Eric Van Wijngaerden

Rising prevalence of HIV-1 non-B subtypes in Belgium: 1983-2001.

This study documented the HIV-1 subtype distribution in 2 Belgian hospitals and determined predictive demographics for non-B subtypes. Overall, subtype B was the most prevalent subtype in this population, followed by subtypes A and C. Several recombinants were detected, circulating recombinants as well as new ones. We found a rise in non-B subtypes from 0% in 1983 to 57% in 2001. The Cochran-Armitage trend test (P < 0.001) as well as the correlation analysis (R = 0.71, P = 0.0006) was highly significant. Recombinants were also increasing in this patient population from 0% in 1983 to 10% in 2001, with good support from the statistical analyses (trend test P < 0.001; correlation analysis R = 0.67, P = 0.0016). Heterosexual route of infection, black African race, African origin of the virus, and year of diagnosis were predictors for infection with non-B subtypes in multivariate analysis. This analysis indicates that the prevalence of non-B subtypes and recombinants in this patient population is high and increasing. Gathering demographic and sequence information from newly diagnosed patients could be useful to further follow the spread of non-B subtypes in Belgium and Europe, but subtyping based on sequence information still remains the most reliable method.

Prevalence and epidemiology of HIV type 1 drug resistance among newly diagnosed therapy-naive patients in Belgium from 2003 to 2006.

This study is the first prospective study to assess the prevalence, epidemiology, and risk factors of HIV-1 drug resistance in newly diagnosed HIV-infected patients in Belgium. In January 2003 it was initiated as part of the pan-European SPREAD program, and continued thereafter for four inclusion rounds until December 2006. Epidemiological, clinical, and behavioral data were collected using a standardized questionnaire and genotypic resistance testing was done on a sample taken within 6 months of diagnosis. Two hundred and eighty-five patients were included. The overall prevalence of transmitted HIV-1 drug resistance in Belgium was 9.5% (27/285, 95% CI: 6.6-13.4). Being infected in Belgium, which largely coincided with harboring a subtype B virus, was found to be significantly associated with transmission of drug resistance. The relatively high rate of baseline resistance might jeopardize the success of first line treatment as more than 1 out of 10 (30/285, 10.5%) viruses did not score as fully susceptible to one of the recommended first-line regimens, i.e., zidovudine, lamivudine, and efavirenz. Our results support the implementation of genotypic resistance testing as a standard of care in all treatment-naive patients in Belgium.

Current levels of drug resistance among therapy-naive HIV-infected patients have significant impact on treatment response

Resistant HIV can be transmitted from one patient t o another. 1 Recent large-scale European research found onetenth of viruses from untreated patients showing at least 1 resistance-related mutation. 2 Such investigations are mainly driven by the concern that resistant virus c ould at some point hamper optimal treatment response. However, the impact of baseline drug resistance on treatment response is not well studied. Various gen otypic interpretation methods are used to assess resistanc e in drug-naive patients. When transmitted resistan ce is the topic of interest, irrespective of treatment, prima ry mutations are considered most indicative. Second ary mutations could also be the result of natural varia tion. However, when interpreting resistance in view of the response to the installed treatment, all positions possibly contributing to the selective advantage of the virus in the presence of drug should be taken into account.

Factors associated with the continuum of care of HIV-infected patients in Belgium

We studied factors associated with the continuum of HIV care in Belgium.

Performance of the VERSANT® HIV-1 Resistance Assays (LiPA) for detecting drug resistance in therapy-naive patients infected with different HIV-1 subtypes

In this study we evaluated the performance of the VERSANT HIV-1 Resistance Assays (LiPA) in detecting drug resistance in therapy-naive HIV-infected patients diagnosed in Belgium in 2000. We compared the results with population sequencing and found concordance to be in line with previous studies in treatment-experienced patients (86.87% for reverse transcriptase (RT); 92.77% for protease (PRO)). Discordance was mainly due to indeterminate reactions on LiPA (8.45% for RT; 6.85% for PRO) and minor discordances (4.13% for RT; 0.25% for PRO). Major discordances were rare (0.46% for RT; 0.12% for PRO). Indeterminate reactions were significantly associated with strains belonging to non-B subtypes.

Evolution of genotypic resistance to enfuvirtide in HIV-1 isolates from different group M subtypes.

BACKGROUNDnEnfuvirtide is active against isolates from different HIV-1 subtypes. In vitro and in vivo studies reveal that resistance mutations are primarily found within the region spanning amino acid 36-45 of gp41. However, most studies include only subtype B strains, while it is known that especially the env region is very divergent among subtypes.nnnOBJECTIVESnTo analyze the gp41 HR1 genetic evolution during failure of enfuvirtide-containing salvage regimens in 19 HIV-1 patients infected with strains from different group M subtypes.nnnSTUDY DESIGNnThe gp41 sequence was determined at baseline and upon failure in 19 patients. For a subset of 7 patients, samples were available after discontinuation of enfuvirtide.nnnRESULTSnOur results confirmed the conserved nature of the HR1 region. Escape mutants during chronic treatment with enfuvirtide were mainly observed within region 36-45. One novel mutation was identified, i.e. S42G in a subtype A1 strain.nnnCONCLUSIONSnDifferent subtypes escape enfuvirtide selective pressure through similar mutational patterns, however a new S42G variant was observed. The in vivo selection of S42G suggests that it might play a role in enfuvirtide resistance. Therefore, it could be considered as a candidate mutation to be included within drug resistance interpretation systems.