Acquired immunodeficiency syndrome and extrapulmonary tuberculosis in the United States.

Of 48,712 acquired immunodeficiency syndrome (AIDS) cases reported to the Centers for Disease Control from October 1987 through March 1989, 1239 (2.5%) were diagnosed with extrapulmonary tuberculosis. Extrapulmonary tuberculosis was diagnosed in 1013 (2.3%) of the US-born persons with AIDS, compared with 26 (8%) of the Mexican-born, 82 (13%) of the Haitian-born, and 4 (1%) of the Cuban-born. Patients with AIDS with and without extrapulmonary tuberculosis were similar in age, except that extrapulmonary tuberculosis was relatively rare in patients with AIDS under the age 10. Compared with white homosexual/bisexual men, black race (odds ratio, 2.7), intravenous drug use (odds ratio, 2.0), heterosexual AIDS transmission category (odds ratio, 1.9), and Hispanic ethnicity (odds ratio, 1.6) were independently associated with extrapulmonary tuberculosis. In 1988, extrapulmonary tuberculosis in persons known to be human immunodeficiency virus seropositive represented 21% of national extrapulmonary tuberculosis morbidity.

Mortality in HIV-1-seropositive women, their spouses and their newly born children during 36 months of follow-up in Kinshasa, Zaïre.

OBJECTIVE: To calculate 3-year mortality rates in HIV-1-seropositive and HIV-1-seronegative mothers, their newborn children and the fathers of these children. DESIGN: Longitudinal cohort study of HIV-1-seropositive, age and parity-matched HIV-1-seronegative pregnant women, their newborn babies and the fathers of these children. SETTING: Obstetric ward and follow-up clinic at a large municipal hospital in Kinshasa, Zaïre. PARTICIPANTS: A total of 335 newborn children and their 327 HIV-1-seropositive mothers and 341 newborn children and their 337 HIV-1-seronegative mothers and the fathers of these children. MAIN OUTCOME MEASURES: Rates of vertical HIV-1 transmission and maternal, paternal and early childhood mortality. RESULTS: The lower and upper bounds of vertical transmission were 27 and 50%, respectively. The 3-year mortality rate was 44% in children with vertically acquired HIV-1 infection, 25% in children with HIV-1-seropositive mothers and indeterminant HIV-1 infection status, and 6% in uninfected children with HIV-1-seronegative mothers. HIV-1-seropositive women who transmitted HIV-1 infection to their most recently born child had lost a greater number of previously born children (mean, 1.5 versus 0.5; P < 0.05), were more likely to have had AIDS at delivery (25 versus 12%; P < 0.01) and were more likely to die during follow-up (22 versus 9%; P < 0.01) than HIV-1-seropositive women who did not transmit HIV-1 infection to their newborn child. Twenty-five out of 239 (10.4%) fathers of children with HIV-1-seropositive mothers, not lost to follow-up, died compared with three out of 310 (1%) fathers of children with HIV-1-seronegative mothers (P < 0.01). CONCLUSIONS: Families in Kinshasa, Zaïre, in which the mother was HIV-1-seropositive experienced a five to 10-fold higher maternal, paternal and early childhood mortality rate than families in which the mother was HIV-1-seronegative.

AIDS orphans in Kinshasa, Zaïre: incidence and socioeconomic consequences.

OBJECTIVE: To determine the incidence, morbidity, mortality, and socioeconomic consequences of becoming an AIDS orphan (a child with an HIV-1-seropositive mother who has died) in Kinshasa, Zaïre. DESIGN: A longitudinal cohort study was undertaken between 1986 and 1990. Within this cohort, a nested case-control study of AIDS orphans was performed. AIDS orphan cases were children with an HIV-1-seropositive mother who had died. Two groups of control children were identified. The first group of control children were age-matched children with HIV-1-seropositive mothers who were alive at the time of death of the AIDS orphan case mother. The second group of control children were children with HIV-1-seronegative mothers who were also alive at the time of death of the AIDS orphan case mother. SETTING: Obstetric ward and follow-up clinic at two large municipal hospitals in Kinshasa, Zaïre. PARTICIPANTS: A total of 466 HIV-1-seropositive women, their children, and the fathers of these children; 606 HIV-1-seronegative women, their children, and the fathers of these children. MAIN OUTCOME MEASURES: AIDS orphan incidence, HIV-1 vertical transmission rate, morbidity, mortality and socioeconomic indicators of the consequences of becoming an AIDS orphan. RESULTS: The AIDS orphan incidence rate was 8.2 per 100 HIV-1-seropositive women-years of follow-up. Vertical transmission of HIV-1 was higher in AIDS orphan cases (41%) than in control children with HIV-1-seropositive mothers (26%; P < 0.05). Among children without vertically acquired HIV-1 infection, morbidity rates and indices of social and economic well-being were similar in AIDS orphans and control children. Five out of 26 (19%) AIDS orphan cases died during follow-up, compared with three out of 52 (6%) control children (P < 0.05). CONCLUSION: During a 3-year follow-up period, children with HIV-1-seropositive mothers had a considerable risk of becoming an AIDS orphan. However, the presence of a concerned extended family appeared to minimize any adverse health and socioeconomic effects experienced by orphan children.

