Development of drug resistance is the inevitable consequence of incomplete suppression of virus plasma levels in HIV-1-infected patients treated with highly active antiretroviral therapy. Resistance mutations previously characterized have been found in B subtype viruses of developed countries. Moreover, mutation profiles for non-B and more divergent B subtype viruses found in developing countries shall be analyzed together with their ex vivo phenotyping in order to establish an exact correlation between the genotyping data and the clinical management counseling for those uncommon virus subtypes. In the present study, we evaluated the mutation profile for individuals infected with B subtype and non-B subtype viruses. Viral DNA fragments corresponding to the RT gene were amplified, sequenced, and subtyped. Phenotyping analysis for reverse transcriptase nucleoside (NRTI) and nonnucleoside inhibitor susceptibility was performed using the recombinant virus assay technology. Brazilian non-B subtypes (subtype F, n = 4, and subtype A, n = 1) isolates showed essentially the same B subtype mutation profile, presenting an NRTI drug resistance with similar MIC50% and MIC90% values for all drugs analyzed regardless of their subtypes. A strong cross-resistance phenotype among AZT, 3TC, and abacavir could be seen in all isolates analyzed. A novel result was that some RT sequences not only revealed the presence of G333D/E mutations but also correlated to the presence of mutation T386I that could abrogate the M184V-surpassing effect of L210W or L210W plus G333D/E. These findings suggest that Brazilian non-B subtype HIV-1 strains use an identical RT drug resistance mutation pattern when compared to B isolates and will contribute to the validation of the genotypic and phenotypic tests in these predominant worldwide-spread viral variants.

The emergence of resistance to antiretroviral drugs is a major obstacle to the successful treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients. In this work, we correlate clinical and virological trends such as viral load (VL) and CD4 counts to genotypic and phenotypic antiretroviral (ARV) resistance profiles of HIV-1 isolates from the B and non-B subtypes found in vertically infected children failing ARV therapy. Plasma samples were collected from 52 vertically HIV-1-infected children failing different ARV therapies. Samples underwent HIV-1 pol sequencing and phenotyping and were clustered into subtypes by phylogenetic analysis. Clinical data from each patient were analyzed together with the resistance (genotypic and phenotypic) data obtained. Thirty-five samples were from subtype B, 10 samples were non-B (subtypes A, C, and F), and 7 were mosaic samples. There was no significant difference concerning treatment data between B and non-B clades. Prevalence of known drug resistance mutations revealed slightly significant differences among B and non-B subtypes: L10I, 21 and 64%, K20R, 13 and 43%, M36I, 34 and 100%, L63P, 76 and 36%, A71V/T, 24 and 0%, and V77I, 32 and 0%, respectively, in the protease (0.0001 < P < 0.0886), and D67N, 38 and 8%, K70R, 33 and 0%, R211K, 49 and 85%, and K219Q/E, 31 and 0%, respectively, in the reverse transcriptase (0.0256 < P < 0.0704). Significant differences were found only in secondary resistance mutations and did not reflect significant phenotypic variation between clade B and non-B.

Estudo de prevalência da co-infecção HIV-sífilis realizado com 830 pacientes em acompanhamento ambulatorial para HIV/aids entre janeiro e maio de 2005 no Hospital na cidade do Rio de Janeiro. Os participantes realizaram exames de VDRL (veneral disease research laboratory), contagens de células CD4+/CD8+ e de carga viral e responderam perguntas sobre características sócio-demográficas e história prévia de sífilis. A prevalência da sífilis foi de 2,7% (22), a relação entre homens e mulheres co-infectados foi de 4:1, aproximadamente. Homossexuais masculinos foram os mais acometidos e não encontramos associação entre co-infecção e idade, escolaridade e parâmetros laboratoriais testados. Do total de casos com sífilis, 73% (16) relataram tratamento prévio; destes, 14 (88%) pacientes foram re-infectados, enquanto 2 (12%) pacientes realizaram tratamento inapropriado. A presença de co-infecção HIV-sífilis em pacientes em acompanhamento rotineiro alerta-nos para necessidade de aconselhá-los a adotar práticas sexuais seguras durante os seus atendimentos ambulatoriais.

We have investigated the phenotypic and genotypic susceptibility of 14 HIV-1 strains isolated from individuals failing HAART therapy to protease inhibitors (PI). Proviral and plasma viral pol gene fragment were amplified, sequenced and subtyped. Nine samples clustered with protease subtype B reference strains and the remaining samples were classified as non-B subtype corresponding to subtype F (n = 4) and subtype A (n = 1). Although all patients were treated with similar P1 drug regimen, the non-B subtype isolates did not present the L90M and 184V mutations and used mainly G48V and V82A/F to achieve drug resistance. A strong cross-resistance phenotype among all four PI was associated with the mutation L90M in the subtype-B isolates, and with G48V and V82A/F in the non-B counterparts. This observation revealed that the non-B viruses tested had specific genotypic characteristics contrasting with the subtype-B isolates.