Pretreatment HIV-1 Resistance in Argentina: Results from the Second Surveillance Study Following World Health Organization Guidelines (2019).

More than 62,000 individuals are currently on antiretroviral treatment within the public health system in Argentina. In 2019, more than 50% of people on ART received non-nucleoside reverse transcriptase inhibitors (NNRTIs). In this context, the second nationwide HIV-1 pretreatment drug resistance surveillance study was carried out between April and December 2019 to assess the prevalence of HIV-1 drug resistance in Argentina using the World Health Organization guidelines. This was a nationwide cross-sectional study enrolling consecutive 18-year-old and older individuals starting ARVs at 19 ART-dispensing centers. This allowed us to estimate a point prevalence rate of resistance-associated mutations (RAMs) with a confidence interval (CI) of 5% (for the total population and for those without antiretroviral exposure). Four-hundred forty-seven individuals were included in the study. The prevalence of mutations associated with resistance was detected in 27.7% (95% CI 25.6-34.9%) of the population. For NNRTI, it was 19.6% (95% CI 16.3-24.5%), for integrase strand transfer inhibitor (INSTI) 6.1% (95% CI 6.1-11.9%), for nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) 3% (95% CI 1.9-5.9%), and for protease inhibitors 1.5% (95% CI 0.7-3.6%). Naive individuals had variants of resistance to NRTIs in 16.8% (95% CI 12.8-21.4) and 5.7% (95% CI 2.9-15.9) to INSTI. For experienced individuals, the prevalence of variants associated with resistance was 30.38% (95% CI 20.8-42.2) for NRTIs and 7.7% (95% CI 2.9-15.9) for INSTI. This study shows an increase in the frequency of nonpolymorphic RAMs associated with resistance to NNRTI. This study generates the framework of evidence that supports the use of schemes based on high genetic barrier integrase inhibitors as the first line of treatment and the need for the use of resistance test before prescribing schemes based on NNRTI. We report for the first time the presence of a natural polymorphism associated with the most prevalent recombinant viral form in Argentina and the presence of a mutation linked to first-line integrase inhibitors such as raltegravir.

Retorno social de la inversión tras eliminar la transmisión vertical de chagas, VIH/sida, HB y sífilis: caso de un municipio de la Provincia de Buenos Aires / Social Return on the investment of the elimination of the vertical transmission of Chagas, HIV / AIDS, HB and Syphilis: Case of a Municipality of the Province of Buenos Aires

Resumen Introducción: se busca cuantificar los retornos de la inversión asociados a una intervención en el sistema público de salud de un municipio de la Provincia de Buenos Aires, Argentina, consistente en el fortalecimiento de la estrategia denominada Eliminación de la Transmisión Maternoinfantil de la Infección por VIH, Sífilis, enfermedad de Chagas Congénita e Infección Perinatal por Hepatitis B (ETMI-PLUS). Metodología: el estudio (cuantitativo) se basa en la metodología de Retorno Social de la Inversión (RSI). Se establecieron definiciones ad-hoc para la medición de los retornos sobre la base de los datos disponibles provenientes de diversas fuentes: información primaria de la Secretaría de Salud del MAB; tasas de transmisión congénita de cada enfermedad notificados al Sistema Nacional de Vigilancia de Salud; presupuestos detallados de los recursos asignados al proyecto por parte de la Fundación Mundo Sano y costos de tratamientos e insumos de nomencladores oficiales. Resultados: por cada peso invertido para reforzar la ETMI-PLUS en el MAB, se obtuvo un retorno de casi 4 pesos, gracias a las mejoras en la eliminación vertical de las cuatro enfermedades y al descenso de las complicaciones cardiacas en las mujeres embarazadas diagnosticadas con chagas y tratadas oportunamente. Conclusiones: estos resultados sugieren la existencia de una relación retorno-inversión favorable, analizada bajo una perspectiva conservadora, ya que, se incluyen exclusivamente los ahorros para el sistema de salud y se excluyen otras dimensiones de los retornos vinculadas con las mejoras en los resultados alcanzados.

