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BackgroundThe spread of SARS-CoV-2 and the COVID-19 pandemic have caused significant morbidity and mortality worldwide. The clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 and HIV co-infection remain uncertain.MethodsWe conducted a matched retrospective cohort study of adults hospitalized with a COVID-19 illness in New York City between March 3, 2020, and May 15, 2020. We matched 30 people with HIV (PWH) with 90 control group patients without HIV based on age, sex, and race/ethnicity. Using electronic health record data, we compared demographic characteristics, clinical characteristics, and clinical outcomes between PWH and control patients.ResultsIn our study, the median age (interquartile range) was 60.5 (56.6–70.0) years, 20% were female, 30% were black, 27% were white, and 24% were of Hispanic/Latino/ethnicity. There were no significant differences between PWH and control patients in presenting symptoms, duration of symptoms before hospitalization, laboratory markers, or radiographic findings on chest x-ray. More patients without HIV required a higher level of supplemental oxygen on presentation than PWH. There were no differences in the need for invasive mechanical ventilation during hospitalization, length of stay, or in-hospital mortality.ConclusionsThe clinical manifestations and outcomes of COVID-19 among patients with SARS-CoV-2 and HIV co-infection were not significantly different than patients without HIV co-infection. However, PWH were hospitalized with less severe hypoxemia, a finding that warrants further investigation.

Antiretroviral therapy during pregnancy and breastfeeding is a proven strategy to help prevent mother to child transmission of HIV-1. Pharmacokinetic and physiologic changes during pregnancy affect absorption and distribution of effective antiretroviral therapy, and can result in lower therapeutic concentrations of drug although this may not impact mother to child transmission. Continued antiretroviral therapy postpartum can help to prevent transmission via breastfeeding in resource-limited settings, but more importantly, help preserve a mother’s health, which is critical to child survival. Current commercially available tools may be inadequate to assess the acquisition of drug resistant viral populations late in pregnancy, and therapeutic drug monitoring is not widely available. There is little longitudinal information on pharmacokinetics of antiretroviral agents during pregnancy and the postpartum period to help guide dosing and regimen choices, though very recently some data have become available and incorporated into new treatment guidelines. Consideration of fetal risks in the timing and choice of agents further narrows the spectrum of choices among the many antiretroviral agents now available. Postpartum challenges to adherence can further erode the effectiveness of antiretroviral therapy and potentially compound the issue of adequacy of dosing in late pregnancy. In resource rich settings, frequent monitoring of pregnant women for regimen tolerance, adherence and virologic success, with intensification of such monitoring postpartum, are strategies that may help preserve maternal health. Often women are intensively monitored during pregnancy, and subsequently less frequently at postpartum when more adherence issues can occur. These problems are compounded in resource-limited settings where continued drug availability may be the predominant challenge and choices of antiretroviral agents are narrow. Pregnancy represents one (and often more than one) time point in the continuum of a woman’s life, and it is important that in the course of treating mothers and infants to prevent vertical transmission of HIV, strategies that preserve future treatment options are critical to both maternal and child health.

Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of mother-to-child transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and coformulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF).Nonpregnant women with plasma HIV-1 RNA of ≥500 copies per milliliter, previously cART exposed for pMTCT only, were eligible if they were off ART for ≥24 weeks before entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA400 copies/mL) at 24 weeks.Fifty-four women were enrolled between October 2007 and December 2009; 52 of 54 completed 24 weeks of follow-up. Median baseline CD4 T-cell count was 265/mm and baseline plasma HIV-1 RNA was 4.6 log10 copies per milliliter. Median prior cART duration was 14 weeks, and median time elapsed from the last pMTCT dose to entry was 22 months. Virologic response at 24 weeks was observed in 42 of 52 women or 81% (exact 95% confidence interval: 68% to 90%). There were no differences in response by country, by number, or class of prior pMTCT exposures. Although confirmed virologic failure occurred in 8 women, no virologic failures were observed in women reporting perfect early adherence.In this first prospective clinical trial studying combination antiretroviral retreatment in women with a history of pregnancy-limited cART, the observed virologic response to TDF/FTC and EFV at 24 weeks was 81%. Virologic failures occurred and correlated with self-reported nonadherence.

