Cellular replication of human immunodeficiency virus type 1 occurs in vaginal secretions.

Most human immunodeficiency virus type 1 (HIV-1) transmission worldwide is the result of exposure to infectious virus in genital secretions. However, current vaccine candidates are based on virus isolates from blood. In this study, vaginal secretions from HIV-1-infected women were examined for evidence of cellular viral replication that produced virus with properties different from that in blood. Multiply spliced HIV-1 messenger RNA, which is found only in cells replicating virus, was detected in all vaginal lavage samples tested. There was a strong correlation between the amounts of multiply spliced HIV-1 messenger RNA and of cell-free HIV-1 RNA in the lavage samples. In addition, significant genotypic differences were found in cell-free virus from matched blood plasma and vaginal secretions. Moreover, drug resistance-associated mutations appeared in plasma virus several months before appearing in vaginal virus. These findings indicate that cellular replication of HIV-1 occurs in vaginal secretions and can result in a virus population with important differences from that in blood.

Correlation of human immunodeficiency virus type 1 RNA levels in blood and the female genital tract.

In this study, the correlations of human immunodeficiency virus type 1 (HIV-1) RNA levels in blood plasma, vaginal secretions, and cervical mucus of 52 HIV-1-infected women were determined. The amount of cell-free HIV-1 RNA in blood plasma was correlated with that in vaginal secretions (Spearman's rank correlation coefficient (r) = 0.64, P<.001). In both blood plasma and vaginal secretions, the amounts of cell-free and cell-associated HIV-1 RNA were highly correlated (r=0.76, P<.01 and r=0.85, P<.01, respectively). Cell-free HIV-1 RNA levels in blood plasma and vaginal secretions were negatively correlated with CD4+ T lymphocyte count (r=-0.44, P<.01 and r=-0.40, P<.01, respectively). Similar to the effect observed in blood plasma, initiation of antiretroviral therapy significantly reduced the amount of HIV-1 RNA in vaginal secretions. These findings suggest that factors that lower blood plasma virus load may also reduce the risk of perinatal and female-to-male heterosexual transmission by lowering vaginal virus load.

The association between cigarette smoking and selected HIV-related medical conditions.

OBJECTIVE: To clarify the effect of cigarette smoking on the development of conditions associated with HIV infection. DESIGN: Prospective and retrospective cohort study, with interview and examination twice a year since 1988. METHODS: Data on 516 HIV-infected men from cohorts of homosexual and bisexual men in San Francisco, Denver and Chicago, who were repeatedly interviewed and examined between 1988 and 1992, were analysed. After excluding men who did not have well-defined dates of seroconversion and those who were classified as ex- or intermittent smokers, 232 men remained for analysis: 106 were smokers and 126 were non-smokers. Univariate and Kaplan-Meier survival analyses were performed to assess the relationship between cigarette smoking and loss of CD4+ T-lymphocytes, diagnosis of any AIDS-defining illness, and specific diagnosis of Kaposi's sarcoma, Pneumocystis carinii pneumonia (PCP), oral candidiasis, hairy leukoplakia, and community-acquired pneumonia. RESULTS: By univariate analyses, cigarette smoking was not associated with clinical AIDS, loss of CD4+ cells, Kaposi's sarcoma or PCP, but was significantly associated with oral candidiasis [relative risk (RR), 1.32; 95% confidence interval (CI), 1.02-1.70], hairy leukoplakia (RR, 1.51; 95% CI, 1.15-1.99), and community-acquired pneumonia (RR, 2.62; 95% CI, 1.30-5.27). Dose-response effect was also evident for these three conditions (all P < 0.01). Kaplan-Meier survival analysis indicated no association between cigarette smoking and time of progression to clinical AIDS, Kaposi's sarcoma (KS), or PCP (P = 0.62, 0.54 and 0.11, respectively) but showed that cigarette smokers developed oral candidiasis, hairy leukoplakia, and pneumonia more quickly than non-smokers (P = 0.031, 0.006 and 0.009, respectively). CONCLUSIONS: Cigarette smoking was not associated with an increased likelihood or rate of developing KS, PCP or AIDS, but was associated with developing community-acquired pneumonia, oral candidiasis, and hairy leukoplakia in these HIV-infected men.

