Casais heterossexuais sorodiscordantes para o HIV-1 : estudo comportamental e de biomarcadores para avaliar práticas sexuais de risco, adesão ao tratamento antirretroviral e transmissão sexual do HIV com outras infecções sexualmente transmissíveis

Base teórica: A epidemia da infecção pelo HIV avança devido à transmissão sexual. Reconhecendo que as estratégias de mudança comportamental não são suficientes, os pesquisadores, hoje, voltam o olhar para o uso de antirretrovirais (ARV) como prevenção da transmissão sexual do HIV em três estratégias principais: PrEP ou profilaxia pré-exposição, PEP ou profilaxia pós-exposição eTasP ou tratamento como prevenção. Nesse cenário, sabese que todas as pessoas infectadas sexualmente pelo HIV, já foram um dia um casal sorodiscordante. Pessoas nessa situação são muito importantes para estudos de avaliação dos fatores facilitadores ou protetores da transmissão sexual do HIV. Sabe-se que as outras Infecções Sexualmente Transmissíveis (IST) são fatores biológicos facilitadores da transmissão sexual do HIV enquanto o uso de ARV com carga viral indetectável é o principal fator protetor desta transmissão, dando origem à disseminação da campanha U=U (Indetectável = Não transmissível). Objetivo: O principal objetivo deste estudo foi avaliar o impacto das outras ISTs e a adesão aos ARV na transmissão sexual do HIV em casais heterossexuais sorodiscordantes cujo índice estava em uso de ARV. Metodos: Estudo transversal aninhado em uma coorte retrospectiva de casais heterossexuais sorodiscordantes para o HIV com uma amostra fixa de 200 casais e 100 solteiros com HIV recebendo tratamento ARV há três meses ou mais, em acompanhamento no serviço especializado em atendimento de pessoas vivendo com HIV/AIDS (PLVHA) no sul do Brasil. Todos assinaram termo de consentimento, responderam questionário demográfico e comportamental pelo audio computer-assisted self-interviews (ACASI), coletaram amostras de sangue e de secreção genital para marcadores biológicos. Todos os parceiros HIV negativos eram aconselhados e testados para o HIV-1. Para a avaliação dos marcadores biológicos foi utilizado o método Real Time Polymerase Chain Reaction (RT-PCR) (©Abott) para a quantificação da carga viral sérica do HIV-1. A carga viral da secreção genital foi avaliada por método de RT-PCR com kit COBAS (©Roche). Swab vaginal para o teste Rapid Stain Identification of Human Semen (RSID) foi utilizado como biomarcador de sexo vaginal desprotegido. Resultados: As características demográficas, comportamentais e de marcadores biológicos foram semelhantes entre casais e solteiros. A correlação entre PCR da secreção vaginal e carga viral sérica foi significativa na presença de Infecções Sexualmente Transmissíveis (IST) (r=0,359; P=0,017). Houve associação entre o relato de adesão pelo ACASI e a carga viral sérica indetectável (P<0,0001). A análise de regressão logística demonstrou que o regime de ARV com comprimido único (RCU) duplica a chance de adesão. A maioria dos casos índices era do sexo feminino (70%). A mediana do tempo de relacionamento dos casais foi de 72 meses. Cinco parceiros se infectaram sendo quatro homens e uma mulher com uma incidência de infecção aguda pelo HIV de 2,5% (IC95%:0,8% a 5,7%). O teste RSID avaliou sexo vaginal desprotegido com resultado positivo em 12,1% das mulheres. Os resultados das medidas de carga viral no plasma foram mais elevados nos índices dos casais que transmitiram o HIV do que nos que não transmitiram (P=0,002). A presença de IST foi significativamente maior nos casais que soroconverteram (60,0% X 13,3%;OR=9,75; IC95%:1,55 – 61,2; P=0,023). Conclusão: Investir no uso de ARV como comprimido único é a principal ferramenta para melhorar a adesão. A adesão ao uso de ARV com carga viral indetectável é o principal fator de não transmissão do HIV entre casais sorodiscordantes e neste estudo o que foi preditor de transmissão foi o tempo de carga viral indetectável e a presença de outras ISTs.Theoretic background: Sexual transmission as the major HIV epidemic driver. Knowing that behavior changing strategies are not sufficient to detain the epidemics, researchers currently are turning attention to the use of antiretrovirals (ARV) as one of three ways for curtailing HIV spread: PrEP, or pre-exposure prophylaxis; PEP, or post exposure prophylaxis; and TasP, or treatment as prevention. In this scenario, it is assumed that every single sexually infectedperson, has been part of a serodiscordant couple. Those persons are important for demographic, behavioral and biological studies which can reveal factors facilitating or deterring the HIV transmission. In this context, is known that sexual transmitted infections (STI) one cofactor for HIV transmission and undetectable viral load achieved by antiretroviral treatment makes a HIV infected person virtually incapable of transmission (undetectable = untransmissible). Objetives: Main objetives were the assessment of HIV sexual transmission among serodiscordant couples on which the índex was using ARV in the presence of other IST and also evaluate adherence to ARV. Methods: A cross sectional study nested in retrospective cohort with 200 serodiscordant couples to HIV and 100 single persons receiving ARV treatment for at least three months under follow up at a major HIV/AIDS referral Service in Southern Brazil. Informed Consent has been obtained, after which a thorough behavioral and demographic questionnaire was responded through the audio computer-assisted self-interviews (ACASI). Blood and genital secretion samples were collected for viral load testing. All HIV-negative partners were counseled after testing. HIV-1 viral load was measured by Real Time Polymerase Chain Reaction (Abbott® RT-PCR) with threshold of detection of 40 copies. Vaginal viral load was measured by RT-PCR (Roche COBAS®) which had a treshold of 17 copies. Unprotected sexual intercourse was measured by RSID (Rapid Sexual Identification of Human Semen) in self collected vaginal secretion. Results: Demographic, behavioral and biological markers were similar between couples and single participants. Women with HIV-1 serotype C had more often detectable vírus in genital secretion (P=0,006). Correlation between vaginal and serum viral load was significant in presence of STI (r=0,359; P=0.017). There was association between ACASI report of adherence and undetectable serum viral load (P<0,0001). Logistic regression analysis found single tablet ARV double the chance of adherence to treatment. Mean plasma vírus load results were higher in HIV transmitters compared to non-transmitters (p=0.02). IST were present significantly more common among seroconverting couples (60,0% X 13,3%; OR=9,75;IC95%:1,55 – 61,2; P=0,023). Conclusion: Single tablet ARV was found to be the single most efficient tool to increase adherence to antiretroviral treatment. Undetectable viral load is the main factor associated with non transmission of HIV among serodiscordant couples. HIV transmission was associated with presence of STI and a shorter time with serum undetectable viral load

