HIV Type-1 Group O Infection in Gabon: Low Prevalence Rate But Circulation of Genetically Diverse and Drug-Resistant HIV Type-1 Group O Strains

Abstract

The goals of this study conducted in Gabon were to determine the prevalence rate of HIV-1 group O (HIV-1/O) infections and to characterize the genetic diversity of HIV-1/O strains as well as implications on antiretroviral (ARV) drug resistance. During 2010-2011, 1,176 samples from HIV-positive subjects were tested at the CIRMF (Centre International de Recherches Médicales de Franceville) retrovirology laboratory using an in-house serotyping assay. Plasma HIV-1/O RNA viral loads (VL) were determined using the Abbott RealTime HIV-1 assay. After full genome sequencing, drug resistance patterns were analyzed using two different algorithms (Agence Nationale de Recherches sur le SIDA et les hépatites virales and Stanford). Overall, four subjects (0.34%) were diagnosed as HIV-1/O infected. One subject, untreated by ARVs, died 2 months after HIV-1/O diagnosis. One was lost to follow-up. Two additional patients, treated with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, showed CD4 counts <200/mm(3) and VL results of 101,000 and 10,050 cp/ml. After full-length genome sequencing of these two strains, we found a wide range of natural polymorphism in the protease (≥15 substitutions) and gp41 (N42D mutation) genes, as well as in the gag and gag-pol cleavage sites. No resistance mutation was detected in the integrase gene. These two strains harbored the Y181C mutation making them resistant to NNRTIs. M41L, M184V, and T215Y mutations were also found for one strain, making it resistant to all NRTIs by the Stanford algorithm. Even if HIV-1/O infection is low in Gabon, an accurate diagnosis and a reliable virological follow-up are required in Central Africa to optimize ARV treatments of HIV-1/O-infected patients.

HIV-1 Group O Genotypes and Phenotypes: Relationship to Fitness and Susceptibility to Antiretroviral Drugs

“…[1][2][3][4] As the HIV epidemic progresses, group O prevalence has continued to decrease in the population with rates now as low as 0.55% in 2004 and 1% in 2008. 2,[5][6][7][8] Nonetheless, with HIV-1 prevalence at *5% in Cameroon, HIV-1 group O may be responsible for more than 30,000 infections. 9 Apart from their high genetic variation, group O HIV-1 isolates show some phenotypic differences relative to HIV-1 group M. Specifically, more than 60% of group O strains are naturally resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as nevirapine (NVP), efavirenz (EFV), and etravirine (ETV).…”

“…11 In Cameroon and Gabon, high frequency of group O in the HIV-infected populations creates challenges for treatment strategies, which in best practice requires phenotypic and genotypic testing before treatment of a group O infection. 8,13 Interestingly, EFV+emtricitabine (or lamivudine/ 3TC)+tenofovir (or zidovudine) are the first line regimens most commonly used across the African continent, despite pre-existing EFV resistance in *30,000 of 600,000 HIV-1-infected patients in Cameroon. 3,9,14 Due to the high costs in genotyping and drug resistance testing, about 1%-2% of patients in some areas of Cameroon, Gabon, and Equatorial Guinea where group O dominates will immediately fail an NNRTI-based treatment due to a HIV-1 group O infection.…”

HIV-1 Group O Integrase Displays Lower Enzymatic Efficiency and Higher Susceptibility to Raltegravir than HIV-1 Group M Subtype B Integrase

“…Because HIV-O integrase already bears L74I, the acquisition of Q148 substitutions during RAL treatment might especially compromise the use of DTG in group O viruses, and more information on this topic is needed. Until now, however, RAL-based therapy has been effective for HIV-O-infected patients, and no resistance-associated substitutions have been reported in the integrase coding regions of HIV-O patients failing treatment with INSTIs (11,47). As stated, the structure of HIV-O integrase differs from that of HIV-M by some key residues that are close to the catalytic site, i.e., I74 and A153.…”

High Rate of Simian Immunodeficiency Virus (SIV) Infections in Wild Chimpanzees in Northeastern Gabon

“…Group M, the HIV-1 pandemic form, has so far infected at least 60 million people and caused more than 25 million deaths [ 15 ], whereas groups N and P are found exclusively in Cameroon with only a few infected individuals [ 16 , 17 ]. HIV-1 group O is mainly present in west Central Africa with low prevalence rates (<0.5% of HIV infected individuals) [ 18 , 19 , 20 ].…”