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October 7, 2014 Issue

Clinical Practice Points

Medical Knowledge
Patient Care

Efficacy and Tolerability of 3 Nonnucleoside Reverse Transcriptase Inhibitor–Sparing Antiretroviral Regimens for Treatment-Naive Volunteers Infected With HIV-1. A Randomized, Controlled Equivalence Trial

Although nonnucleoside reverse transcriptase inhibitor (NNRTI)–based antiretroviral therapy is recommended for the initial treatment of HIV-infected adults and adolescents, some patients are not good candidates for NNRTIs. This randomized trial found high and equivalent rates of virologic control with some differences in tolerability and adverse effect profiles among 3 NNRTI-sparing antiretroviral regimens.

Use this study to:

  • Start a teaching session with a multiple-choice question. We’ve provided one below.
  • Review the major classes of antiretroviral drugs (nucleoside and nucleotide transcriptase inhibitors, NNRTIs, protease, fusion and integrase inhibitors). Use the information in In The Clinic: Management of Newly Diagnosed HIV Infection and ACP Smart Medicine HIV Disease.
  • Ask how one should choose initial therapy for HIV infection.
  • Ask your learners what the limitations are to the use of the NNRTI efavirenz. What problems are encountered with ritonavir-boosted protease inhibitor–containing therapy?
  • Ask how the results of this open-label, randomized equivalence trial are helpful. What are its limitations? How might the open-label design have affected management during the study? The authors address this in the Discussion section.

Medical Knowledge

In the Clinic


Sleep difficulties are reported in 35% to 50% of adults annually, and up to 20% of adults with symptoms may meet diagnostic criteria for insomnia disorder. Are your learners skilled at detecting and managing insomnia?

Use this concise review to:

  • Review how to take an effective sleep history.
  • Ask what conditions need to be considered in patients with insomnia. Are any diagnostic studies needed? Which ones? When?
  • What is effective management?
  • Use the multiple-choice questions at the end to organize a teaching session and introduce new topics for discussion. Log on to enter your answers to earn CME for yourself.
  • Download the already prepared teaching slides to help prepare and run a session.

The Science of Medicine

Practice Based Learning and Improvement
Systems-based Practice

Improvement Interventions Are Social Treatments, Not Pills

Support From Hospital to Home for Elders. A Randomized Trial

This well-conducted, rigorous randomized, controlled trial found no effect of an intensive intervention involving predischarge patient education and follow-up telephone calls on the number of emergency room visits or hospital readmissions. The editorialist points out the struggle between the requirement for rigidly adhered-to protocols in clinical research, and the need to respond and adapt “social” interventions to the “facts on the ground.” Improvement interventions need to be evaluated using methods appropriate for the unstable, context-dependent and time-dependent nature of social treatments—which is what improvement interventions are.

Use these papers to:

  • Review briefly what the intervention was, and ask your learners why they thought it did not work. The trial actually found a potential increase in the number of ER visits among the participants who received the “intervention.” Ask your learners how that might have happened. Can we assume that “educational interventions” can do no harm?
  • Read the editorial, and ask your learners what the “plan-do-study-act” cycle is. Consider asking someone from your hospital’s quality improvement team to join your discussion.
  • Ask your learners what challenges those involved in “improvement science” face when aiming to conduct “experiments” that adhere to the principles we teach in “evidence-based medicine.”
  • Ask if you can “generalize” the findings from a study like this one (regardless of whether “positive” or “negative”) to another practice location. Why might the generalizability of results from a study of “social interventions” be different from those of a pharmaceutical intervention?

Society and Medicine

Systems-based Practice

Sesame Street Goes to Jail: Physicians Should Follow

Thinking Outside the Box: Hospitals Promoting Employment for Formerly Incarcerated Persons

In 2013, Sesame Street launched a new character with an incarcerated father, indicative of how commonly incarceration affects the lives of American families. The authors of a commentary argue that physicians have a duty to engage in addressing the problems that result from and perpetuate incarceration. The authors of another commentary point out the difficulty a history of incarceration poses to former prisoners seeking employment following their release from prison, adding to the risk for worsening physical and mental illness and propagating health disparities. They call for expanded programs encouraging employers, including health systems, to cease excluding these individuals from their potential work pools, as a means of helping to eliminate rather than perpetuate the cycle of incarceration.

