End-of-study safety, immunogenicity, and efficacy of quadrivalent HPV (types 6, 11, 16, 18) recombinant vaccine in adult women 24-45 years of age.

BACKGROUND: Previous analyses from a randomised trial in women aged 24-45 years have shown the quadrivalent human papillomavirus (qHPV) vaccine to be efficacious in the prevention of infection, cervical intraepithelial neoplasia (CIN), and external genital lesions (EGLs) related to HPV 6/11/16/18. In this report, we present end-of-study efficacy, safety, and immunogenicity data with a median follow-up time of 4.0 years. METHODS: We enrolled 3819 24-45-year-old women with no history of cervical disease or genital warts in the past 5 years. Women received quadrivalent vaccine or placebo at day 1, and at months 2 and 6. Ascertainment of CIN/EGL was accomplished through Pap testing, genital inspection, and cervicovaginal sampling (every 6 months). The main analysis was conducted in a per-protocol efficacy population (that received three doses, was naive to the relevant HPV types at day 1, and remained free of infection through month 7). Efficacy was also estimated in other naive and non-naive populations. RESULTS: Vaccine efficacy against the combined incidence of persistent infection, CIN/EGL related to HPV6/11/16/18 in the per-protocol population was 88.7% (95% CI: 78.1, 94.8). Efficacy for women who were seropositive and DNA negative for the relevant vaccine HPV type at the time of enrolment who received at least 1 dose was 66.9% (95% CI: 4.3, 90.6). At month 48, 91.5, 92.0, 97.4, and 47.9% of vaccinated women were seropositive to HPV 6/11/16/18, respectively. No serious vaccine-related adverse experiences were reported. CONCLUSIONS: The qHPV vaccine demonstrated high efficacy, immunogenicity, and acceptable safety in women aged 24-45 years, regardless of previous exposure to HPV vaccine type.

KSHV antibodies among Americans, Italians and Ugandans with and without Kaposi's sarcoma.

A major controversy regarding Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) is whether or not it is a ubiquitous infection of humans. Immunoassays based on KSHV- and Epstein-Barr virus (EBV)-coinfected cell lines show that most US AIDS-KS patients have specific antibodies to KSHV-related antigens. We have developed a sensitive indirect immunofluorescence assay (IFA) based on an EBV-negative, KSHV-infected cell line, BCP-1. When we used this IFA assay, KSHV-related antibodies were found in 71-88% of serum samples from US, Italian and Ugandan AIDS-KS patients, as well as all serum samples examined from HIV-seronegative KS patients. Although none of the US blood donors examined were KSHV seropositive by IFA, intermediate and high seroprevalence rates were found in Italian and Ugandan control populations. Antibody kinetics showed that more than half of the AIDS-KS patients who were examined IgG-seroconverted before KS development, and antibody levels did not decline after seroconversion. For these patients, seropositivity rates increased linearly with time, suggesting that the rate of infection was constant and that the risk of developing KS once infected with KSHV is not highly dependent on the duration of infection. These data strongly suggest that KSHV is not ubiquitous in most populations and that the virus may be under strict immunologic control in healthy KSHV-infected persons.

Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection.

Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV-1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV-1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections.

Efficacy of caspofungin as salvage therapy for invasive aspergillosis compared to standard therapy in a historical cohort.