Kaposi's sarcoma-associated herpesvirus infection prior to onset of Kaposi's sarcoma.

OBJECTIVES: Kaposi's sarcoma-associated herpesvirus (KSHV), a newly discovered human gammaherpesvirus, is found in the majority of KS lesions from patients with and without AIDS. Peripheral blood mononuclear cells (PBMC) were examined for KSHV DNA to determine whether viral infection precedes onset of this neoplasm. DESIGN: Randomized and blinded case-control study of prospectively collected PBMC samples from ongoing cohort studies. METHODS: Paired PBMC drawn before and after KS onset from 21 AIDS-KS patients were compared to paired PBMC from 23 high-risk HIV-infected homo-/bisexual patients who did not develop KS and to a single PBMC sample from 19 low-risk, HIV-infected hemophiliac patients. Extracted DNA samples were amplified by polymerase chain reaction (PCR) using two non-overlapping nested primer sets to control for potential PCR contamination. RESULTS: In all comparisons, patients who went on to develop KS were significantly more likely to show evidence of KSHV infection prior to onset of KS than either control group. Of PBMC samples from AIDS-KS patients drawn prior to KS, 52% were positive for KSHV DNA whereas both high- and low-risk control groups had lower rates of PBMC infection (9-13%). KSHV infection can precede KS onset by up to 21 months among AIDS-KS patients. CONCLUSIONS: AIDS-KS patients are significantly more likely to show evidence of KSHV infection in PBMC prior to KS onset than control HIV-infected patients. Because identical PBMC samples from cases and controls were examined blindly, these results are not caused by a bias in tissue sampling. Homo-/bisexual and hemophiliac AIDS patients who do not develop KS appear to have a low prevalence of infection. These findings indicate that KSHV infection is specifically associated with the subsequent development of KS in AIDS patients.

Recent infection with human immunodeficiency virus and possible rapid loss of CD4 T lymphocytes.

To assess a hypothesized trend that persons recently infected with the human immunodeficiency virus (HIV) may have more rapid declines in absolute CD4 T-lymphocyte (CD4+ cell) counts than those who were HIV-infected in earlier years, sequential CD4+ cell counts in three groups who had definable dates of HIV seroconversion between 1978 and 1992 were reviewed. The CD4+ cell counts examined were from some of the longest extant studies in the United States: 100 homosexual and bisexual men engaged in ongoing observational cohort studies in San Francisco, Denver, and Chicago since 1978 (Group 1); 89 persons in South Carolina infected after 1986 (Group 2); and 155 injecting drug users participating in an observational cohort study in Baltimore since 1988 (Group 3). For all groups, individually and in the aggregate, mean CD4+ cell counts declined rapidly in the first year after HIV infection and then stabilized. However, there was no clear trend for lower (or higher) CD4+ cell counts by fixed time after HIV seroconversion among those seroconverting in recent compared with earlier calendar years. These data do not support a hypothesized trend for more rapid loss of CD4 T lymphocytes--and, by implication, more pathogenic strains of HIV-1--among persons acquiring HIV infection in recent years.

The spectrum of medical conditions and symptoms before acquired immunodeficiency syndrome in homosexual and bisexual men infected with the human immunodeficiency virus.