Abstract Introduction: we seek to quantify the returns on investment associated with an intervention in the public health system of a Municipality of the Province of Buenos Aires, Argentina. This intervention consists of strengthening the strategy for the Elimination of Mother-to-Child Transmission of HIV Infection, Syphilis, Congenital Chagas Disease and Perinatal Hepatitis B Infection, a strategy called ETMI-PLUS. Methodology: the study (quantitative) is based on the Social Return on Investment (RSI) methodology. Ad-hoc definitions are established for the measurement of returns based on the information available from various sources: primary information from the Ministry of Health of the MAB; rates of congenital transmission of each disease reported to the National Health Surveillance System; detailed budgets of the resources assigned to the project by Fundación Mundo Sano and costs of treatments and supplies from official nomenclators. Results: for each argentinean peso invested in strengthening the ETMI-PLUS in the MAB, a return of almost 4 pesos would have been obtained thanks to the improvements in the vertical elimination of the 4 diseases and the reduction of cardiac complications in pregnant women.Conclusions: these results suggest the existence of a return / investment relationship favorable to the intervention, analyzed under a conservative analysis since savings for the health system are exclusively included and other dimensions of returns associated with improvements in results are excluded.

Consenso Argentino de toxoplasmosis congénita 2020 / Argentine Consensus of congenital toxoplasmosis

Resumen La transmisión vertical de la infección por Toxoplasma gondii ocurre cuando la madre se infecta por primera vez en el transcurso del embarazo. El diagnóstico de la infección materna y la del re cién nacido se logra con el conjunto de pruebas serológicas, hallazgos clínicos y ecográficos. El reconocimiento temprano de la infección materna permite un tratamiento que reduce la tasa de transmisión y el riesgo de daño en el producto de la concepción. El objetivo de este consenso de expertos fue revisar la literatura científica para actualizar las recomendaciones de práctica clínica respecto de la prevención, el diagnóstico y el tratamiento de la toxoplasmosis congénita en nuestro país.

Abstract Mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. Diag nosis of maternal infection and the newborn is achieved by a combination of serological tests, clinical features and ultrasound images. An early diagnosis of maternal infection allows treatment that offers a reduction both in transmission rate and risk of congenital damage. The aim of this expert consensus was to review the scientific literature which would enable an update of the clinical practice guideline of prevention, diagnosis and treatment of congenital toxoplasmosis in our country.

[Argentine consensus of congenital toxoplasmosis]. / Consenso argentino de toxoplasmosis congénita 2020.

Mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. Diagnosis of maternal infection and the newborn is achieved by a combination of serological tests, clinical features and ultrasound images. An early diagnosis of maternal infection allows treatment that offers a reduction both in transmission rate and risk of congenital damage. The aim of this expert consensus was to review the scientific literature which would enable an update of the clinical practice guideline of prevention, diagnosis and treatment of congenital toxoplasmosis in our country.

La transmisión vertical de la infección por Toxoplasma gondii ocurre cuando la madre se infecta por primera vez en el transcurso del embarazo. El diagnóstico de la infección materna y la del recién nacido se logra con el conjunto de pruebas serológicas, hallazgos clínicos y ecográficos. El reconocimiento temprano de la infección materna permite un tratamiento que reduce la tasa de transmisión y el riesgo de daño en el producto de la concepción. El objetivo de este consenso de expertos fue revisar la literatura científica para actualizar las recomendaciones de práctica clínica respecto de la prevención, el diagnóstico y el tratamiento de la toxoplasmosis congénita en nuestro país.

