Publications

BACKGROUND

In healthy, HIV seronegative, CMV seropositive adults, a large proportion of T cells are CMV-specific. High-level CMV-specific T cell responses are associated with accelerated immunologic aging ("immunosenesence") in the elderly population. The impact of untreated and treated HIV infection on the frequency of these cells remains undefined.

METHODOLOGY/PRINCIPAL FINDINGS

We measured the proportion of CD4+ and CD8+ T cells responding to CMV pp65 and IE proteins was measured using flow cytometry in 685 unique HIV seronegative and seropositive individuals. The proportion of CMV-specific CD8+ T cells was consistently higher in the HIV-seropositive subjects compared to the HIV-seronegative subjects. This HIV effect was observed even in patients who lacked measurable immunodeficiency. Among the HIV-seropositive subjects, CMV-specific CD8+ T cell responses were proportionately lower during recent infection, higher during chronic untreated infection and higher still during long-term antiretroviral treated infection. The CD8+ T cell response to just two CMV proteins (pp65 and IE) was approximately 6% during long-term therapy, which was over twice that seen in HIV-seronegative persons. CMV-specific CD4+ T cell responses followed the same trends, but the magnitude of the effect was smaller.

CONCLUSIONS/SIGNIFICANCE

Long-term successfully treated HIV infected patients have remarkably high levels of CMV-specific effector cells. These levels are similar to that observed in the elderly, but occur at much younger ages. Future studies should focus on defining the potential role of the CMV-specific inflammatory response in non-AIDS morbidity and mortality, including immunosenescence.

Determination of HIV-1 subtype may be important in the management of HIV-infected individuals, particularly with regard to deciding the CD4 cell count at which to initiate antiretroviral therapy. Non-B subtypes, A and D, are prevalent in Uganda, and individuals infected with subtype D seem to have faster disease progression compared with those infected with subtype A. We examined the level of apoptosis in CD4+ T cells in a study cohort of volunteers infected with subtypes A and D infection. Although the levels of apoptosis in the activated CD4+ cells significantly decreased with viral suppression, CD4+ apoptosis in individuals infected with subtype D were found to be significantly higher compared with those infected with subtype A before antiretroviral treatment. Surface expression of PD-1 on CD4 cells in subtype D was substantially higher compared with that in subtype A (P = 0.03). This difference was not observed in the CD8 population (P > 0.05). Our findings suggest that the infecting HIV subtypes exert an independent influence on the disease outcome in response to antiretroviral treatment.

BACKGROUND

Patients with HIV have increased risk for cardiovascular disease, but the underlying mechanisms remain unknown. The purpose of this study was to determine the prevalence of echocardiographic abnormalities among asymptomatic HIV-infected individuals compared with HIV-uninfected individuals. Methods/Results- We performed echocardiography in 196 HIV-infected adults and 52 controls. Left ventricular ejection fraction, left ventricular mass indexed to the body surface area, and diastolic function were assessed according to American Society of Echocardiography standards. Left ventricular mass index was higher in HIV-infected patients (77.2 g/m(2) in patients with HIV versus 66.5 g/m(2) in controls, P<0.0001). Left ventricular ejection fraction was similar in both groups. Eight (4%) of the patients with HIV had evidence of left ventricular systolic dysfunction (defined as an EF <50%) versus none of the controls; 97 (50%) had mild diastolic dysfunction compared with 29% of the HIV-uninfected subjects (P=0.008). After adjustment for hypertension and race, HIV-infected participants had a mean 8 g/m(2) larger left ventricular mass index compared with controls (P=0.001). Higher left ventricular mass index was independently associated with lower nadir CD4 T-cell count, suggesting that immunodeficiency may play a role in this process. After adjustment for age and traditional risk factors, patients with HIV had a 2.4 greater odds of having diastolic dysfunction as compared with controls (P=0.019).

CONCLUSIONS

HIV-infected patients had a higher prevalence of diastolic dysfunction and higher left ventricular mass index compared with controls. These differences were not readily explained by differences in traditional risk factors and were independently associated with HIV infection. These results suggest that contemporary asymptomatic patients with HIV manifest mild functional and morphological cardiac abnormalities, which are independently associated with HIV infection.