The full range and occurrence of medical conditions in persons infected with human immunodeficiency virus (HIV) before they develop illnesses that define acquired immunodeficiency syndrome (AIDS) have not been systematically or completely described. In a retrospective and prospective cohort study, 1,073 homosexual and bisexual men in three US cities were interviewed and examined twice per year from January 1988 to September 1992. Study participants were from San Francisco, California (273 HIV-seropositive and 432 HIV-seronegative men), Denver, Colorado (107 positive and 129 negative men), and Chicago, Illinois (54 positive and 78 negative men). A total of 305 HIV-positive men had specifiable dates of HIV seroconversion (mean of 15.3 months between the last negative and the first positive HIV antibody test). Besides much increased incidences of thrush (incidence relative risk (IRR) = 23.3) and hairy leukoplakia (IRR = 551), the following conditions also occurred significantly more frequently in HIV-positive men than in HIV-negative men: anal herpes (incidence density (ID) = 10.7/100 person-years; IRR = 7.7); sinusitis requiring antibiotics (ID = 6.2/100 person-years; IRR = 2.1); anal warts (ID = 5.8/100 person-years; IRR = 2.7); seborrhea (ID = 3.8/100 person-years; IRR = 6.6); community-acquired pneumonia (ID = 1.4/100 person-years; IRR = 2.7); skin cancers (ID = 1.0/100 person-years; IRR = 2.2); and seizures, often apparently "breaking through" prior anticonvulsant therapy (ID = 0.8/100 person-years; IRR = 5.6). First episodes of hairy leukoplakia, thrush, and skin cancer occurred at low mean CD4 counts (mean counts were less than 350 cells/microliters) and late in HIV infection (mean times were more than 8 years after HIV seroconversion). Many medical problems, some not widely appreciated, occur in HIV-infected men before they develop AIDS-defining illnesses, signifying considerable morbidity from pre-AIDS HIV infection.

Use of therapeutic and prophylactic drugs for AIDS by homosexual and bisexual men in three US cities.

OBJECTIVE: To determine the use of AIDS drugs and therapies by populations with relatively good access to health care. DESIGN: Prospective cohort study, with interview and examination twice a year since 1988. SETTING: Two public-health departments (San Francisco Department of Health and Denver Disease Control Service) and a private clinic (Howard Brown Memorial Clinic, Chicago). PARTICIPANTS: HIV-seropositive homosexual and bisexual men in San Francisco (311 men), Denver (120 men) and Chicago (59 men). INTERVENTIONS: HIV counseling and testing at each visit. MAIN OUTCOME MEASURES: Time and duration of use of drugs used for AIDS and Pneumocystis carinii pneumonia (PCP) treatment and prophylaxis. RESULTS: Zidovudine and pentamidine use increased from 1987 through 1989 in all three cities. In San Francisco in 1987, only 17 out of 110 (15%) HIV-seropositive men without AIDS reported taking zidovudine. By 1990, over 90% of AIDS patients and approximately 80% of HIV-seropositive men with low CD4+ cell counts (< 200 x 10(6)/l) had taken zidovudine; most men who by 1990 had never taken zidovudine (82%) or PCP prophylaxis (95%) had not been recommended these therapies because they did not have symptoms and their absolute CD4+ cell counts were > 200 x 10(6)/l. However, overall in the three cities, only 68% of the AIDS patients and 63% of the men with low CD4+ cell counts had taken zidovudine for more than 6 months by 1990. Most men who had stopped taking zidovudine (67%) did so because of toxicity; however, 64% of respondents gave reasons other than drug toxicity as a or the sole reason why they discontinued zidovudine. CONCLUSIONS: AIDS therapeutic and prophylactic drugs were increasingly (and appropriately) recommended to and accepted by these cohorts after 1987, but had limited consistent use because of toxicity, adverse side-effects, and several other less readily appreciated reasons. These data do not indicate that zidovudine use in San Francisco would mainly account for the observed slowing in the rate of increase of AIDS cases in homosexual and bisexual men in this city after 1987.

Transmission of human immunodeficiency virus type 1 from a seronegative organ and tissue donor.