Update process ofthe National Agenda for Public Health Research 2021-2022 / Proceso de actualización de la agenda nacional de investigación en salud pública 2021-2022

RESUMEN INTRODUCCIÓN : Una Agenda Nacional de Investigación en Salud Pública (ANISP) participativa y con priorización temática constituye un elemento estratégico para generar recomendaciones y políticas públicas basadas en evidencia, que imparten positivamente en la salud de las poblaciones y permitan lograr los objetivos sanitarios. En la actualización de la ANISP participaron la Dirección de Investigación en Salud (DIS) del Ministerio de Salud de la Nación (MSAL), a través de la Red Ministerial de Investigación en Salud (REMINSA), y actores de los niveles gubernamentales provinciales y nacionales pertenecientes a los sectores público, privado, de la salud, académico y de investigación. Se adaptó la herramienta original propuesta por la Organización Panamericana de la Salud, utilizada en el proceso en 2019. La actualización abarcó diferentes etapas. La selección de los temas contó con la legitimidad, reconocimiento y participación de los actores vinculados a la salud, a la gestión gubernamental y privada y a la investigación científica; se trabajó de manera federal y transversal, por consenso con las redes provinciales y un Comité Central Asesor en el MSAL. A partir de los lineamientos preliminares obtenidos, se elaboró una encuesta en línea semiestructurada, que fue distribuida a todos los actores federales y recibió 431 respuestas. El proceso resultó en 55 lineamientos priorizados, divididos en 6 áreas temáticas y 33 subtemas, seleccionados por votación según importancia, impacto y factibilidad.

ABSTRACT INTRODUCTION : A participatory National Public Health Research Agenda (ANISP) with thematic prioritization is a strategic element to generóte evidence-based recommendations and public policies that have a positive impact on the health of populations and enable to achieve health objectives. The Directorate of Health Research (DIS) ofthe Argentine Ministry of Health (MSAL), through the Ministerial NetWork of Health Research (REMINSA), along with adors from the provincial and national government levels belonging to public, privóte, health, academic and research sectors participated in the update of the ANISP. They adapted the original tooI proposed by the Pan American Health Organizatlon and used in the process in 2019. The update included different stages. The selection ofthe topics had the legitimacy, recognition and participation ofthe actors involved, related to health, to government and privóte management and to scientific research; the work was conducted in a federal and transversal manner by consensus with the provincial networks and a Central Advisory Committee in the MSAL. Based on the preliminary guidelines obtained, a semi-structured online survey was developed and distributed to all federal actors, receiving 431 responses. The process resulted in 55 priorilized guidelines, divided into 6 thematic oreas and 33 sub-themes, selected by voting according to importance, impact and feasibility.

Proceso de actualización de la Agenda Nacional de Investigación Salud Pública 2021-2022 / Update process of the National Agenda for Public Health Research 2021-2022

INTRODUCCIÓN: Una Agenda Nacional de Investigación en Salud Pública (ANISP) participativa y con priorización temática constituye un elemento estratégico para generar recomendaciones y políticas públicas basadas en evidencia, que impacten positivamente en la salud de las poblaciones y permitan lograr los objetivos sanitarios. En la actualización de la ANISP participaron la Dirección de Investigación en Salud (DIS) del Ministerio de Salud de la Nación (MSAL), a través de la Red Ministerial de Investigación en Salud (REMINSA), y actores de los niveles gubernamentales provinciales y nacionales pertenecientes a los sectores público, privado, de la salud, académico y de investigación. Se adaptó la herramienta original propuesta por la Organización Panamericana de la Salud, utilizada en el proceso en 2019. La actualización abarcó diferentes etapas. La selección de los temas contó con la legitimidad, reconocimiento y participación de los actores vinculados a la salud, a la gestión gubernamental y privada y a la investigación científica; se trabajó de manera federal y transversal, por consenso con las redes provinciales y un Comité Central Asesor en el MSAL. A partir de los lineamientos preliminares obtenidos, se elaboró una encuesta en línea semiestructurada, que fue distribuida a todos los actores federales y recibió 431 respuestas. El proceso resultó en 55 lineamientos priorizados, divididos en 6 áreas temáticas y 33 subtemas, seleccionados por votación según importancia, impacto y factibilidad

Situación laboral de personas viviendo con el virus de inmunodeficiencia humana en la provincia de Buenos Aires / Employment of people living with HIV in the province of Buenos Aires

