Polyunsaturated Fatty Acid Composition in Breast Milk Plasma of HIV-infected and Uninfected Mothers in Relation to Infant Clinical Outcomes.

BACKGROUND: The increased coverage of prevention of mother to child transmission (PMTCT) services has significantly reduced paediatric HIV infection incidence. The aim of the study was to compare breast milk omega-6 and omega-3 polyunsaturated fatty acid profiles of HIV infected and uninfected mothers and determine the association between fatty acid profiles and postnatal transmission of HIV, morbidity/mortality of HIV exposed and unexposed infants. METHODS: A prospective cohort study of 57 HIV infected and 57 HIV uninfected lactating mothers was conducted in Gweru, Zimbabwe from July 2019 to March 2020. The women's 114 babies (term and preterm) were also enrolled and stratified by HIV exposure and infection status. The mother-infant pairs were followed up at 6 weeks, 16 weeks and 6 months postpartum to determine, HIV transmission rate, breast milk polyunsaturated fatty acid profiles as well as infant clinical outcomes. RESULTS: The mean breast milk docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels in HIV uninfected mothers (0.82 ± 0.92; 0.47 ± 0.75 µg/ml respectively) at 6 weeks postpartum were significantly higher compared to those of HIV infected mothers (0.33 ± 0.32; 0.08 ± 0.14 µg/ml) respectively. The same pattern was observed at 16 weeks postpartum in terms of DHA and EPA mean concentration. However, the arachidonic acid (AA) levels and AA/DHA ratio measured at 6 weeks postpartum were significantly higher in HIV infected mothers (2.31 ± 2.01; 17.18 ± 52.47 respectively) compared to HIV uninfected mothers (0.82 ± 0.54; 9.71 ± 21.80; P < .001). A higher morbidity rate was observed amongst HIV exposed infants than HIV unexposed infants (3.26 ± 0.13; 2.49 ± 0.09; P < .001) respectively. A significant positive correlation was observed between AA and infant morbidity (r = .388; P < .001). CONCLUSION: Deficiencies in breast milk omega-3 fatty acids were observed in HIV infected women. Maintaining a healthy balance between omega-6 and omega-3 fatty acid diets is critical for breast feeding mothers regardless of their HIV status. The adverse clinical outcomes observed amongst HIV exposed infants emphasise their vulnerability under conditions of maternal universal antiretroviral therapy.

Levels of Total Antioxidant Capacity, sCD14, and TGF-ß2 in Breast Milk Plasma of HIV-Infected and HIV-Uninfected Lactating Women.

Introduction: Breast milk provides nourishment for infants and nonnutritive bioactive factors, which possess key protective and developmental benefits essential in shaping the infant immune system. However, the impact of human immunodeficiency virus (HIV) and universal antiretroviral therapy (ART) on breast milk nutritional composition and immunity status is not well documented. Objective: The study aimed to compare breast milk immune factors; total antioxidant capacity (TAC), soluble cluster of differentiation 14 (sCD14), and transcription growth factor-beta 2 (TGF-ß2) levels between HIV-infected and HIV-uninfected lactating mothers and determine the association between breast milk parameters with HIV disease progression and duration of ART. Methods: Breast milk sCD14, TAC, and TGF-ß2 were quantified using enzyme-linked immunosorbent assays and spectrophotometric techniques in 57 HIV-infected breast feeding mothers on option B+ therapy for prevention of vertical transmission of HIV and 57 HIV-uninfected mothers at 6 weeks postpartum. The plasma HIV viral load was measured on enrollment and demographic data were recorded. Results: Mean breast milk plasma TAC levels were significantly lower in HIV-infected mothers (1,250.5 ± 280.4 µmolTE/L) compared to the HIV-uninfected participants (1,915.4 ± 326 µmolTE/L; p < 0.001). Soluble CD14 levels in HIV-infected mothers were significantly higher (7,059.3 ± 1,604.7 ng/mL) compared to the HIV-uninfected group (5,670.7 ± 1,268.3 pg/mL; p < 0.001). Similarly, TGF-ß2 concentration was also significantly elevated in the HIV-infected mothers (1,426.1 ± 695.4 pg/mL) compared to the HIV-uninfected counterparts (709.2 ± 196.8 pg/mL; p < 0.001). A positive correlation was observed between breast milk plasma sCD14 concentration and the plasma viral load (r = 0.576, p < 0.001), while a significant negative correlation was observed with the duration of ART (r = -0.285, p = 0.032). TAC and TGF-ß2 concentrations were inversely correlated with plasma viral load levels. Conclusion: HIV-infected mothers are at risk of oxidative stress. Nutritional intervention with antioxidant rich foods is recommended for this vulnerable group during breastfeeding.

