Search

AbstractHIV-1 CRF02_AG accounts for >50% of infected individuals in Cameroon. CRF02_AG prevalence has been increasing both in Africa and Europe, particularly in Italy because of migrations from the sub-Saharan region. This study investigated the molecular epidemiology of CRF02_AG in Cameroon by employing Bayesian phylodynamics and analyzed the relationship between HIV-1 CRF02_AG isolates circulating in Italy and those prevalent in Africa to understand the link between the two epidemics. Among 291 Cameroonian reverse transcriptase sequences analyzed, about 70% clustered within three distinct clades, two of which shared a most recent common ancestor, all related to sequences from Western Africa. The major Cameroonian clades emerged during the mid-1970s and slowly spread during the next 30 years. Little or no geographic structure was detected within these clades. One of the major driving forces of the epidemic was likely the high accessibility between locations in Southern Cameroon contributing to the mobility of the population. The remaining Cameroonian sequences and the new strains isolated from Italian patients were interspersed mainly within West and Central African sequences in the tree, indicating a continuous exchange of CRF02_AG viral strains between Cameroon and other African countries, as well as multiple independent introductions in the Italian population. The evaluation of the spread of CRF02_AG may provide significant insight about the future dynamics of the Italian and European epidemic. [ABSTRACT FROM AUTHOR]

AbstractTo date, very little information is available regarding the evolution of drug resistance mutations during treatment interruption (TI). Using a survival analysis approach, we investigated the dynamics of mutations associated with resistance to nucleoside analogue reverse transcriptase inhibitors (NRTIs) during TI. Analyzing 132 patients having at least two consecutive genotypes, one at last NRTI-containing regimen failure, and at least one during TI, we observed that the NRTI resistance mutations disappear at different rates during TI and are lost independently of each other in the majority of patients. The disappearance of the K65R and M184I/V mutations occurred in the majority of patients, was rapid, and was associated with the reemergence of wild-type virus, thus showing their negative impact on viral fitness. Overall, it seems that the loss of NRTI drug resistance mutations during TI is not an ordered process, and in the majority of patients occurs without specific interaction among mutations. [ABSTRACT FROM AUTHOR]

AbstractLittle information is available about the prevalence of resistance mutations to reverse transcriptase (RT) and protease (PR) inhibitors of HIV-1, after the introduction of antiretroviral treatment in Bulgaria. To fill this gap, we analyzed 80 plasma samples from HIV-1-infected Bulgarian patients, 22 naive at antiretroviral treatment (ARV) and 58 ARV experienced. The subtypes B and A resulted in the two most prevalent (41 patients and 18 patients, respectively). The proportion of subtype B among naive and treated patients was similar in each group (57 vs. 47, p 0.62), while a major proportion of subtypes A was present in drug-naive patients rather than in treated patients [8/22 (36.4) vs. 10/58 (17.2), p 0.08]. Two (9.1) naive patients and 40 (70.1) drug-experienced patients had viruses carrying at least one mutation conferring resistance to ARV drugs. Of 57 patients having experience with nucleoside reverse transcriptase inhibitors (NRTI), 32 (56.1) had NRTI resistance mutations; 8/14 (57.2) patients having experience with non-NRTI (NNRTI) had viruses carrying NNRTI resistance mutations; and 21/46 (45.7) patients having experience with protease inhibitors (PI) had PI resistance mutations. The commonest resistance mutations resulted in the NRTI mutation M184V (42.1) and the PI mutation L90M (24.1). In conclusion, due to the detection of the substantial transmission of resistant variants to newly infected individuals, continuous surveillance is required, since greater access to highly active antiretroviral therapy (HAART) will be expected in Bulgaria. Furthermore, surveillance of PR and RT sequences is also convenient to monitor the introduction of nonsubtype B HIV-1 strains in Bulgaria. [ABSTRACT FROM AUTHOR]

AbstractEarly recognition of virologic failure in patients with extensive drug resistance receiving salvage-HAART is essential to avoid exposure to subinhibitory regimens. We studied plasma viral load (PVL) decline and rates of drug-resistance mutation (DRM) accumulation in such patients. A prospective, 48 week study of 38 heavily pretreated patients receiving genotypic resistance testing (GRT)-guided HAART was conducted. The rate of PVL decline was studied by weekly PVL determinations. To assess DRM accumulation, serial GRTs were performed in all nonresponders (never reaching PVL <50 or two PVLs >50 copies/ml after suppression). Over 48 weeks, 10 patients (26) were nonresponders. Receiving less then two fully active drugs and having an elevated number of PI and NRTI mutations at baseline were strongly associated with virologic failure. There was no evidence of a difference in the change from baseline PVL to week 1 and 2 between responders and nonresponders. By contrast, PVL reductions from week 2 to week 3 and thereafter were significantly greater for responders (p< 0.01). Among nonresponders, the incidence rates per patient-month (95 CI) of emergent DRM were 0.67 (0.13–1.20), 0.40 (0.00–0.74), and 0.37 (0.00–0.75) at weeks 4, 8, and 24, respectively. Having limited baseline resistance, receiving at least two fully active drugs, and showing constant PVL reductions from week 2 to week 3 and thereafter were predictive of virologic response. In contrast, early changes in PVL levels were not. Virologic failure was associated with detection of emergent DRMs. Virologic rebound in patients on salvage-HAART should be addressed aggressively. [ABSTRACT FROM AUTHOR]

Enfuvirtide is the first of a new class of antiretroviral drugs that inhibits HIV entry. It is a 36 amino acid synthetic peptide that mimics the HR2 region of the HIV-1 gp41, preventing the fusion of viral and cellular membranes. Up to now, enfuvirtide was designed based on the HIV-1 B-subtype gp41, and resistance mutations to the fusion inhibitor have been investigated primarily in individuals infected with this subtype. To fill the gap, we analyzed the full length gp41 protein sequence of HIV-1 non-B strains from individuals receiving enfuvirtide-containing regimens. No primary resistance to the enfuvirtide binding domain (36–45 residues) was found. Resistance mutations were detected at follow-up visits and were comparable to those described among B-subtype HIV-1-infected patients; no sequence changes were detected in crucial HR1HR2 gp41 sites such as the cytotoxic T lymphocyte epitope, cysteine loop, ectodomain, and 5-helix interaction and binding region. [ABSTRACT FROM AUTHOR]

AbstractHuman immunodeficiency virus type 2 (HIV-2), originally restricted to Western Africa, is now spreading to Western European countries because of migration from endemic areas. Therefore, it is mandatory to enforce the surveillance and improve the diagnostics of this neglected infection. In this report, we describe a case of HIV-2 infection affecting an Italian citizen along with three cases from India. Phylogenetic analysis showed that the viral strain identified in the Italian patient clustered with a strain isolated from an immigrant living in France. Of the three Indian strains, two clustered together and were statistically supported, whereas one clustered with a strain from Guinea Bissau. The description of the first case of HIV-2 infection in an Italian citizen indicates that the virus is spreading from endemic areas to countries involved in migration. A strict monitoring and improvement of the diagnostic molecular tools are necessary to avoid misdiagnosis with relevant clinical consequences. [ABSTRACT FROM AUTHOR]