Clinical case 19 Lin, I-Yao (Sally)

Case 19 Having been confined in the hospital for almost a month due recurrent pneumonia, Mr. XXX, 42 y/o, married, a dance instructor in Japan for almost 10 years was diagnosed to have AIDS. Having been confined in the hospital for almost a month due recurrent pneumonia, Mr. XXX, 42 y/o, married, a dance instructor in Japan for almost 10 years was diagnosed to have AIDS. 1.Aside from the antibacterial combination given how are you going to manage your patient using your Reverse Transcriptase inhibitor? 2.What examination/s should you request before and during the treatment? And what would you watch for? 3.In case there is a significant clinical or immunological deterioration during you RT inhibitor treatment. What will be your next drug regimen?

Non-nucleoside reverse transcriptase (NNRITs) Non-nucleoside reverse transcriptase (NNRITs) inhibit HIV by binding noncompetitively to the reverse transcriptase. A single dosage of nevirapine at the time of labor has been shown to decrease perinatal transmission of the virus. Side effects of NNRITs include rash, increased AST and ALT, and Steven-Johnson syndrome (more likely with nevirapine) inhibit HIV by binding noncompetitively to the reverse transcriptase. A single dosage of nevirapine at the time of labor has been shown to decrease perinatal transmission of the virus. Side effects of NNRITs include rash, increased AST and ALT, and Steven-Johnson syndrome (more likely with nevirapine) Nucleoside analog reverse transcriptase (NRITs) Nucleoside analog reverse transcriptase (NRITs) constrain HIV replication by incorporating into the elongating strand of DNA, causing chain termination. All nucleoside analogs have been associated with lactic acidosis, presumably related to mitochondrial toxicity. constrain HIV replication by incorporating into the elongating strand of DNA, causing chain termination. All nucleoside analogs have been associated with lactic acidosis, presumably related to mitochondrial toxicity.

reverse transcriptas e - the enzyme produced by HIV and other retroviruses that allows them to synthesize DNA from their RNA. reverse transcriptas e - the enzyme produced by HIV and other retroviruses that allows them to synthesize DNA from their RNA.

Laboratory findings with HIV infection TestSignificance HIV enzyme-linked immunosorbent assay (ELISA) Screening test for HIV infection.50%(+) within 22 day after HIV transmission; 95%(+) within 6 weeks after transmission. Sensitivity ＞ 99.99%; To avoid false(+) results, repeatedly reactive results must be confirmed with Western blot. Western blot Confirmatory test for HIV. Specificity when combined with ELISA > 99.99%. Indeterminate results with early HIV. Infection, HIV-2 infection, autoimmune disease, pregnancy, and recent tetanus toxoid administration. Complete blood count Anemia, neutropenia, and thrombocytopenia common with advanced HIV infection.

Absolute CD4 lymphocyte count Most widely used predictor of HIV progression. Risk of progression to an AIDS opportunistic infection or malignancy is high with CD4 < 200 cells/μL. CD4 lymphocyte percentage Percentage may be more reliable than the CD4 count. Risk of progression to an AIDS opportunistic infection or malignancy is high with percentage <20%. HIV viral load test These tests measure the amount of actively replicating HIV virus. Correlate with disease progression and response to antiretroviral drugs. Best tests available for diagnosis of acute HIV infection; however, false(+) are common, especially when the viral load is low. Laboratory findings with HIV infection

Single or Combine drug for treatment

HIV resistance testing (during the treatment) HIV resistance testing is done using two different types of assays: genotypic, in which the reverse transcriptase and the polymerase genes are sequenced using different techniques, and phenotypic, in which the behavior of HIV in vitro in the presence of antiretroviral drugs is examined. Results of resistance testing can be used to guid ART. HIV resistance testing is done using two different types of assays: genotypic, in which the reverse transcriptase and the polymerase genes are sequenced using different techniques, and phenotypic, in which the behavior of HIV in vitro in the presence of antiretroviral drugs is examined. Results of resistance testing can be used to guid ART.

Genotype Resistance Testing (GeneSeq ™ HIV) New infection and early lines of therapy genotypic testing can provide relatively straightforward information for early-stage treatment planning; test results become more difficult to interpret as treatment experience increases. Phenotype Resistance Testing (PhenoSense ™ HIV) Treatment failure in middle lines of therapy as the number of mutations increases phenotypic testing provides individualized, "quantitative" results through a direct measure of drug susceptibility; quantitative nature provides insight into degrees of susceptibility rather than the "Yes" or "No" results of genotyping that can be complex.

Combined Phenotype + Genotype Resistance Testing (PhenoSense GT ™ ) Later stages of therapy with multi-drug resistant virus the degree of susceptibility (phenotype) plus the build-up of mutations (genotype) are highly valuable pieces of information for optimizing therapy after multiple treatment failures; genotype identifies mixtures of wild- type and resistant viruses. Combined testing is most appropriate after 2nd- line regimen failure. Viral Fitness (Replication Capacity) Available with PhenoSense HIV and PhenoSense GT The Replication Capacity (RC) assay measures HIV's ability to make copies of itself, or replicate. RC testing is a way to measure the fitness of HIV. The test is performed by comparing an individual's virus to a reference, or wild-type, virus that is known to be good at making copies of itself. The wild-type virus has an RC of 100%. Knowing the RC of a patient's virus can help healthcare providers decide whether to delay, start, stop, switch, or interrupt treatment for the patient.

Combination therapy Combination therapy (three drug used) (three drug used) ↓ Two nucleoside reverse transcriptase inhibitors Two nucleoside reverse transcriptase inhibitors + A non-nucleoside reverse transcriptase inhibitor A non-nucleoside reverse transcriptase inhibitor or or One protease inhibitor One protease inhibitor