Presence of the variant mannose-binding lectin alleles associated with slower progression to AIDS. Amsterdam Cohort Study

OBJECTIVE: To examine the association between mannose-binding lectin (MBL) polymorphism and progression to AIDS and death in HIV-1 infection. DESIGN AND METHODS: In 131 HIV-1-infected homosexual seroconverters, survival analyses were performed to determine both the association between MBL genotype and time from HIV-1 seroconversion to AIDS and death, and time from AIDS to death. RESULTS: Of the 131 seroconverters, of whom 61 developed AIDS, 76 were typed as homozygous wild-type and 55 as carriers of variant alleles (52 heterozygous and three homozygous variant alleles). A Survival analyses suggested that HIV-1-infected men with the variant alleles progressed somewhat slower to AIDS [relative hazard (RH), 0.62; 95% confidence interval (CI), 0.36-1.10] and death (RH, 0.73; 95% CI, 0.42-1.25). Interestingly, CD4+ T-cell count determined at the moment of AIDS was found to be significantly lower among persons with the mutation (97 x 10(6)/l versus 204 x 10(6)/l; P=0.03). Furthermore, when AIDS-free times before the diagnosis of an opportunistic infection were compared with those preceding a diagnosis of Kaposi's sarcoma, Kaposi's sarcoma diagnosis was more postponed than that of an opportunistic infection (RH, 0.21; 95% CI, 0.05-0.95; versus RH, 0.67; 95% CI, 0.35-1.27). CONCLUSION: Indications for a weak pre-AIDS protective effect of variant MBL alleles were demonstrated.     

Cigarette smoking, bacterial pneumonia, and other clinical outcomes in HIV-1 infection. Terry Beirn Community Programs for Clinical Research on AIDS

Cigarette smoking has been associated with impaired immune defenses and an increased risk of certain infectious and neoplastic diseases in HIV-1 seronegative populations. We examined the relationship between cigarette smoking and clinical outcome in a prospective cohort of 3221 HIV-1-seropositive men and women enrolled in the Terry Beirn Community Programs for Clinical Research on AIDS. Differences in clinical outcomes between never, former, and current cigarette smokers were assessed using proportional hazards regression analysis. After adjustment for CD4+ cell count, prior disease progression, use of antiretroviral therapy, and other covariates, there was no difference between current smokers and never smokers in the overall risk of opportunistic diseases [relative hazard (RH) = 1.05; 95% confidence interval (CI) 0.90-1.23; p = 0.52] or death (RH = 1.00; 95% CI 0.86-1.18; p = 0.97). However, current smokers were more likely than never smokers to develop bacterial pneumonia (RH = 1.57; 95% CI 1.14-2.15; p = 0.006), oral candidiasis (RH = 1.37; 95% CI 1.16-1.62; p = 0.0002), and AIDS dementia complex (RH = 1.80; 95% CI 1.11-2.90; p = 0.02). In addition, current smokers were less likely to develop Kaposi's sarcoma (RH = 0.58; 95% CI 0.39-0.88; p = 0.01) and several other non-respiratory tract diseases. If confirmed by other studies, these findings have important clinical implications.     

Effects of malaria infection in human immunodeficiency virus type 1-infected Ugandan children

