Table of Contents
Objective: To determine incidence of and reasons for discontinuation of abacavir within the first six months of therapy.
Methods: Retrospective study performed in the cohort of HIV-infected adults who started abacavir in a medical unit between 1997 and December 2000. All adverse drug reactions (ADRs) (especially hypersensitivity) observed in this cohort were reported. The association between drugs and complications were evaluated, using the French method to assess unexpected and toxic drug reactions. According to the variables studied, statistical analysis was performed using the two test, Fisher's exact test, Mann-Whitney, Wilcoxon, or Kruskal-Wallis tests.
Results: All 331 patients treated with abacavir during this time period were included in this study. Early discontinuation of abacavir was observed in 34.1 percent of patients, the main reasons being adverse effects (20.8 percent), virologic failure (3.3 percent), drug holidays (2.7 percent), poor adherence (2.7 percent), and death (1.8 percent). Adverse effects were mostly represented by hypersensitivity reactions. After retrospective analysis, abacavir was stopped for likely hypersensitivity in 8.5 percent of patients, for doubtful hypersensitivity in 4.2 percent, and for other adverse effects in 8.1 percent of patients.
Conclusions: This study shows that abacavir is mainly stopped during the first six months of therapy for ADRs. The rate of likely hypersensitivity reaction observed in this study (8.5 percent) is higher than that observed in clinical trials (5 percent). After retrospective evaluation, the causality assessment of abacavir is not always certain. [Ann Pharmacother 2003;37(10):1392-1397.]
Hendricks K.M. et al.
Background: Lipodystrophy has been described with increasing frequency in patients infected with HIV. This study focused on the identification of dietary components that may predispose HIV-positive patients to the development of fat deposition.
Objective: We evaluated differences in past dietary intake between men with HIV who developed fat deposition and those who did not.
Design: This nested case-control study consisted of 47 cases and 47 controls from the Nutrition for Healthy Living cohort. Food records from six to 24 months before development of fat deposition in cases were analyzed and compared with food records from controls by using t tests for normally distributed nutrients and Wilcoxon rank-sum tests for nutrients with skewed distributions.
Results: HIV-positive patients without fat deposition had greater overall energy intakes (kcal/kg; P=0.03) and greater intakes of total protein (P=0.01), total dietary fiber (P=0.01), soluble dietary fiber (P=0.01), insoluble dietary fiber (P=0.03), and pectin (P=0.02) than did HIV-positive patients with fat deposition. Those without fat deposition also tended to currently perform more resistance training (P=0.05) and to not be current smokers (P=0.05).
Conclusions: Our results indicate that an overall high-quality diet, rich in fiber and adequate in energy and protein, may be beneficial in preventing the development of fat deposition in persons infected with HIV. The results of this study further emphasize that a healthy lifestyle, including exercise and avoidance of unhealthy behaviors such as smoking, may also be similarly beneficial. [Am J Clin Nutr 2003;78(4):790-795.]
Klugman K.P. et al.
Background: Acute respiratory tract infections caused by Streptococcus pneumoniae are a leading cause of morbidity and mortality in young children. We evaluated the efficacy of a 9-valent pneumococcal conjugate vaccine in a randomized, double-blind study in Soweto, South Africa.
Methods: At six, 10, and 14 weeks of age, 19,922 children received the 9-valent pneumococcal polysaccharide vaccine conjugated to a noncatalytic cross-reacting mutant of diphtheria toxin (CRM197), and 19,914 received placebo. All children received Haemophilus influenzae type b conjugate vaccine. Efficacy and safety were analyzed according to the intention-to-treat principle.
Results: Among children without human immunodeficiency virus (HIV) infection, the vaccine reduced the incidence of a first episode of invasive pneumococcal disease due to serotypes included in the vaccine by 83 percent (95 percent confidence interval, 39 to 97; 17 cases among controls and three among vaccine recipients). Among HIV-infected children, the efficacy was 65 percent (95 percent confidence interval, 24 to 86; 26 and 9 cases, respectively). Among children without HIV infection, the vaccine reduced the incidence of first episodes of radiologically confirmed alveolar consolidation by 20 percent (95 percent confidence interval, 2 to 35; 212 cases in the control group and 169 in the vaccinated group) in the intention-to-treat analysis and by 25 percent (95 percent confidence interval, 4 to 41; 158 and 119 cases, respectively) in the per-protocol analysis (i.e., among fully vaccinated children). The incidence of invasive pneumococcal disease caused by penicillin-resistant strains was reduced by 67 percent (95 percent confidence interval, 19 to 88; 21 cases in the control group and seven in the vaccinated group), and that caused by strains resistant to trimethoprim-sulfamethoxazole was reduced by 56 percent (95 percent confidence interval, 16 to 78; 32 and 14 cases, respectively).
