Treatment interruption after pregnancy: effects on disease progression and laboratory findings.

OBJECTIVE: To assess clinical progression and inflammatory markers among women stopping or continuing antiretroviral therapy (ART) after pregnancy. METHODS: ART-naïve women with CD4+ lymphocyte counts >350 cells/uL initiating ART during pregnancy had clinical events and laboratory markers compared over one year postpartum between those stopping (n = 59) or continuing (n = 147) ART. RESULTS: Slopes in CD4 count and HIV RNA did not differ between groups overall and in subsets of ZDV or combination therapy. The hazard ratio (HR) of a new class B event was 2.09 (95% CI 0.79-5.58) among women stopping ART, 1.24 (0.31-4.95) in those stopping ZDV, and 2.93 (0.64-13.36) among those stopping combination therapy. Women stopping ART had increased immune activation. No significant differences were seen in C-reactive protein, lipids, leptin, or interleukin-6. CONCLUSIONS: While changes in CD4 and HIV RNA levels over one year were similar between women stopping or continuing ART postpartum, higher immune activation among women stopping therapy requires further study.

Preferential suppression of CXCR4-specific strains of HIV-1 by antiviral therapy.

To initiate infection, HIV-1 requires a primary receptor, CD4, and a secondary receptor, principally the chemokine receptor CCR5 or CXCR4. Coreceptor usage plays a critical role in HIV-1 disease progression. HIV-1 transmitted in vivo generally uses CCR5 (R5), but later CXCR4 (X4) strains may emerge; this shift heralds CD4+ cell depletion and clinical deterioration. We asked whether antiretroviral therapy can shift HIV-1 populations back to R5 viruses after X4 strains have emerged, in part because treatment has been successful in slowing disease progression without uniformly suppressing plasma viremia. We analyzed the coreceptor usage of serial primary isolates from 15 women with advanced disease who demonstrated X4 viruses. Coreceptor usage was determined by using a HOS-CD4+ cell system, biological and molecular cloning, and sequencing the envelope gene V3 region. By constructing a mathematical model to measure the proportion of virus in a specimen using each coreceptor, we demonstrated that the predominant viral population shifted from X4 at baseline to R5 strains after treatment. Multivariate analyses showed that the shift was independent of changes in plasma HIV-1 RNA level and CD4+ cell count. Hence, combination therapy may lead to a change in phenotypic character as well as in the quantity of HIV-1. Shifts in coreceptor usage may thereby contribute to the clinical efficacy of anti-HIV drugs.

Serum HIV-1 p24 antibody, HIV-1 RNA copy number and CD4 lymphocyte percentage are independently associated with risk of mortality in HIV-1-infected children. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

OBJECTIVE: The role of HIV-1 antibody in modulating disease progression must be assessed in the context of other immune and viral load markers. We evaluated the association between HIV-1 p24 antibody, HIV-1 RNA, immune complex-dissociated (ICD) p24 antigen, CD4 cell percentage, and mortality in a cohort of 218 HIV-infected children enrolled in a trial of intravenous immunoglobulin prophylaxis of bacterial infections. METHODS: CD4 cell percentage was measured and sera collected and stored at baseline and every 3 months on study (1988-1991). Stored sera were assayed for HIV-1 p24 antibody, HIV-1 RNA, and ICD p24 antigen. Mortality was recorded during the trial and updated through 1996 (mean total follow-up, 6.3 years). RESULTS: Eighty-one (37%) children died; probability of mortality for children with baseline HIV-1 p24 antibody concentrations of undetectable (< 1), 1-4, 5-124, and > or = 125 reciprocal titer units (RTU) was 61, 50, 24, and 10%, respectively. A 3.5-fold increase in the relative risk (RR) of death [95% confidence interval (CI), 2.2-5.5] was observed among children with baseline HIV-1 p24 antibody concentration < 5 RTU compared with > or = 5 RTU. In multivariate analyses, p24 antibody, HIV-1 RNA, and CD4 cell percentage but not ICD p24 antigen were independently associated with mortality; the RR of death increased by 1.7 (95% CI, 1.3-2.1) for each log10 decrement in baseline HIV-1 p24 antibody. CONCLUSIONS: HIV-1 p24 antibody, HIV-1 RNA and CD4 cell percentage independently predict mortality amongst infected children. Whereas CD4 cell percentage provides an estimate of the general degree of immune suppression, HIV-1 p24 antibody could provide an easily obtained, inexpensive assessment of CD4 cell function and could augment prognostic information provided by CD4 cell count and viral load for clinical management of infected children.