Both the World Health Organization and the United States Department of Health and Human Services have recently substantially revised perinatal HIV treatment guidelines based on emerging data, much of it from the developing world. Management of HIV infection in pregnancy and delivery is complicated by concerns for maternal and fetal drug toxicity, acquisition of antiretroviral resistance, prior therapy, co-infections with other viruses, as well as incident opportunistic infections. Intrapartum and peripartum obstetric management, including the role of Caesarean section, continue to evolve in the setting of maternal HIV infection. Finally, new data have expanded the role of antiviral therapy in allowing safer infant feeding choices for HIV-infected mothers in resource-limited settings.

The role of antiretroviral treatment (ART) in pregnant and breastfeeding women for prevention of mother-to-child transmission (pMTCT) of HIV has become simple: control of maternal HIV viremia with highly active combination ART effectively blocks MTCT. Details, however, are complex. Lifetime optimal health for mother and child must be balanced with potential toxicities associated with such treatment. The pharmacokinetics of ART in pregnancy and transfer of ART through the placenta and in breast milk are also important considerations in optimizing the health of mother and infant. Management of opportunistic infections in the setting of pregnancy, and limitations in access to, and lack of safety data for newer combination therapies also impact the complexity of managing HIV in pregnancy. ART as preexposure prophylaxis (PreP) for serodiscordant couples planning pregnancies and the use of PreP in serodiscordant couples during pregnancy and breastfeeding have emerged as strategies in which HIV treatment is the primary prevention.

The success of antiretroviral therapies for prevention of mother-to-child transmission of HIV in the developed world has prompted a wide array of research efforts, from improved implementation of voluntary counseling and testing programs to innovative approaches for short-course peripartum prophylaxis to understanding the dynamics of HIV transmission via breastfeeding. Clinical trials of modified short-course peripartum regimens which are applicable to resource-limited areas are demonstrating much lower transmission rates and preliminary data are emerging on limiting transmission via breastfeeding. Some of the most recent data on these topics are reviewed. Primary prevention of HIV in women of childbearing age combined with efforts to prevent mother-to-child transmission of HIV offer the best hope for addressing the burden of HIV in women and children.

The biological correlates of an effective immune response that could contain or prevent HIV infection remain elusive despite substantial scientific accomplishments in understanding the interactions among the virus, the individual and the community. The observation that some individuals appear to possess resistance to HIV infection or its consequences has generated a host of epidemiologic investigations to identify biological or behavioral characteristics of these individuals. These data might hold the keys to developing appropriate strategies for mimicking the effective responses of those who appear immune. In this paper we review genetic mechanisms including the role of chemokines and their receptors, cytokines, host genetic immune response to HIV infection, local immune response correlating with behavioral variables, co-infection and immune based mechanisms that have been elucidated so far. We offer suggestions for how to use these observations as platforms for future research to further understand natural resistance to HIV infection through cohort studies, population genotype sampling, mathematical modeling of virus–host interactions and behavioral analyses.