Accurate detection of maternal antibodies to HIV in newborn whole blood dried on filter paper.

OBJECTIVE: The testing of neonatal blood specimens dried on filter paper for maternal HIV antibodies, using an enzyme immunoassay (EIA) with confirmation of repeatedly reactive specimens by immunoblot (IB), was first described in 1987. It has been used to conduct large, unlinked, anonymous HIV seroprevalence surveys for surveillance of HIV in child-bearing women in several countries. We directly assessed the sensitivity and specificity of this combination of tests to detect maternal HIV antibodies. SETTING: Serum samples obtained from mothers delivering at a major hospital in Kinshasa, Zaire were screened for HIV antibody using the rapid assay HIVCHEK. DESIGN: Plasma from HIVCHEK-positive women and age-matched negative controls were tested by enzyme-linked immunosorbent assay (ELISA); repeatedly reactive specimens were confirmed by Western blot (WB). Two days after delivery, whole blood was obtained from each newborn by heel-stick, dried on filter paper, and tested by EIA. Repeatedly reactive specimens were confirmed by IB. MAIN OUTCOME MEASURE: The serologic status of neonatal filter-paper specimens was compared with that of corresponding maternal plasma. RESULTS: The testing of neonatal filter-paper specimens using EIA, with confirmatory testing of repeatedly reactive specimens using IB, was 100.0% sensitive [of the 192 ELISA-positive and WB-positive maternal plasma specimens, 192 of the corresponding newborn filter-paper specimens were EIA-positive and IB-positive; 95% confidence interval (CI), 98.1-100]. The detection of maternal HIV antibodies was 99.6% specific using this combination of tests (of the 281 ELISA-negative or ELISA-positive but WB-negative maternal plasma samples, 280 of the corresponding newborn filter-paper specimens were EIA-negative or EIA-positive but IB-negative; 95% CI, 98.0-100). CONCLUSIONS: Maternal HIV antibodies can be detected accurately by testing neonatal blood dried on filter paper, using EIA with confirmation of repeatedly reactive specimens by IB. This approach can facilitate the determination of HIV seroprevalence in child-bearing women in countries with neonatal screening programs, or where serum or plasma is difficult to obtain.

PIP: Neonatal blood specimens dried on filter paper have been tested for maternal HIV antibodies in large, unlinked, anonymous HIV seroprevalence surveys toward the surveillance of HIV in child-bearing women in several countries. This study assesses the sensitivity and specificity of this combination of tests. The standard approach involves first testing the sample via an enzyme immunoassay (EIA), then confirming repeatedly reactive specimens through immunoblot (IB). To test this methodology, serum samples were obtained from mothers delivering at a major hospital in Kinshasa, Zaire, and screened with rapid assay HIVCHEK for antibody to HIV. Plasma from HIVCHEK-positive women and age-matched negative controls were then subjected to ELISA, with repeatedly reactive samples confirmed with Western blot. Whole blood was later obtained by heel-stick from each newborn 2 days after delivery, dried on filter paper, and tested by EIA and IB for confirmation. The serologic statuses of neonatal filter-paper specimens were then compared with those of corresponding maternal plasma. 100% sensitivity was achieved by testing neonatal filter-paper specimens with EIA and confirming with IB. The combination of tests also proved 99.6% specific for detecting maternal HIV antibodies; both results are at 95% confidence intervals. These results demonstrate that maternal HIV antibodies can therefore be detected accurately by testing neonatal blood dried on filter paper, using EIA, then confirming repeatedly reactive specimens via IB. This approach may help determine HIV seroprevalence in childbearing women in countries with neonatal screening programs or where serum or plasma is difficult to obtain.