Conclusions: Vaccination with a 9-valent pneumococcal conjugate vaccine reduced the incidence of radiologically confirmed pneumonia. The vaccine also reduced the incidence of vaccine-serotype and antibiotic-resistant invasive pneumococcal disease among children with and those without HIV infection. [N Engl J Med 2003;349(14):1341-1348.]
Rouet F. et al.
Objective: To describe plasma human immunodeficiency virus type 1 (HIV-1) RNA levels in African HIV-1-infected children in relation to the timing of infection and disease progression.
Methods: A retrospective cohort study was conducted of 80 children who were born to HIV-1-positive mothers and clinically followed from birth to 18 months of age in the ANRS 049 Ditrame project, Abidjan, Côte d'Ivoire (West Africa). The diagnosis and timing of pediatric HIV-1 infection were determined prospectively according to HIV-1 DNA polymerase chain reaction results. A total of 364 HIV-1 RNA viral load (VL) measurements were assessed retrospectively. Kaplan-Meier analyses and proportional hazards models were used to evaluate the prognostic value of pediatric VL and covariates for HIV disease progression or death.
Results: Mean initial positive VL was significantly lower among children who were infected in utero (4.94 log10 /mL, n=12) than in children who were infected later (5.6-6.1 log10 /mL, n=68). In the first six months after diagnosis, HIV-1 RNA levels peaked (6 log10 /mL), regardless of timing of infection. Then, a slow decline (overall slope, -0.076 log10 copies/mL/mo) was observed until 18 months of age. A 1 log10 higher value of the pediatric peak VL (risk ratio [RR]: 1.85; 95 percent confidence interval [CI]: 1.0-3.44) and of the maternal VL at delivery (RR: 1.90; CI: 1.16-3.12) were independently associated with an increased risk of rapid progression to acquired immune deficiency syndrome (AIDS) or death at 18 months of life (23 AIDS diagnoses and 31 deaths). Disease progression or death was more rapid for girls than for boys (RR: 2.26; CI: 1.39-4.96).
Conclusions: In Africa, pediatric HIV-1 RNA levels are very close to those described in industrialized countries and seem to be predictive of AIDS stage or death, as in industrialized countries. With antiretroviral therapy becoming more widely available, the early identification and monitoring of pediatric HIV disease remains of paramount importance in Africa. [Pediatrics 2003;112(4):e289-e289.]
Nolan D. et al.
Background: The use of HIV protease inhibitors (PIs) as a component of combination antiretroviral therapy in HIV-infected patients has been associated with dyslipidemia, but its significance as a risk factor for cardiovascular disease is unclear. Endothelial dysfunction is an early phase of atherogenesis that may be assessed non-invasively with ultrasonography in vivo.
Aim: To evaluate vascular function and investigate potential determinants of endothelial dysfunction of the peripheral circulation in PI-treated, HIV-infected men with dyslipidemia.
Design: Observational, case-control study.
Methods: We studied 24 HIV-infected, PI-treated men with dyslipidemia and 24 normolipidemic, healthy male controls matched for age and body mass index. Brachial artery endothelial function was studied using high-resolution ultrasound and computerized edge-detection software. This non-invasive technique measured post-ischemic flow-mediated dilatation (FMD), and the endothelium-independent vasodilatory response to glyceryl trinitrate (GTN).
Results: Within the HIV patient group, FMD was significantly associated with percentage of "naive" CD4 + 45RA + T cells (P=0.03), while plasma lipid/lipoprotein and insulin levels, body mass, and smoking status did not correlate with endothelial function. FMD was not significantly different between the study group and the controls.
Conclusions: The atherogenic potential of PI-associated dyslipidemia may be attenuated in HIV-infected patients with decreased immune competence, reflecting a possible contribution of cell-mediated immune responses to the pathogenesis of atherosclerosis. [QJM 2003;96(11):825-832.]
Taha T.E. et al.
Background: In sub-Saharan Africa, most women present late for delivery with unknown HIV status, which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV. We aimed to determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone.
Methods: We randomly assigned 1,119 babies of Malawian women with HIV-1 who presented late (i.e., within two hours of expected delivery) to either nevirapine alone or nevirapine and zidovudine. Both drugs were given immediately after birth: one dose of nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for one week (4 mg/kg weight). Infant HIV infection was determined at birth and at six to eight weeks. Primary outcome was HIV infection in babies at six to eight weeks in those not infected at birth. Analysis was by intention to treat.
Findings: The overall rate of mother-to-child transmission at six to eight weeks was 15.3 percent in 484 babies who received nevirapine and zidovudine and 20.9 percent in 468 babies who received nevirapine only (P=0.03). At six to eight weeks, in babies who were HIV negative at birth, 34 (7.7 percent) babies who had nevirapine and zidovudine and 51 (12.1 percent) who received nevirapine only were infected (P=0.03) -- a protective efficacy of 36 percent. This finding remained after controlling for maternal viral load and other factors at baseline. Adverse events were mild and of similar frequency in the two groups.
