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This study aimed to investigate the seroprevalence of cytomegalovirus (CMV) infection and risk factors associated with CMV acquisition among pregnant women in Zimbabwe. In a cross-sectional study, pregnant women were recruited in late gestation, seeking antenatal care at council clinics in three high-density suburbs in Harare, Zimbabwe. Anti-CMV IgM and IgG antibodies were quantified in serum using an enzyme-linked immunosorbent assay. Antibody avidity tests were used to distinguish active infection from viral reactivation in anti-CMV IgM-positive cases. Five hundred and twenty four women were recruited: 278 HIV infected and 246 HIV uninfected. Current or active CMV infection defined as IgM positive+low avidity was detected in 4.6% (24/524), 95% confidence interval (CI): 3–6.9 in all women, 5.8% (16/278) in the HIV infected and 3.3% (8/246), 95% CI: 1.4–6.3 in the HIV uninfected. IgG seroprevalence was 99.6% (522/524), 95% CI: 98.6–99.9 in all women. Notably, the difference in the prevalence of active CMV infection between the HIV-infected and HIV-uninfected women was not statistically significant (p = 0.173). The study shows a low prevalence of primary or active CMV infection among the pregnant women, but the IgG seroprevalence suggests high previous CMV exposure. Importantly, CMV seroprevalence was not associated with the HIV status of the women, perhaps due to the ubiquitous exposure of the population to CMV.

Aims: Long term use of antiretroviral therapy subpopulation living with human immunodeficiency virus is associated with disturbances in blood lipids profiles which are not routinely monitored. More data on such disturbances are needed to persuade the country’s program to institute routine monitoring. This study sought to determine the prevalence and timing of dyslipidaemia in HIV/AIDS naïve people on ART at in Zimbabwe. Place and Duration of Study: The study was conducted at Mpilo Central Hospital Opportunistic Infections Clinic in Bulawayo, Zimbabwe over a period of three months. Methods: A cross-sectional study was conducted in HIV-infected persons receiving highly active anti-retroviral treatment at Mpilo Central Hospital Opportunistic Infections Clinic. Lipid assays were determined by Elisa methods. Viral loads and CD4 were measured using the COBAS® TaqMan® and BD FACSCount™ Flow Cytometer, respectively. Results: A total of 149 consenting participants were enrolled and most (63.2%) were females. The median age of the respondents was 43 years and their median CD4 count was 436 cells/μl after a median duration on ART of 36 months. Viral load was 35 (60.4%) years. NNRTI (90.6%) were the more commonly prescribed HAART. The prevalence of dyslipidaemia was 70.2%. Hypercholesterolaemia was observed in 72 (48.3%) patients with 26 being male and 46 being female. High levels of LDL-cholesterol (LDL-c ≥ 3.0 mmol/L) were found in 115 patients with 74 of them being female. Hypertriacylglycerolaemia (TAG ≥ 2.0 mmol/L) was present in 8 cases. The proportion of patients with a low HDL-cholesterol (HDL-c < 1.0 mmol/L) was 15.3% while those with a ratio of TC/HDL-c ≥ 4.1 were 87.5%. Conclusion: The study demonstrated a high prevalence of dyslipidaemia in HIV-patients receiving HAART. There is a need for the Country’s HIV program to institute laboratory monitoring of blood lipids in patients over one year on HAART.

