HIV-1 Archives - Revista Brasileira de Ginecologia e Obstetrícia
Summary
Rev Bras Ginecol Obstet. 2009;31(12):609-614
DOI 10.1590/S0100-72032009001200006
PURPOSE: to describe the genetic diversity of HIV-1 isolates from serum positive women followed up at a reference center. METHODS: transversal study, including 96 women with two ELISA serological tests and a Western Blot confirmatory test. The viral charge was determined by the b-DNA kit, and the counting of T CD4 and T CD8 lymphocytes, by the Excalibur flow cytometry, from the samples of peripheral blood. The extraction and purification of pro-viral DNA was performed by the polymerase (PCR) chain reaction, using the QIAamp Blood kit (Qiagen Inc., Chatsworth, CA, U.S.A.). Sequencing of the pol region was done in 52 isolates with the 3100 Genetic Analyzer (Applied Biosystems Inc., Foster City, CA), and the genotyping was assessed by the Rega Subtyping Tool. The resistance pattern to anti-retrovirals (ARV) was inferred by the algorithm from the Stanford HIV Resistance data bank. Participants' clinical stages were defined as A, B or C, according to the criteria established by the Center for Diseases Control (CDC). For statistical analysis, the χ2 test was used for the categorical variables and the Student's t test, for the numerical variables. RESULTS: The average age of the sample, the disease and treatment average duration were respectively: 33.7 years old, 3.8 and 2.5 years. The viral charge average was log10 2.3 copies/mL; the T CD4 e T CD8 lymphocytes, 494.9 cells/µL and 1126.4 cells/µL. Concerning the clinical stage, 30 women were in stage A, 47 in B and 19 in C. Sequencing from the 52 isolates found 33 of B subtype, 4 of F, 1 of C and 14 of BF recombinant. The analysis of resistance to ARV has shown 39 (75.0%) susceptible isolates, 13 (25.0%) resistant to reversal transcriptase inhibitors (RTIN), and 3 (5.7%) resistant to protease inhibitor (PI). CONCLUSIONS: There has been a large variety of HIV-1 and a high percentage of isolates resistant to ARV in the studied sample.
Summary
Rev Bras Ginecol Obstet. 2009;31(12):609-614
DOI 10.1590/S0100-72032009001200006
PURPOSE: to describe the genetic diversity of HIV-1 isolates from serum positive women followed up at a reference center. METHODS: transversal study, including 96 women with two ELISA serological tests and a Western Blot confirmatory test. The viral charge was determined by the b-DNA kit, and the counting of T CD4 and T CD8 lymphocytes, by the Excalibur flow cytometry, from the samples of peripheral blood. The extraction and purification of pro-viral DNA was performed by the polymerase (PCR) chain reaction, using the QIAamp Blood kit (Qiagen Inc., Chatsworth, CA, U.S.A.). Sequencing of the pol region was done in 52 isolates with the 3100 Genetic Analyzer (Applied Biosystems Inc., Foster City, CA), and the genotyping was assessed by the Rega Subtyping Tool. The resistance pattern to anti-retrovirals (ARV) was inferred by the algorithm from the Stanford HIV Resistance data bank. Participants' clinical stages were defined as A, B or C, according to the criteria established by the Center for Diseases Control (CDC). For statistical analysis, the χ2 test was used for the categorical variables and the Student's t test, for the numerical variables. RESULTS: The average age of the sample, the disease and treatment average duration were respectively: 33.7 years old, 3.8 and 2.5 years. The viral charge average was log10 2.3 copies/mL; the T CD4 e T CD8 lymphocytes, 494.9 cells/µL and 1126.4 cells/µL. Concerning the clinical stage, 30 women were in stage A, 47 in B and 19 in C. Sequencing from the 52 isolates found 33 of B subtype, 4 of F, 1 of C and 14 of BF recombinant. The analysis of resistance to ARV has shown 39 (75.0%) susceptible isolates, 13 (25.0%) resistant to reversal transcriptase inhibitors (RTIN), and 3 (5.7%) resistant to protease inhibitor (PI). CONCLUSIONS: There has been a large variety of HIV-1 and a high percentage of isolates resistant to ARV in the studied sample.
