The ethics of placebo-controlled trials for perinatal transmission of HIV in developing countries

Structural and phenotypic modifications of rat thymocytes from birth up to one year of age, i.e. during maturation and at the beginning of the involutive process of the thymus are described. Since the biological significance and the mechanisms of thymic involution are still a matter of debate, this study aims at clarifying the complexity of the compensatory events occurring during this relatively neglected period of time. Thymuses from Sprague-Dawley rats were analyzed morphologically and morphometrically by light and electron microscopy. At the same time, thymocyte subsets, isolated from the same animals, were characterized by flow cytometry according to physical parameters and phenotypic markers. Results indicate that major changes occur during the first month from birth and from six months onward. In particular, already during the first weeks after birth, thymocytes undergo a slight reduction of mitoses associated with an increased number of apoptoses. Moreover, during the same period of time, flow cytometry revealed an expansion of small thymocytes and changes in thymocyte subsets such as increase of CD4+CD8+ and CD5+alpha(beta)TCR- and a decrease of CD4-CD8-, CD4-CD8+ cells. The thymus of adult rats was characterized by time-dependent decrease of both mitoses and apoptoses, progressive physical disconnection among cells, increase of necrotic areas and fibrosis. Around one year of age tissue changes were associated with a dramatic reduction of the population of large thymocytes and the rise of numerous small thymocytes that were unexpectedly negative for all tested markers. By contrast, medium-size thymocytes exhibited a marked decrease of CD4+CD8+ and CD5+alpha(beta)TCR- subsets. In conclusion, our data indicate that thymus undergoes, with time, a complex remodeling and suggest that thymic involution is not only a simple shrinkage of the organ but rather the result of a series of compensatory mechanisms among different cell populations in a setting of progressive involution.     

Maternal viral genotypic zidovudine resistance and infrequent failure of zidovudine therapy to prevent perinatal transmission of human immunodeficiency virus type 1 in pediatric AIDS Clinical Trials Group Protocol 076

Maternal samples were assessed from 96 women enrolled in Pediatric AIDS Clinical Trials Group protocol 076 to determine the prevalence of human immunodeficiency virus type 1 (HIV-1) genotypic zidovudine resistance at entry, if zidovudine resistance developed on study, and the role of zidovudine resistance in vertical transmission of HIV-1 despite zidovudine therapy. Low and high levels of genotypic resistance were assessed by differential hybridization, oligoligation, or direct sequencing of plasma HIV-1 RNA for codons K70R and T215Y/F. None of the women had high-level genotypic resistance to zidovudine at study entry or delivery. For low-level zidovudine resistance, the 95% confidence intervals were 0.3%-6.8% for baseline prevalence and 0.3%-14% for delivery incidence. Low-level zidovudine resistance, adjusted for plasma viral RNA level at delivery, was not strongly associated with an increase in vertical transmission risk (odds ratio, 4.8; 95% confidence interval, 0.2-131; P = .35).     

Prevention of perinatal transmission of HIV in Arkansas

In 1994, the Centers for Disease Control and Prevention (CDC) recommended zidovudine (ZDV) prophylaxis to reduce perinatal transmission of HIV. Caregivers at the University of Arkansas for Medical Sciences (UAMS) instituted a program of universal voluntary HIV testing of pregnant females combined with maternal education regarding ZDV prophylaxis in October 1994. Since that time, 7 of 39 (18%) infants referred to Arkansas Children's Hospital (ACH) for evaluation of perinatal HIV exposure have been infected compared to 21 of 53 (40%) referred prior to October 1994, (p = 0.042). Unfortunately, of the 39 infants referred to ACH after October 1994, 21 were born to HIV-infected mothers who did not comply with prophylaxis. Fifteen of these mothers were not offered intravenous ZDV during delivery; five have children infected with HIV. These data indicate the need for increased efforts by health officials in Arkansas to institute nationally recommended methods of prevention of perinatal HIV.     

