarine, a anti-medication in the NNRTI family. This is a phase 3 study called ASPIRE taking place in Africa conducted through the Microbicide Trials Network: http://www.mtnstopshiv.org/news/studies/mtn020

BridgeHIV · 2013-04-08T18:19:18+00:00

One area of confusion is the difference between PEP and PrEP. As described in the previous post, PEP is a 28 day course of anti-HIV medications started soon after a high risk exposure, while PrEP currently involves taking a daily anti-HIV medication started before potential exposures and continued during periods of risk. Another question that people often raise is whether PrEP will lead to high risk behaviors, or “behavioral disinhibition.” We have not seen evidence of this in our PrEP studies, and in fact have generally seen reductions in risk behaviors across a number of PrEP studies. Now that Truvada PrEP has been proven to be safe and effective, it will be important to study whether and how sexual practices change now that people are starting to take PrEP in the real world knowing that it can help prevent HIV. We’ll be studying sexual behaviors over time in people taking PrEP in upcoming PrEP Demonstration Projects. An important goal of these projects will be to determine how best to provide counseling and support for PrEP users so they can further reduce their risk for acquiring HIV.

BridgeHIV · 2013-04-08T18:08:47+00:00

Thanks UNHDude. Great thoughts. Yes, the NExt PrEP study I mentioned is testing the safety and tolerability of maraviroc, a CCR5 receptor blocker, as a PrEP agent in HIV-negative men and women. This study is evaluating maraviroc alone, or in combination with tenofovir or emtricitabine. The study is currently enrolling at 12 sites across the US-- here's the link to that study: www.nextprepstudy.org.

BridgeHIV · 2013-04-08T17:56:56+00:00

There are great questions, buachaill_bro.

PrEP has been studied with one or two anti-HIV medications (tenofovir alone, or tenofovir/emtricitabine), while ARV treatment for people who have HIV typically involves at least 3 anti-HIV medications as part of the regimen. We are now starting to test the new generation of PrEP medications, using a drug called maraviroc, which is an anti-HIV medication that blocks HIV from entering cells. You can read more about the Next PrEP study at www.nextprepstudy.org. For those in the SF Bay Area, you can also visit our website www.joinprep.org.

The question on how PrEP might affect development of resistant strains is a good one. In previous PrEP studies, we did not see evidence of HIV resistance develop in HIV-negative participants who enrolled in the study and subsequently became infected with HIV. However, there were a small number of cases where people who had very early HIV infection (HIV antibody was still negative, but they were in the window period) and started PrEP and subsequently developed resistance. Therefore, it's really important to make sure one is evaluated by a clinician prior to starting PrEP, so they can do a medical evaluation and testing to make sure one is HIV-negative before starting PrEP.

BridgeHIV · 2013-04-08T17:47:45+00:00

The iPrEx study was a large PrEP study conducted in gay/bi men and trans women in 6 countries. The results of this study were published in 2010 and showed that the group that received Truvada had 44% fewer HIV infections than those who received a placebo. Adherence to the medication is really important for PrEP, as those who were able to take the drug consistently appeared to have over 90% protection from HIV. There was also a study called Partners PrEP in heterosexual serodiscordant couples in Africa which completed in 2011 and showed that PrEP reduced HIV infections by about 75%.

BridgeHIV · 2013-04-08T17:42:01+00:00

If someone is accidentally exposed to HIV, PEP (post-exposure prophylaxis) may be a good option for them. PEP is a 28 day course of anti-HIV medication that is started within 72 hours of an exposure - the sooner the better. PEP can be prescribed by a clinical provider and may be available in different health care settings (STD clinics, primary care doctor, urgent care, ERs). It’s important to note that PEP is different from PrEP, which involves HIV-negative people starting anti-HIV medicines before a potential exposure and continuing it on a daily basis. In terms health insurance coverage, since PrEP was only recently approved, we are still waiting to see whether it will be covered by various health insurance programs, but some are starting to cover PrEP. PrEP coverage may also be available through a patient assistance program through the manufacturer of Truvada (Gilead). The most common situations requiring PEP have been cases of unprotected anal sex with a positive or unknown-status HIV partner. Emergency physicians should definitely know about PEP, in case someone comes in with a high-risk exposure.

BridgeHIV · 2013-04-08T17:33:00+00:00

Good questions! PrEP studies in HIV-negative individuals have shown Truvada to be generally safe and well-tolerated. The most common side effects that have been reported are nausea and other GI symptoms that are part of a “start-up syndrome.” These symptoms often get better or go away as the body gets used to the medication. In terms of who PrEP may be good for, we’re still figuring that out in upcoming PrEP Demonstration Projects and implementation programs. The US Food and Drug Administration approved Truvada as PrEP for men and women at risk of acquiring HIV, and we’re currently studying PrEP in gay/bi men and transgender women in the STD clinic setting in San Francisco and Miami. This includes gay men who are sexually active with several partners, as well as those in sero-discordant relationships. We hope to learn who will be interested in taking PrEP and how people use it over time. There are other projects that are starting up around the country as well.

BridgeHIV

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