BACKGROUND: Since 1985, donors of organs or tissues for transplantation in the United States have been screened for human immunodeficiency virus type 1 (HIV-1), and more than 60,000 organs and 1 million tissues have been transplanted. We describe a case of transmission of HIV-1 by transplantation of organs and tissues procured between the time the donor became infected and the appearance of antibodies. The donor was a 22-year-old man who died 32 hours after a gunshot wound; he had no known risk factors for HIV-1 infection and was seronegative. METHODS: We reviewed the processing and distribution of all the transplanted organs and tissues, reviewed the medical histories of the donor and HIV-1-infected recipients, tested stored donor lymphocytes for HIV-1 by viral culture and the polymerase chain reaction, and tested stored serum samples from four organ recipients for HIV-1 antigen and antibody. RESULTS: HIV-1 was detected in cultured lymphocytes from the donor. Of 58 tissues and organs obtained from the donor, 52 could be accounted for by the hospitals that received them. Of the 48 identified recipients, 41 were tested for HIV-1 antibody. All four recipients of organs and all three recipients of unprocessed fresh-frozen bone were infected with HIV-1. However, 34 recipients of other tissues--2 receiving corneas, 3 receiving lyophilized soft tissue, 25 receiving ethanol-treated bone, 3 receiving dura mater treated with gamma radiation, and 1 receiving marrow-evacuated, fresh-frozen bone--tested negative for HIV-1 antibody. Despite immunosuppressive chemotherapy, HIV-1 antibody appeared between 26 and 54 days after transplantation in the three organ recipients who survived more than four weeks. CONCLUSIONS: Although rare, transmission of HIV-1 by seronegative organ and tissue donors can occur. Improvements in the methods used to screen donors for HIV-1, advances in techniques of virus inactivation, prompt reporting of HIV infection in recipients, and accurate accounting of distributed allografts would help to reduce further this already exceedingly low risk.

Health care workers with AIDS. National surveillance update.

OBJECTIVES: To characterize health care workers with the acquired immunodeficiency syndrome (AIDS) in the United States and to evaluate the role of occupational transmission of the human immunodeficiency virus (HIV). DATA SOURCE: National AIDS surveillance data. METHODS: Health care workers with AIDS are reported to the Centers for Disease Control by state and local health departments. Health care workers who do not report a nonoccupational risk for HIV infection are termed undetermined risk cases and are investigated by health departments using a standard protocol. RESULTS: Through June 30, 1990, there were 5425 cases of AIDS in health care workers reported in the United States. Three of these workers developed AIDS following well-documented occupational exposure to HIV-infected blood. Of the 539 health care workers initially reported without a nonoccupational risk, follow-up investigations were completed for 303. Nonoccupational risk factors were established for 237 (78.2%) of the 303 investigated health care workers; 66 workers (21.8%) remained in the undetermined category. Follow-up information was incomplete for 236 health care workers who also remained in the undetermined category, resulting in 5120 health care workers (94.4%) with AIDS with nonoccupational risks for HIV infection. Overall, health care workers were more likely than non-health care workers with AIDS to have an undetermined risk for HIV infection (5.6% vs 2.8%; P less than .001). While many of the 66 investigated health care workers had jobs involving contact with patients and/or potential contact with blood, none reported percutaneous, mucous membrane, or cutaneous exposures to blood or body fluids known to be infected with HIV. CONCLUSION: Surveillance data suggest that most health care workers with AIDS acquired their HIV infection through a nonoccupational route.

Childbearing and childrearing practices in Mormonism.

PIP: Mormons, who have the highest birth rates in the US, have unique childbearing attitudes and practices that should be understood by the health care practitioners who work with this population. There are several million members of the Church of Jesus Christ of Latter-day Saints in the US, and 70% of the population of Utah is Mormon. Family life is the basic unit of the religion, with women expected to serve as childbearers while men preside over the family and provide for the physical and spiritual needs of the children. Both premarital sex and adultery are prohibited, and marriage below the age of 18 years is rare. In keeping with the Mormon belief that heaven is full of millions of spirits awaiting an earthly body, birth control and abortion are also forbidden. Since the female body is regarded as the tabernacle of the spirit and the residence of God's spirit children, a high priority is given to prenatal care. Most Mormons adhere to the hegemonic model in the US physician visits in the prenatal period and delivery in a hospital. In the postpartum period, Mormon women are relieved of routine household and child care duties by extended family and church ward members. Breastfeeding is encouraged for both its health and bonding advantages. From a young age, Mormon children are given responsibilities such as household duties and the tending of younger siblings. Mothers play a key role in their children's religious education, and parents who do not rear their children strictly according to Mormon gospel are condemned. Since most deliveries of Mormon infants occur in hospitals, neonatal nurses should be mindful of the patriarchal structure of the family, expect parents to process medical information in spiritual terms, grant requests for priesthood blessings, requests for priesthood blessings and not advocate contraceptive usage.^ieng