Managing HIV in 2013: What the Specialist Needs to Know About Implementing “Test & Treat” and Fostering Adherence

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Paul Sax, MD

Paul Sax, MD
Brigham and Women's Hospital
Harvard Medical School
Boston, Massachusetts

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The standard of care for HIV continues to evolve rapidly, challenging the ability of clinicians to stay abreast of changes. In 2012 alone, the standard for initiation of antiretroviral therapy has gone from treating patients on the basis of specific disease and patient characteristics to treating all patients with an HIV diagnosis.1,2 In fact, the standard of care for HIV is now moving towards a more comprehensive “test and treat” approach, which calls for regular testing and initiation of antiretroviral therapy in all HIV‐positive individuals. This approach has not only been shown to prolong life and improve health in these individuals, but it may also offer the greatest hope for prevention of transmission. In order to achieve optimal outcomes at both the individual and public health levels, clinicians need to understand how to integrate these strategies in their own practices. In this activity, Dr. Paul Sax provides expert insights that may help clinicians integrate these latest strategies and advances into their practice.

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What is the optimal CD4-cell count at which to initiate antiretroviral therapy in patients with a new diagnosis of HIV?

Dr. Sax: Well, the latest Department of Health and Human Services guidelines, which were updated last in February of 2013, state that antiretroviral therapy is recommended for all HIV-infected individuals to reduce the risk of disease progression.1 Now, the strength of this recommendation varies based on the CD4-cell count.

Narrator: Specifically, there is greater urgency in starting antiretroviral therapy in someone with a CD4-cell count of less than 350 cells/mm3 versus someone with a higher CD4-cell count of greater than 500 cells/mm3.

Dr. Sax: So in those patients who fall into the former category, starting antiretroviral therapy is [a] time-sensitive priority.  For those in the latter category, it is less important that it be done immediately, but certainly antiretroviral therapy still could benefit that individual.

Narrator: Ongoing research3 will further evaluate the use of immediate versus delayed antiretroviral therapy in patients with CD4 counts greater than 500 cells/mm3. Furthermore, clinicians should consider comorbid conditions and the willingness and readiness of the patient to start therapy when making decisions about initiating antiretroviral therapy.

Dr. Sax: The guidelines also state that antiretroviral therapy is recommended for HIV-infected individuals for the prevention of transmission of HIV.1 This additional benefit of HIV therapy is something that emerged in Study [HPTN] 052, which was published in 2011, and it demonstrated a 96% reduction in the risk of transmission from an infected person to an uninfected person, in a prospective, randomized clinical trial.4

Now, all of these recommendations for HIV therapy for all patients could not really take place unless there had been substantial progress in the success of HIV treatment. I think it's useful to look at two studies that really highlight this progress, both done in Baltimore out of the Johns Hopkins HIV program. In 1999, a paper was published showing that the virologic suppression rates in patients in this clinic from 1996 to 1998 were only 37%.5 By contrast, a paper was published in 2011 showing that the rate of virologic suppression is now 87% among those prescribed treatment.6

So the vast majority of people who are prescribed HIV therapy and who show up for their regular outpatient care are successfully treated, which means that we can be confident that, if people take the medications that we are prescribing today, they will most likely virologically suppress. Those who do not have successful treatment are, by and large, those who have very poor medication adherence. And that is still a challenge, but it's in a minority of patients.

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What are some of the proven strategies to ensure that patients with HIV are engaged in HIV care after diagnosis and initiation of therapy (eg, not skipping clinical appointments or follow-up)?

Dr. Sax: One issue that might come up is that patients may be complacent about the diagnosis of HIV, especially if they have no symptoms referable to being HIV-positive. People who have high CD4-cell counts and no symptoms, or even people with low CD4-cell counts or no symptoms, may actually believe that this virus does not pose a threat to them. This is something that requires a great deal of health education. One strategy that I use is I say to them, "I know you're feeling well now, and you don't feel like you can take a medication, because why should you? But the goal is to keep you feeling well, because, over time, we know that this virus can eventually make people quite sick”. And, for those with high CD4-cell counts, I also say, “The benefit of going on treatment right now is you could potentially have a life expectancy that's comparable to people who are HIV-negative.”1,7,8

What can we do about patients who are lost to follow-up because of lapses in insurance coverage? I just want to emphasize, that's only one of the factors associated with poor adherence to follow-up visits.