Objective: To document infection with HIV type 1 (HIV-1) group M non-B subtypes in individuals living in New York City. Design: From October 1999 through April 2003, HIV-1-seropositive individuals were selected from 3 clinics in New York City based on having risk factors for infection with HIV-1 non-B subtypes. Methods: HIV-1 RNA was extracted from plasma samples, and partial gag, pol, or env genes were amplified by PCR analysis. The infecting HIV- 1 group M subtype was determined based on results of either heteroduplex mobility assay or sequencing and phylogenetic analysis. Results: Ninety-seven subjects were enrolled in the study. Of the 97 subjects, 91 (94%) were selected based on having emigrated from a non-European country, while 6 (6%) were native United States citizens. Subtypes were successfully determined in 53 (55%) of the 97 plasma samples tested. The subtypes in 2 plasma samples were unclassifiable. HIV-1 infections were classified as those due to the following group M subtypes: A (n = 4; 7%), B (n = 12; 22%), C (n = 8; 15%), F (n = 2; 4%), CRF01―AE-like (n = 7; 13%), CRF02―AG-like (n = 19; 34%), an intersubtype recombinant form G gag /A env (n = 1; 2%), and unclassifiable viruses (n = 2; 4%). Conclusion: This study reveals infection with a broad variety of HIV-1 group M subtypes mostly in the immigrant population of New York City as well as how several non-B subtypes are being introduced into the United States.

To evaluate the safety and effectiveness of hysterectomy vs. cone biopsy in HIV seropositive patients with carcinoma in situ of the cervix (CIS).We performed a retrospective case-control study of all HIV seropositive patients diagnosed with carcinoma in situ of the cervix from 1989 to 1995. A control group of HIV(-) women with CIS was also ascertained matched for date of diagnosis of CIS, race and age.There were 439 patients with CIS, of which 45 were HIV seropositive (10.3%). Nine were treated by hysterectomy, 30 by cone biopsy, and six remained untreated. Overall, 63% of HIV(+) patients did not receive any follow-up Pap smear (44% of hysterectomy patients, 50% of cone biopsy patients, and 83% of untreated patients; chi(2) P=0.41). According to Pap smear results, 67% (10/15) cone biopsy patients and 60% (3/5) hysterectomy patients had an abnormal Pap smear after treatment (P=0.9). Median time to recurrence was 12 months in hysterectomy patients vs. 14 months in cone biopsy patients. Deaths occurred in 22% of hysterectomy patients, 17% of cone biopsy patients, and 50% of untreated patients, none due to cervical cancer. Median time to death from presentation was 27.5 months for hysterectomy patients, 11 months for cone biopsy patients, and 7 months for untreated patients (P0.05). There were no complications in the hysterectomy group, however, two patients were readmitted after cone biopsy for bleeding. When compared to HIV(-) women with CIS, HIV(+) patients were more likely to be treated by hysterectomy (chi(2) P=0.01).All patients diagnosed with CIS should be counseled regarding HIV prevention and testing because of a significant seropositive rate. Compliance with gynecologic follow-up is very poor in this patient population. Special efforts should be made to enhance compliance. Cone biopsy and hysterectomy appear to be equally safe and effective in the treatment of CIS. CIS in HIV patients is a poor prognostic indicator for death from any cause.

Objective: In a large multi-center clinical trial of combination reverse transcriptase inhibitors (RTls), we assessed the impact of antiretroviral therapy on neurological function, the relationship between neurological and systemic benefit, and the prognostic value of neurological performance in late HIV-1 infection. Design: Neurological evaluations incorporated in a randomized, multi-center trial of combination antiretroviral therapy. Setting: Forty-two AIDS Clinical Trials Group sites and seven National Hemophilia Foundation sites Patients: Adult HIV-infected patients (n = 1313) with CD4 counts < 50 × 10 6 cells/l. Interventions: Four combinations of reverse transcriptase inhibitors consisting of zidovudine (ZDV), alternating monthly with didanosine (ddl), or in combination with zalcitabine (ddC), ddl or ddl and nevirapine. Main outcome measures: Mean change from baseline of a four-item quantitative neurological performance battery score, the QNPZ-4, administered to 1031 subjects. Results: Triple therapy and ZDV/ddl combination preserved or improved neurological performance over time compared with the alternating ZDV/ddl and ZDV/ddC regimens (P < 0.001), paralleling their impact on survival in the same trial as previously reported. QNPZ-4 scores were predictive of survival (P < 0.001), after adjusting for CD4 counts and HIV-1 plasma RNA concentrations. Conclusions: Combination antiretroviral therapy can have a salutary effect on preserving or improving neurological function. Superior systemic treatments may likewise better preserve neurological function. The significant association of poor neurological performance with mortality, independent of CD4 counts and HIV-1 RNA levels indicates that neurological dysfunction is an important cause or a strong marker of poor prognosis in late HIV-1 infection. This study demonstrates the value of adjunctive neurological measures in large therapeutic trials of late HIV-1 infection.