HIV-1 heterosexual transmission and association with sexually transmitted infections in the era of treatment as prevention

Objectives: HIV-1 heterosexual transmission among individuals on antiretroviral treatment (ART) with undetectable viremia is extremely rare. The aim of this study was to evaluate the risk of sexual HIV-1 transmission and other sexually transmitted infections (STIs) in HIV-1 serodifferent couples while the index partner is on ART. Methods: HIV transmission was evaluated in 200 HIV-1 heterosexual serodifferent couples in a stable relationship (≥3 months). All HIV-positive individuals had been on ART for ≥3 months and had been followed up for a median preceding time of 4.5 years (range 0.3–16 years) at the HIV couples clinic at Hospital Nossa Senhora da Conceição in Porto Alegre, Brazil. Following written informed consent, participants responded to demographic/behavioral questionnaires. Quantitative PCR for HIV RNA, T-cell subsets, and STI testing (syphilis, herpes, human papillomavirus, gonorrhea, and bacterial vaginosis) were performed. Self-collected vaginal swabs were obtained for quantitative HIV genital viral load testing. Results: Among 200 couples, 70% of index partners were female. Five seroconversions were observed; the HIV infection incidence was 2.5% (95% confidence interval 0.8% to 5.7%). Mean plasma viral load results were higher in HIV transmitters compared to non-transmitters (p = 0.02). The presence of STIs was significantly greater in couples who seroconverted (60.0% vs. 13.3%; odds ratio 9.75, 95% confidence interval 1.55–61.2; p = 0.023). The duration of undetectable HIV viremia and presence of STIs were associated with HIV transmission. Conclusions: Undetectable viremia was the main factor associated with non-transmissibility of HIV in this setting

Antiretroviral adherence and virologic suppression in partnered and unpartnered HIV-positive individuals in southern Brazil