Clinical, virologic, and immunologic effects of combination therapy with ribavirin and isoprinosine in HIV-infected homosexual men.

We evaluated the clinical, immunologic, and virologic effects of oral treatment with ribavirin and isoprinosine for up to 3 months in asymptomatic, HIV-culture-positive homosexual men. Fifteen consecutive men received isoprinosine 4 g/day (1 g q.i.d.), and 800 (9 men) or 1,200 mg/day (6 men) of ribavirin. Five men in each ribavirin dosage group completed at least 2 months of treatment. No unexpected toxicities were observed. Eight minor HIV-related events occurred in six men while on study. All men remained HIV-positive, and time to positive culture decreased by at least 4 days in three men from each treatment group. Serum p24 levels did not change in two men who were p24 antigenemic and received 800 mg/day of ribavirin. Treatment was associated with a generalized lymphopenia affecting all lymphocyte subsets including CD4, which was partially reversible 1 month after stopping treatment. Most of the men remained anergic on DTHS skin testing. No improvements were noted in in vitro lymphoproliferative responses to antigens or in NK cell activity (which decreased significantly in the 1,200 mg/day ribavirin group). Although well tolerated at the doses employed, the combination of ribavirin and isoprinosine produced an unexpected generalized lymphopenia and did not exhibit HIV-suppressive or immunorestorative effects.

Effect of lithium carbonate in HIV-infected patients with immune dysfunction.

Ten homosexual men received oral lithium carbonate at doses that maintained their serum lithium concentrations between 0.5 and 1.5 mEq/L. Prior to treatment all patients had HIV isolated from PHA-activated peripheral blood lymphocytes (PBLs) using a quantitative antigen-capture enzyme-linked immunosorbent assay (ELISA) assay for detection, and had an absolute number of CD4 (helper) lymphocytes of less than 300/mm3. Eight of 10 patients developed symptoms of drug toxicity requiring discontinuation of the drug in 7 patients. Two patients completed only 4-5 weeks of lithium therapy, and 5 patients received 7-8 weeks. All patients remained culture positive for HIV during the trial, and viral titers as measured by the antigen capture assay were unchanged or increased. There were no significant changes in the absolute number of CD4 lymphocytes, CD4/CD8 ratio, or phytohemagglutinin (PHA) or tetanus toxoid induced proliferative responses. There was a significant decrease in mixed lymphocyte reaction (MLR). Lithium carbonate demonstrated no immunorestorative or antiviral activity when given in therapeutic doses. Drug toxicity limited therapy in the majority of patients.

Serum vitamin A concentrations in a North American cohort of human immunodeficiency virus type 1-infected children. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

BACKGROUND: Vitamin A deficiency is associated with increased risks of vertical transmission of HIV-1 (HIV) and of disease progression and mortality among HIV-infected adults. The objectives of the study were to describe serum vitamin A concentrations among HIV-infected children in the National Institute of Child Health and Human Development IVIG Clinical Trial, to examine changes in vitamin A concentrations and to investigate the relationships between vitamin A concentrations and morbidity and mortality. METHODS: Blood was collected from children at baseline and at 3-month intervals throughout the study. Serum samples were stored at -70 degrees C at a central repository until retrieved for vitamin A assay. Samples were hexane-extracted and assayed by high performance liquid chromatography. The rate of change in vitamin A concentrations, calculated by fitting a linear regression model, was expressed as micrograms/dl/year. RESULTS: The median vitamin A concentration at baseline (n = 207 children) was 31.0 microg/dl [range, undetectable (< 10 microg/dl) to 98 microg/dl]. The rate of change in vitamin A concentrations (n = 180 children) did not vary significantly by any factor other than baseline vitamin A concentration. Baseline vitamin A concentration was not associated with morbidity (incidence of infections, growth failure, CD4+ percent decline below 15%, increases in serum HIV RNA concentrations above either 10(5) or 10(6) copies/ml or acute care hospitalization). Neither baseline vitamin A concentration nor the rate of change of vitamin A concentrations was associated with mortality. CONCLUSIONS: Among these North American children with relatively normal vitamin A concentrations, vitamin A was not observed to be associated with morbidity or mortality.

Quantification of human immunodeficiency virus type 1 p24 antigen and antibody rivals human immunodeficiency virus type 1 RNA and CD4+ enumeration for prognosis. National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial Study Group.

