Ana Maria Salustiano Cavalcanti

Antiretroviral resistance in individuals presenting therapeutic failure and subtypes of the human immunodeficiency virus type 1 in the Northeast Region of Brazil

This study aimed to analyze human immunodeficiency virus (HIV) mutation profiles related to antiretroviral resistance following therapeutic failure, and the distribution of hiv subtypes in the Northeast Region of Brazil. A total of 576 blood samples from AIDS patients presenting therapeutic failure between 2002 and 2004 were analyzed. The genotyping kit viroSeq was used to perform viral amplification in order to identify mutations related to hiv pol gene resistance. An index of 91.1% of the patients presented mutations for nucleoside reverse transcriptase inhibitors (nrti), 58.7% for non-nucleoside reverse transcriptase inhibitors (nnrti), and 94.8% for protease inhibitors (pi). The most prevalent mutations were 184V and 215E for nrti, 103N and 190A for nnrti. Most mutations associated with PIs were secondary, but significant frequencies were observed in codons 90 (25.2%), 82 (21.1%), and 30 (16.2%). The resistance index to one class of antiretrovirals was 14%, to two classes of antiretrovirals 61%, and to three classes 18.9%. Subtype B was the most prevalent (82.4%) followed by subtype F (11.8%). The prevalence of mutations related to nrti and nnrti was the same in the two subtypes, but codon analysis related to PI showed a higher frequency of mutations in codon 63 in subtype B and in codon 36 in subtype F. The present study showed that there was a high frequency of primary mutations, which offered resistance to nrti and nnrti. Monitoring patients with treatment failure is an important tool for aiding physicians in rescue therapy.

Prevalence of mutations related to HIV-1 antiretroviral resistance in Brazilian patients failing HAART

BACKGROUND Current guidelines for antiretroviral (ARV) therapy recommend at least triple-drug combination, the so-called highly active antiretroviral therapy (HAART). Not all patients respond to HAART and the development of drug resistance remains one of the most serious obstacles to sustained suppression of HIV. OBJECTIVE In an attempt to correlate the HIV therapeutic failure with reverse transcriptase (RT) and protease resistance mutations, we describe the ARV resistance profile in patients failing HAART in Brazil. We studied 267 Brazilian HIV-1 infected patients failing HAART looking for mutations in RT and protease genes. The mutation profile of the viruses infecting these individuals were deduced and correlated to laboratorial parameters. STUDY DESIGN Two different HIV-1 genomic regions were targeted for PCR amplification, the protease (pro) and pol RT (palm finger region) genes. The mutations related to drug resistance in RT gene was analyzed using a line probe assay (LIPA(R)) and pro amino acids positions 82 and 90 were screened through RFLP using HincII restriction digestion. RESULTS There was strong correlation between the mutation in the pro and RT genes and therapeutic failure. The main mutation found in RT gene was the M184V (48%) followed by T69D/N (47%), T215Y/F (46%), M41L (39%), and L74V (7%). In the pro gene the main mutation found was L90M (26%) followed by dual substitution in L90M and V82A (6%). All mutations profiles matched very well with the patients drug regimen. CONCLUSIONS This study has shown that 84.7% of HIV infected subjects failing HAART for more than 3 months presented viral genomic mutations associated with drug resistance.

Primary resistance of human immunodeficiency virus type 1 in a reference center in Recife, Pernambuco, Brazil

To assess the prevalence of primary resistance of human immunodeficiency virus type 1 (HIV-1) to antiretrovirals, 84 patients chronically infected with HIV without prior antiretroviral treatment from Northeast Brazil were studied. Genotyping was performed using the ViroSeq Genotyping System. Thimidine analog mutations occurred in 3 (3.6%) patients. Accessory mutations related to NRTI occurred in 6 (7.1%) and related to PI in 67 (79.8%). Subtypes B (72.6%), F (22.6%), B/F 3 (3.6%), and C (1.2%) were detected. A low prevalence of major mutations related to NRTI in patients chronically infected by HIV was observed.

Primary resistance of HIV to antiretrovirals among individuals recently diagnosed at voluntary counselling and testing centres in the metropolitan region of Recife, Pernambuco

Determining the prevalence and type of antiretroviral (ARV) resistance among ARV-naïve individuals is important to assess the potential responses of these individuals to first-line regimens. The prevalence of primary resistance and the occurrence of recent infections among individuals with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) were identified among recently diagnosed patients at five sexually transmitted disease/AIDS testing and counselling centres in the metropolitan region of Recife (RMR), Pernambuco, Brazil, between 2007-2009. One-hundred and eight samples were analysed using the Calypte® BED assay. Males predominated (56%), as did patients aged 31-50 years. Twenty-three percent presented evidence of a recent HIV infection. The median CD4+ T lymphocyte count was 408 cells/mm³ and the median viral load was 3.683 copies/mL. The prevalence of primary resistance was 4.6% (confidence interval 95% = 1-8.2%) based on criteria that excluded common polymorphisms in accordance with the surveillance drug resistance mutation criteria. The prevalence of resistance to non-nucleoside reverse transcriptase, nucleoside/nucleotide reverse transcriptase and protease inhibitors were 3.8%, 1.5% and 0.8%, respectively. Fifty-seven percent of strains were from clade B, 37.7% were clade F and 3.1% were clade C; there were no statistically significant differences with respect to resistance between clades. Recent infection tended to be more common in men (p = 0.06) and in municipalities in the south of the RMR (Jaboatão dos Guararapes and Cabo de Santo Agostinho) (p = 0.046). The high prevalence of recent infection and the high prevalence of non-B strains in this poor Brazilian region merit further attention.

