Associations of inflammation-related proteome with demographic and clinical characteristics of people with HIV in South Africa.

PURPOSE: Elevated levels of inflammation associated with human immunodeficiency virus (HIV) infection are one of the primary causes for the burden of age-related diseases among people with HIV (PWH). Circulating proteins can be used to investigate pathways to inflammation among PWH. EXPERIMENTAL DESIGN: We profiled 73 inflammation-related protein markers and assessed their associations with chronological age, sex, and CD4+ cell count among 87 black South African PWH before antiretroviral therapy (ART). RESULTS: We identified 1, 1, and 14 inflammatory proteins significantly associated with sex, CD4+ cell count, and age respectively. Twelve out of 14 age-associated proteins have been reported to be associated with age in the general population, and 4 have previously shown significant associations with age for PWH. Furthermore, many of the age-associated proteins such as CST5, CCL23, SLAMF1, MMP-1, MCP-1, and CDCP1 have been linked to chronic diseases such as cardiovascular disease and neurocognitive decline in the general population. We also found a synergistic interaction between male and older age accounting for excessive expression of CST5. CONCLUSIONS AND CLINICAL RELEVANCE: We found that advanced age may lead to the elevation of multiple inflammatory proteins among PWH. We also demonstrated the potential utility of proteomics for evaluating and characterizing the inflammatory status of PWH.

Crosstalk between Host Genome and Metabolome among People with HIV in South Africa.

Genome-wide association studies (GWAS) of circulating metabolites have revealed the role of genetic regulation on the human metabolome. Most previous investigations focused on European ancestry, and few studies have been conducted among populations of African descent living in Africa, where the infectious disease burden is high (e.g., human immunodeficiency virus (HIV)). It is important to understand the genetic associations of the metabolome in diverse at-risk populations including people with HIV (PWH) living in Africa. After a thorough literature review, the reported significant gene−metabolite associations were tested among 490 PWH in South Africa. Linear regression was used to test associations between the candidate metabolites and genetic variants. GWAS of 154 plasma metabolites were performed to identify novel genetic associations. Among the 29 gene−metabolite associations identified in the literature, we replicated 10 in South Africans with HIV. The UGT1A cluster was associated with plasma levels of biliverdin and bilirubin; SLC16A9 and CPS1 were associated with carnitine and creatine, respectively. We also identified 22 genetic associations with metabolites using a genome-wide significance threshold (p-value < 5 × 10−8). In a GWAS of plasma metabolites in South African PWH, we replicated reported genetic associations across ancestries, and identified novel genetic associations using a metabolomics approach.

Comparing effectiveness of first-line antiretroviral therapy between peri-urban and rural clinics in KwaZulu-Natal, South Africa.

OBJECTIVES: Viral suppression (VS) is the hallmark of successful antiretroviral therapy (ART) programmes. We sought to compare clinic retention, virological outcomes, drug resistance and mortality between peri-urban and rural settings in South Africa after first-line ART. METHODS: Beginning in July 2014, 1000 (500 peri-urban and 500 rural) ART-naïve patients with HIV were enrolled and managed according to local standard of care. Clinic retention, virological suppression, virological failure (VF), genotypic drug resistance and mortality were assessed. The definition of VS was a viral load ≤1000 copies/ml. Time to event analyses were stratified by site, median age and gender. Kaplan-Meier curves were calculated and graphed with log-rank modelling to compare curves. RESULTS: Based on 2741 patient-years of follow-up, retention and mortality did not differ between sites. Among all 1000 participants, 47%, 84% and 91% had achieved VS by 6, 12 and 24 months, respectively, which was observed earlier in the peri-urban site. At both sites, men aged < 32 years had the highest proportion of VF (15.5%), while women aged > 32 years had the lowest, at 7.1% (p = 0.018). Among 55 genotypes, 42 (76.4%) had at one or more resistance mutations, which did not differ by site. K103N (59%) and M184V (52%) were the most common mutations, followed by V106M and K65R (31% each). Overall, death was infrequent (< 4%). CONCLUSIONS: No significant differences in treatment outcomes between peri-urban and rural clinics were observed. In both settings, young men were especially susceptible to clinic attrition and VF. More effective adherence support for this important demographic group is needed to achieve UNAIDS targets.