OBJECTIVE: Since heterosexual transmission of HIV in the United States is occurring at an increasing rate, especially among black and Hispanic couples and those in which one member has a history of intravenous drug use, we sought to study the heterosexual transmission of HIV in couples. DESIGN: Multiple logistic regression analysis of risks for HIV infection in female partners. METHODS: We enrolled 158 non-intravenous drug user (IVDU) steady heterosexual partners of HIV-infected individuals (indexes) in this study. Of these, 93% were women, 54% were Hispanic whites, 23% were black and 65.6% were partners of IVDU. RESULTS: In a multiple logistic regression analysis of risks for HIV infection in female partners, the strongest predictors of transmission were AIDS or AIDS-related complex (ARC) in the index [adjusted odds ratios (OR), 16.81; P < 0.001 and 12.53; P = 0.003, respectively], a history of anal intercourse (adjusted OR, 10.81; P < 0.001) and bleeding as a result of intercourse (adjusted OR, 4.90; P < 0.05). Female-to-male transmission was detected in seven out of 11 couples at risk. Ethnicity, number of episodes of vaginal intercourse, number of other sexual partners and history of sexually transmitted infections were not significantly associated with transmission to women. CONCLUSION: Our study demonstrates that health of the index, anal intercourse and bleeding as a result of intercourse are the major determinants of sexual transmission of HIV to women in couples.

Background: Pharmacokinetic (PK) interactions between lopinavir/ ritonavir (LPV/r) and transdermally delivered ethinyl estradiol (EE) and norelgestromin (NGMN) are unknown. Methods: Using a standard noncompartmental PK analysis, we compared EE area under the time―concentration curve (AUC) and NGMN AUC during transdermal contraceptive patch administration in HIV-1―infected women on stable LPV/r to a control group of women not on highly active antiretroviral therapy (HAART). In addition, EE AUC after a single dose of a combination oral contraceptive pill including EE and norethindrone was measured before patch placement and was compared with patch EE AUC in both groups. Contraceptive effects on LPV/r PKs were estimated by measuring LPV/r AUC at baseline and during week 3 of patch administration. Results: Eight women on LPV/r, and 24 women in the control group were enrolled. Patch EE median AUC 0―168 h was 45% lower at 6010.36 pg·h·mL ―1 in those on LPV/r versus 10911.42 pg·h·mL ―1 in those on no HAART (P = 0.064). Pill EE median AUC 0―48 hours was similarly 55% lower at 344.67 pg·h·mL ―1 in those on LPV/r versus 765.38 pg·h·mL ―1 in those on no HAART (P = 0.003). Patch NGMN AUC 0―168 h however, was 138.39 ng·h·mL ―1 , 83% higher in the LPV/r group compared with the control AUC of 75.63 ng·h·mL ―1 (P = 0.036). After 3 weeks on the patch, LPV AUC 0―8 h decreased by 19%, (P = 0.156). Conclusions: Although PKs of contraceptive EE and NGMN are significantly altered with LPV/r, the contraceptive efficacy of the patch is likely to be maintained. Larger studies are indicated to fully assess contraceptive efficacy versus risks of the transdermal contraceptive patch when co-administered with protease inhibitors.

