Morbidity and Mortality According to Latest CD4+ Cell Count among HIV Positive Individuals in South Africa Who Enrolled in Project Phidisa

Abstract

BackgroundShort-term morbidity and mortality rates for HIV positive soldiers in the South African National Defence Force (SANDF) would inform decisions about deployment and HIV disease management. Risks were determined according to the latest CD4+ cell count and use of antiretroviral therapy (ART) for HIV positive individuals in the SANDF and their dependents.Methods and FindingsA total of 7,114 participants were enrolled and followed for mortality over a median of 4.7 years (IQR: 1.9, 7.1 years). For a planned subset (5,976), progression of disease (POD) and grade 4, potentially life-threatening events were also ascertained. CD4+ count and viral load were measured every 3 to 6 months. Poisson regression was used to compare event rates by latest CD4+ count (<50, 50–99, 100–199, 200–349, 350–499, 500+) with a focus on upper three strata, and to estimate relative risks (RRs) (ART/no ART). Median entry CD4+ was 207 cells/mm3. During follow-up over 70% were prescribed ART. Over follow-up 1,226 participants died; rates ranged from 57.6 (< 50 cells) to 0.8 (500+ cells) per 100 person years (py). Compared to those with latest CD4+ 200–349 (2.2/100py), death rates were significantly lower (p<0.001), as expected, for those with 350–499 (0.9/100py) and with 500+ cells (0.8/100py). The composite outcome of death, POD or grade 4 events occurred in 2,302 participants (4,045 events); rates were similar in higher CD4+ count strata (9.4 for 350–499 and 7.9 for 500+ cells) and lower than those with counts 200–349 cells (13.5) (p<0.001). For those with latest CD4+ 350+ cells, 63% of the composite outcomes (680 of 1,074) were grade 4 events.ConclusionRates of morbidity and mortality are lowest among those with CD4+ count of 350 or higher and rates do not differ for those with counts of 350–499 versus 500+ cells. Grade 4 events are the predominant morbidity for participants with CD4+ counts of 350+ cells.

Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection

“…This finding indicates that damage to the immune system may occur early in the course of HIV infection. 42 It further supports the need for better markers of impaired immune function and research on treatments to use along with antiretroviral therapy to reduce disease among HIV-positive patients.…”

Immediate initiation of cART is associated with lower levels of cerebrospinal fluid YKL-40, a marker of microglial activation, in HIV-1 infection

“…Using this marker, we provide evidence for a benefit of cART in AHI compared with CHI, supporting a mechanism through which early cART confers neuroprotective effects. In the context of work suggesting damage to the immune system occurs early in HIV infection 21 and the push to provide immediate cART regardless of CD4 count, our work provides specific information on the mechanism of benefit for early treatment. Finally, given the persistence of HIV-associated neurocognitive disorders despite widespread cART, the association between YKL-40 and NFL 7 suggests the value of assessing whether it is possible to identify predispositions to neuronal injury using YKL-40 as a prognostic marker.…”

Ten years of antiretroviral therapy: Incidences, patterns and risk factors of opportunistic infections in an urban Ugandan cohort

“…However, recent publications show that even patients with good immune reconstitution are still at risk of acquiring OIs [ 23 , 24 ]. Most prevalent factors associated with the occurrence of OIs while on ART include malnutrition, younger age and low CD4 cell count at ART start [ 25 – 31 ].…”