In a non-comparative study, caspofungin was effective salvage therapy for approximately half of the patients refractory to or intolerant of standard antifungal agents for invasive aspergillosis. To establish a frame of reference for these results, we compared the response to caspofungin with responses to other antifungal agents in a historical cohort of similar patients. The efficacy could be evaluated in 83 patients who received caspofungin 50 mg daily after a 70-mg loading dose. The historical control group, identified through a retrospective review of medical records, included 214 evaluable patients possibly refractory to or intolerant of ≥1 week of standard antifungal therapy. All patients had documented invasive aspergillosis. Favorable response was defined as a complete or partial response to therapy. Underlying diseases, baseline neutropenia, corticosteroid use, and sites of infection were similar in both studies. Most patients had received amphotericin B formulations and/or itraconazole, and were refractory to standard therapy. Favorable response rates were 45% with caspofungin and 16% with standard therapy. The unadjusted odds ratio for a favorable response (caspofungin/standard therapy) was 4.1 (95% confidence interval: 2.2, 7.5). After adjusting for potential imbalances in the frequency of disseminated infection, neutropenia, steroid use, and bone marrow transplantation between groups, the odds ratio remained at 4.1 (2.1, 7.9). Although only tentative conclusions about relative efficacy can be drawn from retrospective comparisons, caspofungin appeared to be at least as efficacious as an amphotericin B formulation and/or itraconazole for the treatment of invasive aspergillosis in patients refractory to or intolerant of their initial antifungal therapy.

Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study.

The chemokine receptor 5 (CKR5) protein serves as a secondary receptor on CD4(+) T lymphocytes for certain strains of human immunodeficiency virus-type 1 (HIV-1). The CKR5 structural gene was mapped to human chromosome 3p21, and a 32-base pair deletion allele (CKR5Delta32) was identified that is present at a frequency of approximately0.10 in the Caucasian population of the United States. An examination of 1955 patients included among six well-characterized acquired immunodeficiency syndrome (AIDS) cohort studies revealed that 17 deletion homozygotes occurred exclusively among 612 exposed HIV-1 antibody-negative individuals (2.8 percent) and not at all in 1343 HIV-1-infected individuals. The frequency of CKR5 deletion heterozygotes was significantly elevated in groups of individuals that had survived HIV-1 infection for more than 10 years, and, in some risk groups, twice as frequent as their occurrence in rapid progressors to AIDS. Survival analysis clearly shows that disease progression is slower in CKR5 deletion heterozygotes than in individuals homozygous for the normal CKR5 gene. The CKR5Delta32 deletion may act as a recessive restriction gene against HIV-1 infection and may exert a dominant phenotype of delaying progression to AIDS among infected individuals.

Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors.

HIV-1-infected long-term nonprogressors are a heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. CC chemokine receptor 5 (CCR5) has recently been identified as an important coreceptor for HIV-1 entry into CD4+ T cells. A mutant allele of CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes. The frequency of CCR5 heterozygotes is increased among HIV-1- infected long-term nonprogressors compared with progressors; however, the host defense mechanisms responsible for nonprogression in CCR5 heterozygotes are unknown. We hypothesized that nonprogressors who were heterozygous for the mutant CCR5 gene might define a subgroup of nonprogressors with higher CD4+ T cell counts and lower viral load compared with CCR5 wild-type nonprogressors. However, in a cohort of 33 HIV-1-infected long-term nonprogressors, those who were heterozygous for the mutant CCR5 gene were indistinguishable from CCR5 wild-type nonprogressors with regard to all measured immunologic and virologic parameters. Although epidemiologic data support a role for the mutant CCR5 allele in the determination of the state of long-term nonprogression in some HIV-1- infected individuals, it is not the only determinant. Furthermore, long-term nonprogressors with the wild-type CCR5 genotype are indistinguishable from heterozygotes from an immunologic and virologic standpoint.

Comparison of clinical symptoms of human immunodeficiency virus disease between intravenous drug users and homosexual men.