A comparison of the proliferative responses of lymphocytes to human immunodeficiency virus (HIV) antigens from long-term, seronegative heterosexual partners of HIV-infected subjects, from normal unexposed controls and from healthy seropositive heterosexual partners or seropositive, asymptomatic men, reveals that lymphocytes from healthy seropositive individuals with strong proliferative responses to recall, microbial antigens respond only minimally to HIV proteins or envelope peptides, and that even these low responses do not occur in all individuals. If the frequency of responses to several HIV antigens are analyzed, lymphocytes from both HIV-exposed seropositive and seronegative partners of infected individuals proliferate to HIV antigens to a greater degree than lymphocytes from unexposed, normal control individuals. Although lymphocytes from seropositive partners proliferate to a greater degree than those from seronegative partners, the latter are more similar to seropositive partners than they are to normal controls. This observation suggests that these seronegative partners may have become sensitized to HIV antigens through sexual exposure but without infection, and/or that the presence or development of these small immune responses in some individuals might be associated with a failure to become infected.

Antiretroviral therapy in early HIV infection may enhance outcome and viral control may be better in acute versus recent infection 24 weeks after treatment interruption.A prospective trial of treatment stratified by acute versus recent HIV-1 infection. If HIV viral load50 copies/ml after at least 52 weeks, treatment was interrupted. If viremia rebounded, treatment and interruption were repeated. The primary endpoint was maintaining viral load less than 5000 copies/ml for 24 weeks following treatment interruption.Of the 121 patients enrolled at 15 sites, ninety-five percent were men, median age was 34 years; 69% were white. Median viral load was higher in acute HIV-1 infection (210 000 copies/ml) than recent HIV-1 infection (43 000 copies/ml). The 73 primary endpoint patients (28 acute HIV-1 infection, 45 recent HIV-1 infection) had significantly higher baseline CD4 T-cell counts (P = 0.044) and lower viral load (P = 0.016). The primary endpoint was achieved in 29 (40%) of the 73 and in 24% of the 121 enrolled overall. There was no significant outcome difference (P = 0.81) between the acute HIV-1 infection [43%, 95% confidence interval (CI) 24-63%] and recent HIV-1 infection (38%, 95% CI 24-53%) groups. Differences after longer follow-up can not be ascertained by this trial. Baseline viral load less than 100 000/ml 22/46 (48%) compared with more than 100 000/ml, 7/27 (26%) and higher baseline CD4 immune activation predicted success.Forty percent of patients treated during acute HIV-1 infection or recent HIV-1 infection sustained a viral load less than 5000 copies/ml after 24 weeks of treatment interruption.

Context: Approaches to preserve or enhance immune function in HIV-1 infection are needed. Objectives: To examine the ability of daily low-dose interleukin-2 (IL-2) in combination with antiretroviral therapy to preserve circulating CD4 T-cell counts, the clinical safety and tolerability of this treatment, and safety with respect to changes in plasma HIV-1 RNA levels. Design: Twenty-four-week, phase 2, multicenter, randomized, open-label trial conducted at 12 AIDS Clinical Trials Units between September 1995 and May 1997. Participants: A total of 115 HIV-infected persons with screening CD4 T-cell counts between 300 and 700 cells/mm 3 who were on stable single- or dual-nucleoside therapy for at least 2 months, 11% of whom were also on a protease inhibitor at study entry. Interventions: Patients were randomly assigned to receive 1L-2 at a dose of 1 million IU subcutaneously once daily plus continued antiretroviral therapy (ART + IL-2, n = 57) vs. continued ART alone (ART alone, n = 58). IL-2 dose reductions were made for objective or subjective toxicities. All subjects randomly assigned to the IL-2 arm who interrupted ART were also required to discontinue IL-2 for the same period. Main Outcome Measures: The primary endpoint was a decrease in CD4 + T-cell count from baseline; the safety analysis was based on change in plasma HIV RNA by bDNA; and clinical safety and tolerability were analyzed by standard clinical criteria. Results: Of the patients with a baseline CD4 + T-cell count recorded, 15 (27%) of 55 patients randomly assigned to ART alone had a drop of ≥25% in their CD4 + T-cell count and 23 (41%) of 56 patients randomly assigned to ART + IL-2 had a drop of ≥25% in their CD4 + T-cell count at some time over the 24 weeks of the study. This difference was not statistically significant. There was a statistically significant greater variance in CD4 + T-cell counts in the IL-2-treated group. More patients in the IL-2 group had at least a 25% increase in CD4 + T-cell counts over baseline (34 vs. 13%, P=0.007). A comparison of grade 3 or worse toxicity showed no differences between the arms, but IL-2 was associated with significantly more grade 2 or worse general body symptoms, primarily discomfort and fatigue. There was no significant difference between the groups with regard to changes in plasma HIV RNA, lymphocyte proliferation, natural killer cell activity, skin test responses to recall antigens, or antibody responses to immunization. Plasma markers of immune activation all increased significantly in IL-2 recipients. Conclusions: In patients with baseline CD4 + T-cell counts ≥300 cells/mm 3 primarily treated with single- or dual-nucleoside ART, subcutaneously administered IL-2 at a dose of I million IU daily for up to 24 weeks had low toxicity but showed no consistent benefit in preventing decline in CD4 + T-cell counts and minimal evidence of immunologic improvement vs. continued ART alone.

