Jorge Figueiredo Senise

HIV-infected pregnant women have greater adherence with antiretroviral drugs than non-pregnant women

The objective of the study was to evaluate the influence of pregnancy on the level of adherence with antiretroviral (ARV) drugs, in a prospective cohort of 72 pregnant women and 79 non-pregnant women. Adherence was measured by pill counting and self-reporting. Women were deemed adherent if 95% or more of all ARV had been taken as prescribed, in two occasions. According to pill counting, 43.1 and 17.7% of pregnant and non-pregnant women, respectively, met the criteria of adherence (P = 0.001); in the postpartum, adherence declined to 20.6% (P = 0.002). In both groups, adherence rates by self-reporting were significantly higher as compared with pill counting (P = 0.001). In multivariate regression analysis, age >29 years (odds ratio [OR] 3.58, confidence interval [CI] 95% 0.10–0.75, P = 0.011), mean number of pills/day <6 (OR 2.53, CI 95% 1.07–6.01, P = 0.035), and being pregnant (OR 3.33, CI 95% 1.36–8.13, P = 0.008) were independently associated to greater adherence.

Short-term antiretroviral therapy to prevent mother-to-child transmission is safe and results in a sustained increase in CD4 T-cell counts in HIV-1-infected mothers.

Short‐term antiretroviral therapy (START) to prevent mother‐to‐child transmission (MTCT) is currently recommended for all HIV‐1‐infected pregnant women. The objective of this study was to assess the effect on CD4 cell counts and viral load dynamics the withdrawal of START after birth could generate.

The management of HIV-infected pregnant women.

Purpose of review The purpose of this article is to update the current practice in the management of HIV-infected pregnant women and present evidence-based recommendations for the reduction of mother-to-child transmission. Recent findings Early and sustained control of HIV viral replication is associated with decreasing residual risk of transmission and favors initiating antiretroviral drugs sufficiently early in naive women to suppress viral replication by the third trimester; however, this potential benefit must be balanced against the unknown long-term outcome of first-trimester drug exposure. Efavirenz should whenever possible be avoided in the first trimester of gestation, but its use seems well tolerated for 39 days after last menstrual period when the neural tube closes. Raltegravir may be considered in special circumstances in pregnancy. Summary The HIV viral load and the risk factors for prematurity must be considered when deciding when to start antiretroviral treatment in each individual pregnant woman. A ritonavir-boosted protease inhibitor combined with two nucleoside reverse transcriptase inhibitors is currently the most widely used regimen. Among protease inhibitors, lopinavir combined with ritonavir is the most frequently used; however, atazanavir combined with ritonavir is a good alternative. Elective cesarean section is the best delivery mode for pregnant women with viral loads more than 50 copies/ml.

HIV-1 viremia during the first 28 weeks of pregnancy is not associated with mother-to-child transmission

It is currently recommended that antiretroviral prophylaxis to prevent mother-to-child transmission (MTCT) of HIV be initiated at 14 weeks of gestation. However, the relevance of early-gestation HIV viral load level for intrauterine MTCT is unknown. The objective of this study was to determine the relationship between prenatal maternal viral load and intrauterine MTCT. Records of HIV-infected pregnant women in two centers in Brazil, from 1999 to 2004 were analyzed. Three pregnancy periods were considered: earlier than 14 weeks, 14 to 27 6/7 weeks, and 28 weeks of gestation or more. Peripartum HIV exposure was also computed. Maximum viral load in each period was the measure of HIV exposure. Four hundred fifty-seven HIV-infected pregnant women were evaluated, but 53 were excluded. The MTCT rate was 0.49% (2/404-95% confidence interval (CI95) = 0.14-1.79%). Newborns were not breast-fed. Median viral load for the earlier-than-14-week period was 9,900 copies/mL (P25-75 1,000-50,775 copies/mL), 8,350 copies/mL (P25-75 707-42,000 copies/mL) for the 14 to 27 6/7-week period, and 435 copies/mL (P25-75 90-7,775 copies/mL) after the 28-week period. The peripartum median viral load was 400 copies/mL (P25-75 80-500 copies/mL). MTCT in mothers with VL > 1,000 copies/mL during the first 14 weeks (0.67%, 2/298) was not different from those with VL =1,000 copies/mL (0.0%, 0/96, P=1). Analogously, in the 14 to 27 6/7-week period, MTCT was similar in groups with VL higher (0.68%, 2/292) or lower (0%, 0/106) than 1,000 copies/mL (P=1). Regarding VL >1,000 copies/mL at 28-weeks-or-later and at peripartum periods, MTCT rates were 1.15% (2/173, P = 0.18) and 2.8% (2/71, P = 0.03), respectively. Intrauterine transmission does not seem to be influenced by HIV viremia during the first 28 weeks of pregnancy.