BACKGROUND: To compare the prevalence of human immunodeficiency virus (HIV)-related clinical symptoms among male intravenous drug users and homosexual men stratified by HIV serostatus and CD4 cell levels. METHODS: A cross-sectional sample using concurrent longitudinal studies of the natural history of HIV-1 infection among intravenous drug users (N = 539) and homosexual men (N = 932) was recruited in Baltimore, Md. Participants were administered a risk behavior interview and physical examination, and had hematologic tests evaluated in a similar calendar period. RESULTS: Both risk groups demonstrated an inverse relationship between frequency of symptoms and CD4 cell count. Fever, night sweats, and lymphadenopathy were not evaluated because pilot data suggested a confounding association with drug injection. Among those with mild to moderate immune suppression, intravenous drug users were significantly more likely than homosexual men to experience fatigue, weight loss, diarrhea, and shortness of breath; to have oral candidiasis, palpable spleen, and lower mean weight on physical examination; and abnormal hematocrit, platelets, and total lymphocyte counts. However, participants in either risk group with CD4 cell levels below 0.2 x 10(9)/L experienced similar frequency of all clinical symptoms. Self-reported oral candidiasis increased fourfold with HIV infection and was as likely in both groups at all CD4 cell levels. Duration and recency of intravenous drug use was not significantly associated with the higher frequency of most clinical symptoms. CONCLUSION: Social factors are an important consideration in evaluating the association between clinical symptoms and HIV immunosuppression. Except for oral candidiasis, there are limitations for the use of clinical symptoms as intermediate outcome measures for HIV infection among intravenous drug users.

Epidemiology of acute respiratory illness during an influenza outbreak in a nursing home. A prospective study.

We observed an influenza epidemic caused by influenza A/Arizona/82 (H3N2) in a nursing home during 1982 to 1983. A survey indicated that 59% of the residents were immunized before the outbreak. The outbreak was observed to begin in November, peak in February, and disappear in April. A significant level of herd immunity may have accounted for the slow progression through the nursing home. In addition, serologic evidence of concurrent infection with respiratory syncytial virus, parainfluenza virus, and Mycoplasma pneumoniae was present in many residents. Epidemics of influenza in a closed, partially immunized population in a nursing home may proceed at a slower rate than in an open, largely unimmunized community. By monitoring for infection with other respiratory agents, the complex nature of the outbreak in this nursing home became evident.

Association of influenza immunization with reduction in mortality in an elderly population. A prospective study.

We prospectively studied the efficacy of influenza vaccine during an influenza A/Arizona/80 (H3N2) outbreak at the Jewish Home and Hospital for the Aged in New York in the winter season of 1982 to 1983. All patients had been offered influenza vaccine before the outbreak; 181 chose to be vaccinated and 124 refused vaccination but agreed to participate in the study. Among those with serologic evidence of influenza infection, respiratory illness was significantly more common in the unvaccinated group (six of 14 vs one of 22). The overall mortality was 13 (7.2%) of 181 in the vaccinated group and 22 (17.7%) of 124 in the control group. The vaccinated and the control groups were examined for comparability. A logistic regression analysis, which controlled for differences in sex and level of nursing care, indicated that the difference in mortality was still significant, with a summary odds ratio of 2.7. The relative risk of death in the unvaccinated group was comparable at 2.18. Influenza vaccine reduced the mortality by 59% in the vaccinated group compared with the control group.

Direct comparison of the relationship between clinical outcome and change in CD4+ lymphocytes in human immunodeficiency virus-positive homosexual men and injecting drug users.

BACKGROUND AND METHODS: To compare rates of decline of CD4+ lymphocytes among human immunodeficiency virus-positive homosexual men and injecting drug users, we followed up prevalent human immunodeficiency virus-positive homosexual men and current or former injecting drug users from February 1988 through August 1991. Subjects were free of acquired immunodeficiency syndrome at study entry and had semiannual clinical and laboratory evaluation, including measurement of T-cell subsets, under common protocols. Initial levels and rates of change of CD4+ lymphocyte counts were compared according to cohort membership and clinical progression, defined by the development of thrush or an acquired immunodeficiency syndrome--defining illness. Median follow-up was 30 months for both cohorts. RESULTS: At study entry, homosexual men had lower absolute numbers of circulating CD4+ lymphocytes than did injecting drug users (459/microL [0.46 x 10(9)/L] vs 509/microL, respectively). During follow-up, homosexual men exhibited a faster decline in CD4+ lymphocyte counts as well as more frequent development of HIV-related symptoms (thrush or acquired immunodeficiency syndrome). In both cohorts, initial levels of CD4+ lymphocytes and rates of decline in these cells were strongly associated with progression of disease, defined as remaining asymptomatic, onset of thrush, or onset of acquired immunodeficiency syndrome. Once homosexual men and injecting drug users were stratified by disease progression, their initial levels and rates of decline of CD4+ lymphocyte counts were similar. Thus, crude differences between the two study groups largely resulted from differences in development of clinical symptoms. CONCLUSIONS: In these cohorts of homosexual men and injecting drug users, clinical outcome was much more important than risk group membership in determining changes in CD4+ lymphocyte numbers. The close similarity between the groups also suggests that drug use, ethnicity, and socioeconomic status play a minor role in the progression of human immunodeficiency virus infection.