BACKGROUND: Malaria causes severe morbidity and mortality in many areas of Africa where HIV-1 infection is also prevalent. Immunosuppression is associated with both diseases but most reports do not find significant interactions between them. METHODS: A collaborative study of HIV-1 infection in Ugandan women and their infants was established between the Ministry of Health, Makerere University, Kampala, and Case Western Reserve University in 1988. Four hundred fifty-eight infants, including 77 HIV-1-infected, 232 seroreverter and 125 control children born to HIV-1-negative mothers and 24 of indeterminate status were followed closely from birth for 4 years. Data on these infants were reviewed with respect to episodes of general illness and infections, suspected and confirmed episodes of malaria, onset and frequency of malaria, use of chloroquine and occurrence of selected illnesses after episodes of febrile illnesses. Thick and thin blood smears for malaria were obtained from children with fever. RESULTS: There was no association between occurrence of febrile illnesses and childrens' HIV-1 category. The relative rates of occurrence were 1.0 (95% confidence interval (CI), 0.8 to 1.2) and 1.1 (95% CI 0.9 to 1.4) for the HIV seroreverter and control children compared with the HIV-infected children. Although there was no association (P = 0.83) between HIV-1 status and a smear being taken during a febrile episode, there was an increase in smears positive for malaria parasitemia among seroreverter (risk ratio, 1.5; 95% CI 1.1 to 1.9) and control infants (risk ratio, 1.6; 95% CI 1.2 to 2.2) compared with HIV-1-infected infants. The level of parasitemia was similar in each group. A greater proportion of malaria episodes among the HIV-infected group than among the control groups resulted in hospitalizations (P = 0.001) and blood transfusions (P = 0.02). There was a positive association between time to clinical AIDS and absence of malaria (adjusted for follow-up age) in infected children (P = 0.02). Use of chloroquine was similarly high in each HIV-1 category (80%). CONCLUSIONS: In this group of HIV-infected children there was no significant increase in malarial episodes as compared with their HIV-negative controls. The results suggest a possibility that malaria may offer some protection against HIV-1 progression or that chloroquine used to treat malaria may have a direct effect against the HIV-1 virus.     

Immune markers and viral load after HIV-1 seroconversion as predictors of disease progression in a cohort of haemophilic men

OBJECTIVE: To assess the prognostic value of HIV RNA levels measured shortly after HIV seroconversion and whether markers of immune response (CD4+ and CD8+ T-cell counts, IgA and IgG) measured at the same time, continue to provide prognostic information once the HIV RNA level is known. DESIGN AND METHODS: HIV RNA levels were measured approximately 2.5 years after seroconversion in 97 haemophilic men followed for up to 17 years. Levels of CD4+ and CD8+ T cells, IgA and IgG were measured within 1 year of the HIV RNA level. The relationships between these markers and progression to AIDS and death were studied using Kaplan-Meier plots and proportional hazards regression models. RESULTS: High HIV RNA levels were associated with faster progression to AIDS and shorter survival in univariate Cox regression models. High IgA and IgG levels were also associated with faster disease progression. In multivariate models, high HIV RNA levels remained independently associated with faster disease progression [relative hazard (RH), 1.86; P = 0.01 for AIDS; RH, 1.66; P = 0.05 for death). However, high IgA and IgG levels provided strong independent prognostic information for AIDS and death (IgA: RH, 1.38; P = 0.006 for AIDS; RH, 1.33; P = 0.07 for death; IgG: RH, 1.10; P = 0.02 for AIDS; RH, 1.12; P = 0.01 for death). CONCLUSIONS: Our results confirm the importance of the HIV RNA level in assessing the long-term prognosis in individuals infected with HIV. However, our results suggest that immune activation markers, rather than merely reflecting high HIV RNA levels are important in assessing prognosis in their own right. These findings may improve our understanding of HIV pathogenesis and may aid clinical management of patients.     

Dynamics of viral replication in infants with vertically acquired human immunodeficiency virus type 1 infection

About one-third of vertically HIV-1 infected infants develop AIDS within the first months of life; the remainder show slower disease progression. We investigated the relationship between the pattern of HIV-1 replication early in life and disease outcome in eleven infected infants sequentially studied from birth. Viral load in cells and plasma was measured by highly sensitive competitive PCR-based methods. Although all infants showed an increase in the indices of viral replication within their first weeks of life, three distinct patterns emerged: (a) a rapid increase in plasma viral RNA and cell-associated proviral DNA during the first 4-6 wk, reaching high steady state levels (> 1,000 HIV-1 copies/10(5) PBMC and > 1,000,000 RNA copies/ml plasma) within 2-3 mo of age; (b) a similar initial rapid increase in viral load, followed by a 2.5-50-fold decline in viral levels; (c) a significantly lower (> 10-fold) viral increase during the first 4-6 wk of age. All infants displaying the first pattern developed early AIDS, while infants with slower clinical progression exhibited the second or third pattern. These findings demonstrate that the pattern of viral replication and clearance in the first 2-3 mo of life is strictly correlated with, and predictive of disease evolution in vertically infected infants.     