High HIV-1 incidence in young women masked by stable overall seroprevalence among childbearing women in Kinshasa, Zaïre: estimating incidence from serial seroprevalence data.

OBJECTIVE: To describe the dynamics of the HIV-1 epidemic in childbearing women in Kinshasa, Zaïre, by estimating incidence from serial seroprevalence studies. METHODS: In 1986 and 1989, 5937 and 4623 pregnant women, respectively, were screened for HIV-1 in Kinshasa. We estimated age-specific incidence from two seroprevalence surveys by using a birth-year cohort analysis and adjusting for differences in mortality and fertility between HIV-1-infected and uninfected women. Mortality and fertility data were measured in a cohort of women recruited from the survey in 1986 and followed until 1989. RESULTS: While the overall HIV-1 seroprevalence changed little (5.8% in 1986 and 6.5% in 1989; P = 0.17), the prevalence increased in birth-year cohorts of women under 25 years of age in 1989 from 3.2 to 6.2% (P < 0.001), but decreased for women above 25 years of age from 6.9 to 6.7% (P = 0.7). In addition, new HIV infections between 1986 and 1989 were balanced by a higher mortality and lower fertility observed in HIV-infected women. After adjusting for these effects, we estimated an overall 3-year cumulative HIV-1 incidence of 2.8 per 100 uninfected women [95% confidence interval (CI), 1.4-4.2]. The highest incidence, 5.7 per 100 (95% CI, 3.5-8.0), was in women aged 20-24 years in 1989. CONCLUSION: Despite an overall relatively stable HIV-1 prevalence in childbearing women in Kinshasa between 1986 and 1989, approximately 40% of all HIV-1 infections detected in the 1989 survey occurred between 1986 and 1989, and 60% occurred in women under 25 years of age in 1989.

Impact of HIV counseling and testing among child-bearing women in Kinshasa, Zaïre.

OBJECTIVE: To determine the impact of HIV counseling and testing among child-bearing women. STUDY SETTING: Mama Yemo Hospital in Kinshasa, Zaïre. PARTICIPANTS AND INTERVENTIONS: After informed consent, 187 HIV-seropositive and 177 HIV-seronegative child-bearing women received pre- and post-test counseling for HIV infection. MAIN OUTCOME MEASURES: Participant knowledge of HIV/AIDS and plans for notifying partners of serologic status and contraceptive use at the time of counseling, and actual partner involvement and contraception use 12 months later. RESULTS: During pre-test counseling, participant knowledge of HIV infection was high, although 30% of women were unaware of perinatal HIV transmission, and 50% did not know that HIV infection could be asymptomatic. At post-test counseling, 70% of mothers (47% of HIV-seropositive, 94% of HIV-seronegative) intended to notify their partners and have joint counseling and testing, although after 12 months, only 2.2% of all women and 7.9% of those who desired assistance to notify their partner returned with their partners for joint counseling and testing. Similarly, 86% planned to use birth control (61% condoms), with HIV-seropositive women more likely to prefer condoms than HIV-seronegative women (71 versus 53%; P < 0.001). After 12-months, however, only 20% of HIV-seropositive women reported condom use, and the frequency of pregnancy in both groups was approximately equal. CONCLUSIONS: HIV counseling and testing led to higher rates of contraceptive and condom use, although the actual level was lower than the intended use. To further reduce the risk of heterosexual and perinatal HIV transmission in families with an HIV-infected woman, counseling should also include their male partners.

Preparation for phase III HIV vaccine efficacy trials: methods for the determination of HIV incidence.

