ABSTRACT
BACKGROUND: HIV-positive individuals who maintain an undetectable viral load cannot transmit the virus to others. In 2012, an HIV population-based survey was conducted in Ndhiwa sub-county (Kenya) to provide information on the HIV local epidemic. We carried out a second survey 6 years after the first one, to assess progress in HIV diagnosis and care and differences in the HIV prevalence and incidence between the two surveys. METHODS: A cross-sectional, population-based survey using cluster sampling and geospatial random selection was implemented in 2018, using the same design as 2012. Consenting participants aged 15-59 years were interviewed and tested for HIV at home. HIV-positive individuals received viral load testing (viral suppression defined as <1000 copies/ml) and Lag-Avidity EIA assay (to measure recent infection). The 90-90-90 UNAIDS indicators were also assessed. RESULTS: Overall, 6029 individuals were included in 2018. HIV prevalence was 16.9%. Viral suppression among all HIV-positive was 88.3% in 2018 (vs. 39.9% in 2012, p < 0.001). HIV incidence was 0.75% in 2018 vs. 1.90% in 2012 (p = 0.07). In 2018, the 90-90-90 indicators were 93%-97%-95% (vs. 60%-68%-83% in 2012). CONCLUSION: A two-fold increase in the HIV viral load suppression rate along with a decreasing trend in incidence was observed over 6 years in Ndhiwa sub-county. Achieving high rates of viral suppression in HIV populations that can lead to reducing HIV transmission in sub-Saharan contexts is feasible. Nevertheless, we will need further efforts to sustain this progress.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV-1 , Viral Load/drug effects , Adolescent , Adult , Cluster Analysis , Cross-Sectional Studies , Female , HIV Infections/virology , Humans , Incidence , Kenya/epidemiology , Male , Middle Aged , Prevalence , Young AdultABSTRACT
Different analogues of Capravirine (AG-1549) or S-1153 were prepared by synthesis of 2-(5-benzyl-4-isopropyl-1-methyl-2,3-dihydro-1H-imidazol-2-ylthio)acetamide (3a-c), ethyl [5-benzyl-1-(ethoxymethyl)-4-ethyl-1H-imidazol-2-ylthio]acetate (10), 2-[5-alkyl-4-substituted 1-(pyridin-4-ylmethyl)-1H-imidazol-2-ylthio]acetamides (12a-f), and 2-[5-benzyl-1-(benzyloxymethyl)-4-isopropyl-1H-imidazol-2-ylthio]acetamides (14a-l) from their corresponding amino acids through a sequence of reactions: Dakin-West reaction, hydrolysis, condensation with thiocyanate derivatives, alkylation with 2-iodoacetamide and ethyl chloroacetate, and coupling with 4-pyridylmethyl chloride, ethoxymethyl chloride and benzyloxymethyl chloride. All the synthesized compounds were screened for their activity against HIV-1 (wild type) and some of them (especially Capravirine like structures) were found active.
Subject(s)
Anti-HIV Agents/chemistry , Anti-HIV Agents/chemical synthesis , HIV-1/drug effects , Imidazoles/chemical synthesis , Reverse Transcriptase Inhibitors/chemical synthesis , Virus Replication/drug effects , Anti-HIV Agents/pharmacology , Cell Line/virology , Humans , Imidazoles/chemistry , Imidazoles/pharmacology , Reverse Transcriptase Inhibitors/chemistry , Reverse Transcriptase Inhibitors/pharmacology , Structure-Activity Relationship , Sulfur CompoundsABSTRACT
alpha-Aminoketone hydrochlorides 2a-d were synthesized by Dakin-West reaction from L-phenylalanine and L-cyclohexylalanine followed by hydrolysis in acidic medium. Treatment of 2a-d with aqueous potassium thiocyanate afforded 1, 3-imidazole-2-thiones 3a-d which were alkylated with methyl iodide to give 2-methylsulfanyl-1H-imidazoles 4a-d with 4-benzyl/4-cyclohexylmethyl and 5-ethyl/5-isopropyl substituents. Coupling of 4a-d with ethoxymethyl chloride or benzyloxymethyl chloride furnished N-1 5a-d and N-3 6a-h alkylated products. The synthesised compounds were tested for their activity against HIV-1. The most active compounds have a cyclohexylmethyl group in the 5-position of 6 and showed an activity against HIV-1 comparable to the activity of Nevirapine.