Influenza vaccine and pneumonia mortality in a nursing home population.

The effectiveness of immunization against influenza in elderly persons is uncertain. A retrospective cohort study in a New York City nursing home examined the occurrence of pneumonia and its related mortality over three consecutive influenza seasons (Nov 1 through April 30, 1979 to 1980, 1980 to 1981, and 1981 to 1982). Nearly one half of approximately 450 residents (mean age, 84 years) accepted immunization each year. The vaccinated and unvaccinated groups were similar. The attack rate of pneumonia did not differ significantly between the vaccinated and unvaccinated groups in any of the three influenza seasons. When influenza was occurring in the community (1979 to 1980 and 1980 to 1981), however, the risk of death from pneumonia in the unvaccinated group was three-fold higher than in the vaccinated group (60% vs 18% and 73% vs 25%, respectively). In a year when influenza was specifically sought and not found in the facility (1981 to 1982), however, vaccination did not affect pneumonia-related mortality. This study also suggests that estimates of mortality due to pneumonia should include deaths that occur up to 60 days after onset of pneumonia; shorter follow-up may overestimate the protective effect of vaccination.

HIV infection is not associated with Reiter's syndrome: data from the Johns Hopkins Multicenter AIDS Cohort Study.

Reiter's syndrome has been reported to occur in up to 10% of patients with HIV infection. However, no properly controlled epidemiological studies have been conducted to determine whether HIV infection is an independent risk factor or whether the immunodeficiency induced by HIV infection is permissive for infection with other arthritogenic organisms. The prevalence and incidence of Reiter's syndrome were determined in 1133 homosexual/bisexual men enrolled in the Johns Hopkins Multicenter AIDS Cohort Study. There was no difference in the prevalence of Reiter's syndrome at entry into the study in 1984 between 357 HIV-positive and 776 HIV-negative men: five per 1000 in both groups. During 5 years' follow-up, one case of Reiter's syndrome developed among each group of HIV-positive and HIV-negative men. These data fail to support a direct etiological role for HIV infection in the development of Reiter's syndrome.

A survey of occupational blood contact and HIV infection among traditional birth attendants in Rwanda.

OBJECTIVE: To investigate the risk of occupationally acquired HIV infection among traditional birth attendants (TBA) in Rwanda, Africa. DESIGN AND METHODS: A serosurvey was conducted among 219 TBA practicing in a rural but densely populated area in southern Rwanda. Each TBA was interviewed about sociodemographic information, work-related habits and practices, and presence of nonoccupational risk factors for HIV infection. The frequency of skin exposure to HIV-infected blood was estimated for each TBA from HIV seroprevalence data collected previously from pregnant women stratified by the geographic zones in which the TBA practiced. RESULTS: Four TBA (1.8%) tested HIV-1-antibody-positive; all four had reported nonoccupational risk factors for HIV infection. We estimated that the 215 HIV-negative TBA had 2234 potentially infectious blood-skin contacts out of a total of approximately 35,000 deliveries assisted in the past 5 years. However, we found no evidence of HIV infection caused by occupational blood contact (none out of 2234; upper limit of the 95% confidence interval because of one potentially infectious blood-skin contact = 0.2%). CONCLUSION: Although these findings may not be universal to all TBA in Africa, the risk of occupationally acquired HIV infection among TBA appears small. The high frequency of blood-skin contact among TBA in Rwanda highlights the need to include infection control precautions in the training of TBA.

