HSV-2 Infection as a Potential Cofactor for HIV Disease Progression and Selection of Drug Resistance Mutations in Adults under WHO-Recommended First-Line Antiretroviral Therapy: A Multicentric, Cross-Sectional Study in Cameroon, Central African Republic, Chad, and Gabon.

Abdoulaye Mihimit,Hélène Péré,Jean De Dieu Longo,Cecilia Costiniuk,Bertin Hig-Zounet Tchombou,Gérard Grésenguet,Sandrine Moussa,François-Xavier Mbopi-Keou,Laurent Bélec,Frédéric Talla,Donato Koyalta,Chatté Adawaye,Charlotte Charpentier,Ralph-Sydney Mboumba Bouassa

doi:10.3390/tropicalmed5030136

Abstract

Although herpes simplex virus-2 (HSV-2) infection is a known cofactor for HIV transmission in Central Africa, its role in HIV disease progression is unclear. The aim of this study was to examine the potential link between HSV-2 infection and HIV disease progression, in addition to identifying the presence of genes conferring HIV antiretroviral resistance mutations. This was a cross-sectional study involving 302 HIV-infected adults in Central Africa with virological failure (viral load >1000 copies/mL) on first-line antiretroviral therapy from four different countries. The seroprevalence of HSV-2 was 32% (96/302). Amongst the HIV-infected individuals who were HSV-2 seropositive, the mean HIV viral load and CD4 count were 4.82 ± 0.83 log copies/mL and 243 ± 144 cells/microliter, respectively. Among the HIV-infected individuals who were HSV-2-seronegative, the mean HIV viral load and CD4 count were 3.48 ± 0.44 log copies/mL and 646 ± 212 cells/microliter, respectively (p < 0.001). There was a statistically significant relationship (p < 0.001) between HSV-2 seropositivity and the presence of resistance mutations to antiretrovirals (ARV), non-nucleoside reverse transcriptase inhibitors (NNRTI), and nucleoside reverse transcriptase inhibitors (NRTI) with odds ratios of 9.7, 10, and 11.9, respectively. There was no link between HSV-2 serostatus and protease inhibitor (PI) resistance mutations. There was a substantial accumulation of resistance mutations in HSV-2-seropositive compared to -seronegative patients. These findings support the link between HIV disease progression and HSV-2 infection. An association was observed between the presence of NNRTI and NRTI resistance mutations and HSV-2 seropositivity.

Highlights

Sub-Saharan Africa is the region of the world most profoundly affected by the HIV epidemic
Our study, conducted with 302 HIV-infected individuals with virological failure under first-line therapy in four countries in Central Africa, enabled us to demonstrate an association between herpes simplex virus-2 (HSV-2) seropositivity and HIV disease progression, as measured by increased HIV plasma viral load and reduction in CD4 T-cell count compared to those who were HSV-2-seronegative
Our study demonstrated an association between the selection of HIV variant antiretroviral resistance mutations and HSV-2 infection

Summary

Introduction

Sub-Saharan Africa is the region of the world most profoundly affected by the HIV epidemic. A major turning point in the HIV epidemic was the expansion of access to antiretroviral therapy (ART), with a concomitant reduction in the number of HIV-attributable deaths [1,2,3]. This new hope seems compromised by the appearance of HIV strains carrying antiretroviral resistance mutations [4]. Many factors may contribute to the emergence of antiretroviral-resistant HIV strains in Africa. Biological progression is characterized by a reduction in the CD4 T-cell count and a rise in the HIV plasma viral load [14]. In N’Djamena, an elevated prevalence (64%) of antiviral resistant strains was found in adults with HIV under first-line ART [17]

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