Una de las variables para medir la calidad de vida de las personas que viven con el virus de inmunodeficiencia humana (VIH) es el trabajo. El objetivo de este estudio fue comparar, discriminando por género, la situación laboral de personas que viven con VIH en Buenos Aires, Argentina. Es un estudio comparativo realizado en tres hospitales entre abril y julio de 2015. Se evaluó: rango de edad, género, tratamiento antirretroviral, carga viral, personas a cargo, autopercepción del estado de salud, nivel educativo, situación laboral, acceso a beneficio social, comparación entre ingresos con el salario mínimo, oficio. α=5% a dos colas. Se realizó test de Mann-Whitney-Wilcoxon y Fisher. Se realizaron 82 encuestas. Un 87,2% tenían entre 20 y 59 años; relación hombre (H)/mujer (M): 1/1; el 84,1% bajo tratamiento antirretroviral y 67,1% tenían carga viral indetectable. El 54,9% con personas a su cargo. La mediana de autopercepción de salud fue de 7,94, sin diferencias entre el sexo (p=0,35). El 48,8% de los H y 50% de las M tuvieron como máximo 7 años de educación formal. El 17,1% de los H y 7,5% de las M se encontraban desocupadas (p=0,03); trabajo informal en 65,8% de H y 37,5% de las M, pero el 47,5% de las M son amas de casa. El 32,9% de las personas no reciben beneficio social, 20% de M y 43,9% de H (p=0,03). El ingreso de las personas correspondió al 64,8% del salario mínimo. La situación económica del país cambió, queda ver si la situación laboral también lo hizo

One of the variables to measure the quality of life of people living with the Human Immunodeficiency Virus (HIV) is labour. The objective was to compare the labour situation of people living with the HIV in Buenos Aires discriminating by gender. Comparative study in 3 hospitals between April and July 2015. The following were evaluated: age range, idg, antiretroviral treatment, viral load, dependents, self-perception of health status, educational level, work situation, access to social benefits, comparison between income and minimum wage, occupation. α=5% to two queues. Mann-Whitney-Wilcoxon and Fisher tests were conducted. 82 surveys were performed. 87.2% between 20 and 59 years old; male (M)/female (F) ratio: 1/1; 84.1% under antiretroviral treatment and 67.1% had undetectable viral load. 54.9% with dependents. The median self-perception of health was 7.94 with no differences between sexes (p=0.35). 48.8% of the M and 50% of the F had at most 7 years of formal education. 17.1% of the men and 7.5% of the women were unemployed (p=0.03); informal work accounted for 65.8% of the men and 37.5% of the women, but 47.5% of the women were housewives. 32.9% of the people do not receive social benefits, 20% of F and 43.9% of M (p=0.03). The income of the people corresponded to 64.8% of the minimum wage. The economic situation of the country has changed, and it remains to be seen if the employment situation has changed as well

Congenital Cytomegalovirus and HIV Perinatal Transmission.

BACKGROUND: Congenital cytomegalovirus (CMV) infection (cCMV) is an important cause of hearing loss and cognitive impairment. Prior studies suggest that HIV-exposed children are at higher risk of acquiring cCMV. We assessed the presence, magnitude and risk factors associated with cCMV among infants born to HIV-infected women, who were not receiving antiretrovirals during pregnancy. METHODS: cCMV and urinary CMV load were determined in a cohort of infants born to HIV-infected women not receiving antiretrovirals during pregnancy. Neonatal urines obtained at birth were tested for CMV DNA by qualitative and reflex quantitative real-time polymerase chain reaction. RESULTS: Urine specimens were available for 992 (58.9%) of 1684 infants; 64 (6.5%) were CMV-positive. Mean CMV load (VL) was 470,276 copies/ml (range: < 200-2,000,000 copies/ml). Among 89 HIV-infected infants, 16 (18%) had cCMV versus 42 (4.9%) of 858 HIV-exposed, uninfected infants (P < 0.0001). cCMV was present in 23.2% of infants with in utero and 9.1% infants with intrapartum HIV infection (P < 0.0001). Rates of cCMV among HIV-infected infants were 4-fold greater (adjusted OR, 4.4; 95% CI: 2.3-8.2) and 6-fold greater among HIV in utero-infected infants (adjusted OR, 6; 95% CI: 3-12.1) compared with HIV-exposed, uninfected infants. cCMV was not associated with mode of delivery, gestational age, Apgar scores, 6-month infant mortality, maternal age, race/ethnicity, HIV viral load or CD4 count. Primary cCMV risk factors included infant HIV-infection, particularly in utero infection. CONCLUSION: High rates of cCMV with high urinary CMV VL were observed in HIV-exposed infants. In utero HIV infection appears to be a major risk factor for cCMV in infants whose mothers have not received combination antiretroviral therapy in pregnancy.

Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission.

BACKGROUND: Sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Treponema pallidum (TP), and cytomegalovirus (CMV) may lead to adverse pregnancy and infant outcomes. The role of combined maternal STIs in HIV mother-to-child transmission (MTCT) was evaluated in mother-infant pairs from NICHD HPTN 040. METHODOLOGY: Urine samples from HIV-infected pregnant women during labor were tested by polymerase chain reaction (PCR) for CT, NG, and CMV. Infant HIV infection was determined by serial HIV DNA PCR testing. Maternal syphilis was tested by VDRL and confirmatory treponemal antibodies. RESULTS: A total of 899 mother-infant pairs were evaluated. Over 30% had at least one of the following infections (TP, CT, NG, and/or CMV) detected at the time of delivery. High rates of TP (8.7%), CT (17.8%), NG (4%), and CMV (6.3%) were observed. HIV MTCT was 9.1% (n = 82 infants). HIV MTCT was 12.5%, 10.3%, 11.1%, and 26.3% among infants born to women with CT, TP, NG or CMV respectively. Forty-two percent of HIV-infected infants were born to women with at least one of these 4 infections. Women with these infections were nearly twice as likely to have an HIV-infected infant (aOR 1.9, 95% CI 1.1-3.0), particularly those with 2 STIs (aOR 3.4, 95% CI 1.5-7.7). Individually, maternal CMV (aOR 4.4 1.5-13.0) and infant congenital CMV (OR 4.1, 95% CI 2.2-7.8) but not other STIs (TP, CT, or NG) were associated with an increased risk of HIV MTCT. CONCLUSION: HIV-infected pregnant women identified during labor are at high risk for STIs. Co-infection with STIs including CMV nearly doubles HIV MTCT risk. CMV infection appears to confer the largest risk of HIV MTCT. TRIAL REGISTRATION: NCT00099359.

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes.

BACKGROUND: Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. METHODS: Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. RESULTS: Of 1373 maternal urine samples, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery and death) were noted in infants of women with CT and NG (23/35, 65.7%) compared with NG (16/28, 57.1%), CT (84/214, 39.3%) and no STI (405/1096, 37%, P = 0.001). Death (11.4% vs. 3%, P = 0.02), low birth weight (42.9% vs. 16.9%, P = 0.001) and preterm delivery (28.6% vs. 10.2%, P = 0.008) were higher among infants of CT and NG-coinfected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV infected after controlling for maternal syphilis (odds ratio: 3.5, 95% confidence interval: 1.4-8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (odds ratio, 1.35; 95% confidence interval, 1.03-1.76). CONCLUSIONS: STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants.

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.

Hypertension, preeclampsia and eclampsia among HIV-infected pregnant women from Latin America and Caribbean countries.