Combination antiretroviral therapy and recent declines in AIDS incidence and mortality

The reasons for recent declines in AIDS incidence and mortality may include advances in treatment, but these may be confounded by earlier declines in the incidence of human immunodeficiency virus (HIV) infection. To determine whether the declines in AIDS and mortality may, in part, stem from wider use of combination antiretroviral therapy, 622 HIV-positive men with well-characterized dates of seroconversion were followed. In this group, combination therapy came into widespread use in only 1996. In a Cox proportional hazards model, the 1996 calendar period was significantly associated with slower progression to AIDS (relative hazard [RH]=0. 19, 95% confidence interval [CI], 0.05-0.69, P=.01) and death (RH=0. 45, 95% CI, 0.21-0.95, P=.04). Declines in incidence of HIV infection, changes in HIV virulence, and end-point underreporting cannot fully explain the decline in AIDS and death in 1996. The introduction of combination antiretroviral therapy as the standard of care may already have had measurable effects.     

Effect of foscarnet on quantities of cytomegalovirus and human immunodeficiency virus in blood of persons with AIDS

Four intravenous dosages of foscarnet given for 10 days were compared with no therapy in persons with AIDS who had asymptomatic cytomegalovirus (CMV) viremia. CMV viremia was quantitated by endpoint cell dilution microcultures, pp65 antigenemia assay, and measurement of CMV DNA in peripheral blood leukocytes by a quantitative-competitive PCR. Human immunodeficiency virus type 1 (HIV-1) viremia was quantitated by endpoint cell dilution microculture, serum p24 antigen assay, and PCR for HIV-1 RNA in plasma. Twenty-seven subjects who had received a median of 22 months of nucleoside antiretroviral therapy were enrolled. Twenty-two subjects received foscarnet, which was well tolerated and decreased the CMV burden, as reflected by all three indicator assays. During the 10 days of dosing, the level of CMV viremia, as measured by 50 percent tissue culture infective doses, decreased from 117.5 to 12.7 (P = 0.001), the amount of CMV DNA decreased from 20,328 copies to 622 copies per 150,000 leukocytes (P = 0.02), and the level of CMV pp65 antigenemia decreased from 14.9 to 1.6 positive peripheral blood mononuclear cells per 50,000 leukocytes (P = 0.008). A significant pharmacodynamic relationship was found between the peak foscarnet concentration and a decrease in the level of CMV antigenemia (P < 0.05). Foscarnet had no effect on quantitative HIV-1 microcultures during the 10 days of treatment, but the HIV-1 p24 antigen level in serum decreased significantly, from 454 to 305 pg/ml (P = 0.01). Also, a significant pharmacodynamic relationship was seen between plasma HIV-1 RNA concentrations and both peak foscarnet concentration (P < 0.01) and the area under the foscarnet time-concentration curve (P < 0.05). Reductions in the levels of CMV and HIV-1 viremia correlated quantitatively with systemic exposure to foscarnet, whereas control subjects actually experienced an increase in CMV and HIV-1 burdens. The dual antiviral activity of foscarnet shown in this trial encourages investigation of its use in combination with other antiretroviral therapies for persons with AIDS.     

Serum levels of human immunodeficiency virus type 1 (HIV-1) RNA after seroconversion: a predictor of long-term mortality in HIV infection

A cohort of 79 homosexual men with documented dates of human immunodeficiency virus type 1 (HIV-1) seroconversion and baseline CD4 cell counts of > or = 500/microL were followed for up to 11.5 years. HIV-1 RNA was measured from stored sera obtained a median of 7 months after the estimated seroconversion date. AIDS progression and mortality among the men were studied, stratified by median baseline levels of HIV-1 RNA. AIDS progression rates at 11.5 years were 69% and 34%, respectively, among those with higher versus lower than median baseline virus loads (> or = 3040 copies/mL; P = .002), and mortality rates were 61% and 27%, respectively (P = .003). Survival curves continued to diverge throughout the 11.5 years, suggesting that the future clinical course of HIV-1 infection may already be determined at the earliest phases of disease. Initiation of definitive treatment very early in HIV-1 infection may be essential.     

