Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women

More than half of the 35 million persons currently living with HIV-1 infection are women, and a majority live in the sub-Sahara Africa region. Antiretroviral medications used as pre-exposure prophylaxis have been proven to be effective in preventing contracting the HIV-1 virus. However in a few other trials, it was shown that adherence to the tenofovir-containing pills and vaginal gels was low which means that there needs to be more options out there for women so that they can be more compliant and adherent to the drug and prevent the spread of HIV-1 infections. In this trial the researchers decided that since vaginal rings provide sustained and controlled release of medication, it would be a good idea to test out as an antiretroviral-containing form of protection. Since it could provide long-acting HIV-1 protection and reduce overexposure of the active ingredient and deliver the agent right at the site of the viral transmission.

The trial lasted from August 2012 to June 201 with a population of 2,629 healthy, sexually active, nonpregnant, HIV-1–seronegative women between the ages of 18 and 45 years at 15 research sites. Women were randomly assigned with a ratio of 1:1 to either receive either a silicone elastomer vaginal matrix ring containing 25 mg of dapivirine or a placebo vaginal ring. It ended up being 1313 in the dapivirine group and 1316 in the placebo group. Each ring is inserted for 4 weeks and then replaced with a new one, and the women were counseled how to insert/remove the ring and to wear it for the month. They also returned for monthly follow-up visits to test and monitor for HIV and were also give additional adherence counseling.

The results concluded that, the median age of the population was 26 years old, 41% were married, 99.5% reported having a primary sexual partner during the 3 month before trial enrollment, 57% reported use of a condom, and 64% reported their partner knew they would be using a vaginal ring for a research trial. The medium follow up time was 1.6 years, and the longest was 2.6 years. Pregnancy occured at an incident of 3.9/100 person-years in dapivirine and 4.0/100 person-years in placebo group. Across all the sites a total of 168 incident HIV-1 infections occurred during the use period, 71 in dapivirine group and 97 in the placebo group. Incidents of HIV-1 infection in the dapivirine group was lowered by 27% than placebo group. The effectiveness was significant bit not high. The efficacy of HIV-1 protection differed significantly with different age groups, an efficacy of 61% for women 25 or older, and 10% for women under 25. Adherence was also lower in women 18-21  than those older than 21, this emphasizes a greater need for prevention strategies for women of this age group to better help them from contracting HIV-1 infections.

Baeten JM, Palanee-Phillips T, Brown ER, ect al. Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women. N Engl J Med. doi: 10.1056/NEJMoa1506110 (published 22 Feburary 2003)

http://www.nejm.org/doi/full/10.1056/NEJMoa1506110#t=article

Antiretroviral Pre-exposure Prophylaxis: Opportunities and Challenges for Primary Care Physicians

Almost all adults are sexually active and many do not adhere to safe sex strategies. There are populations that are particularly at risk for HIV for many reasons, including living in a low-income community and lack of proper sex education. Unfortunately, despite the increased numbers of treatments for HIV, the infection rate is still high. Even those at risk engage in risky sexual behaviors because of “therapeutic optimism”, the belief that HIV is no longer a serious illness.

Many ideas have been thrown around to address this issue, but an extreme solution that is becoming popular would be to administer an antiretroviral pre-exposure prophylaxis (PrEP) medication to those at risk. There are many pros and cons to this concept. An obvious benefit would be the prevention of further infections. Also, it would force those at risk to come in for regular check-ups, where they could be counseled on safe sex and regular HIV testing. However, many concerns have also been raised. For example, the medication recommended, tenofovir, is costly, and would be extremely expensive to distribute to the public. Supporters of the idea counteract this statement by pointing out the cost is much less than that of the medications that would be used to treat an HIV infected person. Another potential drawback would be patients might decide to relay on the medication and continue risky sexual behaviors. One could also argue that those at risk are not adherent using condoms or mechanisms for safe sex, so why would they be adherent with this medication?

Personally, I think there are better alternatives out there to prevent the spread of HIV than prescribing those at risk an expensive, medically risky medication. I think that money should go towards educating those at risk and providing HIV screening days to alleviate the number of sexually active adults who do not know they are infected. As a student pharmacist, it is easy to want to prescribe a medication to solve problems, but I think many disease states can be prevented by simple lifestyle changes.

Do you think the administration of a preventative drug like tenofovir would work to prevent the spread of HIV?

 

Read the original article here.