Abbreviated regimens of zidovudine prophylaxis and perinatal transmission of the human immunodeficiency virus

BACKGROUND: The Pediatric AIDS Clinical Trials Group Protocol 076 reported a reduction in the rate of perinatal transmission of the human immunodeficiency virus (HIV) from 25.5 percent to 8.3 percent with a three-part regimen of zidovudine given ante partum, intra partum, and to the newborn. We examined the effects of abbreviated zidovudine regimens on perinatal HIV transmission using data from the HIV polymerase-chain-reaction (PCR) testing service of the New York State Department of Health. Pregnant women who received abbreviated regimens rather than the recommended regimens did so because of limited prenatal care or by choice. METHODS: The requisition form used by the PCR testing service included information on the demographic characteristics of the infants and the timing of any perinatal treatment with zidovudine. We also analyzed data on the timing of zidovudine prophylaxis collected by chart review in a subgroup of 454 infants as a means of validating the results in the entire cohort. RESULTS: From August 1, 1995, through January 31, 1997, specimens from 939 HIV-exposed infants who were 180 days of age or younger were submitted for PCR testing. The rates of perinatal HIV transmission varied depending on when zidovudine prophylaxis was begun. When treatment was begun in the prenatal period, the rate of HIV transmission was 6.1 percent (95 percent confidence interval, 4.1 to 8.9 percent); when begun intra partum, the rate was 10.0 percent (3.3 to 21.8 percent); when begun within the first 48 hours of life, the rate was 9.3 percent (4.1 to 17.5 percent); and when begun on day 3 of life or later, the rate was 18.4 percent (7.7 to 34.3 percent). In the absence of zidovudine prophylaxis, the rate of HIV transmission was 26.6 percent (21.1 to 32.7 percent). CONCLUSIONS: These results confirm the efficacy of zidovudine prophylaxis and suggest that there are reductions in the rates of perinatal transmission of HIV even with the use of abbreviated regimens that are begun intra partum or in the first 48 hours of life.     

Perinatal transmission of HIV in women receiving zidovudine: abstract and commentary

We describe a case of thrombotic thrombocytopenic purpura (TTP) resistant to conventional therapy with fresh-frozen plasma (FFP)-plasma exchange (PEX) as well as to steroids, immunoglobulins, vincristine, dipyridamole, dextran and iloprost, achieving complete remission with cryosupernatant-plasma exchange. Our case shows the effectiveness of cryosupernatant PEX, when FFP-PEX and alternative therapies have failed.     

Functional status and well-being in a placebo-controlled trial of zidovudine in early symptomatic HIV infection

To determine the effect of zidovudine on functional status and well-being in patients with early symptomatic human immunodeficiency virus (HIV) infection, 70 subjects in a randomized, placebo-controlled trial (ACTG Protocol 016) were observed for 1 year using a brief quality-of-life questionnaire. Thirty-four subjects were assigned to placebo and 36 subjects to zidovudine, 200 mg orally every 4 h (1,200 mg daily). Functional status and well-being were measured every 3 months using a 30-item self-administered questionnaire derived from health ratings from the Medical Outcomes Study. The mean changes from baseline for zidovudine versus placebo groups were compared using paired and two-sample t tests. Subjects receiving a placebo reported better quality of life compared to baseline than subjects receiving zidovudine at 24 weeks for all dimensions of well-being, including overall health, energy, mental health, health distress, pain, and quality of life. The difference between the two groups' changes from baseline for overall health was 11.5 points on a 100-point scale (p = 0.02), and 11.1 points for energy (0.002). There were no differences between changes from baseline along various dimensions of functional status (physical, social, role, and cognitive function). At 52 weeks both groups reported worse overall health than at baseline, and changes in scores were more similar for the two groups. Although zidovudine has previously been demonstrated to delay progression of disease for patients with mildly symptomatic HIV infection, early in treatment the net effect of a 1,200 mg daily dose of zidovudine may diminish patients' subjective well-being.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of vertical HIV transmission with zidovudine: projected impact of HIV testing and prenatal care