Local cerebral blood flow, local cerebral glucose utilization, and flow-metabolism coupling during sevoflurane versus isoflurane anesthesia in rats

Antepartum plasma hepatitis C virus (HCV) RNA was quantified in 155 mothers coinfected with HCV and human immunodeficiency virus type 1 (HIV-1), and HCV RNA was serially assessed in their infants. Of 155 singleton infants born to HCV antibody-positive mothers, 13 (8.4%) were HCV infected. The risk of HCV infection was 3.2-fold greater in HIV-1-infected infants compared with HIV-1-uninfected infants (17.1% of 41 vs. 5.4% of 112, P = .04). The median concentration of plasma HCV RNA was higher among the 13 mothers with HCV-infected infants (2.0 x 10(6) copies/mL) than among the 142 mothers with HCV-negative infants (3.5 x 10(5) copies/mL; P < .001), and there were no instances of HCV transmission from 40 mothers with HCV RNA concentrations of < 10(5) copies/mL. Women dually infected with HIV-1 and HCV but with little or no detectable HCV RNA should be reassured that the risk of perinatal transmission of HCV is exceedingly low.     

Anthropometric indicators of human immunodeficiency virus infection in infants with early and late symptoms in the first months of life

Standardised growth indices (Z-scores of weight-for-age, WA, length-for-age, LA, weight-for-length, WL, according to the reference data of the World Health Organization) have been compared for the first 4 months of life among 119 infants born to mothers affected by the type-1 human immunodeficiency virus (HIV). Infants were subdivided according to their HIV serostatus and the clinical expression of the disease. Uninfected status (n = 92), late (>6 months, n = 18) and early (<3 months, n = 9) onset of symptoms among the HIV infected defined three groups. Infants with early symptoms showed the lowest median WA and LA Z-scores at all times and the LA difference with their uninfected counterparts was already significant at birth. Infants with late symptoms showed early differences in WL and then in WA also compared with the uninfected ones. A < -0.40 LA Z-score at birth gave a 5.9 relative risk (RR) to be an infant with early symptoms (95% CI = 1.2-27.4) while a negative WL Z-score at 2 months of age gave a 4.2 RR for the HIV seropositivity (95% CI = 2.1-8.3). CONCLUSION: Linear growth is the first parameter to be negatively affected among human immunodeficiency virus seropositive infants with early symptoms. In infants with late symptoms the lack of rapid WA and WL increase found among uninfected patients may be viewed as an early anthropometric indicator of HIV status.     

Potential risk factors for vertical HIV-1 transmission in Catalonia, Spain: the protective role of cesarean section. The Working Group on HIV-1 Vertical Transmission in Catalonia

OBJECTIVE: To evaluate the roles of certain potential risk factors on the vertical transmission of HIV-1. DESIGN: Prospective registry of infants born to HIV-1-infected women in Catalonia (north-east Spain) from 1987 to 1992. METHODS: A total of 599 infants, born in Catalan hospitals to 520 women who were identified as being HIV-1-infected during gestation or at delivery, were included. Data on mode of delivery, birth weight, gestational age and breast-feeding as well as the mother's age, her route of HIV-1 infection, clinical stage and p24 antigenaemia, were recorded. HIV-1 infection status of 489 (82%) of the infants was determined according to the criteria of the US Centers for Disease Control and Prevention. Risk estimates and odds ratio (OR) were calculated and logistic regression was performed. RESULTS: The overall rate of vertical transmission was 18.6% (95% confidence interval, 15.2-22.0%). Multivariate analyses revealed that Cesarean section was associated with a lower rate of vertical transmission (OR = 0.3; P = 0.001), as was maternal HIV-1 infection via injecting drug use (OR = 0.44; P = 0.02). Breast-feeding (OR = 6.9; P = 0.001), very low birth weight (< 1500 g; OR = 6.3; P = 0.001) and p24 antigenaemia (OR = 4.6; P = 0.04) were all related to increased risk. The crude rate of HIV-1 transmission was 6% among Cesarean births compared with 21% for infants born via vaginal deliveries. The population-attributable risk for vaginal deliveries was 61.7%. CONCLUSIONS: The results show a protective effect of Cesarean section in the absence of zidovudine prophylaxis. However, current research should be directed towards the individual and combined effects that antiretroviral agents and Cesarean section may have on mother-to-child HIV-1 infection.     

Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania

BACKGROUND: In HIV-1-infected women, poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes. We assessed the effects of vitamin A and multivitamins on birth outcomes in such women. METHODS: In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and 27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a randomised, double-blind, placebo-controlled trial with a 2x2 factorial design. We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets. We did analyses by intention to treat. RESULTS: 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02). Multivitamin supplementation decreased the risk of low birthweight (<2500 g) by 44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (<34 weeks of gestation) by 39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43% (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect on these variables. Multivitamins, but not vitamin A, resulted in a significant increase in CD4, CD8, and CD3 counts. INTERPRETATION: Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women. The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained.     

Herpes zoster, immunological deterioration and disease progression in HIV-1 infection

OBJECTIVE: To study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. DESIGN AND METHODS: A total of 966 homosexual participants in The Amsterdam Cohort Study were studied. Herpes zoster was defined by its characteristic clinical presentation. Incidence was calculated using Poisson regression, cumulative incidence by the Kaplan-Meier product-limit method and the prognostic value was evaluated using Cox proportional hazards model. RESULTS: The incidence of first episodes of herpes zoster was 3.31 per 1000 person-years (PY) in HIV-seronegatives and 51.51 per 1000 PY in HIV-1-seropositive individuals. Recurrences only occurred in HIV-1-positive patients (25.6%). Cumulative incidences of first episodes increased linearly with the duration of follow-up. In HIV-1-seropositives the incidence was 31.2 per 1000 PY at CD4+ cells > or = 500 x 10(6)/l, 47.2 per 1000 PY [relative risk (RR), 1.51; 95% confidence interval (CI), 0.78-2.94] at CD4+ cells 200-499 x 10(6)/l and 97.5 per 1000 PY (RR, 3.13; 95% CI, 1.54-6.32) at CD4+ cells < 200 x 10(6)/l. Besides CD4+ cell counts, CD3 monoclonal antibodies and phytohaemagglutinin-induced T-cell reactivity were independent predictors for herpes zoster. The hazard ratio for AIDS after herpes zoster was 1.6 (95% CI, 1.1-2.4) and for death 1.7 (95% CI, 1.1-2.5), but these were not independent from CD4+ cell counts. CONCLUSION: In HIV-1 infection the incidence of herpes zoster increases with the decrease of CD4+ cell counts and T-cell reactivity, but herpes zoster is not an independent predictor for disease progression.     

Mutagenic activation of aromatic amines by molluscs as a biomarker of marine pollution

Prior studies of the association between socioeconomic status and length of survival among persons infected with the human immunodeficiency virus (HIV) have produced conflicting results. To investigate this issue further, the authors examined data on 18,167 San Francisco, California, residents aged 13 years or older who were diagnosed with acquired immunodeficiency syndrome (AIDS) between January 1, 1985, and December 31, 1995. Three validated US census-based measures of socioeconomic status were used: poverty, predominantly working class neighborhood, and low educational level. Median length of survival was found to be similar for persons living in neighborhoods characterized by poverty (22 months) and those in higher income neighborhoods (23 months), for persons living in predominantly working class neighborhoods (22 months) and those in predominantly professional/managerial neighborhoods (23 months), and for persons living in neighborhoods characterized by low educational level (23 months) and those in neighborhoods characterized by higher educational level (23 months). After adjustment for sex, age, ethnicity, AIDS risk group, site of AIDS diagnosis, time period of AIDS diagnosis, and AIDS-indicator illness, no association was found between survival and living in a neighborhood characterized by poverty (relative hazard (RH)=1.03, 95% confidence interval (CI) 0.97-1.08), between survival and working class occupations (RH=1.03, 95% CI 0.98-1.08), or between survival and low educational level (RH=0.96, 95% CI 0.90-1.01). The lack of an association between socioeconomic status and length of survival with AIDS may be due to the high mortality from AIDS in the era prior to highly effective antiretroviral therapy or to similar levels of access to care in San Francisco.     