Growth Trajectories of HIV Exposed and HIV Unexposed Infants. A Prospective Study in Gweru, Zimbabwe.

BACKGROUND: With the increasing HIV seroprevalence among women of childbearing age in sub-Saharan Africa, limited data on growth outcomes of HIV exposed infants under current policies of universal maternal antiretroviral therapy exist. METHODS: The longitudinal growth patterns of 114 HIV exposed and unexposed infants were assessed and compared. The prevalence and factors associated with malnutrition were established. Infants under prevention of mother to child transmission care were recruited at 6 weeks post-delivery as were their HIV unexposed counterparts. Weight and length measurements were recorded at birth, 6 and 16 weeks postpartum. RESULTS: HIV vertical transmission rate was 8.8%. HIV exposed infants had significantly lower mean birth weights compared to HIV unexposed infants (2.9 ± 0.3; 3.2 ± 0.5; P < .001) respectively. Mean weight/length-for-age z-scores for HIV exposed, uninfected (HEU) infants were significantly below those of the HIV unexposed infants during follow up. By 6 weeks of age, 28.5% of HEU infants were malnourished while no malnutrition was evident in HIV unexposed infants. A gestational age <37 weeks (OR: 3.83; 95% CI: 1.03-14.30; P = .045) and HIV exposure (OR: 1.62; 95% CI: 0.17-15.73; P = .017) substantially increased the risk of stunting. CONCLUSION: Growth deficits were witnessed in HIV exposed infants compared to HIV unexposed infants. There is need for early nutritional monitoring and support among HIV exposed infants.

HLA-C*18:01 and KIR2DL2+C1 genetic variants are associated with low viral load in cART naïve HIV-infected adult Zimbabweans.

INTRODUCTION: Polymorphisms in killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) gene families are implicated in differential outcomes of HIV infection. However, research findings on the influence of KIR and HLA-C polymorphism on HIV disease progression remain inconclusive. We thus investigated the association of KIR and HLA-C gene polymorphisms with plasma HIV load (VL) and CD4+ T lymphocyte (CD4) count in 183 chronically HIV-infected, combination antiretroviral therapy (cART) naïve Zimbabweans of Bantu origin. METHODOLOGY: The presence or absence of 15 KIR genes were determined using sequence specific primer polymerase chain reaction while HLA-C typing was performed using chain termination DNA sequencing. Plasma VL was determined using the Cavidi Exavir viral load version 3 assay while CD4+ T lymphocytes were enumerated using flow cytometry. VLs and CD4 counts were compared between gene/genotype carriers and non-carriers using Mann-Whitney ranksum test. RESULTS: HLA-C*18:01 allele carriers had a significantly lower median log10 VL (2.87copies/mL [IQR;2.3-3.2]) than the non-C*18:01 carriers (3.33copies/mL [IQR; 2.74-3.9]), p = 0.018. Further, median log10 VL was significantly lower in KIR2DL2+C1 carriers (2.745 [IQR; 2.590-2.745]) than non-KIR2DL2+C1 carriers (3.4 [IQR; 2.746-3.412]), p = 0.041. Comparison of CD4 + T lymphocyte counts between C*08:02 allele carriers and non-C*08:02 carriers showed a significantly higher median CD4 count in C*08:02 carriers (548cells/µL [IQR;410-684]) than in non-carriers (428cells/µL [IQR;388-537]), p = 0.034. CONCLUSION: We conclude that the HLA-C*18:01 and KIR2DL2+C1 genetic variants are associated with low VL while the C*08:02 is associated with high CD4+ T lymphocyte count among cART naïve Zimbabwean adults with chronic HIV infection.