OBJECTIVES: To evaluate the incidence of and risk factors for hypertensive disorders in a cohort of HIV-infected pregnant women. METHODS: Hypertensive disorders (HD) including preeclampsia/eclampsia (PE/E) and pregnancy induced hypertension, and risk factors were evaluated in a cohort of HIV-infected pregnant women from Latin America and the Caribbean enrolled between 2002 and 2009. Only pregnant women enrolled for the first time in the study and delivered at ≥20 weeks gestation were analyzed. RESULTS: HD were diagnosed in 73 (4.8%, 95% CI: 3.8%-6.0%) of 1513 patients; 35 (47.9%) had PE/E. HD was significantly increased among women with a gestational age-adjusted body mass index (gBMI) ≥25 kg/m(2) (OR = 3.1; 95% CI: 1.9-5.0), hemoglobin (Hg) ≥11 g/dL at delivery (OR = 2.1; 95% CI: 1.2-3.6) and age ≥35 years (OR = 1.8; 95% CI: 1.1-3.2). PE/E was increased among women with a gBMI ≥25 kg/m(2) (OR = 3.0; 95% CI: 1.5-6.0) and Hg ≥11 g/dL at delivery (OR = 2.8; 95% CI: 1.2-6.5). A previous history of PE/E increased the risk of PE/E 6.7 fold (95% CI: 1.8-25.5). HAART before conception was associated with PE/E (OR = 2.3; 95% CI: 1.1-4.9). CONCLUSIONS: HIV-infected women, with a previous history of PE/E, a gBMI ≥25 kg/m(2), Hg at delivery ≥11 g/dL and in use of HAART before conception are at an increased risk of developing PE/E during pregnancy.

Missed opportunities for prevention of mother-to-child transmission of HIV-1 in the NISDI Perinatal and LILAC cohorts.

OBJECTIVE: To evaluate cases of mother-to-child transmission of HIV-1 at multiple sites in Latin America and the Caribbean in terms of missed opportunities for prevention. METHODS: Pregnant women infected with HIV-1 were eligible for inclusion if they were enrolled in either the NISDI Perinatal or LILAC protocols by October 20, 2009, and had delivered a live infant with known HIV-1 infection status after March 1, 2006. RESULTS: Of 711 eligible mothers, 10 delivered infants infected with HIV-1. The transmission rate was 1.4% (95% CI, 0.7-2.6). Timing of transmission was in utero or intrapartum (n=5), intrapartum (n=2), intrapartum or early postnatal (n=1), and unknown (n=2). Possible missed opportunities for prevention included poor control of maternal viral load during pregnancy; late initiation of antiretrovirals during pregnancy; lack of cesarean delivery before labor and before rupture of membranes; late diagnosis of HIV-1 infection; lack of intrapartum antiretrovirals; and incomplete avoidance of breastfeeding. CONCLUSION: Early knowledge of HIV-1 infection status (ideally before or in early pregnancy) would aid timely initiation of antiretroviral treatment and strategies designed to prevent mother-to-child transmission. Use of antiretrovirals must be appropriately monitored in terms of adherence and drug resistance. If feasible, breastfeeding should be completely avoided. Presented in part at the XIX International AIDS Conference (Washington, DC; July 22-27, 2012); abstract WEPE163.

Three postpartum antiretroviral regimens to prevent intrapartum HIV infection.

BACKGROUND: The 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. METHODS: Within 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.).

Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities.

OBJECTIVES: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r) dosing during the third trimester of pregnancy. METHODS: We evaluated data on pregnant women from NISDI cohorts (2002-2009) enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. RESULTS: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day) (Group 1)] and 70 increased dosing [(> 800/200 mg/day) (Group 2)]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts > 500 cells/mm³. Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. CONCLUSION: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants.

Lopinavir/ritonavir dosing during pregnancy in Brazil and maternal/infant laboratory abnormalities

