Reduction of Maternal–Infant Transmission of HIV Type 1 With Zidovudine Treatment

This article summarizes the landmark results of Pediatric AIDS Clinical Trials Group Protocol 076. Pregnant women between 14 and 34 weeks with a CD4 count above 200 and no indication for antiretroviral therapy were randomized to zidovudine treatment or placebo. Zidovudine was shown to reduce HIV transmission from mother to child by 67.5%. Zidovudine treatment was not associated with neonatal death, premature birth, fetal growth or structural abnormalities. The majority of maternal adverse effects were obstetric complications that were not associated with either placebo or intervention groups. It reviews study design, findings, and limitations. This study is then situated in historical context and in reference to current guidelines.

Prenatal Zidovudine Treatment Modifies Early Development of Rat Osteoid – Confocal Microspectroscopy Analysis

Autofluorescence of the bone extracellular matrix (ECM) has not been widely explored although the ECM plays a very important role in bone development. In our research we focused on examining the bone matrix of very young animals due to the intense growth process during the first month of life. Structure images and fluorescence spectra of the bone surface were carried out using confocal fluorescence microscope Eclipse Ti-S inverted CLSM (NIKON, Japan) for compact tibia of healthy 7-, 14- and 28-day-old rat newborns after prenatal zidovudine administration in comparison with control. Spectral features of ECM autofluorescence were analyzed statistically by taking into consideration p < 0.05. The CLSM technique allows for simultaneous examination of the structure and autofluorescence from selected areas of the bone surface. Excessive autofluorescence of ECM after prenatal zidovudine administration influences bone growth incommensurably to the newborns’ age. Therefore the possibility of an additional non-enzymatic mechanism of collagen cross-linking in the first two weeks of life of newborn rats prenatally treated with zidovudine has been considered. Our results suggest that ECM autofluorescence can be an indicator of bone development in the normal and pathological state.

Short-Term Effect of Zidovudine on Plasma and Genital Human Immunodeficiency Virus Type 1 and Viral Turnover in These Compartments

ABSTRACT The effect of zidovudine on plasma and genital human immunodeficiency virus type 1 (HIV-1) was determined in 42 antiretroviral-naive HIV-1-seropositive women in Nairobi. After 7 days of zidovudine treatment, HIV-1 RNA levels decreased by 0.5 to 1.1 log10 in plasma and genital secretions. HIV-1 RNA half-life following zidovudine treatment was 4.7, 1.3, and 0.9 days in plasma, cervix, and vagina, respectively, and significantly shorter in genital secretions than in plasma (P < 0.001). Defining the short-term effect of zidovudine on plasma and genital HIV-1 is important for improving perinatal HIV-1 interventions.

Long-term effects of high-dose zidovudine treatment on neuropsychological performance in mildly symptomatic HIV-positive patients: Results of a randomized, double-blind, placebo-controlled investigation

This study examined the treatment outcome of high-dose (1500 mg/day) zidovudine (AZT) on neuropsychological (NP) functioning (Trailmaking Test A & B, WAIS-R Digit Symbol, and Rey Auditory Verbal Learning Test) across a 12-month period in mildly symptomatic HIV-1 seropositive men (n = 46 at entry) enrolled in a randomized, double-blind, placebo-controlled trial (VA Cooperative Studies Program #298). Neither short-term (0–6 months) nor long-term (0–12 months) AZT administration revealed enhancement in NP performance. The results suggest that, although AZT may afford patients prophylactic benefits, protracted high-dose AZT treatment does not improve NP functioning in mildly symptomatic HIV-positive individuals. (JINS, 2001, 7, 27–32)

Factors associated with neuropsychological performance in HIV-seropositive subjects without AIDS

Background. Previous research has suggested that several factors may influence the presence of cognitive impairment in human immunodeficiency virus (HIV) infection. The objective of this study was to assess the impact of cognitive reserve capacity and other variables on neuropsychological performance in early HIV infection.Methods. The neuropsychological performance of 100 HIV-seropositive subjects without AIDS (71 men and 29 women) was compared with that of 63 seronegative controls (51 men and 12 women). Measures included a neuropsychological battery, a medical examination and a psychiatric assessment. Cognitive reserve scores were based on a combination of years in school, a measure of educational achievement, and an estimate of pre-morbid intelligence.Results. HIV-positive subjects had longer reaction time latencies than HIV-negative subjects. Those in the HIV-positive group with low cerebral reserve scores showed the poorest performance on the neuropsychological tests. The prevalence of cognitive impairment was significantly higher in the HIV-positive group (27%) than in the controls (3·2%). Multiple regression analysis and logistic regression analysis were used to identify factors associated with global neuropsychological performance and cognitive impairment. Older age, lower cerebral reserve scores and not being on zidovudine treatment were associated with lower global neuropsychological scores and with the presence of cognitive impairment.Conclusions. Our results suggest that although cognitive impairment is not characteristic of early HIV infection, there is a subgroup of subjects who perform more poorly than expected. A lower reserve capacity, older age and not being on zidovudine treatment are factors that lower the threshold for neuropsychological abnormalities in cases of early HIV infection.