HIV-1 diversity and drug resistance mutations among people seeking HIV diagnosis in voluntary counseling and testing sites in Rio de Janeiro, Brazil

Submitted by Anderson Silva ([email protected]) on 2014-12-10T17:22:57Z No. of bitstreams: 1 HIV-1 diversity and drug resistance mutations among people seeking HIV diagnosis in voluntary counseling and testing sites in Rio de Janeiro, Brazil.pdf: 620367 bytes, checksum: d980f2bbdb214e81f1295940e077b147 (MD5)Approved for entry into archive by Anderson Silva ([email protected]) on 2014-12-10T17:23:12Z (GMT) No. of bitstreams: 1 HIV-1 diversity and drug resistance mutations among people seeking HIV diagnosis in voluntary counseling and testing sites in Rio de Janeiro, Brazil.pdf: 620367 bytes, checksum: d980f2bbdb214e81f1295940e077b147 (MD5)Made available in DSpace on 2014-12-11T11:56:49Z (GMT). No. of bitstreams: 1 HIV-1 diversity and drug resistance mutations among people seeking HIV diagnosis in voluntary counseling and testing sites in Rio de Janeiro, Brazil.pdf: 620367 bytes, checksum: d980f2bbdb214e81f1295940e077b147 (MD5) Previous issue date: 2014Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Comunicação e Informação Cientifica e Tecnológica em Saúde. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, BrasilThe remarkable viral diversity remains a big challenge to the development of HIV vaccines and optimal therapy worldwide. In the latest years, as a consequence of the large expansion of highly active antiretroviral therapy (HAART) availability worldwide, an increase in transmitted drug resistance mutations (TDRM) has been observed, varying according the region. This study assessed HIV-1 diversity and TDRM profile over time among newly HIV-1 diagnosed individuals from Rio de Janeiro, Brazil. Blood samples were collected from individuals seeking HIV diagnosis in four voluntary counseling and testing (VCTs) sites located in the Rio de Janeiro Metropolitan Area, in 2005–2007. Recent (RS) and long-term (LTS) HIV-1 seroconverters were distinguished using BED-CEIA. Pol viral sequences were obtained for 102 LTS identified in 2005 and 144 RS from 2005–2007. HIV-1 subtype and pol recombinant genomes were determined using Rega HIV-1 Subtyping Tool and by phylogenetic inferences and bootscanning analyses. Surveillance of HIV-1 TDRM to protease and reverse transcriptase inhibitors were performed according to the Calibrated Population Resistance (CPR) Tool 6.0. Overall, subtype B remains the most prevalent in Rio de Janeiro in both LTS and RS HIV-1 infected individuals. An increased proportion of recombinant samples was detected over time, especially in RS heterosexual men, due to the emergence of CRF02_AG and URF samples bearing a subtype K fragment. The prevalence of HIV-1 samples carrying TDRM was high and similar between LTS and RS (15.7% vs 14.6%) or age (25yo 16.6%) along the study period. The high resistance levels detected in both populations are of concern, especially considering the dynamics of HIV-1 diversity over time. Our results suggest that the incorporation of resistance testing prior to HAART initiation should be highly considered, as well as permanent surveillance, aiming to carefully monitoring HIV-1 diversity, with focus on CRF/URF emergence and putative transmissio

Syphilis in HIV-infected Mothers and Infants Results from the NICHD/HPTN 040 Study

Background: Untreated syphilis during pregnancy is associated with spontaneous abortion, stillbirth, prematurity and infant mortality. Syphilis may facilitate HIV transmission, which is especially concerning in low-and middle-income countries where both diseases are common.Methods: We performed an analysis of data available from NICHD/HPTN 040 (P1043), a study focused on the prevention of intrapartum HIV transmission to 1684 infants born to 1664 untreated HIV-infected women. This analysis evaluates risk factors and outcomes associated with a syphilis diagnosis in this cohort of HIV-infected women and their infants.Results: Approximately, 10% of women (n = 171) enrolled had serological evidence of syphilis without adequate treatment documented and 1.4% infants (n = 24) were dually HIV and syphilis infected. Multivariate logistic analysis showed that compared with HIV-infected women, co-infected women were significantly more likely to self-identify as non-white (adjusted odds ratio [AOR] 2.5, 95% CI: 1.5-4.2), to consume alcohol during pregnancy (AOR 1.5, 95% CI: 1.1-2.1) and to transmit HIV to their infants (AOR 2.1, 95% CI: 1.3-3.4), with 88% of HIV infections being acquired in utero. As compared with HIV-infected or HIV-exposed infants, co-infected infants were significantly more likely to be born to mothers with venereal disease research laboratory titers >= 1:16 (AOR 3, 95% CI: 1.1-8.2) and higher viral loads (AOR 1.5, 95% CI: 1.1-1.9). of 6 newborns with symptomatic syphilis, 2 expired shortly after birth, and 2 were HIV-infected.Conclusion: Syphilis continues to be a common co-infection in HIV-infected women and can facilitate in utero transmission of HIV to infants. Most infants are asymptomatic at birth, but those with symptoms have high mortality rates.NICHDUCLA Center for AIDS ResearchUCLA AIDS InstituteBoehringer Ingelheim Pharmaceuticals Inc. (BIPI)GlaxoSmithKline on behalf of ViiV HealthcareDavid Geffen UCLA Sch Med, Los Angeles, CA USAEunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USAWESTAT Corp, Rockville, MD 20850 USAHosp Fed Serv Estado, Rio de Janeiro, BrazilHosp Geral Nova Iguacu, Nova Iguacu, BrazilFundacao Oswaldo Cruz Fiocruz, Inst Oswaldo Cruz, Lab AIDS & Immnol Mol, Rio de Janeiro, BrazilUniv Witwatersrand, Perinatal HIV Res Unit, Chris Hani Baragwanath Hosp, Johannesburg, South AfricaUniv Stellenbosch, Tygerberg Hosp, Cape Town, South AfricaHosp Conceicao, Porto Alegre, RS, BrazilHosp Femina, Oporto, PortugalIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv São Paulo, BR-14049 Ribeirao Preto, SP, BrazilFdn Maternal & Infant Hlth FUNDASAMIN, Buenos Aires, DF, ArgentinaUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilFundacao Oswaldo Cruz Fiocruz, Lab Pesquisa Clin DST & AIDS, Inst Pesquisa Clin Evandro Chagas, Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, São Paulo, BrazilNICHD: HHSN267200800001CNICHD: U01 AI047986UCLA AIDS Institute: 5P30 AI28697Web of Scienc