OBJECTIVE: Accurate estimates of HIV incidence that reflect the effect of non-vaccine interventions (education, counselling, condom promotion, and possibly sexually transmitted disease treatment) and that may be provided in a Phase III vaccine efficacy trial, are needed so that vaccine trial population sample sizes can be accurately determined. In order to avoid delays in the implementation of efficacy trials, well characterized cohorts must also be developed and available to participate in such trials. We reviewed the potential study populations, the epidemiologic methods for the determination of HIV incidence (using open cohort, closed cohort, and seroprevalence data methods), and the need for the development of population cohorts in preparation for Phase III HIV vaccine efficacy trials. SETTING: Phase III trials in developed and developing countries. METHODS: Comparison of open and closed cohorts and those using seroprevalence data to estimate HIV incidence. RESULTS: Open and closed cohorts each have disadvantages and advantages. However, the open cohort may be more suitable for determining estimates of HIV incidence that reflect non-vaccine interventions and for the development of a well characterized cohort available to participate in efficacy trials. CONCLUSION: Careful preparation of research infrastructures and population cohorts will help ensure the successful conduct of scientifically and ethically sound HIV vaccine efficacy trials in the future.

Cross-reactivity on western blots in HIV-1 and HIV-2 infections.

To examine cross-reactivity of antibodies to heterologous antigens, on HIV-1 and HIV-2 Western blots, we tested sera from 1362 consecutive tuberculosis (TB) patients and 2127 consecutive blood donors. Specimens positive on enzyme-linked immunosorbent assay (ELISA) for HIV-1 or HIV-2 were further characterized by synthetic peptide-based tests, and tested by HIV-1- and HIV-2-specific Western blots. Dual serologic reactivity on synthetic peptide tests was proportionately more frequent in HIV-positive TB patients than in blood donors, and HIV-2 reactivity less frequent. Positive HIV-1 Western blots were seen in 73-83% of specimens specifically characterized as positive for HIV-2 on synthetic peptide tests. Cross-reactivity to HIV-2 Western blots by HIV-1-positive specimens was significantly more frequent in TB patients (35%) than in asymptomatic donors (9%; P less than 0.001). Using recently recommended criteria for HIV-2 Western blot interpretation (presence of two env bands) reduced the overall proportion of HIV-1-positive specimens having a positive HIV-2 Western blot from 27.5 to 16.4%, with [corrected] minimal effect on sensitivity in the diagnosis of HIV-2 reactivity on specimens positive on synthetic peptide tests.

Evidence from Zaire that breast-feeding by HIV-1-seropositive mothers is not a major route for perinatal HIV-1 transmission but does decrease morbidity.

Breast-feeding as a route of HIV-1 transmission during infancy but also as a protective measure against early childhood morbidity has been investigated prospectively in children born to HIV-1-seropositive mothers and control children born to age- and parity-matched HIV-1-seronegative women. The mothers of all study children had been enrolled antenatally at a maternity hospital in Kinshasa, Zaire, which served a relatively affluent group of women who sometimes chose not to breast-feed their infants. In 106 children born to HIV-1-seropositive women, the rate of HIV-1 transmission was 21% in 28 infants exclusively breast-fed, 19% in 68 infants both breast- and bottle-fed and 0% in 10 infants who were bottle-fed only (P = 0.35). In contrast, non-HIV-1-infected children of both HIV-1-seropositive and HIV-1-seronegative mothers who were exclusively breast-fed compared with uninfected children who were not exclusively breast-fed had significantly lower incidence rates of acute diarrhea, fever and lower respiratory tract infection. The lack of a dose-response effect between breast-feeding and perinatal HIV-1 transmission and the presence of a protective effect of breast-feeding against common causes of early childhood morbidity and mortality support the current World Health Organization recommendation that breast-feeding should continue to be promoted in all developing countries, including those with high HIV-1 prevalence rates in women of childbearing age.

Fertility rates in 238 HIV-1-seropositive women in Zaire followed for 3 years post-partum.

Birth-control use and fertility rates were prospectively determined in 238 HIV-1-seropositive and 315 HIV-1-seronegative women in Kinshasa, Zaire, during the 36-month period following the delivery of their last live-born child. No women delivered children during the first follow-up year. Birth-control utilization rates (percentage use during total observation time) and fertility rates (annual number of live births per 1000 women of child-bearing age) in the second year of follow-up were 19% (107.4 per 1000) for HIV-1-seropositive women and 16% (144.7 per 1000) for HIV-1-seronegative women. In the third year of follow-up these rates were 26 (271.0 per 1000) and 16% (38.6 per 1000) for HIV-1-seropositive and HIV-1-seronegative women, respectively (P less than 0.05 for the difference in birth-control utilization and fertility rates between seropositive and seronegative women in the third year of follow-up). Seven (2.9%) of the 238 HIV-1-seropositive women initially included in the study brought their sex partners in for HIV-1 testing; three (43%) of these men were found to be HIV-1-seropositive. New HIV-1 infection did not have a dramatic effect on the fertility of seropositive women. The nearly uniform unwillingness of HIV-1-seropositive women to inform husbands or sexual partners of their HIV-1 serostatus accounted in large part for the disappointingly high fertility rates in seropositive women who had been provided with a comprehensive program of HIV counseling and birth control. Counseling services for seropositive women of child-bearing age which do not also include these women's sexual partners are unlikely to have an important impact on their high fertility rates.