We sought to estimate the impact of maternal HIV testing and prenatal care on the potential to reduce vertical transmission through zidovudine (AZT) use by HIV-infected mothers. We evaluated the prepartum maternal HIV diagnosis rate, prenatal care, disease stage, and vertical transmission rate (from a two-part mixture model) using New York State Medicaid and vital statistics data for HIV-infected mothers and their singletons in 1985-90. We used published data to estimate the effect of AZT on vertical transmission and expert input to define other parameters for the model. Our HIV-infected (N = 1514) had a vertical transmission rate of 27.0%. HIV was diagnosed prepartum for 39.5% of women in 1990. Transmission would have been 22.2% if AZT had been taken only by the subset of women diagnosed prepartum with HIV and receiving prenatal care by 34 weeks gestation (86.7%). Transmission would have dropped to 11.2% if all women had been diagnosed prepartum with HIV and received adequate prenatal care. The observed deficiencies in prenatal care and maternal HIV diagnosis rates in this Medicaid population-based cohort must be addressed to realize the promise of AZT to reduce vertical transmission.     

A psychoeducational approach to prevent HIV transmission among injection drug users.

Describes a psychoeducational approach to AIDS risk reduction for injection drug users. The psychoeducational strategy not only provides information, but also focuses on psychological principles useful in the promotion of behavior change. The intervention is divided into 3 sessions covering (1) injection equipment sterilization and risk reduction in relation to drug use, (2) condom use and risk reduction for sexual activities, and (3) discussion of HIV antibody testing and a review. This program was designed as a small-group intervention for injection drug users within the context of an ongoing drug rehabilitation program. The content was customized to a target population of primarily African-American men who abuse cocaine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perinatal intervention trial in Africa: effect of a birth canal cleansing intervention to prevent HIV transmission

BACKGROUND: Perinatal transmission of human immunodeficiency virus (HIV) type 1 contributes significantly to infant mortality. Exposure in the birth canal may account for some transmission. We examined the efficacy of a birth canal washing procedure in reducing perinatal transmission in Malawi. METHODS: The infection status of infants of 3327 control women (conventional delivery procedures) was compared with that of 3637 infants of intervention-delivered women. The infants' HIV status was determined by polymerase chain reaction on dried blood spots collected at 6 and 12 weeks of age. The intervention consisted of manual cleansing of the birth canal with a cotton pad soaked in 0.25% chlorhexidine, which was done on admission in labour and every 4 h until delivery. FINDINGS: No adverse reactions to the intervention procedure were seen. 2094 (30%) of the enrolled women were HIV-infected, and 59% of their infants were seen in follow-up. Among 982 vaginal vertex singleton deliveries to HIV-infected women, 269 (27%) infants were infected. The intervention had no significant impact on HIV transmission rates (27% in 505 intervention women compared with 28% in 477 control women), except when membranes were ruptured more than 4 h before delivery (transmission 25% in the intervention group vs 39% in the control group). INTERPRETATION: If birth canal exposure is an important risk factor, different or additional methods to reduce the risk of perinatal HIV transmission should be tested. Alternatively, perhaps birth canal exposure is not a major contributor to perinatal infection risk.     

Efficacy of zidovudine and human immunodeficiency virus (HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced disease: results of Pediatric AIDS Clinical Trials Group protocol 185

Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (IVIG) without HIV antibody. Subjects had baseline CD4 cell counts /=200/microL) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P=. 75). The Kaplan-Meier transmission rate for HIVIG recipients was 4. 1% (95% confidence interval, 1.5%-6.7%) and for IVIG recipients was 6.0% (2.8%-9.1%) (P=.36). The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HIV disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission.     

Beverage alcohol as a constraint to development in the Third World

The patterns of production and consumption of beverage alcohol throughout the Third World pose a constraint to economic and social development. A multidisciplinary academic literature has arisen in response to this phenomenon. It has done so over two rather distinct time periods. The first began to take shape during the 1970s and continued through the mid to late 1980s. It gave rise to a set of three rather discrete foci: 1) on developing theoretical frameworks across academic disciplines, 2) on identifying beverage alcohol's development impact, and 3) on the generating and implementing of alcohol policies. Since the 1980s the literature has maintained those foci, but contributions to the literature did a more complete job of integrating them into more complete (and less discrete) treatments.