BACKGROUND: The sensitivity, specificity and positive predictive value of baseline serum concentrations of HIV-1 immune complex-dissociated (ICD) p24 antigen for predicting disease progression and mortality were assessed and compared with results obtained for HIV-1 ICD p24 antigen with HIV-1 p24 antibody and for HIV-1 RNA with CD4+ lymphocyte percent. METHODS: Data from HIV-infected children enrolled in a North American clinical trial (National Institute of Child Health and Human Development Intravenous Immunoglobulin Clinical Trial) were analyzed. Disease progression was defined as growth failure, CD4+ lymphocyte percent decline to <15% after study entry or development of an AIDS-defining opportunistic infection. RESULTS: Baseline samples were available for ICD p24 antigen testing (median concentration, 319 pg/ml; range, <50 to 15,640) in 240 children. The combination of detectable ICD p24 antigen and low p24 antibody was more sensitive but less specific than the combination of high HIV-1 RNA and low CD4+ lymphocyte percent in predicting disease progression and mortality. Using receiver operating characteristic curves, the specificity of ICD p24 antigen with p24 antibody for classifying children's disease progression or mortality was as great as, or greater than, HIV-1 RNA with CD4+ lymphocyte percent at points on the curve corresponding to higher sensitivity. CONCLUSIONS: The use of ICD p24 antigen with p24 antibody to identify children at high risk of disease progression or mortality could be a viable alternative to the more expensive and technically difficult HIV-1 RNA and CD4+ lymphocyte assays in resource-poor settings, including developing countries where the majority of children with HIV-1 infection reside.

Effectiveness of highly active antiretroviral therapy among HIV-1 infected women.

STUDY OBJECTIVE: To describe the impact of highly active antiretroviral therapy (HAART) on mortality, morbidity, and markers of HIV disease progression in HIV infected women. DESIGN: Data collected from the Women's Interagency HIV Study, a prospective cohort study that enrolled women between October 1994 and November 1995. SETTING: Six clinical consortia based in five cities in the United States (New York, NY; Washington, DC; Los Angeles, CA; San Francisco, CA; and Chicago, IL). PARTICIPANTS: A total of 1691 HIV seropositive women with a study visit after April 1996. MAIN RESULTS: Beginning in April 1996, the self reported use of HAART increased over time, with more than 50% of the cohort reporting HAART use in 1999. There was a 23% decline per semester in the incidence of AIDS from April 1996 (95% confidence intervals (CI) -29% to -16%). Furthermore, there was a 21% decline of the semiannual mortality rates among those with AIDS at baseline (95% CI -27% to -14%) and an 11% decline among those AIDS free at baseline (95% CI -3% to -18%). CD4+ lymphocyte counts either increased (women with baseline AIDS) or stabilised (women without baseline AIDS) after April 1996, and HIV RNA levels dramatically declined in both groups, although the percentage of women with HIV RNA above 4000 cps/ml remained stable at approximately 40% since mid-1997. CONCLUSIONS: Despite concerns regarding the use of antiretroviral therapies in this population, the use of therapies led to improved immunological function, suppressed HIV disease activity, and dramatic declines in morbidity and mortality.

Volatile compounds of endophyte-free and infected tall fescue (Festuca arundinacea Schreb.).

Volatile compounds produced by intact plants and ground leaf tissue from endophyte-infected (E+) and endophyte-free (E-) tall fescue (Festuca arundinacea Schreb.) were collected by a purge-and-trap procedure and analyzed by gas chromatography/mass spectrometry The volatile compound profile from ground leaf tissue was similar between E+ and E- clonal plants; however, the sheaths of E+ clonal plants produced higher levels of 1-octen-3-ol, a characteristic volatile compound derived from lipid peroxidation in fungi, which was absent in E- clonal plants. Intact plants produced fewer volatiles than macerated leaves. At 25 degrees C, (Z)-3-hexen-1-ol acetate was the most abundant compound, accounting for 77 and 89% of the total volatile emission from E+ and E- plants, respectively. Higher temperature (32 degrees C) significantly reduced the production of (Z)-3-hexen-1-ol acetate. Nonanal was the most abundant compound at 32 degrees C accounting for 52 and 45% of the total volatile emission from E+ and E- plants. Treatment of E+ and E- plants with jasmonic acid (JA) dramatically altered the volatile compound profile. The levels of (E)-beta-ocimene increased more than 200-fold and accounted for at least 43% of the total volatile emission. Although the presence of endophyte resulted in some qualitative and quantitative differences in the production of volatile compounds, they are unlikely to account for the differences in insect resistance between E+ and E- plants. Nevertheless, the production of a unique spectrum of volatiles after JA treatment may represent a significant plant-based defense response in tall fescue that is independent of endophyte.