Evidence of marked sexual behavior change associated with low HIV-1 seroconversion in 149 married couples with discordant HIV-1 serostatus: experience at an HIV counselling center in Zaire.

To determine the effect of an HIV-1 counselling program on 149 married Zairian couples with discordant HIV-1 serology, the rates of HIV-1 seroconversion and reported condom utilization have been observed during 382.4 person-years of follow-up (minimum follow-up time per couple of 6 months). Before determination of HIV-1 serostatus and counselling, less than 5% of these couples had ever used a condom. One month after notification of HIV-1 serostatus and counselling, 70.7% of couples reported using condoms during all episodes of sexual intercourse. At 18 months follow-up, 77.4% of the 140 couples still being followed reported continued use of condoms during all episodes of sexual intercourse. At the time of notification of HIV-1 serostatus, 18 couples experienced acute psychological distress. Home-based counselling by trained nurses resolved these difficulties in all but three couples who subsequently divorced. Intensive counselling following notification of HIV-1 serostatus led to low rates of HIV-1 seroconversion (3.1% per 100 person-years of observation) in Zairian married couples with discordant HIV-1 serostatus who voluntarily attended an HIV counselling center.

HIV infection and breast-feeding: policy implications through a decision analysis model.

OBJECTIVES: (1) To develop a comprehensive decision analysis model to compare mortality associated with HIV transmission from breast-feeding with the mortality from not breast-feeding in different populations and (2) to perform sensitivity analyses to illustrate critical boundaries for guiding research and policy. METHODS: Using a decision tree, mortality rates were estimated for all children, children born to mothers infected during pregnancy, and children born to mothers who were uninfected at delivery. Given various assumptions about child mortality rates, relative risks of mortality among children who are not breast-fed compared with those who are (R), rates of HIV transmission from breast-feeding, HIV prevalence, and HIV incidence, scenarios were created and sensitivity analysis used to delineate critical boundaries. RESULTS: Our model shows that only in situations where R is approximately < or = 1.5 and HIV incidence/prevalence is high (prevalence > 10%, incidence > 5%) would universal breast-feeding result in equal or higher mortality compared with non-breast-feeding. Among populations in many developing countries, where there is a high relative risk of mortality if breast-feeding is not practiced, if R > 3, overall mortality is almost always lower among children who are breast-fed, even by HIV-infected mothers. In situations where maternal HIV status is known, the decision whether to breast-feed is largely dependent on the magnitude of additional mortality risk if the child is not breast-fed. The model illustrates the importance of distinguishing between population and individual recommendations. CONCLUSIONS: Based on available data, the model supports current World Health Organization and Centers for Disease Control recommendations on HIV infection and breast-feeding. Given the importance of breast-feeding and the global impact of HIV infection, more research is needed, especially to clarify the range of HIV transmission rates from breast-feeding and to expand specific assessments of relative risks for different areas of the world.

PIP: HIV/AIDS specialists have developed and applied 3 different scenarios to a comprehensive decision analysis model to estimate mortality rates for children of mothers infected with HIV during pregnancy and for children of mothers who were not infected with HIV during delivery. Scenario I represents Central Africa where HIV prevalence and incidence are high. Some scenario I assumptions are HIV prevalence in pregnant women of 30% and proportion of initially uninfected women who become infected after delivery during lactation (d) of 6%. Scenario II is a population where HIV epidemic is rather recent (e.g., some parts of Asia). Its assumptions are HIV prevalence of 5%, and s is 2%. Scenario III symbolizes high-risk populations in North America and Western Europe (HIV prevalence and s = 1%). The scenarios also consider child mortality rates and relative risks (RRs) of mortality of breast fed children and those who were not breast fed. Universal breast feeding would effect equal or higher mortality than non-breast feeding, when the RR of mortality is no more than 1.5 and HIV prevalence/incidence is high (high prevalence = 10% and high incidence = 5%). In developing countries, where the RR of mortality is high if children are not breast fed (RR 3), breast fed children have almost always lower child mortality than those who are not breast fed, regardless of HIV infection status. The decision to breast feed when the HIV status is known depends greatly on the degree of an additional mortality risk if an infant is not breast fed. The model substantiates WHO and CDC recommendations: HIV-positive women in the UK and the US should not breast feed, while those in developing countries with high RR of child mortality should breast feed. Additional research would define the range of HIV transmission rates from breast feeding and increase specific assessments of RRs for various parts of the world.