Summary
Rev Bras Ginecol Obstet. 2008;30(1):19-24
DOI 10.1590/S0100-72032008000100004
PURPOSE: The aim of this article is to evaluate the use of nevirapine HIV-infected pregnant women in our service. METHODS: a retrospective study was performed between January 2003 and December 2006 analysing all women prescribed nevirapine in pregnancy. Exclusion criteria included: (1) women who started nevirapine before pregnancy, (2) patients with abnormal baseline liver enzymes, and (3) women with incomplete liver biochemistry data. Evaluated parameters included age, weeks of exposure to nevirapine, gestational age in the begginning of medication, weeks of follow-up, viral load, CD4 cells count and serum aminotransferase levels. The incidence of adverse hepatic and/or cutaneous effects was determined and correlated to the CD4 cells count. Statistical analysis were performed using Fisher’s exact test and t-Student test when appropriate, with a statistical significance level of p<0,05. RESULTS: one hundred fifty-seven women met the inclusion criteria. Thirty-one (19.7%) presented cutaneous and/or hepatic toxicity. Skin rash accounted for 77.4% of toxicities and liver function abnormalities were noted in 22.6% of women exhibiting toxicities. Grade 1, 2 and 3 hepatotoxicities were observed in 0.6, 2.5 and 1.3%, respectively. Baseline CD4 counts, viral loads and transaminases were similar in pregnant women with nevirapine adverse effects and those without reaction. Median absolute CD4 cell counts were 465.4 and 416.6 cells/µL in women with and without side effects, respectively (p=0.3). All patients who experienced hepatotoxicity had pretreatment CD4 counts superior to 250 cells/µL. CONCLUSIONS: The incidence of adverse events with nevirapine in our study was high, but most of them were cutaneous. There was no correlation between high CD4 counts and adverse events when analysing both cutaneous and hepatic reactions; nevertheless, hepatotoxicity occurred only in pregnant women with CD4 counts >250 cells/µL.
Summary
Rev Bras Ginecol Obstet. 2008;30(1):19-24
DOI 10.1590/S0100-72032008000100004
PURPOSE: The aim of this article is to evaluate the use of nevirapine HIV-infected pregnant women in our service. METHODS: a retrospective study was performed between January 2003 and December 2006 analysing all women prescribed nevirapine in pregnancy. Exclusion criteria included: (1) women who started nevirapine before pregnancy, (2) patients with abnormal baseline liver enzymes, and (3) women with incomplete liver biochemistry data. Evaluated parameters included age, weeks of exposure to nevirapine, gestational age in the begginning of medication, weeks of follow-up, viral load, CD4 cells count and serum aminotransferase levels. The incidence of adverse hepatic and/or cutaneous effects was determined and correlated to the CD4 cells count. Statistical analysis were performed using Fisher’s exact test and t-Student test when appropriate, with a statistical significance level of p<0,05. RESULTS: one hundred fifty-seven women met the inclusion criteria. Thirty-one (19.7%) presented cutaneous and/or hepatic toxicity. Skin rash accounted for 77.4% of toxicities and liver function abnormalities were noted in 22.6% of women exhibiting toxicities. Grade 1, 2 and 3 hepatotoxicities were observed in 0.6, 2.5 and 1.3%, respectively. Baseline CD4 counts, viral loads and transaminases were similar in pregnant women with nevirapine adverse effects and those without reaction. Median absolute CD4 cell counts were 465.4 and 416.6 cells/µL in women with and without side effects, respectively (p=0.3). All patients who experienced hepatotoxicity had pretreatment CD4 counts superior to 250 cells/µL. CONCLUSIONS: The incidence of adverse events with nevirapine in our study was high, but most of them were cutaneous. There was no correlation between high CD4 counts and adverse events when analysing both cutaneous and hepatic reactions; nevertheless, hepatotoxicity occurred only in pregnant women with CD4 counts >250 cells/µL.
Summary
Rev Bras Ginecol Obstet. 2005;27(12):768-778
DOI 10.1590/S0100-72032005001200010
Knowledge about the factors or situations that influence the vertical transmission (VT) of human immunodeficiency type 1 (HIV-1) has led to the implementation of strategies which have promoted a rate decline along the years, from 40% to less than 3% nowadays. One of the major advances in the area has been the prophylactic administration of zidovudine (AZT), in the prenatal phase (oral route), in the predelivery phase (intravenous route) and to the newborn (oral route). This intervention may reduce HIV-1 VT 68%, thus being the most effective isolated strategy used so far. In the chronological sequence of advances, it has been observed that a high viral load is the main risk indicator for this type of transmission. As AZT does not reduce the viral load and does not control the residual rate observed in HIV-1 VT, the use of prophylactic schemes using three antiretroviral drugs has been encouraged. Elective caesarean section completes the range of obstetric strategies with major impact on the reduction of HIV-1 VT. Its effectiveness is linked to the observation of the criteria for its indication: viral load assessed after the 34th week of pregnancy with levels over 1000 copies/mL, gestation over 38 weeks confirmed by ultrasonography, intact chorioamniotic membranes, and performed before labor has started. In cases where normal delivery is indicated, it should be remembered that prolonged chorioamniorrhexis, invasive manipulation of the fetus, delivery with instruments and episiotomy are situations to be avoided. Among the postnatal interventions considered important for the reduction of HIV-1 VT are: pediatric reception (this should be done by trained professionals, avoiding microtraumas in the mucosa during the sucking maneuvers, use of neonatal AZT (for a period of six weeks) and bottle feeding. Special attention should be given to the orientation for the mother, in order to prevent acute infection by HIV-1 in this period, what would markedly increase virus VT rate.
