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CD4 & Nadir CD4 & Viral Load Increase Risk for
Comorbidities....studies from 2009-2012
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Jules Levin, NATAP
START Study confirmed the data, information & HHS Guidelines that have been found in studies over recent years all suggesting & recommending early ART to prevent onset for comorbidities, now the START study results found early ART prevented AIDS & non-AIDS events - the study evaluated AIDS-related cancer, cardiovascular disease, renal & liver disease and cancer and reported risk of developing serious illness or death was reduced by 53% (41 events for early ART group vs 86 events for deferred ART group, a review by independent data & safety monitoring board recommended these results be released early.
CROI/2009: Multicohort D:A:D Study Pinpoints Non-HIV Death Risk
Factors ......
http://www.natap.org/2009/CROI/croi_28.htm........."Every 100-cell higher CD4 count lowered the overall death risk, as well as the risk of death from AIDS, liver disease, heart disease, and non-AIDS cancers. Compared with a viral load below 400 copies while on antiretroviral therapy, a load above 400 while on therapy heightened the risk of death from all causes, from AIDS, and from liver disease.......Compared with a sub-400 load on therapy, a load below 10,000 copies from while off therapy made death more likely from all causes, AIDS, liver disease, and non-AIDS cancers. A viral load between 10,000 and 100,000 copies while off therapy made death more likely from all causes and from AIDS. And a viral load above 100,000 copies while off therapy raised the risk of every death category considered except non-AIDS malignancies.
http://www.natap.org/2009/HIV/100409_01.htm......4% of patients in a study (CHARTER), had detectable viral loads in CSF (>50 c/ml) even though viral load was undetectable in plasma. But, 31% with detectable viral load in plasma had detectable CSF viral load (>50 c/ml), giving I think a suggestion of the magnitude for potential cognitive impairment that can occur for patients with detectable plasma viral load and the importance and implications of achieving undetectable plasma viral load. Of note, 26% of patients with >2 copies/ml in plasma had > 2 copies in CSF and this was associated with higher scores of cognitive impairment.
2012 HHS Guidelines............http://www.natap.org/2012/HIV/033012_01.htm...........OLDER PATIENTS: IMMEDIATE HAART RECOMMENDED:
Antiretroviral therapy (ART) is recommended in patients >50 years of age, regardless of CD4 cell count (BIII: based on expert opinion, moderate recommendation), because the risk of non-AIDS related complications may increase and the immunologic response to ART may be reduced in older HIV-infected patients. ART-associated adverse events may occur more frequently in older HIV-infected adults than in younger HIV-infected individuals. Therefore, the bone, kidney, metabolic, cardiovascular, and liver health of older HIV-infected adults should be monitored closely. HIV experts and primary care providers should work together to optimize the medical care of older HIV-infected patients with complex comorbidities ".....HIV and the Older Patient
Earlier Initiation of Antiretroviral Therapy Results in Better Neurocognitive Functioning.......
http://www.natap.org/2012/CROI/croi_155.htm......Starting antiretroviral treatment (ART) at higher CD4 cell counts, even when NP dysfunction is mild, appears to be beneficial to the central nervous system......HIV+ participants......with a CD4 cell count > 350/mm3 and enrolled were randomized to immediate (n = 35) or deferred treatment
Influence of ART on Incidence and Prognosis of HIV-1-associated Non-Hodgkin's Lymphoma: European Multi-Cohort Study, CD4 Predicts Non-Hodgkin's Lymphoma......
http://www.natap.org/2009/CROI/croi_181.htm......Suppression of HIV-1 replication and increases in CD4 counts were protective....... More advanced immunodeficiency (CD4 count) is the dominant prognostic factor for mortality in patients with HIV-related NHL.......In multivariable analyses risk factors included low CD4 cell count nadirs, older age, men who have sex with men (MSM), and a history of Kaposi's sarcoma for patients on ART. Time up-dated HIV-1 RNA plasma concentration and CD4 cell count were also associated with developing non-Hodgkin's lymphoma while on ART
HIV and Low CD4 Increases Risk for Heart Disease..........
http://www.natap.org/2010/HIV/081310_04.htm......In multivariable Cox analyses adjusted for 10-y CVR, CD4+ cell count <350 cells/mm3 was associated with incident CVD events (hazard ratio, 1.58 [95% confidence interval, 1.09-2.30], compared with >500 cells/mm3), suggesting an attributable risk of about 20%. In the multivariable case-control analyses, traditional CVD risk factors and latest CD4+ cell count <500 cells/mm3, but not cumulative use of ARV class or individual drugs, were associated with higher odds of experiencing CVD events.......Lower CD4+ cell counts are associated with elevated levels of serum markers of inflammation and increased levels of activated CD4+ T cells. Activated CD4+ T cells are frequently present in atherosclerotic lesions in the general population [23]. The chronic inflammation that accompanies uncontrolled or more advanced HIV disease consists of many of the same inflammatory cells and proinflammatory cytokines that destabilize atherosclerotic plaques. The particles contained in these plaques are immunogenic and trigger an inflammatory cascade that results in plaque rupture and coronary artery thrombosis [22, 23, 37]. The chemokine receptor CCR5 resides in the intima media of arteries, directing monocytes and recruiting T cells to these arteries
HIV Increases Risk for Heart Disease; Nadir CD4 & Heart Disease in HIV.....
http://www.natap.org/2013/HIV/102813_01.htm.......nadir CD4 but not recent CD4, was independently associated with MIs among HIV+ individuals, suggesting the higher MI risk in this population may not be easily reversible
CROI/2011: Lowest CD4 Count Below 200, by Itself, Raises Heart Disease Risk With HIV: HIV Is a Risk Factor for Heart Disease.......http://www.natap.org/2011/CROI/croi_122.htm
CID/2013: CD4 Decline Is Associated With Increased Risk of Cardiovascular Disease, Cancer, and Death in Virally Suppressed Patients With HIV......http://www.natap.org/2013/HIV/080913_01.htm
CROI 2015 - Metabolics / Aging, Senescence / Comorbidities / Inflammation - 3 Exercise Studies / Heart Disease / Statins / Cancers / The Kidney / Bone / TAF / The Brain - neurologic function - (04/01/15)
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