Introduction: In response to the human immunodeficiency virus (HIV) infection, activated immune cells produce several cytokines that alter the immune response and HIV disease progression. We quantified Th1/Th2/Th17 cytokines in an antiretroviral therapy naïve (ART) cohort to investigate their correlation with traditional markers of HIV disease progression; CD4+ T-lymphocytes and virus load (VL). Methods: We enrolled 247 HIV-infected ART-naïve participants into the study. CD4+ T- and CD8+ T-lymphocytes were enumerated using flow cytometry. VL was quantified using the Cavidi ExaVirTM Load assay. IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ levels were quantified using the BD Cytometric Bead Array Human Th1/Th2/Th17 cytokine assay. The Kendall’s rank correlation coefficient was used to determine the correlation between log10 transformed data for cytokine levels and CD4+ T- and CD8+ T-lymphocytes, CD4/CD8 ratio, and VL. Results: The median CD4+ T- and CD8+ T-lymphocyte counts were 458 cells/µL (IQR:405-556) and 776 cells/µL (IQR:581-1064), respectively. The median CD4/CD8 ratio was 0.6 (IQR: 0.45-0.86). The median VL was log103.3.copies/mL (IQR:2.74-3.93). Low CD4+ T-lymphocyte counts (p=0.010) and CD4/CD8 ratio (p=0.044) were significantly correlated with high VL. There was no significant correlation of cytokine levels with CD4+ T-, CD8+ T-lymphocyte counts and CD4/CD8 ratio. However, high levels of IL-17A (p=0.012) and IL-6 (p=0.034) were significantly correlated with high VL. Conclusion: Our study contributes to the little knowledge available on the role of cytokine profiles in the immune response to subtype C HIV infection.

Past studies on the relationship between Killer cell Immunoglobulin-like Receptor (KIR) and Human Leukocyte Antigen (HLA) genetic variation and chronic immune activation (CIA) in HIV infection are not uniformly consistent. Moreover, interferon-γ-induced protein 10 (IP-10) is a soluble biomarker of immune activation, with high plasma concentrations predicting accelerated disease progression in HIV infection. Thus, we investigated the association of KIR and HLA-C genetic polymorphisms with plasma IP-10 concentration in 183 treatment-naive chronically HIV-infected adults of Bantu origin from Zimbabwe. KIR genetic variation was determined using allele-specific primer PCR while HLA-C typing was characterized by sequencing. Plasma IP-10 was quantified using enzyme-linked immunosorbent assay. The KIR2DL3 gene was significantly associated with CIA as observed from IP-10 concentrations among KIR2DL3 carriers (265.20 pg/mL, IQR: 179.99-385.19) compared with KIR2DL3 noncarriers (183.56 pg/mL; IQR: 110.98-230.81; p = 0.001) and among KIR2DL3+HLA-C2 carriers (226.23 pg/mL, IQR: 187.96-394.73) compared with KIR2DL3+HLA-C2 noncarriers (212.86 pg/mL, IQR: 160.15-344.99; p = 0.017), respectively. Similarly, IP-10 concentrations were significantly higher (p = 0.030) in the KIR3DS1 carriers (313.86 pg/mL, IQR: 230.05-469.20) compared with KIR3DS1 noncarriers (246.01 pg/mL, IQR: 169.58-373.32). Thus, KIR and HLA-C could be playing important roles in HIV-associated immune activation. The elevation of IP-10 in KIR2DL3 and KIR2DL3+C2 could potentially be explained by increased IFN-γ secretion from activated NK cell activation due to the absence of KIR2DL3's cognate C1 ligand. To the best of our knowledge, this is the first study on a potential link between KIR and HLA-C genetic determinants and plasma IP-10 concentration in this population sample. Future studies are called for in other world populations for biomarkers of disease progression and mechanisms of IP-10 variability in HIV infection.

Background Maternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll-like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans. Methods In a cross-sectional study, 110 women in late gestation who included 36 CMV infected cases and 74 CMV uninfected, age and HIV status matched controls were enrolled. Twenty single nucleotide polymorphisms in 10 genes which code for proteins involved in immunity against CMV were genotyped using Iplex GOLD SNP genotyping protocol on the Agena MassARRAY® system. Statistical analyses were performed using Stata SE and the ‘Genetics’ and ‘SNPassoc’ packages of the statistical package R. Results The TLR7 rs179008A > T (p TLR9 rs352139T > C (p = 0.049) polymorphism was on the borderline for association with CMV positive (CMV+) status. In contrast, the interleukin (IL)-6 rs10499563T > C (p TLR2 rs1816702C > T (p = 0.001) polymorphisms were associated with CMV negative (CMV-) status. Furthermore, allele frequencies of SNPs in TLR2, TLR4, TLR9, TLR7, IL-6, IL-10, IL-28B, IL-1A and interferon AR1 (IFNAR1) genes are being reported here for the first time in a Zimbabwean population. The allele frequencies in the Zimbabwean population are generally comparable to other African populations but different when compared to European and Asian populations. Conclusions Toll-like receptor and interleukin genetic polymorphisms influence CMV status in late gestation among black Zimbabweans. This is attributable to possible modulation of immune responses to CMV reactivation in a population previously exposed to CMV 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) (P10 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.

