HIV Infection & AIDS in Objective-C

Making QR Code ISO/IEC18004 in Objective-C HIV Infection & AIDS

nearly one-third of patients starting a HAART regimen Patients who have taken various antiretroviral regimens and who now have resistant HIV-1 represent a major challenge for the treating clinician However, the issue of resistant virus does not just concern the treatment-experienced patient Resistance is now also documented in patients who are antiretroviral treatment-naive, but who have been infected with a drug resistant strain primary resistance Cohort studies of antiretroviral treatment naive patients entering care in North America and Western Europe show that roughly 10 12% (and as high as 25%) of recently infected individuals have been infected with a drug-resistant strain of HIV-1 Current expert guidelines recommend resistance testing for patients who are recently infected or newly diagnosed and for pregnant women Resistance testing is also recommended for patients who are on an antiretroviral regimen and have suboptimal viral suppression (ie, viral loads > 1000 copies/ mcL) Both genotypic and phenotypic tests are commercially available and in randomized controlled studies their use has been shown to result in improved short-term virologic outcomes compared to making treatment choices without resistance testing Furthermore, multiple retrospective studies have conclusively demonstrated that resistance tests provide prognostic information about virologic response to newly initiated therapy that cannot be gleaned from standard clinical information (ie, treatment history, examination, CD4 count, and viral load tests) Because of the complexity of resistance tests, many clinicians require expert interpretation of results In the case of genotypic assays, results may show that the mutations that are selected for during antiretroviral therapy are drug-specific or contribute to broad cross-resistance to multiple drugs within a therapeutic class An example of a drugspecific mutation for the reverse transcriptase inhibitors would be the M184V mutation that is selected for by lamivudine or emtricitabine therapy this mutation causes resistance only to those two drugs Conversely, the thymidine analog mutations ( TAMs ) of M41L, D67N, K70R, L210W, T215Y/F, and T219Q/K/E are selected for by either zidovudine or stavudine therapy, but cause resistance to all the drugs in the class and often extend to the nucleotide inhibitor tenofovir when three or more of these TAMs are present Further complicating the interpretation of genotypic tests is the fact that some mutations that cause resistance to one drug can actually make the virus that contains this mutation more sensitive to another drug The M184V mutation, for example, is associated with increased sensitivity to zidovudine, stavudine, and tenofovir The most common mutations associated with drug resistance and crossresistance patterns for NRTIs, NNRTIs, and PIs can be found at http://hivdbstanfordedu Phenotypic tests also require interpretation in that the distinction between a resistant virus and sensitive one is not fully defined for all available drugs Both methods of resistance testing are limited by the fact that they may measure resistance in only some of the viral strains present in an individual Resistance results may also be misleading if a patient is not taking antiretroviral medications at the time of testing Thus, resistance results must be viewed cumulatively ie, if resistance is reported to an agent on one

test, it should be presumed to be present thereafter even if subsequent tests do not give the same result

Epoetin alfa (erythropoietin) is approved for use in HIVinfected patients with anemia, including those with anemia secondary to zidovudine use It has been shown to decrease the need for blood transfusions The drug is expensive, and an endogenous erythropoietin level < 500 mU/mL should be demonstrated before starting therapy The starting dose is 8000 units subcutaneously three times a week The target hematocrit is 35 40% The dose may be increased by 12,000 units every 4 6 weeks as needed to a maximum dose of 48,000 units per week Hypertension is the most common side effect Human G-CSF (filgrastim) and granulocyte-macrophage colony-stimulating factor (GM-CSF [sargramostim]) have been shown to increase the neutrophil counts of HIV-infected patients G-CSF is preferred because of the theoretical concern of GM-CSF-stimulating HIV replication in infected monocytes In patients receiving cytotoxic chemotherapy for lymphoma or Kaposi s sarcoma, daily subcutaneous doses of G-CSF at approximately 5 mcg/kg (a 300 mcg or 480 mcg vial, depending on weight) are given beginning 5 7 days after chemotherapy until the neutrophil count has rebounded to above 1000/mcL G-CSF may also have a role in ameliorating neutropenia caused by other drugs such as zidovudine or ganciclovir, when other therapeutic alternatives are not possible Because the cost of this therapy is approximately $400 per 480 mcg vial, dosage should be closely monitored and minimized, aiming for a neutrophil count of 1000/mcL When the drug is used for indications other than cytotoxic chemotherapy, one or two doses at 5 mcg/kg per week are usually sufficient