“Rage, Rage Against the Dying of the Light”

I braced myself for the challenge that waited for me behind the door of clinic examination room number 8. It was June 2006. I had reviewed Room 8’s chart earlier in the morning, and was aghast to learn how badly the patient’s antiretroviral therapy had been managed. Her treating physician had recently left the area and I had inherited many of her patients. The approach used for antiretroviral management could best be described as “bizarre.”

In an attempt to improve this patient’s adherence, the physician typically would use suboptimal medications in strange combinations, cut the dosing frequency in half, add just one new medication to “failing” regimen after failing regimen, and find many more ways to facilitate the development of resistance to every antiretroviral agent available.

Amber (not her real name), the patient in Room 8, started the conversation by lecturing me about what she would and would not do, and telling me how much she missed her previous physician.  Amber was a single mom of 2 with an attitude. She wasn’t about to take “s..t” from anyone, let alone someone new.

Unfortunately, Amber was dying and didn’t appear to know it. Although she looked clinically well, her CD4+ lymphocyte count was only 5/µL, her HIV RNA level was in the millions of copies per milliliter, and her virus was resistant to every antiretroviral agent available. Out of desperation, I put her on a regimen of ritonavir-boosted darunavir (approved just 1 week earlier) and tenofovir/emtricitabine. At that time, raltegravir, etravirine, and maraviroc had not been FDA-approved, and none of them was available by “compassionate use” protocols at my institution. Amber said that she would do her best to take the new regimen.

I saw her back a month later and ordered a resistance test (VircoType™). The results came back 2 weeks later showing high-level resistance to every drug available, including darunavir, to which her virus showed a 213-fold increase in IC50. Nevertheless, she still appeared clinically well, despite the time bomb inside of her that was about to explode. With nothing but encouragement left to offer, I gave her 4 box-seat tickets to an upcoming Detroit Tigers game, hoping against hope that somehow her destroyed immune system could withstand the daily barrage of microorganisms long enough for new antiretrovirals to be approved.

I discussed her case with colleagues in Toronto in July 2007. By then, she had been hospitalized a few times with acyclovir-resistant herpes simplex ulcerating lesions of the perineum, and azole-resistant esophageal candidiasis. She also was losing weight and complaining of increasing fatigue. My colleagues in Toronto had approval, through compassionate use protocols, to use both etravirine and raltegravir, whereas my university had only approved the protocol for compassionate use of raltegravir. I was unwilling to add just one drug (raltegravir) to her regimen, and so I accepted the offer to send her to Toronto. Unfortunately, neither she nor her family had a car or the resources to travel that far. So we waited expectantly for something, good or bad, to happen. 

We didn’t wait long. In October 2007, with the assistance of colleagues at another Detroit-area hospital who had institutional approval for compassionate use of etravirine, we changed her regimen to ritonavir-boosted saquinavir, enfuvirtide (which she had taken before but stopped because she did not like the injection-site reactions), etravirine, raltegravir, and lamivudine. Unfortunately, she was hospitalized several days later with line-related MRSA sepsis; the line was necessitated by yet another outbreak of acyclovir-resistant perineal herpes simplex virus. After only a day in the hospital, she was frankly psychotic. 

I was covering the hospital that weekend, but did not realize that she was there. By chance, her mother saw me walking by, and begged me to save her daughter’s life. The medical team caring for her was planning to send her to hospice, and was about to stop all of her antiretroviral therapy, in large part because they thought that one of the new antiretrovirals was causing the psychosis. I discussed the situation with her medical team. A PharmD resident, rotating with the team, suggested that perhaps it was the linezolid she was receiving that was causing the psychosis. We stopped the linezolid, continued her antiretrovirals, pulled the line, and were stunned when the psychosis quickly resolved and she was able to leave the hospital 3 days later. 

When I saw her in clinic 1 month later, her CD4+ count had increased to 16/µL (a good sign, but probably not clinically relevant), but her HIV RNA level had dropped more than 3 logs to 763 copies/mL. And she looked great. A month after that, her CD4+ count had risen to 32/µL, although her HIV RNA level came back at 1080 copies/mL. Although I did not mention anything to her, I was worried that her virus had become resistant to both the etravirine and raltegravir. And while her CD4+ count had doubled to 64/µL by January 2008, her HIV RNA level was a discouraging 1460 copies/mL.

Two months later, her HIV RNA level was 14,000 copies/mL and her CD4+ count was 60/µL. Nevertheless, she had gained 6 kg in 6 months, and looked as good as I had ever seen her. A resistance test confirmed resistance to etravirine, but not to raltegravir. On questioning, she acknowledged that she had stopped taking the enfuvirtide, because she “felt so good” that she didn’t think that she needed it.

In the ensuing 5 years, her CD4+ count has risen to, and remained above, 800/µL, with a CD4+ percent of over 30. Her HIV RNA level has remained less than 400 copies/mL. She continues to take all of her antiretrovirals, including her injectable enfuvirtide, reliably. She has gained 40 kg, had a hip replacement, seen her 2 children graduate from high school, and started her own business. During her hospitalization for her hip replacement, I was called by an outraged physician who told me that he would never again care for Amber, because she had “caused a scene.” It turns out that a nurse had told her that she wouldn’t have gotten infected with HIV if she hadn’t abused drugs. Amber screamed at her that she never used drugs, and that the only reason the nurse believed that she did was that she (Amber) was black. I told the physician that Amber was one of the most insightful individuals I had ever met. 

Amber continues to terrorize unsuspecting health care professionals. Only now, she has enlisted me as an ally. She calls me on my cell phone frequently, and especially when another health care professional gives her a hard time. I continue to give her tickets to Tigers games. In addition, whenever I see her, I give her big hugs. And someday, I’m going to tell her, “You go girl. Keep giving them hell. You will outlive me.” Or, as Dylan Thomas wrote, “Do not go gentle into that good night. Rage, rage against the dying of the light.”

I would like to dedicate this blog to the millions of Ambers throughout the world who struggle against the odds on a daily basis and refuse to give in.