Recent HIV infection rates among HIV positive patients seeking voluntary counseling and testing centers in the metropolitan region of Recife - Pe, Brazil

UNLABELLED The BED capture enzyme immunoassay test makes it possible to determine whether individuals were recently infected with HIV. OBJECTIVE In this study, the overall HIV and recent infections prevalences were determined at five Voluntary Counseling and Testing (VCT) centers, in the Metropolitan Region of Recife, Northeastern of Brazil. MATERIAL AND METHODS A cross-sectional study was conducted among users of five VCTs in the metropolitan region of Recife between July 2007 and April 2009. Out of the individuals who tested positive for HIV, 169 were analyzed to assess the prevalence of recent infection by means of the BED-CEIA (BED-Calypte®). RESULTS Out of 46,696 individuals tested 916 (1.96%) turned out positive for HIV infection The highest prevalence was in Recife (3.9%). The prevalence was higher among males (3.93%), and men who have sex with men (MSM) (12.4%). The frequency of recent infections among the 169 subjects evaluated was 23.7%. Recent infections were more common among individuals under 25 years of age. There was slight predominance of men and higher frequency of heterosexuals in both groups, but still a significant portion of MSM (33%). Subtype B predominated, followed by a high proportion of subtype F. CONCLUSIONS Recent infection occurs mainly among young individuals and heterosexuals, despite a significant proportion of recent infection among MSM. These results suggest that preventive actions aimed at the MSM community remains a challenge and efforts focusing this group should continue to be a priority.

Comparison of the epidemiology, profile of mutations, and clinical response to antiretrovirals among subtypes B and F of the human immunodeficiency virus type 1

The authors compared demographic aspects and profile of mutations in 80 patients with subtypes B and F of human immunodeficiency type 1 (HIV-1). Genotyping of the pol region of the reverse transcriptase was performed using the ViroSeq Genotyping System. A total of 61 (76.2%) patients had subtype B and 19 (23.8%) subtype F of the HIV-1. Subtype F tended to be more frequent in heterosexuals and women with a low educational level, but without statistical significance. The frequency of mutations related to nucleoside reverse transcriptase inhibitors and protease inhibitors (PI) was the same in the two subtypes, but mutations related to PI at the codons 63, 77, and 71 were more frequent in subtype B, while mutations at the codons 36 and 20 predominated in subtype F. Sixty-two of the 80 patients infected with subtypes B and F were submitted to antiretroviral therapy for an average of 18-22 months. Undetectable viral loads at the end of follow-up were similar in the two groups, representing 63.8% of subtype B and 73.3% of subtype F (p = 0.715). CD4 lymphocyte counts before and after treatment were similar in the two groups. This study, despite pointing to possible epidemiological and genetic differences among subtypes B and F of HIV-1, suggests that the use of highly active antiretroviral therapy is equally effective against these subtypes.

Estimation of HIV incidence in two Brazilian municipalities, 2013

ABSTRACT OBJECTIVE To estimate HIV incidence in two Brazilian municipalities, Recife and Curitiba, in the year of 2013. METHODS The method for estimating incidence was based on primary information, resulting from the Lag-Avidity laboratory test for detection of recent HIV infections, applied in a sample of the cases diagnosed in the two cities in 2013. For the estimation of the HIV incidence for the total population of the cities, the recent infections detected in the research were annualized and weighted by the inverse of the probability of HIV testing in 2013 among the infected and not diagnosed cases. After estimating HIV incidence for the total population, the incidence rates were estimated by sex, age group, and exposure category. RESULTS In Recife, 902 individuals aged 13 years and older were diagnosed with HIV infection. From these, 528 were included in the study, and the estimated proportion of recent infections was 13.1%. In Curitiba, 1,013 people aged 13 years and older were diagnosed, 497 participated in the study, and the proportion of recent infections was 10.5%. In Recife, the estimated incidence rate was 53.1/100,000 inhabitants of 13 years and older, while in Curitiba, it was 41.1/100,000, with male-to-female ratio of 3.5 and 2.4, respectively. We observed high rates of HIV incidence among men who have sex with men, of 1.47% in Recife and 0.92% in Curitiba. CONCLUSIONS The results obtained in the two cities showed that the group of men who have sex with men are disproportionately subject to a greater risk of new infections, and indicate that strategies to control the spread of the epidemic in this population subgroup are essential and urgent.

Incidence of Recent Human Immunodeficiency Virus Infection at Two Voluntary Counseling Testing Centers in Pernambuco, Brazil, from 2006 to 2009

ABSTRACT This study shows HIV-1 incidence in the northeastern region of Brazil, where the HIV epidemic has spread recently. Incidence was higher among men (1.34%; 95% confidence interval [CI], 1.00% to 1.69%) than among women (0.55%; 95% CI, 0.43% to 0.68%) (P < 0.0001), and there was an association between younger age and recent HIV infection (P < 0.004).

