HIV protease resistance mutations in patients receiving second-line antiretroviral therapy in Libreville, Gabon.

INTRODUCTION: In 2022, the WHO reported that 29.8 million people around the world were living with HIV (PLHIV) and receiving antiretroviral treatment (ART), including 25| 375 people in Gabon (54% of all those living with HIV in the country). The literature reports a frequency of therapeutic failure with first-line antiretrovirals (ARVs) of between 20% and 82%. Unfortunately, data relating to the failure of second-line ARVs are scarce in Gabon. This study aims to determine the profiles of HIV drug resistance mutations related to protease inhibitors in Gabon. METHODOLOGY: Plasma from 84 PLHIV receiving ARVs was collected from 2019 to 2021, followed by RNA extraction, amplification, and sequencing of the protease gene. ARV resistance profiles were generated using the Stanford interpretation algorithm version 8.9-1 ( https://hivdb.stanford.edu ) and statistical analyses were performed using EpiInfo software version 7.2.1.0 (CDC, USA). RESULTS: Of 84 HIV plasma samples collected from 45 men and 39 women, 342 mutations were detected. Of these, 43.3% (148/342) were associated with nucleoside reverse transcriptase inhibitors (NRTIs), 30.4% (104/342) with non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 26.3% (90/342) with protease inhibitors (PIs). Most NRTI mutations were associated with thymidine analogues (TAMs) (50.7%; 75/148), including T215F/V (14.9%; 22/148), D67DN/E/G/N/T (10.1%; 15/148), M41L (9.5%; 14/148), and K70E/KN/S/R (9.5%; 14/148). Resistance mutations related to non-TAM NRTIs (33.1%; 49/148) were M184V (29.1%; 43/148), and L74I/V (8.1%; 12/148). NNRTI mutations were predominantly K103N/S (32.7%; 34/104), V108I (10.6%; 11/104), A98G (10.6%; 11/104), and P225H (9.6%; 10/104). Minor mutations associated with PIs (60.0%; 54/90) were predominantly K20I (15.6%; 14/90) and L10F/I/V (14.5%; 13/90). The major mutations associated with PIs (40.0%; 36/90) were M41L (12.2%; 11/90), I84V (6.7%; 06/90), and V82A (6.7%; 06/90). The four most prescribed therapeutic regimens were TDF + 3TC + LPV/r (20.3%; 17/84), ABC + DDI + LPV/r (17.9%; 15/84), TDF + FTC + LPV/r (11.9%; 10/84), and ABC + 3TC + LPV/r (11.9%; 10/84). CONCLUSION: This study revealed that HIV drug resistance mutations are common in Gabon. The major mutations associated with PIs were M41L, I84V, and V82A. There is a need for access to new NRTIs, NNRTIs, and PIs for a better therapeutic management of PLHIV in Gabon.

Low prevalence of HCV infection with predominance of genotype 4 among HIV patients living in Libreville, Gabon.

BACKGROUND: Gabon is an endemic area for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) and the risk of co-infection is high. METHOD: Between November 2015 and April 2016, we conducted retrospective study on HCV infection among people living with HIV/AIDS (PLHA). A total of 491 PLHA were included in this study and tested for the presence of HCV infection. HIV viral loads were obtained using the Generic HIV viral Load® assay and the CD4+ T cells count was performed using BD FACSCount™ CD4 reagents. HCV screening was performed using the MP Diagnostics HCV ELISA 4.0 kit. HCV genotypes were determined by sequence analysis of NS5B and Core regions. The Mann-Whitney test was used to compare the groups. Chi-2 test and Fisher's Exact Test were used to compare prevalence. RESULTS: HCV seroprevalence was 2.9% (14/491), (95% confidence interval (CI):1.4-4.3%). The percentage of HCV viremic patients, defined by the detection of HCV RNA in plasma, was 57% (8/14), representing 1.6% of the total population. HCV seroprevalence and replicative infection were not statistically differ with gender. The percentage of co-infection increased with age. No correlation with CD4+ T cells count and HIV viral load level was registered in this study. Identified HCV strains were predominantly of genotype 4 (87.5%) including 4k, 4e, 4g, 4p, 4f and 4c subtypes. Only one strain belonged to genotype 2 (subtype 2q). Analysis of the NS5B region did not reveal the presence of resistance-associated substitutions for sofosbuvir. CONCLUSION: A systematic screening of hepatitis C is therefore strongly recommended as well as genotyping of HCV strains in order to adapt treatments for the specific case of people living with HIV/AIDS in Central Africa.

Hepatitis B infection among HIV infected individuals in Gabon: Occult hepatitis B enhances HBV DNA prevalence.

In Gabon, a central African country, human immunodeficiency virus (HIV) and hepatitis B virus (HBV) are endemic. In a recent study, conducted in a semi-urban area (Franceville, Gabon), HBV infection was found to be more prevalent among HIV infected individuals. This study aims to investigate the prevalence and genetic diversity of hepatitis B virus infection among HIV infected individuals, predominantly under antiretroviral therapy, living in fully urbanized area: Libreville, capital of Gabon. Serological and molecular tests were performed to detect HBV infection among patients living with HIV/AIDS (PLHA). We used Monolisa HBsAg ULTRA, Anti-HBc Plus and Anti-HBs Plus EIA kits for serological analyses. HBV DNA viral load (HBV DNA VL) was determined by real time PCR and molecular characterization of HBV strains was performed by sequencing and phylogenetic analysis of partial HBV surface and core genes. At all, 70.2% of patients were under antiretroviral therapy. The prevalence of HBsAg was 8.8% (43/487). Detectable HBV DNA was found in 69.7% (30/43) of HBsAg positive patients and in 17.5% (24/137) HBsAg negative patients. HBV DNA VL was significantly higher among patient with CD4 cell counts less than 200 cells/mm3 than those with CD4 cell counts greater than 500 cells/mm3 (p = 0.008). We confirmed the presence of HBV sub-genotypes QS-A3 (40%), and A4 (20%) and HBV-E genotype (40%). The percentage of resistance to Lamivudine was high (40%) and varied according to the M204V/I motif. Occult hepatitis B infection (OBI) was found in patients with isolated HBcAb and among patients who had completed their HBsAg seroconversion. We detected HBV DNA for one patient without any HBV serological marker. This study provides a new landmark for the comprehension of HBV infection in PLHA in urban areas. OBI enhances HBV DNA prevalence and should be investigated in all HBsAg negative individuals.