Efficacies of US Food and Drug Administration-licensed HIV-1-screening enzyme immunoassays for detecting antibodies to HIV-2.

To determine the efficacy of enzyme immunoassays (EIAs) for antibodies against HIV-1 in detecting HIV-2-infected blood, we tested 55 HIV-2-positive sera with seven Food and Drug Administration-licensed EIA kits. The percentage detection of HIV-2 sera giving positive reactions with these kits varied between the various manufacturers from 60 to 91%. Observations based on a small number of sera (n = 13), suggest that HIV-2-positive blood collected from apparently healthy people (blood donors, prenatal clinics) are detected with a greater frequency (means = 89%) than blood from AIDS patients or patients (n = 32) hospitalized with other infectious diseases (means = 72%). Based on these results and the low incidence of HIV-2 infection observed in the USA, it was concluded that screening with HIV-2-specific tests would not significantly increase the number of HIV-2-positive people detected by current screening programs. However, due to the poor sensitivity of certain HIV-1 assays for HIV-2 antibodies, HIV-2 sera without cross-reacting antibodies will escape detection. Surveillance for HIV-2 might then be improved by the availability of HIV-1 and HIV-2 combination assays.

A comparison of HIV-1 and HIV-2 infections in hospitalized patients in Abidjan, Côte d'Ivoire.

In late 1988, a cross-sectional study of 1715 adult medical patients hospitalized in Abidjan, Côte d'Ivoire, west Africa, showed an overall prevalence of HIV infection of 46% in men and 28% in women. On the basis of specific testing by whole virus enzyme-linked immunosorbent assay (ELISA), Western blot and synthetic peptide ELISA, HIV-1 infection was found in 25%, HIV-2 infection in 4%, and reactivity to both viruses in 11% of male and female patients combined. People infected with HIV-2, as well as those who were reactive to both HIV-1 and HIV-2, had a frequency of AIDS-associated symptoms and signs similar to that in HIV-1-infected patients, and significantly greater than that in seronegative patients. The significance of dual reactivity, and the natural history and disease spectrum of HIV-2 infection, require further study. Synthetic peptide ELISA is valuable for specific serodiagnosis of HIV-1 and HIV-2 infections. Advanced HIV-2 infection in hospitalized patients in Abidjan is associated with the same symptoms and signs as HIV-1 infection.

Continued high HIV-1 incidence in a vaccine trial preparatory cohort of injection drug users in Bangkok, Thailand.

BACKGROUND: A large epidemic of HIV-1 subtype B began among injection drug users (IDUs) in Bangkok in 1988. Despite ongoing prevention efforts, HIV-1 prevalence among IDUs remained at 30-50% through the 1990s. OBJECTIVES: To measure the incidence of HIV-1 infection and related risk factors to guide prevention efforts and to evaluate the feasibility of conducting an HIV vaccine efficacy trial. DESIGN AND METHODS: A prospective cohort study in which IDUs attending methadone treatment programs in Bangkok were screened during 1995-1996 for enrollment into the study. IDUs found to be HIV-seronegative on two occasions were offered enrollment with follow-up visits every 4 months. On each visit participants were evaluated with a questionnaire and serologic testing. RESULTS: A total of 1209 HIV-negative IDUs were enrolled. Through the end of 1998, the overall HIV-1 incidence rate was 5.8 (95% confidence interval, 4.8-6.8) per 100 person-years of follow-up. HIV-1 subtypes E and B accounted for 79 and 21% of infections, respectively. On multivariate analysis, HIV-1 seroconversion was primarily associated with the frequency of heroin injection, the sharing of injection equipment, and incarceration, especially with drug injection. Sexual behavior was not associated with increased risk for HIV-1. Risk factors for infection with HIV-1 subtypes E and B were similar. CONCLUSION: HIV-1 transmission risk remains high among Bangkok IDUs despite methadone treatment and other current prevention strategies. There is an urgent need to address this ongoing epidemic, especially in jails and prisons. This study led to the initiation in 1999 of a phase III HIV-1 vaccine efficacy trial in this population.