Early behavior signs of psychiatric phenotypes in fragile X syndrome.

Whether preschool males with fragile X syndrome can be distinguished from those with idiopathic developmental delay in the four problem behavior areas associated with the fragile X phenotypes was examined. Males with fragile X (n = 41) and age- and IQ-matched controls (n = 16) were rated by their mothers on the Dimensions of Temperament Scale-Revised, the Child Behavior Checklist, and the Aberrant Behavior Checklist--Community. The fragile X group showed deficits in motor skills, increased initial avoidance, decreased social withdrawal, deficits in attention, increased hyperactivity, and positive mood. They were distinguished from controls on all of these variables except hyperactivity and attention. When maternal characteristics were controlled for, the fragile X group showed a significantly higher level of generalized activity level than did controls.

A phase 1 study of ribavirin in human immunodeficiency virus-infected patients.

An open phase 1 study comparing two daily doses of oral ribavirin (1200 and 1600 mg) for 12 weeks was conducted at a single site. Eight human immunodeficiency virus (HIV)-infected adult men with lymphadenopathy or early AIDS-related complex (ARC) symptoms were enrolled in each treatment group. No anti-HIV effect was observed as evaluated by coculture of patients' peripheral blood mononuclear cells or by the level of serum p24 antigenemia. Neither enhancement of two functional lymphocyte markers (specific antigen-induced blastogenesis or interferon-gamma production) nor reduction in serum beta 2-microglobulins was noted. Mild clinical adverse reactions and anemia were observed in both treatment groups. Significant reductions in total lymphocytes, T lymphocytes (CD2 cells), and T lymphocyte subsets (CD4 and CD8 cells) were most notable in the 1600-mg group. Reduction in the lymphocyte populations was most likely due to a direct ribavirin lymphotoxic effect. These observations indicate that ribavirin had no demonstrable beneficial effect on virologic or immunologic HIV surrogate markers at daily doses associated with adverse reactions.

Evaluation of HIV1 infection status by HIV1 PCR and culture methodologies in a small cohort of intravenous drug users.

A small cohort of high-risk intravenous drug users (IVDU) from the Baltimore, MD, area was evaluated for HIV1 infection status and viral load. Quantitative dilution endpoint HIV1 DNA polymerase chain reaction (PCR) results, from HIV proviral DNA from quantitated peripheral blood mononuclear cell (PBMC) lysates, were compared to the dilution endpoint results for HIV PBMC micrococulture. The quantitative dilution endpoint HIV1 PCR was more rapid, sensitive and reproducible. In addition, an HIV1 capture RT-PCR technique was used to qualitatively detect the presence or absence of intact HIV1 virus in IVDU plasma and was compared with plasma culture detection, for HIV1 viraemia. Using the results of the PCR techniques, a rapid molecular assessment of the HIV1 infection status can be attained, which is important, as the IVDU population can be difficult to study prospectively. The PCR techniques can also be used to assess HIV1 burden as well as the potential effectiveness of antiviral therapies. These molecular techniques can be used to monitor the progression of HIV in patients and to evaluate the clinical effects of concurrent substance abuse.

Effects of varying concentrations of bleach on in vitro HIV-1 replication and the relevance to injection drug use.

The use of bleach (hypochlorite) as a disinfectant for drug injection equipment in the intravenous-drug-using population was recommended early in the HIV-1/AIDS epidemic. Epidemiological studies have challenged the use of bleach as an effective measure to prevent HIV-1 transmission. However, in vitro HIV-1 coculture studies have shown that a high concentration of bleach is an effective cytotoxic and potentially virucidal agent. In this study, we demonstrate that HIV-1 peripheral blood mononuclear cell cocultures containing low concentrations of hypochlorite in the media showed earlier conversion to HIV-1 positivity, as measured by the presence of p24 antigen. HIV-1 cocultures with high concentrations of hypochlorite in the culture media, which appeared to be highly cytotoxic, and HIV-1 cocultures without bleach in the media did not exhibit this early p24 antigen positivity. Hypochlorite chemically disinfects by releasing free chlorine that is a potent oxidant. In injection drug equipment, a low residual concentration of bleach is likely to remain in cleaned equipment despite rinsing with water. Low concentrations of oxidants have been shown to enhance tissue inflammation, in vivo, as well as HIV-1 replication in vitro. Previous studies have shown that despite vigorous cleaning of blood-contaminated injection syringes with bleach followed by water, microaggregates of residual blood remained in bleach-cleaned blood-contaminated syringes. Hypothetically, oxidant effects of the residual bleach in the bleach-cleaned syringes could enhance the possibility of infection by remaining HIV-1 contained in a contaminated syringe. We suggest that the likelihood of an injection drug user contracting HIV-1 through the sharing of a bleach-cleaned blood-contaminated syringe may be increased by the cotransmission of residual bleach and its localized tissue-inflammatory effects; however, this has not been statistically proven in epidemiological studies.