Background: Maternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans. Results: The TLR2 rs1816702C/C (p=0.002), TLR7 rs179008C/C (p

Additional file 1: Table 1. Genotype frequencies and univariate logistic regression of SNP with CMV infection status.

Introduction: Vertical transmission of Cytomegalovirus (CMV), resulting in congenital CMV (cCMV) infection could have disabling and potentially fatal effects on the foetus or neonate. Although primary infection probably has a higher risk of leading to cCMV, in highly seropositive populations, a significant risk of vertical transmission is thought to be due to CMV reactivation and or reinfection during pregnancy. In this narrative review, we summarise the prevalence of CMV infection and associated risk factors among pregnant African women, in a setting where primary CMV infection usually occurs during infancy. Methodology: A systematic search of literature published between January 2000 and January 2019, retrieved on five bibliographic databases was performed. Search for relevant articles was performed using the following keywords: cytomegalovirus, CMV, infection, antenatal infections, pregnancy, pregnant women, gravidity, developing countries and Africa, with appropriate qualifiers such as OR, AND. Results: Systematic searching retrieved 11 relevant original research papers. Prevalence of anti-CMV IgG and IgM antibodies ranged from 60-100% and 0-15.5%, respectively. Prevalence of CMV DNA ranged from 0-29%, depending on the specimen used. However, there was no geographic trend for CMV seroprevalence or CMV DNA prevalence across the African continent. Overall, a substantial percentage of women of reproductive-age were CMV seronegative and at risk of primary infection. Associations of sociodemographic factors with CMV infection were inconsistent across all reviewed studies. Conclusions: The limited data and inconsistency of findings from the few studies carried out in Africa calls for prospective studies comparing prevalence and outcomes of cCMV in infants born to women with both primary and reactivated CMV in Africa.

Background: The prevalence of morbidity and mortality associated with liver disease among HIV-infected individuals on combination antiretroviral therapy (ART) is high. Early screening of liver disease is essential, as it provides an opportunity for successful treatment. Hence, there is a need for reliable, inexpensive and non-invasive early markers of hepatic damage.Objectives: Non-invasive algorithms are available for assessing the extent of liver fibrosis as markers of ongoing inflammatory damage. This study compared the use of the FibroTest, Fibrosis-4 (FIB-4) index, APRI test and AST:ALT ratio in assessing liver fibrosis in combination ART-experienced individuals.Methods: In a comparative cross-sectional study, 79 participants between the ages of 8 and 62 years were recruited. The performance of each fibrosis algorithm was determined using established cut-off scores for clinically significant liver fibrosis.Results: The prevalence of liver fibrosis as determined by the FibroTest, FIB-4 index, APRI test and AST: ALT ratio were 19.0%, 21.5%, 12.7% and 79.7%, respectively. For individual biomarkers, A-2M concentration (p < 0.001) and AST activity (p = 0.003) remained significantly elevated in participants with fibrosis than those without as defined by FibroTest and APRI test, respectively, after adjustments for multiple comparisons.Conclusion: Our data demonstrate a high prevalence of asymptomatic liver fibrosis among combination ART-experienced individuals in Zimbabwe, and this warrants adequate monitoring of liver fibrosis in individuals on ART. Discordance of fibrosis results among the algorithms and individual biomarkers and calls for further work in identifying optimal biomarkers for detection of asymptomatic fibrosis.Keywords: Liver fibrosis; Non-invasive methods; Biomarkers; Combination anti-retroviral therapy; Zimbabwe.