A national survey of investigators caring for human immunodeficiency virus (HIV)-infected women was undertaken to describe the clinical presentation of idiopathic genital ulcer disease. Patients with negative syphilis and herpes simplex testing and/or negative genital ulcer biopsy were included in this study. Study participants (n = 29) were generally severely immunocompromised (median CD4 cell count was 50/mm3, and 68% had an acquired immunodeficiency syndrome [AIDS]-defining opportunistic process). Thirty-seven percent had coexistent oral ulcers and 19% had their genital ulcer progress to fistula formation (four rectovaginal and one vaginal-perineal). There was generally a favorable response to topical, systemic, and intralesional steroid treatment. This study suggests that idiopathic or probable aphthous genital ulcers in women have similar clinical characteristics to aphthous oroesophageal ulcers. Although infrequent, these genital ulcers can cause severe morbidity. Further research is warranted to better define the pathophysiology and optimal management.

Corynebacterium diphtheriae infection is still epidemic in the states of the former Soviet Union. To date, no cases have been exported to the United States [1]. An Uzbek national developed severe pharyngitis shortly after entering the United States. Recovery of Corynebacterium pseudodiphtheriticum complicated the diagnostic process. The ubiquity of this organism should be more widely recognized. Three days after arriving in the United States from his native Uzbekistan, a 32-year-old airline crew member was admitted to the hospital with a progressively severe sore throat and dysphagia of 2 days' duration. He noted that he had received "all" immunizations as a child but did not recall any specific details. He was unaware of recent illness in his family, the airline crew, or close contacts. His temperature was 102?F. His tonsils were enlarged bilaterally, and a grayish-white exudate extended from the tonsil to the posterior pharyngeal wall (figure 1). The uvula and soft palate were erythematous and edematous, and there was tender cervical lymphadenopathy. The leukocyte count was 22,000/4tL. Duplicate rapid screening tests for group A streptococci were negative. Epstein-Barr virus IgM viral capsid antigen titers were < 1:10. The patient's history and the findings raised the possibility of imported diphtheria. After consultation with the local health department and Centers for Disease Control and Prevention, 40,000 units of equine diphtheria antitoxin was administered intravenously. Treatment with im procaine penicillin G (600,000 units every 12 hours) was given and changed to that with oral erythromycin after the patient's clinical condition rapidly improved within 24 hours. Cultures of the pharyngeal exudate yielded only a mixture of normal flora. Cultures of nasopharyngeal secretions yielded a heavy, pure growth of pale grayish-white colonies on blood agar and black colonies with a gray halo on Tindale's agar. A gram stain showed gram-positive club-shaped bacilli forming "Chinese letters," which were consistent with C. diphtheriae. On biochemical testing, however, the organism was identified as C. pseudodiphtheriticum.