A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team

BACKGROUND: The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine. METHODS: A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count (50 or fewer vs. 51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily regimens: 600 mg of zidovudine (or stavudine) and 300 mg of lamivudine, or that regimen with 2400 mg of indinavir. The primary end point was the time to the development of the acquired immunodeficiency syndrome (AIDS) or death. RESULTS: The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine, and lamivudine (6 percent) than with zidovudine and lamivudine alone (11 percent; estimated hazard ratio, 0.50; 95 percent confidence interval, 0.33 to 0.76; P=0.001). Mortality in the two groups was 1.4 percent and 3.1 percent, respectively (estimated hazard ratio, 0.43; 95 percent confidence interval, 0.19 to 0.99; P=0.04). The effects of treatment were similar in both CD4 cell strata. The responses of CD4 cells and plasma HIV-1 RNA paralleled the clinical results. CONCLUSIONS: Treatment with indinavir, zidovudine, and lamivudine as compared with zidovudine and lamivudine alone significantly slows the progression of HIV-1 disease in patients with 200 CD4 cells or fewer per cubic millimeter and prior exposure to zidovudine.     

The effect of pregnancy on survival in women infected with HIV: a systematic review of the literature and meta-analysis

OBJECTIVE: To investigate the effect of pregnancy on disease progression and survival in women infected with HIV by a systematic review of the literature and meta-analysis. METHODS: Appropriate publications were identified using electronic and hand searching of relevant journals from 1983 to 1996. Studies were included in the review if they were cohort studies, either prospective or retrospective, or case-control studies which investigated disease progression of pregnant women infected with HIV and included a control group of non-pregnant women infected with HIV for comparison. Methodological quality was assessed for each study. Data were extracted for predetermined outcome measures. Sensitivity analyses were performed to explore the association between pregnancy and disease progression for the following study characteristics: clinical setting (developed or developing countries), methodological quality (high or poor) and whether studies had controlled for potential confounding. RESULTS: Seven studies, all prospective cohorts, were eligible to be included in the review. The summary odds ratio for the risk of an adverse maternal outcome related to HIV infection and pregnancy were as follows: death 1.8 (85% CI 0.99-3.3); HIV disease progression 1.41 (95% CI 0.85-2.33); progression to an AIDS-defining illness 1.63 (95% CI 1.00-2.67) and fall of CD4 cell count to below 200 x 10(6)/L 0.73 (95% CI 0.17-3.06). Sensitivity analyses showed that HIV progression in pregnancy was significantly more common in a developing country setting (odds ratio 3.71, 95% CI 1.82-7.75) than in developed countries (odds ratio 0.55, 95% 0.27-1.11) and also significantly more common in high quality studies when compared to low quality ones, odds ratios 3.71 (95% CI 1.82-7.57) and 0.55 (95% CI 0.27-1.11), respectively. However, there appears to be less progression of HIV disease and progression to AIDS when studies attempted to control for confounding by matching or restriction techniques, although this was not statistically significant in either case. CONCLUSIONS: The findings of this review have implications for women infected with HIV who are pregnant or are considering a pregnancy. There does appear to be an association between adverse maternal outcomes and pregnancy in women infected with HIV, although this association is not strong. The relation may be due to the result of bias including residual confounding. Further large scale observational studies with long term follow up are required before this issue can be fully resolved.     

