We follow the recommendations of these guidelines for patients with virologic failure (especially first line failure), suboptimal suppression, and viral loads less than 1,000 copies/mL, as resistance testing is not sensitive enough to accurately detect mutations for these patients. In our patient population, people rarely come into care during acute HIV seroconversion, so we have not had the chance to do genotyping for this patient group. Unfortunately, many of our patients first come to us with chronic HIV infection, often with CD4 counts less than 100.
It is for this latter group that we have deviated from the guidelines and performed resistance testing. Our rationale for using genotyping for this population is that many of our patients live in an area where their contacts have been treated with HIV therapy and may have transmitted drug-resistant virus. While we have only performed resistance testing on about ten naive patients with chronic HIV infection, we have already seen one patient with a significant mutation in the protease inhibitor class prior to ever taking HIV medication. This patient had been HIV infected over five years ago and had maintained a CD4 count more than 500 and a viral load of about 50,000. However, he had fallen out of care for the past three years and now came back into care due to the development of severe rash, itching and weight loss. His CD4 had decreased to 3, while his viral load was now greater than 750,000. This serious decline in his health prompted us to send for a genotype, which revealed the mutation associated with loss of activity to Viracept (nelfinavir). The patient has now started HIV treatment, and the results of his genotype test definitely impacted on our choice of his initial HIV regimen.
We have also differed from the guidelines in performing resistance testing on pre-treated patients who have discontinued therapy for more than two weeks. We have found that at least 30% of our patients harbor significant resistance mutations despite the interruption in therapy. Many of these patients have retained the K103N mutation associated with resistance to all of the medications in the NNRTI class. In fact, we have seen that NNRTI resistance tends to be persistent, with many patients showing this mutation despite having discontinued NNRTI treatment for more than six months. In light of this, we have found genotyping to be especially useful in helping us avoid prescribing inactive medications.
At our medical centers, we also care for many HIV-positive pregnant women. For these patients, we routinely perform genotype testing before starting HIV medication as it is imperative to design treatment regimens that offer the greatest chance of decreasing their viral load and avoiding maternal-fetal transmission of HIV. The following patient illustrates the value of using resistance testing in this situation. One of our heavily pre-treated patients is now twelve weeks pregnant. Her genotype, done six months ago when her CD4 was 31 and her viral load was 3,496, revealed many significant mutations to virtually all of the medications in the NRTI class as well as high level resistance to medications in the NNRTI and PI classes. Despite this result, she decided not to change her regimen and continued taking Zerit (d4T), Epivir (3TC), Norvir (ritonavir) and Crixivan (indinavir). In the interim, she has had several hospitalizations for psychiatric causes, fragmenting her HIV outpatient care. She returned to care with a CD4 count of 9 and a viral load that had increased to 22,000. We repeated her genotyping and have discovered a genotype showing less severe mutations in the NRTI class, the same NNRTI mutations and no mutations in the PI group. The patient later revealed to us that she had a problem obtaining her HIV medications and has not taken them for more than two weeks. Without the genotype from six months ago, we may have designed a regimen of inadequate NRTI or PI potency. Having serial genotypes for this patient is invaluable as we can now design a regimen with the greatest potential for virologic success.
Jason M. Leider, M.D., Ph.D., is Director of the Adult HIV Service for the North Bronx Health Care Network of Jacobi and North Central Bronx Hospitals.