HIV/AIDS disease manifestations play critical roles on the host's immune response to infections especially cell-mediated immunity which is central in combating many other infections, allowing opportunistic pathogens that otherwise rarely infect humans, to cause disease. There is paucity of information to satisfactorily explain the geographical pathophysiological overlaps of malnutrition, bacterial, parasitic, and viral infections widespread in sub-Saharan Africa (SSA) where HIV burden is much higher than elsewhere. HIV and/or co-infections may worsen HIV related symptoms and outcomes, alter the presentation or/and increase viral virulence consequently, assisting the infectivity. Hence, co-infections are potential cofactors of HIV transmission in SSA. Most of currently published work often underplays co-infections resulting in misleading statistics and conclusions. A lot of studies have been done assessing single infections in isolation or independently yet in real life practical situation such solitary infections are rare. The prevalence of co-infections, how these in isolation or combination modify or modulate HIV transmission remains poorly described. Review Article Duri et al.; BMRJ, 6(2): 84-94, 2015; Article no.BMRJ.2015.061 85

Partial carrier-resistance toPlasmodium falciparummalaria conferred by the sickle cell (HbS) mutation has resulted in the local amplification and positive selection of sickle cell disease (SCD) in malaria-endemic regions and particularly in sub-Saharan Africa (SSA). The present study investigated theβ-globin gene haplotypes, and selected malaria-associated variants among three cohorts of Bantu-speaking individuals from Malawi, Zimbabwe and South Africa compared with reports with data from others SSA populations. The data suggest a south-ward frequency decrease of malaria-associated variants in SSA linked to the evolutionary dynamics of various African populations’ genomes through selective pressure of malaria. These selected genomics differences, positive selection of SCD in malaria-endemic regions among ‘Bantus’ from various part of Africa emphasise the evidence of the dissociation between genetics, anthropology and culture. The present study also showed a relatively prevalent Benin haplotype, which is mostly found in West Africa, among Southern African Blacks and very low Bantu haplotype, which could suggest a major migration route, of Southern Africa Bantu, along the African west coast, post-occurrence of the Sickle cell mutation, which date remain to be fully elucidated.

Introduction: There is growing evidence that polymorphisms in chemokine and chemokine receptor genes influence susceptibility to HIV infection and disease progression. However, not much is documented about the prevalence and effects of chemokine and chemokine receptor gene variations in the Zimbabwean population despite the high burden of HIV/AIDS in the country. This study therefore describes polymorphisms in CCR2, CX3CR1, SDF1 and RANTES genes in a Zimbabwean pediatric population and their effects on HIV infection in children born to HIV-infected mothers. Methodology: A total of 106 children between seven and nine years of age comprising 70 perinatally exposed to HIV (34 born infected [EI] and 36 born uninfected [EU]) and 36 unexposed and uninfected (UEUI) controls were recruited. Six allelic variants in four genes were genotyped using PCR-RFLP and sequencing. Results: Frequencies for minor alleles in the HIV uninfected groups (EU and UEUI) were CCR2 190A (16%), SDF1 801A (2%), CX3CR1 745A (9%), CX3CR1 839T (0%), RANTES In 1.1C (20%), and RANTES -403A (44%). There were significant differences between the EI and EU groups in the distribution of CCR2 190G/A genotype (15% versus 39%, respectively, p = 0.02) and CCR2 190G/A-CX3CR1 745G/G genotype combination (0% versus 33%, respectively, p = 0.002). Conclusions: Our findings suggest that chemokine and chemokine receptor gene variants seem to play an important role in the dynamics of HIV infection and could be used as drug or vaccine targets.