Background: An undetectable serum HIV-1 load is key to effectiveness of antiretroviral (ARV) therapy, which depends on adherence to treatment. We evaluated factors possibly associated with ARV adherence and virologic response in HIV-infected heterosexual individuals. Methods: A cross-sectional study was conducted in 200 HIV-1 serodiscordant couples and 100 unpartnered individuals receiving ARV treatment at a tertiary hospital in southern Brazil. All subjects provided written informed consent, answered demographic/behavioral questionnaires through audio computer-assisted self-interviews (ACASI), and collected blood and vaginal samples for biological markers and assessment of sexually transmitted infections (STIs). HIV-negative partners were counseled and tested for HIV-1. Results: The study population mean age was 39.9 years, 53.6% were female, 62.5% were Caucasian, 52.6% had incomplete or complete elementary education, 63.1% resided in Porto Alegre. Demographic, behavioral and biological marker characteristics were similar between couples and single individuals. There was an association between adherence reported on ACASI and an undetectable serum viral load (P<0.0001). Logistic regression analysis demonstrated that single-tablet ARV-regimens were independently associated with adherence (OR = 2.3; 95CI%: 1.2–4.4; P = 0.011) after controlling for age, gender, education, marital status, personal income, ARV regimen, and median time of ARV use. A positive correlation between genital secretion PCR results and serum viral load was significant in the presence of STIs (r = 0.359; P = 0.017). Although HIV PCR detection in vaginal secretions was more frequent in women with detectable viremia (9/51, 17.6%), it was also present in 7 of 157 women with undetectable serum viral loads (4.5%), p = 0.005. Conclusions: ARV single tablet regimens are associated with adherence. Detectable HIV-1 may be present in the genital secretions of women with undetectable viremia which means there is potential for HIV transmission in adherent individuals with serologic suppression

Treatment as Prevention: Characterization of Partner Infections in the HIV Prevention Trials Network 052 Trial

HIV Prevention Trials Network (HPTN) 052 demonstrated that antiretroviral therapy (ART) prevents HIV transmission in serodiscordant couples. HIV from index-partner pairs was analyzed to determine the genetic linkage status of partner infections. Forty-six infections were classified as linked, indicating that the index was the likely source of the partner’s infection. Lack of viral suppression and higher index viral load were associated with linked infection. Eight linked infections were diagnosed after the index started ART: four near the time of ART initiation and four after ART failure. Linked infections were not observed when the index participant was stably suppressed on ART

Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes

Casais heterossexuais sorodiscordantes para o HIV-1 : estudo comportamental e de biomarcadores para avaliar práticas sexuais de risco, adesão ao tratamento antirretroviral e transmissão sexual do HIV com outras infecções sexualmente transmissíveis