Use these commentaries to:

  • Ask your learners if they know whether any of their patients have been incarcerated, or have family members who are. Is this an issue about which we should be routinely asking? Why or why not? Do they know how common incarceration is?
  • Ask what they think the health consequences might be for their patients whose spouses, children, or other family members are incarcerated. How might knowing about this help in the care of these patients?
  • Do your learners think your health system should employ former inmates? Would this scare them?

Other Teaching Tools: New Statistical Glossary

How accurately can you define a “confidence interval” for your learners? How about an “odds ratio”? Check out Annals of Internal Medicine’s new statistical glossary, an enhanced feature of Annals iPad edition. Download the Annals iPad app for free at the iTunes App store. Then, open an article. Commonly used and important terms are underlined at first usage. Tap to see a brief definition, a more in-depth explanation, as well as examples and sources to learn or teach more.


A 25-year-old woman who is 12 weeks pregnant is found to be HIV positive during a routine pregnancy evaluation. She is asymptomatic. Her medical history is unremarkable, and her only medication is a prenatal vitamin.

On physical examination, vital signs are normal. No lymphadenopathy, thrush, or skin lesions are noted. The remainder of the examination is normal.

Hemoglobin is 11 g/dL (110 g/L). HIV antibody testing is positive by enzyme immunoassay and confirmed by Western blot analysis. CD4 cell count is 865/μL, and HIV RNA viral load is 510 copies/mL. Rapid plasma reagin and hepatitis B serologies are negative. HIV genotyping shows no resistance mutations. The remaining laboratory studies are unremarkable.

Which of the following is the most appropriate management?

A. Begin antiretroviral therapy at the onset of labor
B. Begin tenofovir, emtricitabine, and efavirenz now
C. Begin zidovudine, lamivudine, and lopinavir-ritonavir now
D. Repeat CD4 cell count and treat if 500/μL or lower

Correct Answer
C. Begin zidovudine, lamivudine, and lopinavir-ritonavir now

Key Point
In pregnant women with HIV infection, antiretroviral therapy with zidovudine, lamivudine, and lopinavir-ritonavir can reduce the risk of HIV transmission to the newborn to less than 2% and should be given regardless of CD4 cell count, viral load, or presence or absence of HIV symptoms.

Educational Objective
Manage HIV infection in pregnancy.

The most appropriate management of this pregnant patient is immediate institution of antiretroviral therapy with zidovudine, lamivudine, and lopinavir-ritonavir. About one in four neonates born to women with HIV infection will acquire HIV infection perinatally if antiretroviral therapy is not given. Appropriate antiretroviral therapy can reduce the risk of HIV transmission to the newborn to less than 2%. This patient should receive antiretroviral therapy now, regardless of CD4 cell count, viral load, or presence or absence of symptoms.

Although about two thirds of perinatal HIV transmission occurs during delivery, one third occurs in utero; consequently, antiretroviral therapy should be started now and not withheld until the onset of labor to maximally reduce chances of perinatal transmission.

Efavirenz is contraindicated in women who are or who may be pregnant because of the risk for teratogenicity.

Withholding treatment until there is a decrease in CD4 cell count or onset of HIV symptoms would not be appropriate because all pregnant women with HIV infection should receive antiretroviral therapy to reduce the likelihood for perinatal transmission.

Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. September 14, 2011;1-207. Available at: Accessed December 20, 2011.

This question is derived from MKSAP® 16, the Medical Knowledge Self-Assessment Program.

From the Editors of Annals of Internal Medicine and Education Guest Editor, Gretchen Diemer, MD, FACP, Program Director in Internal Medicine, Thomas Jefferson University.


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