The Level of APOBEC3G (hA3G)-Related G-to-A Mutations Does Not Correlate with Viral Load in HIV Type 1-Infected Individuals

The APOBEC family of mammalian cytidine deaminases, such as APOBEC3G (hA3G), has been demonstrated to function as a host viral restriction factor against HIV-1. hA3G has been shown to cause extensive G-to-A mutations in the HIV-1 genome, which may play a role in viral restriction. To investigate the role of G-to-A mutations in HIV-1 pathogenesis, we isolated, amplified, and sequenced HIV-1 sequences (vif, gag, and env) from 29 therapy-naive HIV-1-infected individuals. The levels of G-to-A mutations correlated with the expression levels of hA3G in the vif (rho = 0.438, p = 0.041) and the env regions (rho = 0.392, p = 0.038), but not in the gag region (rho = 0.131, p = 0.582). There is no correlation between viral load and the level of G-to-A mutations in the vif (rho = 0.144, p = 0.522), env (rho = 0.168, p = 0.391), or gag regions (rho = −0.254, p = 0.279). Taken together, these findings suggest that the hA3G-induced G-to-A mutations may not be the mechanism by which hA3G restricts or controls viral replication. Thus, hA3G might be restricting viral growth in infected individuals through a mechanism that is independent of the cytidine deaminase activities of hA3G

High magnitude of under nutrition among HIV infected adults who have not started ART in Tanzania – a call to include nutrition care and treatment in the test and treat model

BACKGROUND: Undernutrition among people living with HIV (PLWHIV) can be ameliorated if nutrition specific and sensitive interventions are integrated into their HIV care and treatment centers (CTC). Integrated care is lacking despite expansion of antiretroviral therapy (ART) coverage, representing a substantial missed opportunity. This research aims to examine nutritional status and associated risk factors among HIV-positive adults prior to ART initiation in Tanzania in order to characterize existing gaps and inform early integration of nutrition care into CTC. METHODS: We analyzed data from 3993 pre-ART adults living with HIV enrolled in CTCs within the Trial of Vitamin (TOV3) and progression of HIV/AIDS study in Dar es salaam, Tanzania. The primary outcome for this analysis was undernutrition, measured as body mass index (BMI) below 18.5 kg/m2. We conducted descriptive analyses of baseline characteristics and utilized multiple logistic regression to determine independent factors associated with pre-ART undernutrition. RESULTS: Undernutrition was prevalent in about 27.7% of pre-ART adults, with a significantly higher magnitude among males compared to females (30% vs. 26.6%, p < 0.025). Severe undernutrition (BMI < 16.0 kg/m2) was prevalent in one in four persons, with a trend toward higher magnitudes among females (26.2% vs. 21.1% p = 0.123). Undernutrition was also more prevalent among younger adults (p < 0.001), those with lower wealth quintiles (p = 0.003), and those with advanced HIV clinical stage (p < 0.001). Pre-ART adults presented with poor feeding practices, hallmarked by low dietary diversity scores and infrequent consumption of proteins, vegetables, and fruits. After adjusting for confounders and important co-variates, pre-ART undernutrition was associated with younger age, low wealth indices, advanced clinical stage, and low dietary diversity. CONCLUSIONS: One in every four pre-ART PLWHIV presented with undernutrition in Dar es salaam, Tanzania. Risk factors for undernourishment included younger age, lower household income, advanced HIV clinical stage, and lower dietary diversity score. Knowledge of the prevalence and prevailing risk factors for undernutrition among pre-ART PLWHIV should guide targeted, early integration of nutrition interventions into routine HIV care and treatment in high-prevalence, low-income settings such as Tanzania

Assessing environmental enteric dysfunction via multiplex assay and its relation to growth and development among HIV-exposed uninfected Tanzanian infants.

BackgroundEnvironmental enteric dysfunction (EED) may contribute to poor growth and development in young children. While validated EED biomarkers are currently lacking, multiplex assays are able to capture multiple domains of the condition. The purpose of this exploratory study was to examine the relationship between biomarkers of EED and subsequent growth and development among Tanzanian HIV-exposed uninfected (HEU) infants.MethodologyWe enrolled 467 infants of mothers living with HIV who had participated in a trial of vitamin D3 supplementation during pregnancy. Infant serum samples collected at 6 weeks (n = 365) and 6 months (n = 266) were analyzed for anti-flagellin and anti-lipopolysaccharide (LPS) IgA and IgG via ELISA as well as the 11-plex Micronutrient and EED Assessment Tool (MEEDAT), which incorporates two biomarkers of EED [intestinal fatty acid-binding protein (I-FABP) and soluble CD14 (sCD14)]. Outcomes were 12-month growth [length-for-age z-score (LAZ), weight-for-length z-score (WLZ), and weight-for-age z-score (WAZ)] and development [Caregiver Reported Early Development Instruments (CREDI) z-scores] and were assessed using linear regression.FindingsIn primary analyses, higher quartiles of 6-month anti-LPS IgG concentrations were significantly associated with lower LAZ at 12 months (ptrend = 0.040). In secondary analyses, higher log2-transformed 6-week anti-flagellin IgA and 6-month anti-LPS IgA concentrations were significantly associated with lower LAZ at 12 months. No associations were observed between I-FABP or sCD14 and infant growth. However, higher log2-transformed 6-week sCD14 concentrations were significantly associated with lower overall CREDI z-scores, while higher log2-transformed 6-month I-FABP concentrations were significantly associated with higher overall CREDI z-scores.ConclusionsUnlike anti-flagellin and anti-LPS Igs, MEEDAT's biomarkers of EED (I-FABP and sCD14) were not associated with subsequent linear growth among HEU infants in Tanzania. The relationship between EED and infant development warrants further study

Biomarker concentrations (quartiles) at 6 months of age and associations with growth outcomes at 12 months of age.

Biomarker concentrations (quartiles) at 6 months of age and associations with growth outcomes at 12 months of age.</p

Flow diagram for study.

Abbreviations: CREDI, Caregiver Reported Early Development Instruments; EED, environmental enteric dysfunction; FliC, flagellin; Ig, immunoglobulin; LAZ, length-for-age z-score; LPS, lipopolysaccharide; MEEDAT, Multi-Micronutrient and Environmental Enteric Dysfunction Assessment Tool.</p

Biomarker concentrations (quartiles) at 6 weeks of age and associations with growth outcomes at 12 months of age¹.

Biomarker concentrations (quartiles) at 6 weeks of age and associations with growth outcomes at 12 months of age1.</p

Associations between biomarkers concentrations (log₂-transformed) at 6 weeks and 6 months of age and growth outcomes at 12 months of age.

Associations between biomarkers concentrations (log2-transformed) at 6 weeks and 6 months of age and growth outcomes at 12 months of age.</p

Associations between biomarker concentrations (log₂-transformed) at 6 weeks and 6 months of age and CREDI z-scores at 12 months of age.

Associations between biomarker concentrations (log2-transformed) at 6 weeks and 6 months of age and CREDI z-scores at 12 months of age.</p

Descriptive characteristics for 467 infants and their mothers in Dar es Salaam, Tanzania.

Descriptive characteristics for 467 infants and their mothers in Dar es Salaam, Tanzania.</p

Correlation coefficient matrix of biomarker concentrations at 6 weeks and 6 months of age¹.

Correlation coefficient matrix of biomarker concentrations at 6 weeks and 6 months of age1.</p