Background Commencing lifelong antiretroviral therapy (ART) immediately following HIV diagnosis (Option B+), has greatly improved maternal-infant health. Thus, large and increasing numbers of HIV-infected women are on ART during pregnancy, a situation concurrently increasing numbers of HIV-exposed-uninfected (HEU) infants. Compared to their HIV-unexposed-uninfected (HUU) counterparts, HEU infants show higher rates of adverse birth outcomes, mortality, infectious/non-communicable diseases including impaired growth and neurocognitive development. There is an urgent need to understand the impact of HIV and early life ART exposures, immune-metabolic dysregulation, comorbidities and environmental confounders on adverse paediatric outcomes. Methods Six hundred (600) HIV-infected and 600 HIV-uninfected pregnant women ≥20 weeks of gestation will be enrolled from four primary health centres in high density residential areas of Harare. Participants will be followed up as mother-infant-pairs at delivery, week(s) 1, 6, 10, 14, 24, 36, 48, 72 and 96 after birth. Clinical, socio-economic, nutritional and environmental data will be assessed for adverse birth outcomes, impaired growth, immune/neurodevelopment, vertical transmission of HIV, hepatitis-B/C viruses, cytomegalovirus and syphilis. Maternal urine, stool, plasma, cord blood, amniotic fluid, placenta and milk including infant plasma, dried blood spot and stool will be collected at enrolment and follow-up visits. The composite primary endpoint is stillbirth and infant mortality within the first two years of life in HEU versus HUU infants. Maternal mortality in HIV-infected versus -uninfected women is another primary outcome. Secondary endpoints include a range of maternal and infant outcomes. Sub-studies will address maternal stress and malnutrition, maternal-infant latent tuberculosis, Helicobacter pylori infections, immune-metabolomic dysregulation including gut, breast milk and amniotic fluid dysbiosis. Discussion The University of Zimbabwe-College of Health-Sciences-Birth-Cohort study will provide a comprehensive assessment of risk factors and biomarkers for HEU infants’ adverse outcomes. This will ultimately help developing strategies to mitigate effects of maternal HIV, early-life ART exposures and comorbidities on infants’ mortality and morbidity. Trial registration ClinicalTrial.gov Identifier: NCT04087239. Registered 12 September 2019.
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.
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.
BackgroundAchieving and maintaining viral suppression (VS) in people living with HIV/AIDS on antiretroviral therapy (ART) remains a crucial clinical goal, more so in pregnancy to prevent mother-to-child-transmission (MTCT). There is a need to understand VS kinetics and barriers to achieving it in order to meet the target of eliminating HIV-MTCT by 2030.MethodsHIV-infected pregnant women ≥20 weeks of gestation with different durations of Tenofovir/Lamivudine/Efavirenz exposures seeking antenatal care services at four primary health centres in high-density residential areas in Harare, Zimbabwe were enrolled in the University of Zimbabwe Birth Cohort Study. Plasma viral load (VL) was quantified by reverse transcriptase–polymerase chain reaction. Demographic, clinical, socio-economic and HIV- and ART-related factors were tested in multivariable logistic regression analyses as potential predictors for VS and undetectable VL.ResultsFrom March 2016 to June 2019, 608 HIV-infected pregnant women were enrolled. 63 (10.4%) were self-reported-ART-naïve; 324 (53.3%) and 221 (36.3%) initiated ART pre- and post-conception, respectively. Time from ART initiation to VS (VL ≤ 1,000 copies/ml) in 95% of the women was 126 days. Overall lack of VS (VL > 1,000 copies/ml) was observed in 133 (21.9%) women being 76.2, 27.4 and 7.7% in self-reported-ART-naïve, post-conception and pre-conception groups, respectively. Undetectable VL (≤ 50 copies/ml) was observed in 371 (61.2%) and low-level viremia (51–1,000 copies/ml) in 102 (16.8%) women.In multivariable models for all participants regardless of ART exposure, being on ART was the strongest predictor for both VS and undetectable VL (odds ratio 95% confidence interval, OR (CI): 8.9(4.2–19.5) and 8.1(3.2–24.4), respectively). For women on ART, duration of ART use >126 days was the strongest predictor with OR (CI): 6.7(3.3–14.0) for VS and 8.5(5.6–13.1) for undetectable VL. Other relevant predictors for favourable virological outcomes were older maternal age, HIV-status disclosure, absence of ART side effects and self-reported depression. Having a spouse/intimate partner on ART predicted a 4 times higher likelihood for VS.DiscussionLack of VS was frequently observed in this Harare cohort of pregnant women, mainly due to new HIV diagnosis, hence not being on ART and suboptimal duration of ART exposure. Since VS for 95% of women needed about 4 months of ART exposure, eliminating HIV-MTCT will require timely screening and commencing women together with their spouses/intimate partners on ART before pregnancy or early after conception.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier: NCT04087239.
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.
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