Mannose binding lectin (MBL) is a pathogen pattern recognition protein involved in antimicrobial activities. Variation in MBL2 gene has been extensively implicated in differential outcomes of infectious diseases in studies conducted outside Africa, but virtually very little is known on the role of this candidate gene in the African continent. We investigated human genetic variations in MBL2 in a Zimbabwean pediatric population and their putative associations with HIV infection in perinatally exposed children. One hundred and four children aged 7 to 9 years comprising 68 perinatally exposed to HIV (32 who were born infected and 36 who were uninfected) and 36 unexposed controls were recruited. DNA samples were genotyped for MBL2 polymorphisms using PCR-RFLP and sequencing. HIV infected children had markedly variable and significantly lower mean height (p=0.03) and weight (p=0.005) when compared to the uninfected children. Using all samples, frequencies for MBL2 genetic variants for the Zimbabwean population were calculated. Twelve single nucleotide polymorphisms were observed and minor alleles occurred with the following frequencies: −550C>G (G: 0.02), −435G>A (A: 0.08), −428A>C (C: 0.39), −394A>G (A: 0.39), −328AGAGAA ins/del (AGAGAA ins: 0.44), −245G>A (A: 0.05), −221C>G (C: 0.12), −111A>T (T: 0.10), −70C>T (C: 0.46), +4C>T (C: 0.45), novel −595G>A (A: 0.02), and 170G>A (0.24). We found that the MBL2 +4T variant displayed a trend for association with reduced risk of HIV transmission from mother-to-child but the remaining vast majority of the genetic markers did not show a significant association. We conclude (1) the MBL2 gene is highly polymorphic in the Zimbabwean population, and (2) MBL2 genetic variation does not appear to play a major role in influencing the risk of mother-to-child HIV transmission in our study sample. These observations contest the hitherto significant role of this candidate gene for HIV transmission from mother-to-child in non-African populations and thus, further speak to the limits of extrapolating genomic association studies directly to the African populations from studies conducted elsewhere. It is hoped that more OMICS research in a diverse set of African countries can shed further light on the putative role (or the lack thereof ) of this candidate gene in HIV transmission in the continent, a major global health burden in Africa.

Background There is paucity data on the association of vitamin D deficiency (VDD) and active tuberculosis (TB) in southern Africa where the human immunodeficiency virus (HIV) is co-endemic. We examined the association of serum vitamin D concentrations with active pulmonary tuberculosis (PTB) in HIV-infected (n = 284) and uninfected (n = 267) Black Zimbabweans, in Harare, Zimbabwe. Methods We conducted a cross-sectional study of 551 participants comprising 145 HIV+/PTB +, 139 HIV+/PTB−, 134 HIV−/PTB+ and 133 HIV−/PTB−. PTB status was confirmed using sputum by culture, or smear microscopy, or GeneXpert MTB/RIF. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured using a competitive chemiluminescent immunoassay prior to commencement of anti-TB treatment. Results In all four groups, the median vitamin D concentrations were above the 20 ng/ml cut off for VDD. However, the median vitamin D concentrations in all the four groups were below the cut off for vitamin D sufficiency ≥30 ng/ml. The median vitamin D concentrations were significantly higher in PTB+ cases; 24.2 ng/ml (IQR: 18.8–32.0) compared to PTB− controls 20.9 ng/ml (IQR: 17.1–26.9), p

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.

The extremely high prevalence of HIV/AIDS in sub-Saharan Africa and limitations of current antiretroviral medicines demand new tools to optimize therapy such as pharmacogenomics for person-to-person variations. African populations exhibit greater genetic diversity than other world populations, thus making it difficult to extrapolate findings from one population to another. Nevirapine, an antiretroviral medicine, displays large plasma concentration variability which adversely impacts therapeutic virological response. This study, therefore, aimed to identify sources of variability in nevirapine pharmacokinetics and pharmacodynamics, focusing on genetic variation in CYP2B6 and CYP1A2. Using a cross-sectional study design, 118 HIV-infected adult Zimbabwean patients on nevirapine-containing highly active antiretroviral therapy (HAART) were characterized for three key functional single nucleotide polymorphisms (SNPs), CYP2B6 c.516G>T (rs3745274), CYP2B6 c.983T>C (rs28399499), and CYP1A2 g.-163C>A (rs762551). We investigated whether genotypes at these loci were associated with nevirapine plasma concentration, a therapeutic biomarker, and CD4 cell count, a biomarker of disease progression. CYP2B6 and CYP1A2 were chosen as the candidate genes based on reports in literature, as well as their prominence in the metabolism of efavirenz, a drug in the same class with nevirapine. Nevirapine plasma concentration was determined using LC-MS/MS. The mean nevirapine concentration for CYP2B6 c.516T/T genotype differed significantly from that of 516G/G (p C genotypes (p = 0.04). Importantly, the CYP1A2 g.-163C>A SNP was significantly associated with the pharmacodynamics endpoint, the CD4 cell count (p = 0.012). Variant allele frequencies for the three SNPs observed in this Zimbabwean group were similar to other African population groups but different to observations among Caucasian and Asian populations. We conclude that CYP2B6 c.516G>T and CYP2B6 c.983T>C could be important sources of nevirapine pharmacokinetic variability that could be considered for dosage optimization, while CYP1A2 g.-163C>A seems to be associated with HIV disease progression. These inter- and intra-population pharmacokinetic and pharmacodynamics differences suggest that a single prescribed dosage may not be appropriate for the treatment of disease. Further research into a personalized nevirapine regimen is required.