Summary
Rev Bras Ginecol Obstet. 2005;27(12):768-778
DOI 10.1590/S0100-72032005001200010
Knowledge about the factors or situations that influence the vertical transmission (VT) of human immunodeficiency type 1 (HIV-1) has led to the implementation of strategies which have promoted a rate decline along the years, from 40% to less than 3% nowadays. One of the major advances in the area has been the prophylactic administration of zidovudine (AZT), in the prenatal phase (oral route), in the predelivery phase (intravenous route) and to the newborn (oral route). This intervention may reduce HIV-1 VT 68%, thus being the most effective isolated strategy used so far. In the chronological sequence of advances, it has been observed that a high viral load is the main risk indicator for this type of transmission. As AZT does not reduce the viral load and does not control the residual rate observed in HIV-1 VT, the use of prophylactic schemes using three antiretroviral drugs has been encouraged. Elective caesarean section completes the range of obstetric strategies with major impact on the reduction of HIV-1 VT. Its effectiveness is linked to the observation of the criteria for its indication: viral load assessed after the 34th week of pregnancy with levels over 1000 copies/mL, gestation over 38 weeks confirmed by ultrasonography, intact chorioamniotic membranes, and performed before labor has started. In cases where normal delivery is indicated, it should be remembered that prolonged chorioamniorrhexis, invasive manipulation of the fetus, delivery with instruments and episiotomy are situations to be avoided. Among the postnatal interventions considered important for the reduction of HIV-1 VT are: pediatric reception (this should be done by trained professionals, avoiding microtraumas in the mucosa during the sucking maneuvers, use of neonatal AZT (for a period of six weeks) and bottle feeding. Special attention should be given to the orientation for the mother, in order to prevent acute infection by HIV-1 in this period, what would markedly increase virus VT rate.
Summary
Rev Bras Ginecol Obstet. 2005;27(11):698-705
DOI 10.1590/S0100-72032005001100011
One of the most important advances in the control of the spread of infection with type 1 human immunodeficiency virus (HIV-1) occurred within the context of vertical transmission (VT), with a reduction from levels of more than 40% to levels of less than 3%. Technological progress together with a better physiopathological understanding of this infection has permitted the determination of the situations and factors that increase the rates of perinatal transmission of the virus, indicating which interventions are most adequate for its control. The situations of higher risk for VT of HIV involve maternal, adnexal, obstetrical, fetal, viral, and postnatal factors. Among maternal factors, particularly important is viral load, the major indicator of the risk of this form of transmission. However, despite its relevance, viral load is not the only variable in this equation, with the following factors also playing important roles: use of illicit drugs, multiple sex partners and unprotected sex, malnutrition, smoking habit, advanced maternal disease, and lack af access or compliance with antiretroviral drugs. Among the adnexal factors are prolonged chorion-amniorrhexis, loss of placental integrity, and the expression of secondary receptors in placental tissue. Among the obstetrical factors, it should be remembered that invasive interventions in the fetus or amniotic chamber, internal cardiotocography, type of delivery, and contact of the fetus/newborn infant with maternal blood are also important elements to be controlled. Among the fetal factors are the expression of secondary HIV-1 receptors, genetic susceptibility, reduced cytotoxic T-lymphocyte function, and prematurity. Among the viral factors, mutations and syncytium-inducing strains are believed to be risk factors for VT. Finally, there are postnatal factors represented by an elevated viral load in maternal milk, a low antibody concentration in this fluid, clinical mastitis and nipple lesions, which can be grouped within the context of breast-feeding.
