Antiretroviral agents and acid-base balance at delivery of the neonate

Limited evidence is available regarding antiretroviral (ARV) safety for uninfected infants exposed to these drugs in utero. Our objective was to determine if ARV administered to pregnant women is associated with decreasing umbilical arterial pH and base excess in uninfected infants. A prospective study was conducted on 57 neonates divided into three groups: ZDV group, born to mothers taking zidovudine (N = 20), triple therapy (TT) group, born to mothers taking zidovudine + lamivudine + nelfinavir (N = 25), and control group (N = 12), born to uninfected mothers. Umbilical cord blood was used to determine umbilical artery gases. A test was performed to calculate the sample by comparing means by the unpaired one-tailed t-test, with a = 0.05 and ß = 20 percent, indicating the need for a sample of 18 newborn infants for the study groups to detect differences higher than 20 percent. The control and ARV groups were similar in gestational age, birth weight, and Apgar scores. Values of pH, pCO2, bicarbonate, and base excess in cord arterial blood obtained at delivery from the newborns exposed to TT were 7.23, 43.2 mmHg, 19.5 mEq/L, and -8.5 nmol/L, respectively, with no significant difference compared to the control and ZDV groups. We conclude that intrauterine exposure to ARV is not associated with a pathological decrease in umbilical arterial pH or base excess. While our data are reassuring, follow-up is still limited and needs to be continued into adulthood because of the possible potential for adverse effects of triple antiretroviral agents.

Effects of antiretroviral agents during pregnancy on liver enzymes and amylase in HIV-exposed, uninfected newborn infants

This study assessed the effect of antiretroviral drugs administered to pregnant women on amylase and liver enzymes of the neonate. A prospective study was conducted on 52 neonates divided into three groups: infants born to HIV-infected mothers taking zidovudine (ZDV group, n = 18), infants born to mothers taking zidovudine + lamivudine + nelfinavir (TT group, n = 22) and infants born to normal women (control group, n = 12). Umbilical cord blood from the newborn infant was used to determine liver transaminases and amylase. Data were analyzed statistically by nonparametric tests, with the level of significance set at p<0.05. The median levels for TT group newborns were 33.3 U/L for oxaloacetic transaminase, 21.5 U/L for pyruvic transaminase, 1.9 mg/dL for total bilirubin, 153 mg/dL for alkaline phosphatase, and 9.6 U/L for amylase. These results did not differ from those obtained for Control newborns or newborns exposed to ZDV alone. No association was observed between the use of antiretroviral drugs during pregnancy and adverse effects on neonatal amylase and hepatic parameters at birth.

HIV-1 genotypes related to failure of nelfinavir as the first protease inhibitor treatment

Combined antiretroviral therapy results in sustained viral suppression and a decrease in mortality and morbidity due to HIV infection. Intrinsic strength, durability and absence of cross-resistance are key factors in the selection of antiretrovirals. Failure with nelfinavir has been associated with two protease gene mutations, D30N and L90M. The D30N mutation does not result in cross-resistance with other protease inhibitors, and it decreases viral fitness. In order to check for this mutation after failure with nelfinavir, the 246 HIV-1 genotyping test was performed on virus samples from 55 patients with failure of nelfinavir as the first protease inhibitor. Most (84 percent) of the viral strains were of subtype B. Nucleosides associated with mutations (NAM) were observed in 80 percent of the tests; no INS69, complex 151, K65R and L74V mutations, which give multi-resistance to nucleoside analogue reverse transcriptase inhibitors to tenofovir and DDI, respectively, were observed. In the tests for protease gene mutations, the D30N mutation was found in 57 percent, L90M in 18 percent and the wild-type virus in 25 percent. These data are similar to published reports, showing that alternative therapies used after failure with nelfinavir may be more successful, as the D30N mutation does not cause cross-resistance to other protease inhibitors.

Effect of antiretroviral drugs on maternal CD4 lymphocyte counts, HIV-1 RNA levels, and anthropometric parameters of their neonates

OBJETIVOS: Estudar o efeito das drogas anti-retrovirais sobre a quantificação dos linfócitos TCD4 e RNA do HIV-1 de gestantes portadoras do HIV-1 e parâmetros antropométricos de seus neonatos. MÉTODOS: Estudo prospectivo avaliando 57 gestantes e seus neonatos em três grupos: Grupo AZT, gestantes portadoras do HIV utilizando zidovudina (n=20); Grupo TT, mães utilizando zidovudina+lamivudina+nelfinavir (n=25), e Grupo Controle, mulheres saudáveis (n=12). A quantificação dos linfócitos TCD4 e RNA do HIV-1 de gestantes portadoras do HIV foi analisada em dois períodos durante a gestação. O prognóstico perinatal levou em consideração as taxas de pré-termos, restrição de crescimento intra-útero, mortalidade perinatal e transmissão vertical do HIV-1. Os dados foram analisados utilizando-se testes não paramétricos de qui-quadrado, Mann-Whitney, Friedman, Kruskal-Wallys e Wilcoxon para amostras pareadas, considerando-se significativos valores associados a p<0,05. RESULTADOS: Observou-se homogeneidade entre os dados demográficos e antropométricos de realce. A carga viral, inicialmente elevada (14.370 cópias/ml), reduziu-se significativamente no grupo com tratamento tríplice , chegando a 40 cópias/ml. Quanto à contagem de linfócitos CD4, observou-se recuperação significativa nas pacientes do grupo TT, no final da gestação, sendo esse valor significativamente diferente em comparação ao grupo AZT (p = 0,0052). Não se observou diferença entre os grupos quanto à duração da gestação, aos índices de Apgar, e à classificação antropométrica neonatal. Não houve nenhum caso de transmissão vertical do HIV-1. CONCLUSÕES: Os resultados obtidos na presente casuística demonstram eficiência e sugerem segurança no uso de anti-retrovirais na gestação sobre parâmetros antropométricos dos neonatos.

Estimating the length of the first antiretroviral therapy regiment durability in Säo Paulo, Brazil

Brazil was the first country to provide unrestricted, cost-free access to antiretroviral (ARV) medicine for AIDS treatment. However, there is little data about the benefits of such a policy for these patients. We evaluated the duration of benefit obtained with the introduction of ARVs, defined as the durability of the first ARV regiment. We reviewed the medical charts of patients attended from 1996-2000, at the outpatient clinics of the Federal University of Säo Paulo, Brazil. A total of 120 drug-naive HIV-1 infected patients were eligible to participate in the study. About half of the individuals (53 percent) presented with disease symptoms; 59 percent of them had CD4 count below 200 cells/mm³. Mean estimated duration of the benefit of therapy was 14.1 months. The most used regimen in this cohort was Zidovudine/3TC/Indinavir (26 percent), followed by Zidovudine/DDI (17 percent), and Zidovudine/3TC/Nelfinavir (13 percent). The most frequent cause of interruption of therapy was gastrointestinal intolerance. Use of treatment regimens with three drugs was more effective than with two drugs, but only for patients with CD4<200 cells/mm³ or CV>100,000 copies RNA/mL. However, the use of triple therapy was associated with a significantly higher probability of reaching maximum viral suppression, during a longer period (p<0.05).The patients enrolled in the study benefitted from therapy for a limited time, after the introduction of double or triple antiretroviral therapy. The incidence of adverse events was significantly associated with loss of the benefits provided by the initial therapeutic regimen.