Base teórica: A epidemia da infecção pelo HIV avança devido à transmissão sexual. Reconhecendo que as estratégias de mudança comportamental não são suficientes, os pesquisadores, hoje, voltam o olhar para o uso de antirretrovirais (ARV) como prevenção da transmissão sexual do HIV em três estratégias principais: PrEP ou profilaxia pré-exposição, PEP ou profilaxia pós-exposição eTasP ou tratamento como prevenção. Nesse cenário, sabese que todas as pessoas infectadas sexualmente pelo HIV, já foram um dia um casal sorodiscordante. Pessoas nessa situação são muito importantes para estudos de avaliação dos fatores facilitadores ou protetores da transmissão sexual do HIV. Sabe-se que as outras Infecções Sexualmente Transmissíveis (IST) são fatores biológicos facilitadores da transmissão sexual do HIV enquanto o uso de ARV com carga viral indetectável é o principal fator protetor desta transmissão, dando origem à disseminação da campanha U=U (Indetectável = Não transmissível). Objetivo: O principal objetivo deste estudo foi avaliar o impacto das outras ISTs e a adesão aos ARV na transmissão sexual do HIV em casais heterossexuais sorodiscordantes cujo índice estava em uso de ARV. Metodos: Estudo transversal aninhado em uma coorte retrospectiva de casais heterossexuais sorodiscordantes para o HIV com uma amostra fixa de 200 casais e 100 solteiros com HIV recebendo tratamento ARV há três meses ou mais, em acompanhamento no serviço especializado em atendimento de pessoas vivendo com HIV/AIDS (PLVHA) no sul do Brasil. Todos assinaram termo de consentimento, responderam questionário demográfico e comportamental pelo audio computer-assisted self-interviews (ACASI), coletaram amostras de sangue e de secreção genital para marcadores biológicos. Todos os parceiros HIV negativos eram aconselhados e testados para o HIV-1. Para a avaliação dos marcadores biológicos foi utilizado o método Real Time Polymerase Chain Reaction (RT-PCR) (©Abott) para a quantificação da carga viral sérica do HIV-1. A carga viral da secreção genital foi avaliada por método de RT-PCR com kit COBAS (©Roche). Swab vaginal para o teste Rapid Stain Identification of Human Semen (RSID) foi utilizado como biomarcador de sexo vaginal desprotegido. Resultados: As características demográficas, comportamentais e de marcadores biológicos foram semelhantes entre casais e solteiros. A correlação entre PCR da secreção vaginal e carga viral sérica foi significativa na presença de Infecções Sexualmente Transmissíveis (IST) (r=0,359; P=0,017). Houve associação entre o relato de adesão pelo ACASI e a carga viral sérica indetectável (P<0,0001). A análise de regressão logística demonstrou que o regime de ARV com comprimido único (RCU) duplica a chance de adesão. A maioria dos casos índices era do sexo feminino (70%). A mediana do tempo de relacionamento dos casais foi de 72 meses. Cinco parceiros se infectaram sendo quatro homens e uma mulher com uma incidência de infecção aguda pelo HIV de 2,5% (IC95%:0,8% a 5,7%). O teste RSID avaliou sexo vaginal desprotegido com resultado positivo em 12,1% das mulheres. Os resultados das medidas de carga viral no plasma foram mais elevados nos índices dos casais que transmitiram o HIV do que nos que não transmitiram (P=0,002). A presença de IST foi significativamente maior nos casais que soroconverteram (60,0% X 13,3%;OR=9,75; IC95%:1,55 – 61,2; P=0,023). Conclusão: Investir no uso de ARV como comprimido único é a principal ferramenta para melhorar a adesão. A adesão ao uso de ARV com carga viral indetectável é o principal fator de não transmissão do HIV entre casais sorodiscordantes e neste estudo o que foi preditor de transmissão foi o tempo de carga viral indetectável e a presença de outras ISTs.Theoretic background: Sexual transmission as the major HIV epidemic driver. Knowing that behavior changing strategies are not sufficient to detain the epidemics, researchers currently are turning attention to the use of antiretrovirals (ARV) as one of three ways for curtailing HIV spread: PrEP, or pre-exposure prophylaxis; PEP, or post exposure prophylaxis; and TasP, or treatment as prevention. In this scenario, it is assumed that every single sexually infectedperson, has been part of a serodiscordant couple. Those persons are important for demographic, behavioral and biological studies which can reveal factors facilitating or deterring the HIV transmission. In this context, is known that sexual transmitted infections (STI) one cofactor for HIV transmission and undetectable viral load achieved by antiretroviral treatment makes a HIV infected person virtually incapable of transmission (undetectable = untransmissible). Objetives: Main objetives were the assessment of HIV sexual transmission among serodiscordant couples on which the índex was using ARV in the presence of other IST and also evaluate adherence to ARV. Methods: A cross sectional study nested in retrospective cohort with 200 serodiscordant couples to HIV and 100 single persons receiving ARV treatment for at least three months under follow up at a major HIV/AIDS referral Service in Southern Brazil. Informed Consent has been obtained, after which a thorough behavioral and demographic questionnaire was responded through the audio computer-assisted self-interviews (ACASI). Blood and genital secretion samples were collected for viral load testing. All HIV-negative partners were counseled after testing. HIV-1 viral load was measured by Real Time Polymerase Chain Reaction (Abbott® RT-PCR) with threshold of detection of 40 copies. Vaginal viral load was measured by RT-PCR (Roche COBAS®) which had a treshold of 17 copies. Unprotected sexual intercourse was measured by RSID (Rapid Sexual Identification of Human Semen) in self collected vaginal secretion. Results: Demographic, behavioral and biological markers were similar between couples and single participants. Women with HIV-1 serotype C had more often detectable vírus in genital secretion (P=0,006). Correlation between vaginal and serum viral load was significant in presence of STI (r=0,359; P=0.017). There was association between ACASI report of adherence and undetectable serum viral load (P<0,0001). Logistic regression analysis found single tablet ARV double the chance of adherence to treatment. Mean plasma vírus load results were higher in HIV transmitters compared to non-transmitters (p=0.02). IST were present significantly more common among seroconverting couples (60,0% X 13,3%; OR=9,75;IC95%:1,55 – 61,2; P=0,023). Conclusion: Single tablet ARV was found to be the single most efficient tool to increase adherence to antiretroviral treatment. Undetectable viral load is the main factor associated with non transmission of HIV among serodiscordant couples. HIV transmission was associated with presence of STI and a shorter time with serum undetectable viral load

Risk-Taking Behavior for HIV Acquisition during Pregnancy in Porto Alegre, Brazil

Recent studies suggest that acquisition of HIV-1 infection during pregnancy and breastfeeding is associated with a high risk of HIV mother-to-child transmission. This study evaluates risk factors associated with HIV acquisition during pregnancy in women delivering at a large metropolitan medical facility located in the south of Brazil. From February to August 2009, our group conducted a cross-sectional study assessing women’s risk for HIV acquisition by administering an oral survey to peripartum women. Of 2465 participants, 42% (n=1046) knew that partner had been tested for HIV. During pregnancy, 82% (n=2022) of participants never used condoms; yet 97% (n=2399) practiced vaginal sex. Multivariate logistic regression analysis showed that patients with more years of education, in a relationship for more than 1 year, and who knew their own HIV status were more likely to know their partners' HIV status (P<0.05). Those who were in relationship for more than 1 year and were married/living together were more likely to be comfortable discussing HIV testing with partners (P<0.05). In conclusion, women in Brazil are at risk of HIV-infection during pregnancy as they remain sexually active, often do not know their sexual partner’s HIV status, and have minimal condom use