Longitudinal analysis of microbiome composition in Ghanaians living with HIV-1.

Human immunodeficiency virus (HIV) 1 infection is known to cause gut microbiota dysbiosis. Among the causes is the direct infection of HIV-1 in gut-resident CD4+ T cells, causing a cascade of phenomena resulting in the instability of the gut mucosa. The effect of HIV infection on gut microbiome dysbiosis remains unresolved despite antiretroviral therapy. Here, we show the results of a longitudinal study of microbiome analysis of people living with HIV (PLWH). We contrasted the diversity and composition of the microbiome of patients with HIV at the first and second time points (baseline_case and six months later follow-up_case, respectively) with those of healthy individuals (baseline_control). We found that despite low diversity indices in the follow-up_case, the abundance of some genera was recovered but not completely, similar to baseline_control. Some genera were consistently in high abundance in PLWH. Furthermore, we found that the CD4+ T-cell count and soluble CD14 level were significantly related to high and low diversity indices, respectively. We also found that the abundance of some genera was highly correlated with clinical features, especially with antiretroviral duration. This includes genera known to be correlated with worse HIV-1 progression (Achromobacter and Stenotrophomonas) and a genus associated with gut protection (Akkermansia). The fact that a protector of the gut and genera linked to a worse progression of HIV-1 are both enriched may signify that despite the improvement of clinical features, the gut mucosa remains compromised.

Assessment of the Proportion of Recent HIV-1 Infections in Newly-Diagnosed Cases in Ghana.

Accurate monitoring of epidemics is a key strategy for controlling human immunodeficiency virus type-1 (HIV-1) infection. To delineate the characteristics of newly diagnosed cases of HIV-1 infection, we assessed the proportion of recent HIV-1 infections using a recent infection-testing algorithm (RITA). In 2015, 248 cases were newly diagnosed with HIV infection at the Regional Hospital Koforidua, Ghana. Of these, 234 cases (94.4%) were infected with HIV-1 only, four (1.6%) were infected with HIV-2 only, and 10 (4.0%) were co-infected with HIV-1 and HIV-2. All HIV-1 single-seropositive samples were used in the HIV-1 LAg avidity assay for RITA. Our analysis revealed that 18 cases (7.7%) were recently infected, indicating that early diagnosis was not achieved in Ghana. This is the first report to assess the proportion of recent infections in Ghana using a biomarker approach. The accumulation of these data will contribute to the accurate estimation of HIV-1 incidence and prevalence in Ghana.

High-level resistance to non-nucleos(t)ide reverse transcriptase inhibitor based first-line antiretroviral therapy in Ghana; A 2017 study.

Expanding access to effective antiretroviral therapy (ART) is a major tool for management of Human Immunodeficiency Virus (HIV) infection. However, rising levels of HIV drug-resistance have significantly hampered the anticipated success of ART in persons living with HIV (PLWH), particularly those from Africa. Though great strides have been made in Ghana toward achieving the UNAIDS "95-95-95" target, a substantial number of PLWH receiving ART have not attained viral suppression. This study investigated patterns of drug resistance mutations in ART naïve as well as ART-experienced PLWH receiving first-line regimen drugs from Ghana. In a cross-sectional study, blood samples were collected from HIV-1 infected adults (≥18 years) attending HIV/AIDS clinic at the Eastern Regional Hospital, Koforidua, Ghana from September to October 2017. Viral RNA isolated from plasma were subjected to genotypic drug resistance testing for Protease Inhibitors (PI), Reverse Transcriptase Inhibitors (RTI), and Integrase Strand Transfer Inhibitors (INSTI). A total of 95 (84 ART experienced, 11 ART naïve) HIV-1 infected participants were sampled in this study. Sixty percent (50/84) of the ART-experienced participants were controlling viremia (viral load < 1,000 copies/ml). Of the 95 patient samples, 32, 34, and 33 were successfully sequenced for protease, reverse-transcriptase, and integrase regions, respectively. The dominant HIV-1 subtypes detected were CRF02_AG (70%), and A3 (10%). Major drug resistance associated mutations were only detected for reverse transcriptase inhibitors. The predominant drug resistance mutations were against nucleos(t)ide reverse transcriptase inhibitors (NRTI)-M184V/I and non-nucleos(t)ide reverse transcriptase inhibitors (NNRTI)-K103N. In the ART-experienced group, M184V/I and K103N were detected in 54% (15/28) and 46% (13/28) of individuals, respectively. Both mutations were each detected in 33% (2/6) of ART naïve individuals. Multiclass resistance to NRTI and NNRTI was detected in 57% of ART-experienced individuals and two ART naïve individuals. This study reports high-level resistance to NNRTI-based antiretroviral therapy in PLWH in Ghana. However, the absence of major PI and INSTI associated-mutations is a good signal that the current WHO recommendation of Dolutegravir in combination with an NRTI backbone will yield maximum benefits as first-line regimen for PLWH in Ghana.