PIP: Samples of blood from 219 traditional birth attendants (TBA) practicing in a rural, densely populated area in southern Rwanda were tested for the presence of antibody against HIV-1 in an investigation of the risk for acquiring HIV infection occupationally. The TBAs were interviewed for sociodemographic data, on work-related habits and practices, and about nonoccupational risk factors for HIV infection. The researchers also estimated the frequency of skin exposure to HIV-infected blood for each TBA from HIV seroprevalence data collected previously from pregnant women stratified by the geographic zones in which each TBA practiced. Four TBAs tested seropositive for HIV-1 antibody; all had reported nonoccupational risk factors for infection. It was also estimated that the 215 HIV-negative TBAs had 2234 potentially infectious blood-skin contacts out of a total of approximately 35,000 deliveries assisted over the previous past five years. No evidence was therefore found of HIV infection caused by occupational blood contact and the risk of occupationally acquired HIV infection among TBAs seems small. The high frequency of blood-skin contact among TBAs in Rwanda, however, highlights the need to include infection control precautions in the training of TBAs.

Two quick estimates of the HIV prevalence in homosexual men in Los Angeles, New York and San Francisco. The Multicenter AIDS Cohort Study.

Two rough methods are given to estimate the combined HIV prevalence in Los Angeles, New York and San Francisco in homosexual men. Both methods are related to the back calculation technique, and use AIDS surveillance data and information obtained from the Multicenter AIDS Cohort Study. Both methods suggest that the combined HIV prevalence is approximately 100,000, with a possible range of 80,000-140,000.

HIV-1 and pregnant women: associated factors, prevalence, estimate of incidence and role in fetal wastage in central Africa.

The major goals of this study were to measure the current prevalence and estimate the annual incidence of HIV-1 infection in young pregnant women from urban Malawi, to identify factors that were associated with HIV-1 infection, and to examine adverse pregnancy outcomes. Four hundred and sixty-one consecutive pregnant women were studied when they presented for prenatal care. The overall seroprevalence for HIV-1 infection in these urban populations was 17.6% (81 out of 461) during early 1989. Based on previous seroprevalence in similar unselected pregnant women, the estimated annual incidence of HIV-1 seroconversion in urban pregnant women ranged from 3 to 4% per annum between 1985 and 1987 and from 7 to 13% between 1987 and 1989. HIV-1 infection was significantly associated with reactive syphilis serology. Reported history of sexually transmitted disease was also correlated with HIV-1 infection but was not statistically significant. Other variables, such as history of transfusion, history of tuberculosis, parity or occupation were not associated with HIV-1 infection. History of spontaneous abortion was significantly associated with reactive syphilis serology, HIV-1 infection and history of sexually transmitted disease. In logistic regression analysis, HIV-1 infection remained the only significant variable that was correlated with spontaneous abortion. This study suggests that HIV-1 infection may play a role in fetal wastage.

Detection of HIV-1 proviral DNA in sperm from HIV-1-infected men.

OBJECTIVE: Sexual transmission is a major mode of the spread of HIV-1, although the cellular and molecular mechanisms are poorly defined. In this study, we sought to assess the cellular reservoirs of HIV-1 proviral DNA in the semen of HIV-1-infected men. DESIGN AND METHODS: An in situ polymerase chain reaction (IS-PCR), which amplifies specific genes within intact cells, was used to evaluate levels of HIV-1 provirus in seminal cells from HIV-1-infected men in various stages of clinical disease. RESULTS: Initial studies demonstrated HIV-1 provirus in relatively low numbers (1:100 to 1:6000) of both the seminal mononuclear cells and sperm from certain HIV-1-infected men. To extend these findings, 94 seminal samples from HIV-1-infected men were evaluated. HIV-1 proviral DNA was detected in seminal cells of a significant percentage of HIV-1-infected men (45%) at all stages of clinical immunodeficiency. Both seminal mononuclear cells and sperm (35 and 33% of samples studied, respectively) harbored HIV-1 proviral sequences. HIV-1-harboring sperm are shown to stain positively for HIV-1 in the mid-pieces of these cells, with rarer staining of the sperm heads. CONCLUSIONS: HIV-1 proviral DNA can be demonstrated by IS-PCR in seminal mononuclear cells and sperm from certain HIV-1-infected men. The role played by proviral DNA in these cells in the sexual transmission of this retroviral agent will require further study.

