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.

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.

Differential influence of race and environment on indeterminate reactivities to non-treponemal and treponemal antigens by immuno-chromatographic dual syphilis rapid test.

INTRODUCTION: Syphilis rapid test results may be influenced by numerous environmental and genetic factors. METHODS: The proportion of false positive syphilis non-treponemal (NT) and treponemal (T) test results using immuno-chromatographic dual syphilis rapid test on serum from Cameroonian blacks (n=103) versus French blacks (n=104) or French caucasians (n=51), all HIV-negative and free of clinical syphilis, was examined. RESULTS: Black individuals in Cameroon had a significantly higher frequency of false positive NT or T tests than black individuals in France. black individuals in France had a higher frequency of indeterminate NT tests as compared to caucasians in France. CONCLUSION: Both racial and environmental factors may affect immuno-chromatographic dual syphilis rapid testing.

Pitfalls of antiretroviral drug resistance genotyping of HIV-1 Group M and Group N from Cameroon by sequenced-based assays.

BACKGROUND: HIV-1 genotyping for antiretroviral drug resistance mutations (DRMs) were developed based basically on subtype B HIV-1 Group M, which represents only 10% of HIV strains worldwide. In sub-Saharan Africa, non-B subtypes HIV-1 largely predominate and HIV-1 genetic diversity could affect the performance of drug resistance genotyping assays. We compared prospectively the performance of the ViroSeq(®) and Trugene(®) genotyping assays to detect DRM in HIV-1-infected adult patients living in Douala, Cameroun. MATERIALS AND METHODS: DRM in protease (P) and reverse transcriptase (RT) genes were assessed in parallel using both ViroSeq(®) and Trugene(®) assays in plasma samples from 45 first-line antiretroviral treatment-experienced patients in Douala, Cameroon. RESULTS: Trugene HIV-1 Genotyping Assay(®) (Siemens Health Care Diagnostics, NY, USA) and ViroSeq HIV-1 Genotyping System(®)(Celera Diagnostics, CA, USA) assessed equivalently antiretroviral DRMs in P and RT genes from non-B HIV-1 Group M in 44 Cameroonian adults in virological failure; Trugene(®) was slightly more sensitive than ViroSeq(®) (100% vs. 91%). One patient infected by HIV-1 Group N was successfully amplified only by the Trugene HIV-1 Genotyping assay(®), while ViroSeq HIV-1 Genotyping System v2.0(®) assay could not. CONCLUSION: Results showed the higher performance of the Trugene(®) system to detected and amplify P and RT genes targeting DRM to the principal antiretroviral drugs used in sub-Saharan Africa. Discrepancies between the results of HIV viral load assays and molecular tests should alert clinicians and virologists to the possibility of infection by an atypical variant virus, especially in Central Africa where very broad HIV-1 genetic diversity exists.

Association of inconclusive sera for human immunodeficiency virus infection with malaria and Epstein-Barr virus infection in Central Africa.

Among 464 sera from adults in Cameroon, 56 (12.1%) gave inconclusive HIV serology. All were negative for HIV-1 DNA; 44.6% (n = 25) were significantly associated with Plasmodium (42.8%) or Epstein-Barr virus (EBV) (17.8%) infections. In Central Africa, sera giving inconclusive results for HIV are frequently associated with malaria, EBV infection, or both.

Virological failure and HIV type 1 drug resistance profiles among patients followed-up in private sector, Douala, Cameroon.

The rate of virological failure was assessed in 819 patients followed up by the private sector of Douala, the economic capital of Cameroon, and treated according to the World Health Organization (WHO) recommendations. In addition, genotypic resistance testing was carried out in the subgroup of 75 selected patients representative of the 254 patients in virological and/or immunological failure receiving a first-line (83%) or second-line (17%) regimen. Overall, 36% of patients treated by antiretroviral drugs (ARV) were in virological failure, as assessed by plasma viral load above 3.7 log(10) copies/ml under treatment for more than 6 months. According to the immunological status, 17% of patients showed a CD4 T cell count under 200 cells/mm(3) and 37% under 350 cells/mm(3), indicating either ongoing immunorestoration or immunological failure under treatment. Twenty percent of patients in virological failure showed wild-type viruses susceptible to all ARV, likely indicating poor adherence. However, 80% of them displayed plasma virus resistant at least to one ARV drug, mostly to the nucleoside reverse transcriptase inhibitors (NRTIs) class (80%), followed by the non-NRTI class (76%) and the protease inhibitor class (19%), thus reflecting the therapeutic usage of ARV drugs in Cameroon as recommended by the WHO. Whereas the second-line regimen proposed by the 2009 WHO recommendations could be effective in more than 75% of patients in virological failure with resistant viruses, the remaining patients showed a resistance genotypic profile highly predictive of resistance to the usual WHO second-line regimen, including in some patients complex genotypic profiles diagnosed only by genotypic resistance tests. In conclusion, our observations highlight the absolute need for improving viral load assessment in resource-limited settings to prevent and/or monitor therapeutic failure.