HIV-1 Disease Progression and Survival in an Adult Population in Zimbabwe: Is There an Effect of the Mannose Binding Lectin Deficiency?

Abstract

HIV infection remains a major global health burden since its discovery in 1983. Sub-Saharan Africa is the region hardest hit by the HIV/AIDS pandemic where 63% of the 33 million infected people live. While there is marked person-to-person variability in susceptibility, progression, and survival with HIV infection, there is a paucity of predictive diagnostics associated with these clinical endpoints. In this regard, the deficiency in plasma Mannose Binding Lectin (MBL) is a common opsonic defect reported to increase susceptibility infections, including HIV. To the best of our knowledge, we report here the first study on the putative role of MBL deficiency on HIV progression and survival in an African adult population. We hypothesized that MBL deficiency has a role to play in HIV infection by increasing HIV disease progression and decreasing survival. We assessed the role of MBL deficiency on HIV disease progression and survival in a Zimbabwean adult population enrolled in the Mupfure Schistosomiasis and HIV (MUSH) cohort. We analyzed blood samples for MBL levels, MBL2 genotypes, HIV-1 status, viral load, and CD4 + T cell counts. Participants were followed for 3 years wherein the endpoints were measured at baseline, 6 weeks, and 3, 6, 12, 24, and 36 months. Disease progression was measured as the rate of decline in CD4 + T cell counts and the rate of increase in HIV viral load. We assessed 197 HIV positive adults where 83% (164) were women with a median age of 31 years. Prevalence of plasma MBL deficiency (less than 100 lg/L) and MBL2 deficient genetic variants (A/O and O/O genotypes) was 21% (42 out of 197) and 39% (74 out of 190), respectively. We did not observe a significant role to explain individual variation in mortality, change of CD4 + T cell count, and viral load by MBL plasma deficiency or MBL2 genetic variants from baseline to 3 years follow up period in this adult population. We suggest the need for global OMICS research and that the present findings attest to the large betweenpopulation variability in a host of factors that can predispose individuals susceptible to HIV progression and mortality. We therefore cannot recommend at this time the use of plasma MBL levels or MBL2 genetic variants as a prognostic marker in HIV infection, disease progression, and survival in this adult population in Africa.

Endovascular Therapy for Large Vessel Vasculopathy in HIV-infected Patients

“…Human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) remains a major health burden, especially in sub-Saharan Africa where 63% of the 33 million globally infected people live. 1 The registration of >400 000 new HIV infections in South Africa in 2012, 1 places this country at the forefront of the HIV burden worldwide, with KwaZulu-Natal as the epicentre of the AIDS pandemic. 2,3 The last three decades have witnessed the emergence of a heterogeneous range of HIV-associated vascular pathologies under the rubric of "HIV-associated vasculopathy", the pathophysiology of which remains poorly understood.…”

MBL2 gene polymorphisms in HHV-8 infection in people living with HIV/AIDS

“…In contrast, the -550, -221 and exon 1 polymorphisms were studied simultaneously in PLWHA and showed no impact on viral load or TCD4 count [ 53 ], and they were also not associated with viral load, TCD4 count, disease progression, or survival of a population of PLWHA from Africa who was not under antiretroviral therapy [ 28 ]. However, the present study simultaneously evaluated the three main polymorphisms of the MBL2 gene and the high, intermediate and low expression haplotypes and found an association between the HIV/HHV-8 coinfected patients who had the intermediate expression haplotype with TCD4 count when compared with patients monoinfected by HIV.…”

“…The progression of the disease caused by HIV infection is characterized by a decline in TCD4 cell count and an increase in viral load, leading to patient death in the absence of antiretroviral therapy [ 28 ]. Thus, some studies suggest that in HIV/HHV-8 coinfection, severe depletion or inactivation of T cells and HIV replication may be important factors in the clinical evolution of HHV-8 infection and the development of KS [ 4 , 29 – 31 ].…”

Mannose-binding lectin concentrations in people living with HIV/AIDS infected by HHV-8

“…In this context, mannose-binding lectin (MBL) plays a key role in innate immunity as a standard recognition receptor, binding with a high affinity to the residue patterns of carbohydrates present on the surface of viruses or virus-infected cells, especially when the humoral immunity is not fully functional, such as in childhood or in immunosuppressed or immunocompromised populations [13–15]. Thus, MBL contributes to the defence of the innate immune system by initiating the activation of the lectin-complement pathway, which promotes opsonophagocytosis, modulates inflammation and induces cellular lysis [16–18].…”

“…Regarding PLWHA, some studies have shown an association between MBL plasma concentration deficiency and HIV infection or a more rapid disease progression [19–23], and others found no association with this infection, the HIV viral load or the CD4 count [18, 24]. However, the influence of MBL on HHV-8 infection is not known, but for other herpes viruses, studies suggest that MBL deficiency may be a risk factor for the symptomatic development of human herpesvirus 2 (HHV-2) [25] and for cytomegalovirus reactivation (CMV) [14, 26].…”