Incident HIV-1 infection in a cohort of young women in Butare, Rwanda.

OBJECTIVE: To determine the incidence of HIV-1 infection and associated risk factors among young, seronegative, and sexually active women in a mixed rural and urban population in southern Rwanda. DESIGN: A prospective cohort study. METHODS: Between October 1991 and April 1993, we completed a 2-year follow-up survey among HIV-1-seronegative women aged < or = 30 years at the time of their initial HIV-1 screening during pregnancy. All women aged < or = 25 years and a randomly selected sample of 26-30-year olds were invited to participate from five prenatal clinics in the Butare region. The interview focused on potential risk factors for HIV-1 acquisition during the 2-year interval between blood collection. RESULTS: Out of 1524 women selected, 1150 (75%) participated in the follow-up survey. The 2-year incidence of HIV-1 infection was 2.7% [95% confidence interval (CI), 1.8-3.9]. Teenage women were at the highest risk (incidence, 10.5%; 95% CI, 5.2-19.4), with incidence leveling off with increasing age (P < 0.001). Women who began sexual activity recently were also at higher risk; the lowest risk category consisted of women aged 26-30 years with 5 or more years of sexual experience. The more urban the geographic residence of the woman, the more likely she was to have acquired HIV-1 infection (P < 0.001). In the urban and peri-urban zones, the poorest women were at significantly higher risk of incident HIV-1 infection than women reporting higher household income. In a multivariate analysis, young maternal age, marital status (being single, divorced or widowed), multiple sexual partners, and a history of sexually transmitted diseases remained strongly associated with incident HIV-1 infection. Geographic residence, hormonal contraception, and receipt of injections were no longer significantly associated with incident HIV-1 infection when these other factors were accounted for simultaneously. CONCLUSION: Among young Rwandan women, the early years of sexual activity are particularly dangerous for acquisition of HIV-1 infection. Interventions should focus on young teenagers before they become sexually active.

Association between serum vitamin A and E levels and HIV-1 disease progression.

OBJECTIVE: To examine the associations between serum vitamin A and E levels and risk of progression to three key outcomes in HIV-1 infection: first AIDS diagnosis, CD4+ cell decline to < 200 cells x 10(6)/l, and mortality. DESIGN: Non-concurrent prospective study. METHODS: Serum levels of vitamins A and E were measured at the enrollment visit of 311 HIV-seroprevalent homo-/bisexual men participating in the Baltimore/ Washington DC site of the Multicenter AIDS Cohort Study. Cox proportional hazards models were used to estimate the relative hazard of progression to each outcome over the subsequent 9 years, adjusting for several independent covariates. RESULTS: Men in the highest quartile of serum vitamin E levels (> or = 23.5 mumol/l) showed a 34% decrease in risk of progression to AIDS compared with those in the lowest quartile [relative hazard (RH), 0.66; 95% confidence interval (CI), 0.41-1.06)]. This effect was statistically significant when comparing the highest quartile of serum vitamin E to the remainder of the cohort (RH, 0.67; 95% CI, 0.45-0.98). Associations between serum vitamin A levels and risk of progression to AIDS were less clear, but vitamin A levels were uniformly in the normal to high range (median = 2.44 mumol/l). Similar trends were observed for each vitamin with mortality as the outcome, but neither vitamin was associated with CD4+ cell decline to < 200 cells x 10(6)/l. Men who reported current use of multivitamin or single vitamin E supplements had significantly higher serum tocopherol levels than those who were not taking supplements (P = 0.0001). Serum retinol levels were unrelated to intake of multivitamin or single vitamin A supplements. CONCLUSIONS: These data suggest that high serum levels of vitamin E may be associated with slower HIV-1 disease progression, but no relationship was observed between retinol levels and disease progression in this vitamin A-replete population.