Inactivation of human immunodeficiency virus type 1 in blood samples stored as high-salt lysates.

Blood samples to be tested for the presence of parasite DNA by using specific DNA probes are routinely stored in our laboratory as high-salt lysates (HSL). To safeguard against the risk of accidental infection with etiological agents such as the human immunodeficiency virus type 1 (HIV-1) while manipulating large numbers of blood samples in preparation for DNA probing, we determined the residual infectivity of HIV-1 after exposure to HSL components. Both high-titer virus stocks or provirus-carrying cells, suspended either in tissue culture medium or freshly drawn blood, were completely inactivated upon contact with the HSL components. This was verified by the absence of any detectable HIV-1-specific antigen in the supernatants of long-term cultures and the absence of virus-specific DNA fragments after amplification by polymerase chain reaction with DNA from such cultures as target DNA. These results support the conclusion that the virus is in fact completely inactivated by contact with the HSL components, rendering blood specimens stored as HSL noninfectious in regard to HIV-1.

Transformation of triploid bermudagrass (Cynodon dactylon x C. transvaalensis cv. TifEagle) by means of biolistic bombardment.

A transformation system for triploid bermudagrass ( Cynodon dactylon x C. transvaalensis cv. TifEagle) was established with a biolistic bombardment delivery system. Embryogenic callus was induced from stolons and maintained on Murashige and Skoog's medium supplemented with 30 microM dicamba, 20 microM benzylaminopurine, and 100 mg/l myo-inositol. Using the hygromycin phosphotransferase ( hpt) gene as the selectable marker gene, we obtained 75 transgenic lines from 18 petri dishes bombarded. Integration of the hpt gene into genomic DNA and transcription of hpt was confirmed by Southern and Northern blot analyses, respectively. Through suspension culture screening, we obtained homogeneously transformed plants showing stable transcription of the hpt gene.

Production of no-carrier-added 64Cu from zinc metal irradiated under boron shielding.

BACKGROUND: Positron emission tomography offers advantages for radioimmunodiagnosis of cancer but requires radionuclides of appropriate half-life that have high specific activity and high radio-purity. This work was designed to develop a viable method to produce and purify 64Cu, which has high specific activity, for positron emission tomography. METHODS: 64Cu was produced at the University of Missouri Research Reactor by the nuclear reaction, 64Zn(n,p)64Cu. Highly pure zinc metal (99.9999%) was irradiated in a specially designed boron nitrite lined container, which minimized thermal neutron reactions during irradiation. A new two-step procedure was developed to chemically separate the no-carrier-added 64Cu from the zinc metal target. RESULTS: 64Cu recovery for 24 runs averaged 0.393 (+/- 0.007) mCi per milligram of zinc irradiated. The boron-lined irradiation container reduced unwanted zinc radionuclides 14.3-fold. Zinc radionuclides and non-radioactive zinc were separated successfully from the 64Cu. The new separation technique was fast (2 hours total time) and highly efficient for removing the zinc. The zinc separation factor for this technique averaged 8.5 x 10(-8), indicating less than 0.0000085% of the zinc remained after separation. Thus far, the highest 64Cu specific activity at end of irradiation was 683 Ci/mg Cu, with an average of 512 Ci/mg Cu for the last six analyzed runs. CONCLUSION: The boron-lined irradiation container has sufficient capacity for 75-fold larger-sized zinc targets (up to 45 g). The new separation technique was excellent for separating 64Cu, which appears to be a radionuclide with great potential for positron emission tomography.

Expression of pokeweed antiviral proteins in creeping bentgrass.