Background. Apolipoprotein B mRNA-editing catalytic polypeptide like-3G ( APOBEC3G ) is an antiviral enzyme that reduces viral fitness by introducing uracil to thymidine hypermutations in viral genomes. Thus, polymorphisms in the APOBEC3G gene have been implicated in differential outcomes of HIV infection and disease progression. However, there is insufficient evidence on the role of APOBEC3G gene variants on HIV infection, especially in African populations. This study therefore describes polymorphisms in the APOBEC3G gene in a Zimbabwean paediatric population and evaluates their effects on susceptibility to HIV infection among children born to HIV-infected mothers. Methods. A total of 104 children aged between 7 and 9 years, comprising 68 perinatally exposed to HIV (32 born infected (EI) and 36 born uninfected (EU)) and 36 unexposed and uninfected (UEUI) controls were recruited. Allelic variants ( n =5) in the APOBEC3G gene were characterised. Results. Frequencies for minor APOBEC3G alleles in the HIV-uninfected groups (EU and UEUI) were c.557G (40%), g.-90C (32%), g.-571C (12%), c.467-85C (42%), and c.582-162G (6%). APOBEC3G c.467-85C frequency was statistically significantly different when compared to the Masai of Kinyawa, Kenya population (42% v. 18%). None of the single nucleotide polymorphisms individually or as part of haplotypes were significantly associated with HIV infection when comparing the EI and EU groups. Conclusions. Our findings suggest that APOBEC3G polymorphisms alone may not have significant predictive power for inferring genetic susceptibility to vertical transmission of HIV in children perinatally exposed to HIV.

Additional file 2. Table 1: HIV-infected non-transmitting participants. Comparison of characteristics of HIV-infected non-transmitting participants between the study sample and the control sample. Data are expressed as n (%) or median (IQR); min-max unless stated otherwise. P-values to compare patient groups were calculated using the Mann-Whitney U test or Fisher’s exact test where appropriate. Missing data are indicated in the following manner: number of * = number of missing data points. Abbreviations: BMI: body mass index, CMV: cytomegalovirus, HIV: human immunodeficiency virus, WHO: world health organisation, N/A: not applicable. Table 2: HIV-uninfected participants. Comparison of characteristics of HIV-uninfected mothers between the study sample and the control sample. Data are expressed as n (%) or median (IQR); min-max unless stated otherwise. P-values to compare groups were calculated using Mann-Whitney U test or Fisher’s exact test where appropriate. Missing data are indicated in the following manner: number of * = number of missing data points. Abbreviations: BMI: body mass index, CMV: cytomegalovirus, HIV: human immunodeficiency virus, WHO: world health organisation, N/A: not applicable. Table 3: HIV-infected and uninfected study participants. Sample characteristics stratified for HIV status and CMV-DNAemia (4). Data are expressed as n (%) or median (IQR); min-max unless stated otherwise. P-values to compare patient groups were calculated using the Kruskal Wallis test, Mann-Whitney U test or Fisher’s exact test where appropriate. Missing data are indicated in the following manner: number of * = number of missing data points. Abbreviations: BMI: body mass index, CMV: cytomegalovirus, HIV: human immunodeficiency virus, WHO: world health organisation, N/A: not applicable. Table 4: CMV viremic and aviremic participants. Sample characteristics stratified for HIV status, cART exposure and CMV status and analysis of differences in participant groups. Data are expressed as n (%) or median (IQR); min-max unless stated otherwise. For calculation of vertical transmissions only infants that survived the first 6 weeks were included; exclusions due to death are marked with one “†” for each deceased infant. P-values to compare patient groups were calculated using the Kruskal Wallis test, Mann-Whitney U test or Fisher’s exact test where appropriate. Missing data are indicated in the following manner: number of * = number of missing data points. Abbreviations: BMI: body mass index, CMV: cytomegalovirus, cART: combination antiretroviral treatment, HIV: human immunodeficiency virus, WHO: world health organisation, N/A: not applicable. Table 5: Predictors of maternal CMV-DNA load. Linear regression showing the association of different variables with maternal CMV-DNA load in HIV-infected non-transmitting mothers after the removal of 0 outliers by the Tukey's fences method (Q1 – 3×IQR and Q3 + 3×IQR). Results are presented as linear coefficients; p-values are indicated as follows: *: p