Cervical and vaginal shedding of human immunodeficiency virus type 1-infected cells throughout the menstrual cycle

Cervical and vaginal secretions from 17 women infected with human immunodeficiency virus type 1 (HIV-1) were evaluated daily through the course of one menstrual cycle for HIV-1 DNA (21-31 visits per woman). HIV-1-infected cells were detected in 207 (46%) of 450 endocervical swabs and 74 (16%) of 449 vaginal swabs. There was considerable variability in the percentage of positive swabs from each woman, ranging from 4% to 100% of endocervical swabs and from 0 to 71% of vaginal swabs. In multivariate analyses, plasma HIV-1 RNA was significantly associated with shedding of HIV-1-infected cells; each 1-unit increase in the log of plasma virus load was associated with a 5.6-fold increase in the odds of cervical shedding (95% confidence interval [CI], 2.1-14.8) and a 3.9-fold increase in the odds of vaginal shedding (95% CI, 2.1-7.2). There was no discernible pattern of genital tract shedding with phase of the menstrual cycle and no significant association with serum estradiol or progesterone levels.     

Major histocompatibility complex class II DR alleles DRB1*1501 and those encoding HLA-DR13 are preferentially associated with a diminution in maternally transmitted human immunodeficiency virus 1 infection in different ethnic groups: determination by an automated sequence-based typing method

Transmission of human immunodeficiency virus 1 (HIV-1) from an infected women to her offspring during gestation and delivery was found to be influenced by the infant's major histocompatibility complex class II DRB1 alleles. Forty-six HIV-infected infants and 63 seroreverting infants, born with passively acquired anti-HIV antibodies but not becoming detectably infected, were typed by an automated nucleotide-sequence-based technique that uses low-resolution PCR to select either the simpler Taq or the more demanding T7 sequencing chemistry. One or more DR13 alleles, including DRB1*1301, 1302, and 1303, were found in 31.7% of seroreverting infants and 15.2% of those becoming HIV-infected [OR (odds ratio) = 2.6 (95% confidence interval 1.0-6.8); P = 0.048]. This association was influenced by ethnicity, being seen more strongly among the 80 Black and Hispanic children [OR = 4.3 (1.2-16.4); P = 0.023], with the most pronounced effect among Black infants where 7 of 24 seroreverters inherited these alleles with none among 12 HIV-infected infants (Haldane OR = 12.3; P = 0.037). The previously recognized association of DR13 alleles with some situations of long-term nonprogression of HIV suggests that similar mechanisms may regulate both the occurrence of infection and disease progression after infection. Upon examining for residual associations, only only the DR2 allele DRB1*1501 was associated with seroreversion in Caucasoid infants (OR = 24; P = 0.004). Among Caucasoids the DRB1*03011 allele was positively associated with the occurrence of HIV infection (P = 0.03).     

Increasing social variation in birth outcomes in the Czech Republic after 1989

OBJECTIVES: This study investigated social variation in birth outcome in the Czech Republic after the political changes of 1989. METHODS: Routinely collected records on singleton live births in 1989, 1990, and 1991 (n = 380,633) and 1994, 1995, and 1996 (n = 286,907) were individually linked to death records. RESULTS: Mean birthweight fell from 3,323 g to 3,292 g (P < .001) between 1989 and 1991 and then increased to 3,353 g by 1996. The gap in mean birthweight between mothers with a primary education and those with a university education, adjusted for age, parity, and sex of infants, widened from 182 g (95% confidence interval [CI] = 169, 19) in 1989 to 256 g (95% CI = 240, 272) in 1996. Similar trends were found for preterm births. Postneonatal mortality declined most among the better educated and the married. The odds ratio for postneonatal death for infants of mothers with a primary (vs university) education, adjusted for birthweight, increased from 1.99 (95% CI = 1.52, 2.60) in 1989 through 1991 to 2.39 (95% CI = 1.55, 3.70) in 1994 through 1995. CONCLUSIONS: Despite general improvement in the indices of fetal growth and infant survival in the most recent years, social variation in birth outcome in the Czech Republic has increased.