If At First You Don't Succeed . . .

A 48-year-old flight attendant needs a new HIV regimen. At the time of diagnosis (in 1997), he had a CD4 count of 90 cells/mm³ and a viral load of 120,000 copies/mL. He developed a rash after being placed on trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis and also experienced anaphylaxis with fluconazole given for esophageal candidiasis. His first antiretroviral regimen — d4T + 3TC + nelfinavir — led to lipoatrophy and hyperlipidemia and eventually failed, with a genotype showing the M184V (RT), L10V, I54L, A71V, and L90M (PI) mutations.

In 2000, the patient started d4T + ddI + abacavir + efavirenz. One week later, he developed a severe hypersensitivity reaction with fever, generalized erythroderma, and eventual desquamation of skin on his hands and feet. He switched to d4T + ddI + lopinavir/ritonavir and achieved virologic suppression. However, his triglyceride levels increased markedly (to 700–1000 mg/dL) and did not abate with dietary modification, atorvastatin, or fenofibrate.

The patient eventually switched to tenofovir/FTC + ritonavir-boosted atazanavir, which led to some improvement in lipid levels, but his triglyceride levels still intermittently exceeded 500 mg/dL. On the recommendation of a nutritionist friend, he tried high-dose fish oil but developed pill fatigue and stopped all treatment — including antivirals.

The patient now has a viral load of 60,000 copies/mL and a CD4 count of 350 cells/mm³. A recent genotype shows the following:

• Reverse transcriptase: K65R (new mutation compared with 2000 genotype), M184V

• Protease: L10V, I54L, A71V, L90M

• HLA-B*5701: negative

• Tropism test (phenotypic): dual/mixed virus

Would you send a phenotype? Would you have sent a tropism test? If so, phenotypic or genotypic?

Would you resume the prior regimen that was working (tenofovir/FTC + boosted atazanavir)? Why or why not? Why do you think it suppressed viremia despite moderate-to-high level resistance in both RT and PI classes?

When do you think the patient developed the K65R mutation?

What do you think caused the severe hypersensitivity when he was on d4T + ddI + abacavir + efavirenz?

If you would not resume tenofovir/FTC + boosted atazanavir, what new regimen would you start? Does the history of severe prior allergy to multiple medications influence your choice? How about the marked hypertriglyceridemia?

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