Interpretation: Post-exposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counseled and tested before or during pregnancy. The nevirapine and zidovudine regimen is safe and easy to implement. [Lancet 2003;362(9391):1171-7.]
Goldani M.Z. et al.
Objective: Voluntary HIV counseling and testing are provided to all Brazilian pregnant women with the purpose of reducing mother-to-child HIV transmission. The purpose of the study was to assess characteristics of HIV testing and identify factors associated with HIV counseling and testing.
Methods: A cross-sectional study was carried out comprising 1,658 mothers living in Porto Alegre, Brazil. Biological, reproductive and social variables were obtained from mothers by means of a standardized questionnaire. Being counseled about HIV testing was the dependent variable. Confidence intervals, chi-square test and hierarchical logistic model were used to determine the association between counseling and maternal variables.
Results: Of 1,658 mothers interviewed, 1,603 or 96.7 percent (95 percent CI: 95.7-97.5) underwent HIV testing, and 51 or 3.1 percent (95 percent CI: 2.3-4.0) were not tested. Four (0.2 percent) refused to undergo testing after counseling. Of 51 women not tested in this study, 30 had undergone the testing previously. Of 1,603 women tested, 630 or 39.3 percent (95 percent CI: 36.9-41.7) received counseling, 947 or 59.2 percent (95 percent CI: 56.6-61.5) did not, and 26 (1.6 percent) did not inform. Low income, lack of prenatal care, late beginning of prenatal care, use of rapid testing, and receiving prenatal care in the public sector were variables independently associated with a lower probability of getting counseling about HIV testing.
Conclusions: The study findings confirmed the high rate of prenatal HIV testing in Porto Alegre. However, women coming from less privileged social groups were less likely to receive information and benefit from counseling. [Rev Saude Publica 2003;37(5):552-8.]
Marcotte T.D. et al.
Background: Neuropsychological (NP) impairment is a relatively common sequela in human immunodeficiency virus (HIV)-infected individuals with advanced disease. Early antecedents of NP dysfunction, however, remain poorly understood.
Objective: To determine whether early markers of immunocompetence and viral replication in individuals who have undergone seroconversion would be of prognostic value in identifying subjects who would become cognitively impaired.
Methods: Seventy-four subjects with estimable seroconversion dates and normal cognition at baseline (a median of one year after seroconversion) received NP and laboratory evaluations, including reverse transcription-polymerase chain reaction measurements of plasma (n=74) and cerebrospinal fluid (n=47) levels of HIV RNA. Subjects were followed up longitudinally, and were considered to have reached the end point if they became cognitively impaired.
Results: Using Kaplan-Meier estimates, the subgroups with the most rapid progression to NP impairment were (1) subjects with early reductions in CD4 counts (<400 cells/mL at baseline; P=.007) and (2) those with elevated plasma HIV RNA values (>4.5 log10 copies/mL; P=.03) early after seroconversion. Using proportional hazards modeling, the highest-risk subjects had both CD4 counts less than 400 cells/mL and HIV RNA levels greater than 4.5 log10 copies/mL (risk ratio, 6.0; P=.01). In most subjects (7/9 [78 percent]), NP impairment developed before an acquired immunodeficiency syndrome-defining illness.
Conclusions: Neurocognitive outcomes in HIV are strongly influenced by very early systemic virological and immunological events. Patients with high plasma levels of HIV RNA and low CD4 counts early after infection should be aggressively treated to prevent immunological decline and NP deterioration. [Arch Neurol 2003;60(10):1406-12.]
Ananworanich J. et al.
Background: Scheduled treatment interruptions are being evaluated in an effort to decrease costs and side effects of highly active antiretroviral therapy (HAART). A schedule of one week on and one week off therapy offers the promise of 50 percent less drug exposure with continuously undetectable HIV RNA concentration.
Methods: In the Staccato study 600 patients on successful HAART were to be randomized to either continued therapy, CD4-guided therapy, or one week on, one week off therapy. A scheduled preliminary analysis evaluated effectiveness in the one-week-on-one-week-off arm.
Results: Of 36 evaluable patients, 19 (53 percent) had two successive HIV RNA concentrations >500 copies/ml at the end of the week off therapy, and were classified as virological failure. Most of those who failed took didanosine, stavudine, saquinavir, and ritonavir (11 patients). In these patients, there was no evidence of mutations suggestive of drug resistance, and plasma saquinavir levels were within the expected range. Two of three patients failing on triple nucleotides had drug resistance mutations, but nonetheless responded to reintroduction of triple nucleotide therapy. One of two patients taking nevirapine, and one of eight taking efavirenz, also failed. Both had resistance mutations at the time of failure, but not at baseline.
Conclusions: The one-week-on-one-week-off schedule, as tested in the Staccato study, showed an unacceptably high failure rate and was therefore terminated. [AIDS 2003;17(15):F33-F37.]