Iron, haptoglobin phenotype, and HIV-1 viral load: A cross-sectional study among pregnant Zimbabwean women

Background: Viral load is a determinant of HIV-1 progression and transmission. Iron status and the phenotype of haptoglobin, a heme-binding acute phase reactant, may be determinants of viral load. We aimed to describe the effect of iron status, haptoglobin phenotype (Hp), and other predictors on HIV-1 viral load. Methods: Based on a cross-sectional study among 1669 antenatal care attenders (22-35 weeks) in Zimbabwe, 526 (31.5%) were found to be HIV infected. The role of season, age, gravidity, gestational age, malaria parasitemia, Hp, and elevated serum alpha(1)-antichymotrypsin (ACT) as well as serum ferritin, folate, retinol, and beta-carotene on HIV viral load among the 526 HIV-infected women was assessed using multiple linear regression analysis. Results: The distribution of Hp 1-1 (32%), Hp 2-1 (48%), and Hp 2-2 (20%) was not different from that of 53 uninfected women. Mean viral load was 3.85 log(10) (95% CI: 3.77-3.93) genome equivalents (geq)/mL, ranging from 3.77 (95% CI: 3.64-3.90) geq/mL in women with Hp 1-1 to 4.05 (95% CI: 3.81-4.21) geq/mL in women with Hp 2-2. With elevated serum ACT controlled for, women with Hp 2-2 had viral loads twice (95% CI: 1.4-4.0, p = .002) that of women with Hp 1-1, whereas those with serum ferritin <6 mug/L had viral loads less than one third (95% CI: 0.13-0.53, p = .013) that of women with serum ferritin >24 mug/L. Viral loads were also higher in women enrolled in the early rainy season compared with the dry season, in gravidae 4+ compared with gravidae 1 through 3, and in those with moderately elevated compared with low serum alpha(1)-antichymotrypsin, but neither age, gestational age, serum folate, serum retinol, nor serum beta-carotene were predictors. Conclusion: Storage iron, Hp 2-2, and elevated ACT are independent positive predictors of HIV-1 viral load. The positive relationship between serum ferritin and viral load was not the result of an acute phase response or iron accumulation with advanced HIV infection. A possible detrimental role of iron in HIV infection would have serious public health implications.