Three Postpartum Antiretroviral Regimens to Prevent Intrapartum HIV Infection

BACKGROUNDThe safety and efficacy of adding antiretroviral drugs to standard zidovudine prophylaxis in infants of mothers with human immunodeficiency virus (HIV) infection who did not receive antenatal antiretroviral therapy (ART) because of late identification are unclear. We evaluated three ART regimens in such infants.METHODSWithin 48 hours after their birth, we randomly assigned formula-fed infants born to women with a peripartum diagnosis of HIV type 1 (HIV-1) infection to one of three regimens: zidovudine for 6 weeks (zidovudine-alone group), zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life (two-drug group), or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks (three-drug group). The primary outcome was HIV-1 infection at 3 months in infants uninfected at birth.RESULTS A total of 1684 infants were enrolled in the Americas and South Africa (566 in the zidovudine-alone group, 562 in the two-drug group, and 556 in the three-drug group). The overall rate of in utero transmission of HIV-1 on the basis of Kaplan-Meier estimates was 5.7% (93 infants), with no significant differences among the groups. Intrapartum transmission occurred in 24 infants in the zidovudine-alone group (4.8%; 95% confidence interval [CI], 3.2 to 7.1), as compared with 11 infants in the two-drug group (2.2%; 95% CI, 1.2 to 3.9; P=0.046) and 12 in the three-drug group (2.4%; 95% CI, 1.4 to 4.3; P=0.046). The overall transmission rate was 8.5% (140 infants), with an increased rate in the zidovudine-alone group (P=0.03 for the comparisons with the two-and three-drug groups). On multivariate analysis, zidovudine monotherapy, a higher maternal viral load, and maternal use of illegal substances were significantly associated with transmission. The rate of neutropenia was significantly increased in the three-drug group (P < 0.001 for both comparisons with the other groups).CONCLUSIONS In neonates whose mothers did not receive ART during pregnancy, prophylaxis with a two-or three-drug ART regimen is superior to zidovudine alone for the prevention of intrapartum HIV transmission; the two-drug regimen has less toxicity than the three-drug regimen. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD] and others; ClinicalTrials.gov number, NCT00099359.)NICHDHIV Prevention Trials NetworkNational Institute of Allergy and Infectious Diseases (NIAID)National Institute of Mental HealthUniv Calif Los Angeles, David Geffen Sch Med, Div Infect Dis, Los Angeles, CA 90095 USAEunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USAWestat Corp, Rockville, MD USAFundacao Oswaldo Cruz Fiocruz, Lab Pesquisa Clin DST & AIDS, Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, BrazilFundacao Oswaldo Cruz Fiocruz, Lab AIDS & Imunol Mol, Inst Oswaldo Cruz, Rio De Janeiro, BrazilFundacao Oswaldo Cruz Fiocruz, Lab Informacoes Saude, Inst Informacao Cient & Tecnol Saude, Rio De Janeiro, BrazilHosp Fed Servidores Estado, Rio De Janeiro, BrazilHosp Geral Nova Iguacu, Rio De Janeiro, BrazilUniv Witwatersrand, Perinatal HIV Res Unit, Johannesburg, South AfricaChris Hani Baragwanath Hosp, Johannesburg, South AfricaUniv Stellenbosch, Cape Town, South AfricaTygerberg Hosp, Cape Town, South AfricaHosp Conceicao, Porto Alegre, RS, BrazilHosp Femina, Porto Alegre, RS, BrazilIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilUniv Fed Minas Gerais, Belo Horizonte, MG, BrazilUniv Sao Paulo, BR-14049 Ribeirao Preto, SP, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Calif Davis, Davis, CA 95616 USAFdn Maternal & Infant Hlth, Buenos Aires, DF, ArgentinaBoston Univ, Sch Med, Boston, MA 02118 USAUniv Fed Sao Paulo, Sao Paulo, BrazilNICHD: HHSN267200800001CNICHD: N01-HD-8-0001National Institute of Allergy and Infectious Diseases (NIAID): U01 AI047986National Institute of Allergy and Infectious Diseases (NIAID): U01 AI068632National Institute of Mental Health: AI068632Web of Scienc