When the subridge mesoderm of the embryonic chick limb bud is cultured in the absence of the apical ectodermal ridge and adjacent ectoderm, the cells rapidly progress through the various stages of chondrogenesis. During the first day of culture, the cells initiate condensation, and during subsequent days, deposit a cartilage matrix. In the present study, we show that early in the first day there is a progressive 2-fold increase in cell surface galactosyltransferase activity towards endogenous acceptors. Later in the first day, although the cells are still in condensation, endogenous galactosyltransferase activity has decreased, suggesting in situ galactosylation of surface acceptors. During subsequent development, when cartilage matrix is being deposited, surface galactosyltransferase activity remains low. All controls have been performed to insure cell surface localization of enzyme activity. Two other surface glycosyltransferases show very low levels of activity, which do not change significantly during culture. We suggest that during cellular condensation, an interaction between surface galactosyltransferases and acceptors on adjacent cells occurs, and this interaction may be causally related to subsequent chondrogenic differentiation.

Cultures of 10-day rat embryos depleted a protein band with a molecular weight of approximately 125,000 from the rat serum medium. Delayed centrifuged serum differed from immediately centrifuged serum by a reduction in the staining intensity of the 125,000 molecular weight protein band and by the absence of two high molecular weight (>200,000) protein bands.

Head fold stage rat embryos were cultured for 48 hours in vitro on serum taken at various intervals from rats that had been injected ip with either cadmium or cyclophosphamide. Their response was compared to that of embryos cultured for the same period on control serum to which these substances were added directly. One and 4 hour sera from cadmium-injected rats (2.13 mg Cd + +/kg) were lethal. Eight hour serum allowed survival but embryos were exencephalic and contained reduced amounts of protein and DNA. The response to direct cadmium was characteristically different and was related to dosage and the extent to which zero-time embryos had progressed through the head fold stage. At 1.6 ..mu..M, Cd + + susceptible embryos were hemorrhagic, though not exencephalic. One hour serum from rats given cyclophosphamide (180 mg/kg) was lethal. On 4 hour serum, embryos survived but were exencephalic and contained less protein and DNA than controls. Embryos were resistant to direct cyclophosphamide up to 800 ..mu..g per ml of medium. At this concentration, embryos appeared morphologically normal but contained reduced amounts of protein.

To describe symptoms associated with human immunodeficiency virus (HIV) seroconversion, we studied a cohort of 366 injection-drug users (IDUs) with a study design that included recall every 3 months to collect symptom histories using a structured questionnaire. Eleven HIV seroconversions were observed in 621.5 person years at risk (PYAR), equivalent to 1.8 seroconversions/100 PYAR. Cox regression analysis showed ageor = 35 years to be a significant risk factor for HIV seroconversion after controlling for gender, race, and the frequency of drug injection. An embedded case-control analysis then compared symptom histories of HIV seroconverters with those of age-(+/- 5 years) and visit number-matched controls who remained HIV seronegative foror = 3 months longer than the HIV-seroconverters. Multivariate case-control analysis adjusted for injection frequency yielded significant associations of HIV seroconversion with histories of weight lossor = 4.5 kg (seven of 11 cases; odds ratio [OR] = 11.6, 95% confidence interval [CI] 3.1, 43.1) and oral ulcers (three of 11 cases; OR = 7.6, 95% CI = 1.2, 48.2) in the 3 months before the subjects' first HIV-seropositive study visit. We conclude that histories of recent symptoms reported by HIV-seroconverting IDUs differ from those reported by non-HIV-seroconverting IDUs, and weight loss may be particularly common among IDUs experiencing primary HIV infection.