Multiple sexual partners and mother-to-child transmission of HIV-1.

OBJECTIVE: To investigate risk factors for mother-to-child transmission of HIV-1, particularly sexual behavior before and during pregnancy. DESIGN AND METHODS: This study is part of a prospective cohort study in Butare, Rwanda, of 318 HIV-1-seropositive and 309 HIV-1-seronegative women enrolled during pregnancy and followed for a mean duration of 21 months (range, 8-34 months). Clinical follow-up of the mother-infant pairs was performed at 6-week intervals during the first year of life and at 4-month intervals thereafter. Detailed sexual history interviews were conducted during pregnancy and at the first postnatal visit. RESULTS: Of 184 singleton infants born to HIV-1-infected mothers who survived the neonatal period, 32 (17%) children were classified as HIV-1-infected, 130 (71%) as not infected, and 22 (12%) died with indeterminate HIV-1 infection status. The vertical transmission rate was estimated to be between 20 and 29%. Unprotected sexual intercourse with increased number of partners during the past 5 years was strongly associated with mother-to-child transmission (P < 0.001), even after adjustment for maternal CD4/CD8 ratio, parity, history of sexually transmitted diseases, and evidence of genital infection during pregnancy. In a multivariate analysis, excluding children with indeterminate HIV-1 status, odds ratios for vertical transmission were 2.6 [95% confidence interval (CI), 1.0-6.9] for maternal CD4/CD8 ratio < 0.5 and 3.6 (95% CI, 1.1-11.8) for more than three sexual partners versus a single partner. Women with more than one sexual partner during the first trimester of pregnancy were at particularly high risk of transmitting the virus. CONCLUSION: Unprotected sexual intercourse with multiple partners before and during pregnancy in a population with high HIV-1 seroprevalence may well increase the likelihood of HIV-1 transmission from an infected mother to her child.

Solar ultraviolet radiation exposure does not appear to exacerbate HIV infection in homosexual men. The Multicenter AIDS Cohort Study.

OBJECTIVE: To determine the effect of sun exposure on HIV progression. DESIGN: Cross-sectional survey nested within a longitudinal cohort study. SETTING: The Multicenter AIDS Cohort Study. PARTICIPANTS: A total of 1155 white HIV-seronegative and 496 white HIV-seropositive homosexual men, of whom 142 seroconverted during the study. MAIN OUTCOME MEASURES: T-helper lymphocyte decline and AIDS. RESULTS: No positive correlation was found between the development of AIDS or loss of T-helper lymphocytes and (i) phenotypic characteristics associated with enhanced ultraviolet radiation (UVR) sensitivity (hair or eye color, skin type), or (ii) reported UVR exposure (sun lamp/tanning bed use, frequency of beach vacations, sunscreen use), or (iii) composite score of UVR sensitivity and exposure history. The composite scores and individual measures of risk were not correlated with rate of T-helper lymphocyte decline (slope) based upon rank correlation (correlation coefficient, 0.04; P = 0.32). In fact, individuals purposefully seeking the sun had slower T-helper lymphocyte declines. Sensitivity to UVR was also not significantly associated with AIDS [odds ratio (OR), 1.11 per unit of higher composite score; 95% confidence interval (CI), 0.66-1.88; P = 0.63]. Among individuals who were HIV-infected at baseline, those who have been purposely seeking sun exposure were less likely to have AIDS (OR, 0.67; 95% CI, 0.39-1.11; P = 0.12). CONCLUSIONS: These data suggest that phenotypic characteristics of high UVR sensitivity and exposure are not highly correlated with decline in T-helper lymphocyte count or with progression to AIDS.