Long-term survival with HIV-infection : the reverse side of the medal

Abstract

The introduction of highly effective combined antiretroviral therapy (cART) in 1996 resulted in effective, long-term suppression of HIV with consequent recovery of the patient’s immune system. Although the enthusiasm about the effectiveness of current cART remains strong, the ongoing work in the area of HIV disease and treatment complications appears to reflect concerns that these clinical problems will continue to be important and possibly increase over time in the current therapeutic area. There is growing interest in the pathogenesis, treatment and prevention of long-term complications of HIV disease and its therapies. This thesis describes some of the long-term complications of HIV-infection since the introduction of cART. Cardiac and vascular complications are one of the most frequently occurring complications in long-term surviving HIV-infected patients in different ethnical populations. In the first part markers of coagulation, anticoagulation and fibrinolysis are studied to define a possible pathogenic mechanism for the increased risk of cardiovascular disease as a long-term complication in HIV-infected patients. An improvement in markers of inflammation and coagulation after initiation of cART was found. Nevertheless, markers of inflammation and coagulation did not normalize even with undetectable HIV viral load. In the second part of this dissertation the prevalence of human papillomavirus (HPV) infection in the anogenital area and HPV-associated precursor lesions of anogenital malignancies in HIV-infected men and women in the cART era are studied. Non-AIDS defining malignancies have an increasing incidence in the HIV-infected population and are responsible for considerable mortality. These malignancies could be related to co-infection with viruses like the human papillomavirus (HPV) or Epstein-Barr virus. In the second part we observed a generally high HPV prevalence and a high prevalence of cervical and anal dysplasia in both HIV-infected men and women. Screening HIV-infected sexually active women for cervical dysplasia is recommended while screening for anal dysplasia is no common practice. Screening of the HIV-infected population or of certain risk groups, like HIV-infected MSM, for anal dysplasia should become a routine preventive measure. In the third part HIV-related fatigue is studied as another highly prevalent long-term complication of HIV-infection resulting in significant morbidity. In the third part predictors of HIV-related fatigue are studied to guide future treatment strategies for one of the most common debilitating symptoms in chronic HIV-infected patients. In this dissertation, we investigated several aspects of pathophysiology and screening of some of the long-term complications of HIV-infection. It will become more and more important to define which host, viral and environmental risk factors for developing long-term complications are present and relevant in this specific patient population. Risk factors should be integrated into up-to-date guidelines for screening and treatment strategies. Dealing with the reverse side of the medal of prolonged survival due to effective antiretroviral therapy constitutes a present and future challenge for all HIV caregivers.