HIV-1 incidence among people seeking voluntary counseling and testing centers, including pregnant women, in Pernambuco State, Northeast Brazil

The HIV-1 epidemic in Brazil has displayed new characteristics over time, with an increase in heterosexual transmission and a decline in the male-to-female ratio in AIDS cases. HIV screening was offered to patients attending the Voluntary Counseling and Testing Center in Paulista, Greater Metropolitan Recife, Pernambuco State, in Northeast Brazil, to determine HIV-1 incidence. BED capture enzyme immunoassay (BED-CEIA) was used to measure HIV-1 incidence, comparing it to the AxSYM avidity index method (Ax-AI). From 2006 to 2009, 14,014 individuals were tested, and only 18 pregnant women were diagnosed with HIV infection, resulting in 0.15% annual incidence (95%CI: 0-0.33), significantly lower than in men (1.03; 95%CI: 0.45-1.61) and non-pregnant women (0.50; 95%CI: 0.11-0.89). Despite the low HIV-1 incidence in pregnant women, the high rate of recent infection detected during prenatal care emphasizes the need to increase measures to prevent vertical transmission.Abstract The HIV-1 epidemic in Brazil has displayed new characteristics over time, with an increase in het-erosexual transmission and a decline in the male-to-female ratio in AIDS cases. HIV screening was offered to patients attending the Voluntary Coun-seling and Testing Center in Paulista, Greater Metropolitan Recife, Pernambuco State, in North-east Brazil, to determine HIV-1 incidence. BED capture enzyme immunoassay (BED-CEIA) was used to measure HIV-1 incidence, comparing it to the AxSYM avidity index method (Ax-AI). From 2006 to 2009, 14,014 individuals were tested, and only 18 pregnant women were diagnosed with HIV infection, resulting in 0.15% annual inci-dence (95%CI: 0-0.33), significantly lower than in men (1.03; 95%CI: 0.45-1.61) and non-pregnant women (0.50; 95%CI: 0.11-0.89). Despite the low HIV-1 incidence in pregnant women, the high rate of recent infection detected during prenatal care emphasizes the need to increase measures to prevent vertical transmission.HIV-1; Incidence; Infectious Disease Vertical TransmissionNo Brasil, a epidemia do HIV-1 adquiriu novas caracteristicas ao longo do tempo, como o aumento da transmissao heterossexual e um declinio da razao homens:mulheres em casos de AIDS. Foi oferecida triagem para a infeccao pelo HIV a todos os pacientes atendidos no Centro de Testagem e Aconselhamento da cidade de Paulista, Regiao Metropolitana de Recife, Pernambuco, Nordeste do Brasil, com o objetivo de determinar a incidencia do HIV-1. Foi usado o enzimaimunoensaio de captura BED (BED-CEIA) para determinar a incidencia do HIV-1, comparando-o com o metodo de indice de avidez AxSYM (Ax-AI). No periodo analisado, 2006-2009, 14.014 pessoas foram testadas, e apenas 18 gestantes foram diagnosticadas para a infeccao por HIV, resultando em uma incidencia de 0,15% ao ano (IC95%: 0,00-0,33), significativamente menor do que os homens (1,03; IC95%: 0,45-1,61) e mulheres nao-gravidas (0,50; IC95%: 0,11-0,89). Apesar da baixa incidencia de HIV-1 entre as mulheres gravidas, a alta taxa de infeccao recente reforca cuidados no pre-natal para esta infeccao, para evitar a transmissao vertical.

Comparison among the BED capture enzyme immunoassay test and AxSYM avidity index assay for determining recent HIV infection and incidence in two Voluntary Counselling and Testing Centres in Northeast Brazil

The aims of this study were to compare the automated AxSYM avidity assay index with the BED capture enzyme immunoassay test and to calculate the HIV-1 incidence using the BED capture enzyme immunoassay and AxSYM avidity assay index algorithms within a population seeking the Voluntary Counselling and Testing Centres in two municipalities in the Metropolitan Region of Recife, Northeast of Brazil. An analysis was conducted in 365 samples that tested positive for HIV infection from frozen serum collected during the period 2006-2009. There was a similar proportion of males and females; most patients were heterosexual (86%) with a median age of 29 years. Of the 365 samples, 102 (28%) and 66 (18.1%) were identified as recent infections by BED capture enzyme immunoassay and AxSYM avidity assay index, respectively. The HIV-1 total incidence in the BED capture enzyme immunoassay and AxSYM avidity assay index algorithms were: 0.79 (95% CI: 0.60-0.98) and 0.34 (95% CI: -0.04 to 0.72), respectively. Incidence was higher among men. There was good agreement between the tests, with a kappa of 0.654 and a specificity of 95.8%. AxSYM avidity assay index may be helpful in improving the quality of the estimates of recent HIV infection and incidence, particularly when used in a combined algorithm with BED capture enzyme immunoassay.