HIV: Treatment and Comorbidity

Clinicians worldwide strive to improve HIV care for their patients. Antiretroviral therapy prevents HIV related mortality and is lifelong. A clinical evaluation of these treatment strategies is necessary to identify strategies that may jeopardize treatment effectiveness and patient safety.

The first part of this thesis concerns the relative efficacy of treatment with either lamivudine or emtricitabine combined with tenofovir disoproxil-fumarate as nucleoside reverse transcriptase inhibitor backbone. The use of lamivudine is associated with more virological failure in certain treatment regimens for viremic HIV patients.

Antiretroviral drug switches are addressed next. We evaluate three potential high-risk antiretroviral switches due to cytochrome P450 interactions, acquired resistance and dolutegravir monotherapy in aviremic HIV patients. The patients’ safety seems ensured by these switch strategies. HIV maintenance therapy with single tablets containing multiple drugs or drug monotherapy is possible in various clinical situations, including resistance and comorbidities.

Third, we show that exposure to inhibitors of the renal multidrug resistance protein transporter is associated with renal dysfunction in patients treated with tenofovir disoproxil-fumarate. Cardiovascular risks are comparable regardless of rilpivirine or nevirapine treatment and HIV related Kaposi sarcoma or multicentric Castleman’s disease are effectively treated with peginterferon or rituximab.

In the last part, we explore the future management of HIV which should focus on treating acute HIV and cure strategies. Future research can further elucidate optimal first-line treatment, when switch strategies and maintenance therapies are safe and how to counteract comorbidities until a definite answer to the persistence of HIV is formulated.