Mayer, KH. Krakower, DS. Boswell, SL. Antiretroviral Preexposure Prophylaxis: Opportunities and Challenges for Primary Care Physicians. Jama. 2016;0318

Recent advances in management of the HIV/HCV coinfected patient

This paper discusses recent advances in the therapeutic treatment of patients infected with both the human immunosuppressant virus (HIV) and the hepatitis C virus (HCV). Approximately 150 million people across the globe have chronic HCV, which causes inflammation of the liver. The yearly global death toll from diseases related to HCV is at least 350,000. The most common route of HIV/HCV coinfection arises from HIV acquisition via injection drug use. Coinfection of these viruses causes increased risk of fibroses and increased rate of cirrhosis and end-stage liver disease development.

Direct-acting antivirals (DAAs) offer increased efficacy against these viral infections as well as shorter duration of treatment and diminished adverse events. In October and December of 2014, the fixed-dose combination DAA regimens of ledipsavir/sofosbuvir, and ombitasvir/paritaprevir/ritonavir plus dasabuvir were approved, respectively. These new agents have varying mechanisms of action, including NS3/4A protease inhibitors, nucleos(t)ide and non-nucleoside polymerase inhibitors and NS5A replication complex inhibitors. The new HCV treatment regimens have equivalent sustained virologic response rates for HIV/HCV coinfected individuals as they do for HCV monoinfected individuals.

However, complex drug-drug interactions can arise from DAA treatment regimens when used in HIV/HCV coinfection. Many new DAA agents affect or are affected by metabolizing enzymes and membrane transporters because many antiretrovirals are substrates, inhibitors and inducers of metabolizing enzymes, and inhibitors of membrane transporters.

The review also briefly touches on pharmacogenomic testing for HIV/HCV coinfected patients since DAAs are substrates of drug transporters and CYP450 enzymes. Because of this, pharmacokinetics and treatment outcomes could be influenced by genetic variability.

Future Virology Aug. 2015: 981+

Evaluating the Effects of an Interdisciplinary Practice Model with Pharmacist Collaboration on HIV Patient Co-Morbidities

HIV patients are likely to have certain medical co-morbidities at a higher prevalence than members of their age group and are more vulnerable to adverse events related to these problems. For this reason, monitoring of patients with this condition is highly utilized through primary care clinics that specialize in the treatment of the infection in association with chronic disease states. The disease states common among HIV patients over the age of 60 include hypertension (45% of people), diabetes (21% of people), and vascular disease (23% of people). Interdisciplinary practice models used in treatment of patients with this condition have been effective in managing these chronic disease states. Because pharmacists play a crucial role in how HIV patients adhere to medications and treatment guidelines, this study focused on determining if there is a benefit to adding pharmacists to this inter professional team.

This study found that pharmacists were able to help in the management of  lipid levels and the cessation of smoking. Along with this, pharmacists were found to significantly decrease the amount of money these patients spend management of their individual chronic co-morbidities (with average savings of $3,000). For this reason, pharmacists involvement in the primary care of patients with HIV should expand past the provision of medications to include counseling and other services.

I think this study is important due to the fact that it represents how the role of a pharmacist within the health system is constantly changing. We are not only trusted sources of information for medications and proper treatment techniques, but we are also crucial in providing adequate counseling to patients. This is something that I believe has been a major focus throughout our studies in pharmacy school over the course of the year, and as a result, a feel I will be well prepared to fill this role in my future profession. This article makes me want to learn specific ways that I can help patients from this population manage their condition.

Cope R, Berkowitz L, Arcebido R, et al. Evaluating the effects of an interdisciplinary practice model with pharmacist collaboration on HIV patient co-morbidities. AIDS Patient Care and STDs. 2015, 29(8): 445-453

TDF-FTC used for prophylactic treatment in patients at risk for HIV.

In this study, Dr. Molina and colleagues set out to determine the efficacy of prophylactic drugs for the prevention of HIV in homosexual males. In past studies, prophylaxis was tested in heterosexual women, but there was no added efficacy with prophylactic treatment that was attributed to non-adherence issues. The prophylactic drug that was used in this study is called tenofovir disoproxil fumarate (TDF). Two formulations were used for the study: TDF on its own and TDF mixed with emtricitabine. The combination drug used is called TDF-FTC.

The study involved volunteers that were HIV-negative males above the age of 18 that were at risk for contracting HIV. The group was split into the group that would receive the drug and one that would be the placebo group. During the study, the group that received the drug were told that they should take the medication 2-24 hours before sexual activity and two more doses at intervals afterwards. If they were consistently active, the group was told to take the medication every day. The group took a median of 15 pills per month. At the end of the study, the participants were asked to come back with the remaining medication and for blood tests to verify adherence. By the end of the study, it was found that the individuals that received TDF-FTC were 86% less likely to contract HIV over those who use no prophylaxis.