Fungal diseases of creeping bentgrass, an important amenity grass used extensively on golf courses, are a serious problem in golf course management. Transgenic approaches to improving disease resistance to fungal diseases are being explored in many species, and in some cases ribosome-inactivating proteins have been found to be effective. We have generated transgenic creeping bentgrass plants expressing three forms of ribosome-inactivating proteins from pokeweed, which are termed pokeweed antiviral proteins (PAP). PAP-Y and PAP-C are nontoxic mutants of PAP; PAPII is the native form of another ribosome-inactivating protein from pokeweed. In creeping bentgrass, PAP-C transformants did not accumulate the protein, suggesting that it is unstable, and in a field test these plants were not protected from infection by the fungal pathogen Sclerotinia homoeocarpa, the causal agent of dollar spot disease. PAPII transformants could accumulate stable levels of the protein but had symptoms of toxicity; one low-expressing line exhibited good disease resistance. PAP-Y transformants accumulated stable levels of protein, and under greenhouse conditions they appeared to be phenotypically normal.

Detection of HIV-1 by polymerase chain reaction and culture in seronegative intravenous drug users in an inner-city emergency department.

STUDY BACKGROUND: After a health care worker's unprotected exposure to a patient's blood, the current recommendation is to obtain consent from the source for serologic testing for HIV. If the test is negative, no further follow-up of the exposed provider is usually indicated. OBJECTIVE: To determine if patients testing negative for HIV-1 antibody on routine serology harbor occult HIV-1 infection. DESIGN: Cross-sectional, identity-unlinked, patient-related data and blood sample procurement for HIV-1 infection. SETTING: Inner-city university hospital emergency department with high HIV-1 seroprevalence among patients. TYPE OF PARTICIPANTS: IV drug users not known to have HIV-1 infection. MEASUREMENTS: Serum samples were analyzed for HIV-1 antibodies by enzyme immunoassay and Western blot. Peripheral mononuclear cells were analyzed for HIV-1 provirus by polymerase chain reaction and viral culture. MAIN RESULTS: Of 131 patients, 36 (27.5%) were Western blot-confirmed seropositive for HIV-1. Of the 95 seronegative patients, six (6.3%) were polymerase chain reaction positive, and one of these was confirmed with culture. The negative predictive value of standard serology was 93.5% with polymerase chain reaction alone and 98.9% with concordant polymerase chain reaction and culture results. CONCLUSION: There may be a significant number of ED patients in HIV-1 prevalent populations who have occult HIV-1 infection not detectable by serology at the time of a health care provider exposure. Although these data suggest that further prospective study is warranted to better quantify the frequency of this phenomenon, these preliminary data suggest that current Centers for Disease Control recommendations regarding provider exposures may need to be reappraised for certain situations.

Lack of autologous neutralizing antibody to human immunodeficiency virus type 1 (HIV-1) and macrophage tropism are associated with mother-to-infant transmission.

To investigate factors that affect mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1), autologous neutralizing antibody, viral load, and viral tropism were evaluated in 28 pregnant women infected with HIV-1, of whom 8 were transmitters and 20 nontransmitters. One (12%) of 8 transmitters versus 11 (55%) of 20 nontransmitters had autologous neutralizing antibody (P=.04). Plasma levels of HIV-1 RNA and infectious HIV-1 titers (mean+/-SD) in peripheral blood mononuclear cells (PBMC) at delivery did not differ significantly between transmitters and nontransmitters (24, 266+/-10,101 vs. 31,589+/-9128 copies/mL and 29+/-12 vs. 42+/-17 infected cells per 106 PBMC, respectively). However, only transmitters (4 [50%] of 8) were HIV p24 antigen positive. The ability of HIV-1 strains to induce syncytium did not differ between groups (P=.6); however, only non-syncytium-inducing isolates were transmitted. Isolates from 4 (80%) of 5 transmitters versus 2 (18%) of 12 nontransmitters (P=.03) demonstrated increasing replication in macrophages. Thus, lack of autologous neutralizing antibody and increased replication in macrophages were significantly associated with mother-to-infant transmission. In addition, autologous neutralizing antibody was associated with reduced viral load.

Longitudinal variability of human immunodeficiency virus type 1 RNA viral load measurements by nucleic acid sequence-based amplification and NucliSens assays in a large multicenter study.

Human immunodeficiency virus type 1 (HIV-1) RNA measurements were evaluated within an externally controlled multilaboratory program. Three external standards (1.5 x 10(3) to 1.5 x 10(6) copies/ml) were included in 814 assay runs by four laboratories. Results indicate that HIV-1 RNA levels can be measured with a precision equal to that of the pre-highly active antiretroviral therapy era (standard deviations, +/-0.16 to 0.25 log10 units).