In fact, if you look at multiple studies over time, there have been [a number] of risk factors associated with nonadherence9,10: Certainly, low levels of health literacy; age-related challenges, such as polypharmacy, vision loss, cognitive impairment, [or] very young patients, especially those who are adolescents; psychosocial issues, such as active psychiatric disease, homelessness, low social support, stressful life events or psychosis; people who are highly stigmatized by HIV and have nondisclosure of HIV status; people who have active substance abuse, in particular for patients who are using cocaine, crystal methamphetamine, or alcohol. Difficulty with taking medications in general makes adherence more difficult. Complex regimens makes adherence more difficult. And of course, adverse drug effects—people who are very sensitive to these [may be nonadherent].

Now, it's very important that, when you choose [the] initial regimen for patients who are potentially nonadherent, that [you] try to simplify the regimen as much as possible. There's been a tremendous advance in the simplification of preferred regimens.1,11,12 There are now three single-tablet regimens—where people can take just one tablet a day—and that will be successful in the vast majority of patients. And there are additional regimens that, at most, consist of three tablets taken either once- or twice-daily that have high rates of virologic suppression.

You have to individualize the treatment plan. It's very good to encourage an open dialogue with the patients about barriers that might occur regarding adherence, [and] also to engage other non-MD professionals, including nurses, social workers, pharmacists, to try to help support the adherence. And I think it's important also to focus your attention on the patients who have some of the risk factors that I identified previously, because the vast majority of people will be able to take their medications and will be able to follow up with their office visits.

Narrator: Lastly, it is likely beneficial to offer services that promote linkage to and retention in care through collaboration among community-based providers, case managers, and health departments aimed at prevention and testing.

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What are options for patients who have developed resistance to multiple regimens due to poor adherence? So what do the recent data say, and what do the latest guidelines say about this?

Dr. Sax: Well, in my mind, there really are two different scenarios for people who have resistance. Scenario one comes from the patients who were treated with serial monotherapy, predominantly [before] the late 1990s and early 2000s, who often had very long-standing HIV infection. And because they required a new treatment, we typically added a new treatment to their existing regimens or recycled components of their regimens, and therefore they were exposed to really only one active agent. That selected for the highest level of resistance, and those patients were often very, very challenging to treat.  They were frequently quite adherent to therapy, ironically, but we just didn't have enough active drugs. 

All that changed in the period from 2006 to 2008 when we had an explosion of new drug development, including agents that are active against viruses that are highly resistant. These specific agents are raltegravir, etravirine, darunavir, [and] maraviroc. And those regimens actually could now be used even in patients who have highly resistant virus.

The way we would select a regimen is we would look at their resistance profile, both their current resistance profile and their historic resistance profile, and select a new regimen that consists of at least two—and we hope three—active agents against resistant viruses. When that's not possible, even when we can only have a regimen with one and a half new active drugs, we still often achieve virologic suppression. So that's the first group.

The second group [is] people who are just chronically noncompliant with their therapy.  And ironically, those individuals typically do not have high-level drug resistance, because they stop their treatment all at once, or they never take it to begin with, [so] they don't have the selective pressure to select for much in the way of resistance.

There are certain regimens that have a higher barrier to resistance, and for these people, we often use the boosted protease inhibitor–based regimens, because resistance to this class of medications is very difficult to develop, even among people who are noncompliant.

And for this second group of patients, where adherence is the predominant problem, it really has to do with education, engaging them in care, strategies for follow-up, and really [paying] close attention to the more psychosocial aspects [rather] than the complicated resistance pathways.

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  1. DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV‐1‐Infected Adults and Adolescents. Accessed April 30, 2013.
  2. Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rev. 2011;60:1618‐1623.
  3. Accessed May 22, 2013.
  4. Cohen M et al. N Engl J Med. 2011;365:493‐505.
  5. Lucas GM et al. Ann Intern Med. 1999;131:81-87.
  6. Moore RD, Bartlett JG. Clin Infect Dis. 2011;53:600-604.
  7. Antiretroviral Therapy Cohort Collaboration [ART‐CC]. Clin Infect Dis. 2009;48:1138‐1151.
  8. Thompson MA et al. JAMA. 2012;308:387-402.
  9. O’Connor JL et al. J Infect Dis. 2013. Epub ahead of print January 31, 2013.
  10. Andrade AS et al. J Acquir Immune Defic Syndr. 2013;62:282-292.
  11. Antunes F. Acta Med Port. 2012;25:193-196.
  12. Olender S et al. Top Antivir Med. 2012;20:61-86.

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