A Randomized Controlled Trial to Assess Safety, Tolerability, and Antepartum Viral Load with Increased Lopinavir/Ritonavir Dosage in Pregnancy

HIV mother-to-child transmission (MTCT) is significantly reduced if antepartum viral load (apVL) is<50 copies/mL. Pharmacokinetic studies suggest increasing the dosage of lopinavir/ritonavir (LPV/r) in pregnancy. It is important to assess tolerance, safety, and rate of patients presenting a apVL<50 copies/mL when treating with increased dose of LPV/r during pregnancy. Confirmed HIV-infected pregnant women with a fetus at a gestational age of 14-33 weeks were randomly assigned to receive LPV/r 400/100 or 600/150 mg b.i.d. plus two nucleoside analogues (NRTIs). Treatment was discontinued in the case of alanine transaminase (ALT) of grade III elevation or higher, glucose, or triglycerides. Thirty-two women were randomized to the LPV/r 400/100 mg dose, and 31 women were randomized to the 600/150 mg dose. Overall, 9.4% of the women receiving the conventional dose, and 17.2% receiving the increased dose, discontinued treatment because of adverse events (p=0.29). The rates of gastrointestinal (GI) symptoms, laboratory abnormalities, preterm delivery, and low birth weight were similar in both groups. There were no cases of HIV MTCT. Among the women with a baseline VL>50 copies/mL assigned to the conventional dose group, 45% (95% confidence interval [CI] 62.5-27.5%) had a apVL>50 copies/mL compared with 10.5% (95% CI 21.6-0.6%) of those assigned to the increased dose group (p=0.01). There was no significant difference found for the patients with a baseline VL<50 copies/mL. In pregnant women with a baseline VL>50 copies/mL, it may be warranted to initiate LPV/r dosing at 600/150 mg, whereas the conventional dose is sufficient for pregnant women with a baseline VL<50 copies/mL.

Factores asociados a respuesta virológica en mujeres que usaron profilaxis antirretroviral de gran actividad para transmisión materno-fetal del virus de la inmunodeficiencia humana tipo 1

Introduccion El embarazo es una circunstancia unica en la infeccion por el virus de la inmunodeficiencia humana tipo 1 (VIH-1) que necesita respuesta virologica urgente al esquema antirretroviral debido a la influencia de la carga viral plasmatica (CVP) en la transmision materno-fetal (TMF). El objetivo del estudio es evaluar factores relacionados con el tiempo para obtener CVP Metodos Cohorte de gestantes infectadas por el VIH-1 controladas entre 2000 y 2005 con linfocitos CD4+ > 300/μl; uso de profilaxis antirretroviral de gran actividad durante, minimo, 4 semanas; interrupcion posparto de antirretrovirales y evaluaciones de laboratorio disponibles. Resultados Se analizaron 75 gestaciones. Los valores medianos iniciales fueron: CVP de 3,71 log10 copias/ml y 573 linfocitos CD4+/μl. En el 75% de los casos la profilaxis se inicio despues de 26,6 semanas de gestacion y duro hasta 11,7 semanas. El esquema profilactico cambio en 12 embarazos, 7 por toxicidad. El inhibidor de la protease fue parte de 33 profilaxis, 11 con lopinavir. La profilaxis resulto en CVP Conclusiones La profilaxis antirretroviral no deberia postergarse despues de 26-28 semanas de gestacion para alcanzar una CVP 100.000 copias/ml.

Seroprevalence of hepatitis E virus in chronic hepatitis C in Brazil

BACKGROUND AND AIMS Hepatitis E virus infection in patients with underlying chronic liver disease is associated with liver decompensation and increased lethality. The seroprevalence of hepatitis E virus in patients with chronic hepatitis C in Brazil is unknown. This study aims to estimate the seroprevalence of hepatitis E virus in patients with chronic hepatitis C and to describe associated risk factors. METHODS A total of 618 patients chronically infected with hepatitis C virus from three reference centers of São Paulo, Brazil were included. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA). RESULTS Out of the 618 patients tested, 10.2% turned out positive for anti-HEV IgG (95% CI 8.0-12.8%). Higher seroprevalence was found independently associated with age over 60 years (OR=2.04; p=0.02) and previous contact with pigs (OR=1.99; p=0.03). CONCLUSIONS Patients with chronic hepatitis C are under risk of hepatitis E virus superinfection in São Paulo. Contact with pigs is a risk factor for the infection, suggesting a possible zoonosis with oral transmission.

Mother-to-child transmission of hepatitis C virus

Hepatitis C virus (HCV) infection is a worldwide health problem. Based on results of a serosurvey, global prevalence is estimated to be 2,5%, and women account for about 35.8% of the cases. For pregnant women the prevalence is lower and showed a range between 0.24% to 4.3%. Sinse mechanisms and timing of mother to child transmission are not fully understood, efforts are made to assess and understand its risk factors. The purpose of this review was to synthesize the evidence about the mother-to-child transmission of hepatitis C virus and review its risk factors.