Summary
Rev Bras Ginecol Obstet. 2005;27(11):698-705
DOI 10.1590/S0100-72032005001100011
One of the most important advances in the control of the spread of infection with type 1 human immunodeficiency virus (HIV-1) occurred within the context of vertical transmission (VT), with a reduction from levels of more than 40% to levels of less than 3%. Technological progress together with a better physiopathological understanding of this infection has permitted the determination of the situations and factors that increase the rates of perinatal transmission of the virus, indicating which interventions are most adequate for its control. The situations of higher risk for VT of HIV involve maternal, adnexal, obstetrical, fetal, viral, and postnatal factors. Among maternal factors, particularly important is viral load, the major indicator of the risk of this form of transmission. However, despite its relevance, viral load is not the only variable in this equation, with the following factors also playing important roles: use of illicit drugs, multiple sex partners and unprotected sex, malnutrition, smoking habit, advanced maternal disease, and lack af access or compliance with antiretroviral drugs. Among the adnexal factors are prolonged chorion-amniorrhexis, loss of placental integrity, and the expression of secondary receptors in placental tissue. Among the obstetrical factors, it should be remembered that invasive interventions in the fetus or amniotic chamber, internal cardiotocography, type of delivery, and contact of the fetus/newborn infant with maternal blood are also important elements to be controlled. Among the fetal factors are the expression of secondary HIV-1 receptors, genetic susceptibility, reduced cytotoxic T-lymphocyte function, and prematurity. Among the viral factors, mutations and syncytium-inducing strains are believed to be risk factors for VT. Finally, there are postnatal factors represented by an elevated viral load in maternal milk, a low antibody concentration in this fluid, clinical mastitis and nipple lesions, which can be grouped within the context of breast-feeding.
Summary
Rev Bras Ginecol Obstet. 2005;27(7):393-400
DOI 10.1590/S0100-72032005000700005
PURPOSE: to evaluate T cell proliferation and cytokine production in HIV-1-infected pregnant women and their impact on in vitro virus replication. METHODS: peripheral blood from 12 HIV-1-infected pregnant women and from their neonates was collected. As control, 10 samples from non-infected pregnants were also colleted. The CD4+ and CD8+ T cell counts were assayed by flow cytometry. Peripheral blood mononuclear cells (PBMC) and plasma were obtained by centrifugation with and without Ficoll-Hypaque gradient, respectively. The freshly purified PBMC were kept in cultures for seven days with PHA plus r-IL-2, and the lymphoproliferative response was assayed by Trypan blue dye exclusion. In some experiments we added anti-IL-10 monoclonal antibody. The plasma samples and supernatants from cell cultures were stored to determine both peripheral cytokine levels, by ELISA sandwich, and viral load, by RT-PCR. RESULTS: the results showed that the lymphoproliferative response was smaller in cultures obtained from HIV-1-infected women than in control cultures [4.2±0.37 vs 2.4±0.56 (x 10(6) cell/mL), p<0.005]. In both control and infected pregnant women who had low plasma viral load, the level of IL-10 was higher than in those with high viral replication (9.790±3.224 vs 1.256±350 pg/mL, p=0.002). The elevated TNF-alpha production detected in serum (7.200±2.440 pg/mL) and supernatants (21.350±15.230 pg/mL) was associated with higher plasma viral loads and vertical infection. The IL-10 blockade by anti-IL-10 antibodies augmented viral replication in the cell cultures. CONCLUSION: these results indicate that IL-10 production exerts a negative influence on virus replication, diminishing the probability of intrauterine HIV-1 infection.
Summary
Rev Bras Ginecol Obstet. 2005;27(7):393-400
DOI 10.1590/S0100-72032005000700005
PURPOSE: to evaluate T cell proliferation and cytokine production in HIV-1-infected pregnant women and their impact on in vitro virus replication. METHODS: peripheral blood from 12 HIV-1-infected pregnant women and from their neonates was collected. As control, 10 samples from non-infected pregnants were also colleted. The CD4+ and CD8+ T cell counts were assayed by flow cytometry. Peripheral blood mononuclear cells (PBMC) and plasma were obtained by centrifugation with and without Ficoll-Hypaque gradient, respectively. The freshly purified PBMC were kept in cultures for seven days with PHA plus r-IL-2, and the lymphoproliferative response was assayed by Trypan blue dye exclusion. In some experiments we added anti-IL-10 monoclonal antibody. The plasma samples and supernatants from cell cultures were stored to determine both peripheral cytokine levels, by ELISA sandwich, and viral load, by RT-PCR. RESULTS: the results showed that the lymphoproliferative response was smaller in cultures obtained from HIV-1-infected women than in control cultures [4.2±0.37 vs 2.4±0.56 (x 10(6) cell/mL), p<0.005]. In both control and infected pregnant women who had low plasma viral load, the level of IL-10 was higher than in those with high viral replication (9.790±3.224 vs 1.256±350 pg/mL, p=0.002). The elevated TNF-alpha production detected in serum (7.200±2.440 pg/mL) and supernatants (21.350±15.230 pg/mL) was associated with higher plasma viral loads and vertical infection. The IL-10 blockade by anti-IL-10 antibodies augmented viral replication in the cell cultures. CONCLUSION: these results indicate that IL-10 production exerts a negative influence on virus replication, diminishing the probability of intrauterine HIV-1 infection.