Plasma IP-10 Concentrations Correlate Positively with Viraemia and Inversely with CD4 Counts in Untreated HIV Infection.

BACKGROUND: Chronic immune activation is a feature of HIV infection associated with accelerated HIV disease progression. There is conflicting data on the association of biomarkers of immune activation with traditional markers of HIV disease progression; CD4 counts and viral load (VL). OBJECTIVE: The study aimed to determine the association of biomarkers of immune activation; interferon (IFN)-γ-induced protein 10 (IP-10) and soluble cluster of differentiation 14 (sCD14) in chronic HIV infection with traditional markers of HIV disease progression. METHODS: We collected demographic data, enumerated CD4 counts and quantified VL in 183 antiretroviral therapy (ART)-naive adults with chronic HIV infection. Plasma concentrations of IP-10 and sCD14 were quantified in the ART-naive adults with chronic HIV infection and 75 HIV-uninfected controls. RESULTS: IP-10 concentrations were significantly higher in the HIV-infected group (median; 257.40pg/ml, IQR; 174.08-376.32) than in the HIV-uninfected (median; 86.19pg/ml, IQR; 67.70-116.39) (P<0.001). Similarly, sCD14 concentrations were significantly higher in the HIV-infected (median; 1.45µg/ml, IQR; 1.02-2.16) group than in the controls (median; 0.89µ/ml, IQR; 0.74-1.18) (P<0.001). High log10 IP-10 concentrations were positively correlated with high log10 viral loads (Spearman's correlation coefficient [R]=0.21, P=0.003) and inversely correlated with low CD4 counts (R= -0.19, P=0.011). In contrast, log10 sCD14 was not significantly associated with either log10 viral loads (R=0.03, P=0.707) nor CD4 count (R=-0.04, P=0.568). CONCLUSION: We conclude that plasma sCD14 and IP-10 were elevated in the HIV-infected patients compared to HIV-uninfected individuals possibly due to on-going immune activation. In addition, plasma high concentrations of IP-10 but not sCD14 concentrations are associated with high VL and low CD4 count.

KIR Gene Content Diversity in a Zimbabwean Population: Does KIR2DL2 Have a Role in Protection Against Human Immunodeficiency Virus Infection?

Killer cell immunoglobulin-like receptors (KIRs) mediate natural killer cell function through interaction with their cognate human leukocyte antigen ligands. Thus, KIR gene variants have been implicated in resistance or susceptibility to viral infections. However, research on the role of these variants remains contradictory and inconclusive. In the present study, we investigated KIR gene content diversity and its association with human immunodeficiency virus (HIV) infection in an adult Black Zimbabwean population. Presence or absence of 15 KIR genes was determined in 189 HIV-infected adults and 97 HIV-uninfected blood donors using sequence specific primer polymerase chain reaction. Frequencies of KIR genes, genotypes, and haplotypes were compared between the cases and controls to identify putative associations between KIR gene variants and HIV status. We report in this study the frequencies of 15 KIR genes and 43 KIR genotypes (40 known and 3 novel) among Zimbabweans. Importantly, the frequency of the inhibitory KIR2DL2 gene was significantly higher in the uninfected group (62%) compared to the HIV-infected group (47%) (OR = 0.55, 95% CI: 0.33-0.90, p = 0.019). KIR2DL2/2DL2 homozygosity was also significantly higher in the uninfected group (35%) compared to HIV-infected group (53%) (OR = 0.33, 95% CI: 0.16-0.72, p = 0.005) under a recessive model. We conclude that the KIR2DL2 gene may be involved in protection against HIV infection. It may be possible that inhibitory KIR genes may have an important role to play in HIV acquisition among populations of African origin in whom the activating KIR genes are less frequent compared to among Caucasians.