Block 10 Antiretroviral Transplant Immunology

The patient has a low CD4 lymphocyte count, indicating a compromised immune system due to AIDS. The physician decides to add a new drug that prevents fusion and penetration of HIV into the host's cell. Enfuvirtide, a fusion inhibitor, is the most likely drug prescribed in this scenario. Ribavirin, Amantadine, Didanosine, Indinavir, and Saquinavir are not fusion inhibitors and would not be appropriate in this case.

Protease inhibitors are used to treat HIV patients because they curb viral proliferation by preventing viral assembly following infection. Protease is an enzyme that is necessary for the virus to assemble new viral particles. By inhibiting the protease, the virus is unable to properly assemble and release new copies of itself, thereby reducing viral proliferation. This helps to control the viral load in the patient and slow down the progression of the disease.

If a permissive host can be found, the outcome would be pure poliovirus. This is because the nucleic acid of the poliovirus and the capsid of hepatitis A are combined in the composite virus. However, when the composite virus infects a permissive host, it is likely that the host's cellular machinery will recognize and use the capsid of the hepatitis A virus to package the nucleic acid of the poliovirus, resulting in the production of pure poliovirus particles.

Indinavir is a protease inhibitor used in the treatment of HIV. It is known to cause adverse effects such as nephrolithiasis (formation of kidney stones), insulin resistance, fat redistribution, and hyperlipidemia. These side effects are commonly associated with the use of indinavir and are not typically seen with other antiviral agents. Therefore, it is likely that indinavir is the cause of these adverse effects in the 32-year-old man.

The presence of tumor penetration into the muscular layer refers to the stage of the disease rather than the grade of the tumor. Staging refers to the extent or spread of the cancer, while grading refers to the appearance of the cancer cells under a microscope. In this case, the fact that the tumor has invaded deep into the muscle layer indicates a more advanced stage of the disease, regardless of the grade of the tumor.

Organ grafts between genetically identical individuals, such as identical twins, are not rejected even with no immunosuppression because they have the same genetic makeup. This means that the immune system of the recipient recognizes the transplanted organ as "self" and does not mount an immune response against it. As a result, there is no need for immunosuppressive drugs to prevent rejection of the organ.

Saquinavir is a protease inhibitor, which means it inhibits the proteolytic cleavage step of the viral growth cycle. Proteolytic cleavage is a crucial step in the maturation of the HIV virus, where the viral polyprotein is cleaved into individual functional proteins by the viral protease enzyme. By inhibiting this step, saquinavir prevents the formation of mature and infectious viral particles, thus reducing viral replication and the progression of HIV infection.

The most likely triple drug regimen used in this case is Zidovudine + lamivudine + saquinavir. This combination is commonly used in HAART for HIV-positive patients. Zidovudine and lamivudine are nucleoside reverse transcriptase inhibitors (NRTIs) that work by inhibiting the reverse transcriptase enzyme, preventing the replication of the HIV virus. Saquinavir is a protease inhibitor (PI) that inhibits the protease enzyme, preventing the cleavage of viral polyproteins and the production of mature virus particles. This combination of drugs helps to suppress viral replication and improve the CD4 lymphocyte count in HIV-positive individuals.

The most likely outcome in this scenario is graft versus host disease. The MLR result indicates that the donor's lymphocytes are recognizing and attacking the recipient's cells, leading to an increase in the donor's cells but not the patient's cells. This immune response can cause significant damage to the recipient's tissues and organs, resulting in graft versus host disease.

The patient's HIV-1 strain has developed a mutation in the active site of the reverse transcriptase enzyme. This mutation has caused an increase in the viral load. The physician decides to remove emtricitabine, which targets the reverse transcriptase enzyme, from the patient's HAART regimen. Instead, the physician adds a drug that targets the same enzyme but is more effective against the patient's viral strain. Therefore, delavirdine, which is known to target the reverse transcriptase enzyme, is added to the patient's HAART regimen.

The presence of an ulcerating lesion at the inner canthus of the eye, along with a biopsy showing a malignant tumor composed of basaloid cells with hyperchromatic nuclei and prominent nuclear palisading, suggests that the tumor is locally invading the surrounding tissue. Local tissue invasion refers to the spread of tumor cells into nearby structures and is a common mode of spread for basal cell carcinomas, which this patient likely has. This explanation is supported by the information given in the question stem.

The patient's presentation of fat accumulation on the upper back, along with elevated total cholesterol, triglycerides, and blood glucose levels, is consistent with a condition called lipodystrophy, which is a known side effect of certain antiretroviral drugs. Saquinavir, a protease inhibitor commonly used in HAART, has been associated with the development of lipodystrophy. Therefore, Saquinavir is the most likely drug responsible for the signs and lab values observed in this patient.