Dysbiotic Fecal Microbiome in HIV-1 Infected Individuals in Ghana.

HIV-1 infected individuals under antiretroviral therapy can control viremia but often develop non-AIDS diseases such as cardiovascular and metabolic disorders. Gut microbiome dysbiosis has been indicated to be associated with progression of these diseases. Analyses of gut/fecal microbiome in individual regions are important for our understanding of pathogenesis in HIV-1 infections. However, data on gut/fecal microbiome has not yet been accumulated in West Africa. In the present study, we examined fecal microbiome compositions in HIV-1 infected adults in Ghana, where approximately two-thirds of infected adults are females. In a cross-sectional case-control study, age- and gender-matched HIV-1 infected adults (HIV+; n = 55) and seronegative controls (HIV-; n = 55) were enrolled. Alpha diversity of fecal microbiome in HIV+ was significantly reduced compared to HIV- and associated with CD4 counts. HIV+ showed reduction in varieties of bacteria including Faecalibacterium, the most abundant in seronegative controls, but enrichment of Proteobacteria. Ghanaian HIV+ exhibited enrichment of Dorea and Blautia; bacteria groups whose depletion has been reported in HIV-1 infected individuals in several other cohorts. Furthermore, HIV+ in our cohort exhibited a depletion of Prevotella, a genus whose enrichment has recently been shown in men having sex with men (MSM) regardless of HIV-1 status. The present study revealed the characteristics of dysbiotic fecal microbiome in HIV-1 infected adults in Ghana, a representative of West African populations.

Fecal Microbiome Composition in Healthy Adults in Ghana.

Recent studies have indicated an association between gut microbiome composition and various disorders, including infectious diseases. The composition of the microbiome differs among ethnicities and countries, possibly resulting in diversified interactions between host immunity and the gut microbiome. Characterization of baseline microbiome composition in healthy people is an essential step for better understanding of the biological interactions associated with individual populations. However, data on the gut/fecal microbiome have not been accumulated for individuals in West Africa. In the present study, we examined the fecal microbiome composition in healthy adults in Ghana. Toward this, 16S rRNA gene libraries were prepared using bacterial fractions derived from 55 Ghanaian adults, which were then subjected to next-generation sequencing. The fecal microbiome of the Ghanaian adults was dominated by Firmicutes (Faecalibacterium, Subdoligranulum, and Ruminococcaceae UCG-014), Proteobacteria (Escherichia-Shigella and Klebsiella), and Bacteroidetes (Prevotella 9 and Bacteroides), consistent with previous observations in African cohorts. Further, our analysis revealed differences in microbiome composition and a lower diversity of the fecal microbiome in the Ghanaian cohort compared with those reported in non-African countries. This is the first study to describe substantial fecal microbiome data obtained using high-throughput metagenomic tools on samples derived from a cohort in Ghana. The data may provide a valuable basis for determining the association between the fecal microbiome and progression of various diseases in West African populations.