OBJECTIVES: To describe laboratory abnormalities among HIV-infected women and their infants with standard and increased lopinavir/ritonavir (LPV/r) dosing during the third trimester of pregnancy. METHODS: We evaluated data on pregnant women from NISDI cohorts (2002-2009) enrolled in Brazil, who received at least 28 days of LPV/r during the third pregnancy trimester and gave birth to singleton infants. RESULTS: 164 women received LPV/r standard dosing [(798/198 or 800/200 mg/day) (Group 1)] and 70 increased dosing [(> 800/200 mg/day) (Group 2)]. Group 1 was more likely to have advanced clinical disease and to use ARVs for treatment, and less likely to have CD4 counts > 500 cells/mm³. Mean plasma viral load was higher in Group 2. There were statistically significant, but not clinically meaningful, differences between groups in mean AST, ALT, cholesterol, and triglycerides. The proportion of women with Grade 3 or 4 adverse events was very low, with no statistically significant differences between groups in severe adverse events related to ALT, AST, total bilirubin, cholesterol, or triglycerides. There were statistically significant, but not clinically meaningful, differences between infant groups in ALT and creatinine. The proportion of infants with Grade 3 or 4 adverse events was very low, and there were no statistically significant differences in severe adverse events related to ALT, AST, BUN, or creatinine. CONCLUSION: The proportions of women and infants with severe laboratory adverse events were very low. Increased LPV/r dosing during the third trimester of pregnancy appears to be safe for HIV-infected women and their infants.

Lower respiratory tract infections among human immunodeficiency virus-exposed, uninfected infants.

OBJECTIVES: To evaluate whether maternal HIV disease severity during pregnancy is associated with an increased likelihood of lower respiratory tract infections (LRTIs) in HIV-exposed, uninfected infants. METHODS: HIV-exposed, uninfected, singleton, term infants enrolled in the NISDI Perinatal Study, with birth weight >2500g were followed from birth until 6 months of age. LRTI diagnoses, hospitalizations, and associated factors were assessed. RESULTS: Of 547 infants, 103 (18.8%) experienced 116 episodes of LRTI (incidence=0.84 LRTIs/100 child-weeks). Most (81%) episodes were bronchiolitis. Forty-nine (9.0%) infants were hospitalized at least once with an LRTI. There were 53 hospitalizations (45.7%) for 116 LRTI episodes. None of these infants were breastfed. The odds of LRTI in infants whose mothers had CD4% <14 at enrollment were 4.4 times those of infants whose mothers had CD4% ≥29 (p=0.003). The odds of LRTI in infants with a CD4+ count (cells/mm(3)) <750 at hospital discharge were 16.0 times those of infants with CD4+ ≥750 (p=0.002). Maternal CD4+ decline and infant hemoglobin at the 6-12 week visit were associated with infant LRTIs after 6-12 weeks and before 6 months of age. CONCLUSIONS: Acute bronchiolitis is common and frequently severe among HIV-exposed, uninfected infants aged 6 months or less. Lower maternal and infant CD4+ values were associated with a higher risk of infant LRTIs. Further understanding of the immunological mechanisms of severe LRTIs is needed.

Actulización en profilaxis de la transmisión vertical del VIH / Prophylaxis of perinatal HIV transmission: update

Existe un innegable avance en términos de prevención de la transmisión perinatal del VIH, aunque el acceso a las estrategias de reducción continúa siendo limitado en la mayoría de los países pobres y en algunas poblaciones de los países ricos. En la actualidad se dispone de un mejor conocimiento de intervenciones ya probadas y datos sobre nuevos escenarios y acciones preventivas. Los hallazgos más recientes en cada una de ellos se resumen en éste artículo.

There is an undeniable progress in terms of prevention of perinatal transmission of HIV, although access to reduction strategies remains limited in most poor countries and in some populations of rich countries. At present here is a better understanding of proven interventions and data on new scenarios and preventive actions. The latest findings are summarized in this article.

Actulización en profilaxis de la transmisión vertical del VIH / Prophylaxis of perinatal HIV transmission: update

Existe un innegable avance en términos de prevención de la transmisión perinatal del VIH, aunque el acceso a las estrategias de reducción continúa siendo limitado en la mayoría de los países pobres y en algunas poblaciones de los países ricos. En la actualidad se dispone de un mejor conocimiento de intervenciones ya probadas y datos sobre nuevos escenarios y acciones preventivas. Los hallazgos más recientes en cada una de ellos se resumen en éste artículo.(AU)

There is an undeniable progress in terms of prevention of perinatal transmission of HIV, although access to reduction strategies remains limited in most poor countries and in some populations of rich countries. At present here is a better understanding of proven interventions and data on new scenarios and preventive actions. The latest findings are summarized in this article.(AU)