Research topic #2
Evaluation of the risks and outcomes associated with key co-infections and other co-morbidities in HIV-infected persons
Research Topic 2, Aim 1: Documentation of key co-morbidities.
At each site, opportunistic infections (OI)s, malignancies, and other co-infections will be characterized by sex, age group, and risk category, and correlated with outcomes of clinical interventions being offered (eg, ART or specific treatment for the co-morbidity).
Research Topic 2, Aim 2: Assessment of whether underlying viral hepatitis B and C increases the risk of hepatotoxicity in HIV-infected persons receiving ART and in HIV-infected persons receiving concomitant anti-tuberculosis therapy and ART.
The rationale for this is that the global burden of tuberculosis is closely linked to the HIV epidemic. In 2000, 7 to12 % of the estimated 8.3 million new tuberculosis cases worldwide were attributed to HIV infection. HIV-infected tuberculosis patients have a high annual incidence of death and opportunistic infections, primarily because tuberculosis accelerates HIV disease progression. As a result, tuberculosis caused 11% of all adult AIDS deaths in the year 2000.
Research Topic 2, Aim 3: Assessment of whether incomplete immune recovery in patients with full virologic suppression on ART will predict recurrent bacterial infections, malignancy, or another co-morbidity not now categorized as an opportunistic event over a long term.
The rational for this is that despite full virologic suppression, a sizeable proportion of patients never truly recover their CD4 counts to normal range values after initiating HAART. However, such patients appear to do equally well in the short-term compared to those with complete immune recovery. It is unknown if they are more susceptible to conditions not traditionally classified as opportunistic illnesses, such as recurrent bacterial infections, or more severe diseases like lymphomas or carcinomas that might be more common in persons who live extended periods of time with moderate degrees of immunodeficiency. Given that the latter conditions occur infrequently, and may take a long time to develop, collaborations such as this one are ideally suited to examine these questions. We hypothesize that differences will be observed over time between persons with complete and partial immunologic recovery, despite adequate suppression of HIV.
Research Topic 2, Aim 4: To determine whether sentinel diagnoses other than traditional OIs such as recurrent or severe endemic infectious diseases, bacterial pneumonias and sinusitis, or skin and soft tissue infections may reflect worsening immune status.
CD4 counts and survival rates will be assessed across sites for subjects with and without these conditions. The rationale for this is that recurrent bacterial infections of the lungs, sinuses, and skin are frequent causes of morbidity and mortality in persons with HIV/AIDS. Although stage of HIV disease is a consistent risk factor for bacterial pneumonia [Feikin 2004], other bacterial processes such as skin infections have not yet been associated with immune status, although large cohorts of patients have not been examined. Other factors such as IDU, sexual behavior, or trimethoprim-sulfamethoxazole use may also modulate risk of bacterial infections and require evaluation in any analysis. Globally, co-infection of HIV with endemic diseases such as malaria and leishmaniasis is emerging as a serious and increasingly frequent event. We hypothesize that recurrent bacterial infections other than pneumonia and severe manifestations of endemic infections (malaria and leishmaniasis) are associated with HIV disease stage and mortality and may warrant inclusion as clinical events signaling immunodeficiency progression.
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