A readily available HIV medication used as a prophylactic would greatly impact public health. Although this study was performed in France and Canada, the findings could be used to change how health is managed in places where HIV is out of control like Africa. Do you think that treatments like this can be effective in places where people have medication stigmas?

Moline, Jean-Michel MD et. al. On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection. NEJM. 373:2237-2246. Dec. 2015. DOI: 10.1056/NEJMoa1506273

http://www.nejm.org/doi/full/10.1056/NEJMoa1506273#t=abstract

HIV drugs give couples ‘ray of hope’

There are many couples in Kenya where one is HIV positive and the other negative, but they still want to have children which leads to 44% of new HIV infections. PrEP is a new way to use anti-HIV drugs that are normally given to HIV positive people, that could mean couples can try and have children risk-free. The study took over 4,700 couples and the HIV negative person took the PrEP course over 36% and found that having the drug in their system reduced rate of transmission my over 90% and if the HIV positive person took antiretroviral drugs as well then the risk reduces to zero to close to zero.

Once HIV is in the body it hides in hard to access places and make reservoirs making it hard to flush out. However, if the PrEP drugs are in the system of an HIV negative person, when the virus enters, it gets killed. This means HIV doesn’t get the chance to find those reservoirs to hide in and be hard to flush out and ultimately infect the person.

This allows couples to resolve some conflicts that come with finding out that your partner is HIV positive and allows them to have a more normal relationship. It also helps greatly reduced the number of new HIV infections. Not mentioned in this is how this affects the children of HIV positive women. Whether this course also prevents transmission of HIV to the fetus and allow for uninfected children in unknown. Children who are born HIV positive due to their mother contributes to the population of new HIV infections as well and is another issue to be addressed.

Pitt, C. HIV drug gives couples ‘ray of hope’. BBC. 2016.

http://www.bbc.com/news/health-35324450

Carroll JJ, Ngure K, H Renee, ect at. Gendered differences in perceived risks and benefits of oral PrEP among HIV-serodiscordant couples in Kenya. AIDS Care. doi: 10.1080/09540121.2015.1131972 (published 11 January 2016)

 

HIV Interventions in African American Churches

African Americans account for nearly 50% of new HIV cases in America each year. They also tend to experience delayed diagnosis of the infection, meaning that they enter therapy later and are more likely to die from AIDS sooner than white patients. This is because of a higher prevalence of lack of access to health insurance among the African American population, for a variety of reasons. Authors of this article sought to find an appropriate outlet for increasing the availability of HIV education and testing for the African American population, specifically focusing in on the Black Church.

The Black Church has always had a strong influence in promoting social change in African American populations, and it experiences strong and stable attendance from African Americans across the country. Many church leaders support increasing availability of HIV testing for its members, but factors such as lack of HIV training, resources, controversy over condom use, premarital sex, and homosexual relationships, and HIV stigma have largely prevented this from being an effective avenue for intervention and prevention.

This study reports on the half-way point findings of the Taking It to the Pews initiative, a 12 month program aiming to increase HIV testing rates among African American church members and community members through church-planned outreach events. They attempted to do so by (1) stressing the importance of HIV testing, (2) reducing stigma associated with AIDS and HIV testing, and (3) increasing availability and access to testing.

4 churches (2 intervention and 2 control) were assessed in the Kansas City area. The odds of members of the intervention churches reporting receipt of an HIV test at the 6 month follow-up was 2.6 times greater than the control church members. Among the subset of church members who hadn’t received an HIV test within the 6 months before the survey, members of intervention churches were 3.3 times more likely to get tested. 47% of intervention church members versus 28% of control church members had received testing at the 6 month follow-up.

I think this article brings up a lot of great points about our role as pharmacists. Does our role in promoting healthcare stop when we leave the pharmacy at the end of the work day, or do we have a responsibility to start initiatives such as this in our community and other places that we may hold leadership initiatives? What are some appropriate community outlets for us to raise health awareness? Additionally, how can we as pharmacists contribute to removing the stigma that goes along with discussing, educating, and treating diseases such as HIV?

 

Berkeley-Patton J, Bowe-Thompson T, Bradley-Ewing A, et al. Taking it to the pews: a CBPR-guided HIV awareness and screening project with black churches. AIDS Educ Prev. 2010;22(3):218-37.