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 μg/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 between-population 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.

FIG. 1.

Kaplan Meier plot of the 197 HIV-1 infected participants by plasma MBL concentration. Survival time was calculated from baseline data to death or upon censoring. Participants were subdivided into three groups according to plasma MBL concentration, normal levels (above 500 μg/L), reduced/intermediate (100–500 μg/L), and deficient (below 100 μg/L). One hundred and thirty four (113) participants had normal plasma MBL concentrations, 41 had reduced/intermediate levels, and 43 had deficient levels. Log Rank test 0.1129.

FIG. 2.

Kaplan Meier plot of HIV-1 infected participants comparison by MBL2 genotype. Survival time was calculated from baseline data to death or upon censoring. One hundred and sixteen participants (116) had normal A/A MBL2 genotype, 66 had A/O variant MBL2 genotype, and 8 had O/O genotype. Log rank test 0.263.

FIG. 3.

Kaplan Meier plot showing the comparative dose-dependent effect of number of XA haplotypes on survival in the normal A/A MBL2 genotype group only, within the HIV positive stratum. Log rank test 0.6125. Zero X n = 65, One X n = 41, Two X n = 8.

FIG. 4.

Kaplan Meier plot of HIV-1 infected participants comparison by MBL2 genotype. The MBL2 haplotypes were further combined and subdivided into three groups, namely haplotypes that give normal plasma MBL levels (YA/YA, YA/XA), intermediate levels (XA/XA, YA/YO), and deficient levels (XA/YO, YO/YO). Survival time was calculated from baseline data to death or upon censoring. One hundred and ten participants (110) had (YA/YA, YA/XA) MBL2 genotype, 72 had variant (XA/XA, YA/YO) MBL2 genotype, and 8 had (XA/YO, YO/YO) genotype). Log rank test 0.3176.

FIG. 5.

(A) CD4⁺ T cell count (cells/μL) according to genotype. (B) Viral load (copies per mL) according to MBL2 genotype A/A: normal MBL2 genotype, A/O: heterozygous and O/O: MBL2 variant homozygous (n = 190).