Additional file 2. Table 1: HIV-infected non-transmitting participants. Comparison of characteristics of HIV-infected non-transmitting participants between the study sample and the control sample. Data are expressed as n (%) or median (IQR); min-max unless stated otherwise. P-values to compare patient groups were calculated using the Mann-Whitney U test or Fisher’s exact test where appropriate. Missing data are indicated in the following manner: number of * = number of missing data points. Abbreviations: BMI: body mass index, CMV: cytomegalovirus, HIV: human immunodeficiency virus, WHO: world health organisation, N/A: not applicable. Table 2: HIV-uninfected participants. Comparison of characteristics of HIV-uninfected mothers between the study sample and the control sample. Data are expressed as n (%) or median (IQR); min-max unless stated otherwise. P-values to compare groups were calculated using Mann-Whitney U test or Fisher’s exact test where appropriate. Missing data are indicated in the following manner: number of * = number of missing data points. Abbreviations: BMI: body mass index, CMV: cytomegalovirus, HIV: human immunodeficiency virus, WHO: world health organisation, N/A: not applicable. Table 3: HIV-infected and uninfected study participants. Sample characteristics stratified for HIV status and CMV-DNAemia (4). Data are expressed as n (%) or median (IQR); min-max unless stated otherwise. P-values to compare patient groups were calculated using the Kruskal Wallis test, Mann-Whitney U test or Fisher’s exact test where appropriate. Missing data are indicated in the following manner: number of * = number of missing data points. Abbreviations: BMI: body mass index, CMV: cytomegalovirus, HIV: human immunodeficiency virus, WHO: world health organisation, N/A: not applicable. Table 4: CMV viremic and aviremic participants. Sample characteristics stratified for HIV status, cART exposure and CMV status and analysis of differences in participant groups. Data are expressed as n (%) or median (IQR); min-max unless stated otherwise. For calculation of vertical transmissions only infants that survived the first 6 weeks were included; exclusions due to death are marked with one “†” for each deceased infant. P-values to compare patient groups were calculated using the Kruskal Wallis test, Mann-Whitney U test or Fisher’s exact test where appropriate. Missing data are indicated in the following manner: number of * = number of missing data points. Abbreviations: BMI: body mass index, CMV: cytomegalovirus, cART: combination antiretroviral treatment, HIV: human immunodeficiency virus, WHO: world health organisation, N/A: not applicable. Table 5: Predictors of maternal CMV-DNA load. Linear regression showing the association of different variables with maternal CMV-DNA load in HIV-infected non-transmitting mothers after the removal of 0 outliers by the Tukey's fences method (Q1 – 3×IQR and Q3 + 3×IQR). Results are presented as linear coefficients; p-values are indicated as follows: *: p