Elevated concentrations of plasma omega-3 polyunsaturated fatty acids among Alaskan Eskimos.

Eskimos living in rural southwestern Alaska depend on fish and marine mammals as major sources of subsistence food. Fatty acid concentrations in 80 Yupik Eskimos living in either a coastal or river village of southwestern Alaska were compared with those of non-Native control subjects. Concentrations of total plasma omega-3 fatty acids, eicosapentaenoic acid (20:5 omega-3), and docosahexaenoic acid (22:6 omega-3) were 4.3, 13, and 6.8 times higher, respectively, in Native participants than in non-Native control subjects. Concentrations of these fatty acids were higher in coastal-village than in river-village participants; concentrations paralleled consumption of marine mammal oil and marine fish. The ratios of eicosapentaenoic to arachidonic acid for adult coastal- and river-village participants were 1.16 and 0.70, respectively, 14 and 9 times those of non-Native adults, respectively. There was no increase in the mean bleeding times of Native participants of either village.

Lack of association between anti-V3 loop antibody and perinatal HIV-1 transmission in Kinshasa, Zaire, despite use of assays based on local HIV-1 strains.

Maternal antibodies against the V3 loop principal neutralizing domain (PND) have been reported to protect against perinatal HIV-1 transmission. To study this association in an African city with a long-standing HIV epidemic and no established "consensus sequence" for the V3 loop region of gp120, we determined the DNA sequence for the V3 region of HIV-1 from 13 HIV-1-infected residents of Kinshasa, Zaire, and developed peptide enzyme immunoassays (EIAs) reflecting the V3 loop PND for those HIV-1 strains. Using the most broadly reactive locally derived V3 loop peptide in a limited-antigen EIA, there was no significant difference in the perinatal HIV-1 transmission risk between 64 women with anti-V3 loop antibody (transmission risk, 30%) and 104 women without anti-V3 loop antibody (transmission risk, 25%; p = 0.5); this finding was unchanged after we controlled for maternal AIDS and low birth weight. Although we used assays for V3 loop antibody based on local HIV-1 strains and evaluated a large number of mother-child pairs, we found no evidence that maternal anti-V3 loop PND antibody protects against perinatal HIV-1 transmission.

Risk factors for HIV-2 infection in Guinea-Bissau.

To define the epidemiology of HIV-2 infection, we conducted a case-control study among hospitalized patients at an acute care hospital in Bissau, Guinea-Bissau, a country with endemic HIV-2 infection. Among 128 patients with various diagnoses, 23 (18%) were positive for HIV-2 by ELISA and Western blot. One of these patients was serologically reactive for HIV-1 also, but PCR and viral culture revealed the presence of HIV-2 only. To study risk factors, behaviors, and AIDS knowledge related to the acquisition of HIV infection, 22 HIV-2-seropositive and 21 seronegative hospitalized patients were given a physical examination and administered a questionnaire. Among women, transfusion was associated with HIV-2 infection (OR = 14.4, p = 0.02); among men, sex with a prostitute was the principal risk factor (OR = undefined, p = 0.02). Although 79% of HIV-infected patients and controls had heard of AIDS, only 17% of all study participants and 50% of males reporting sex with prostitutes had used condoms in the previous year. These data suggest that the risk factors for HIV-2 infection are similar to those for HIV-1 and support previous studies showing that HIV-2 is the predominant HIV in Guinea-Bissau. Efforts to decrease transmission of HIV-2 should include screening for HIV-2 in blood for transfusion in endemic areas (now done in Bissau) and education about the risk of sexual transmission.

Epidemiology of human immunodeficiency virus infection and acquired immunodeficiency syndrome.

As of December 31, 1988, 82,764 cases of acquired immunodeficiency syndrome (AIDS) and more than 46,000 AIDS-related deaths had been reported in the United States. In 1987, AIDS deaths accounted for 9% of the total mortality among men 25 to 34 years of age. Projections suggest that the impact of human immunodeficiency virus (HIV) infection on morbidity and mortality in young adults and children will continue to increase, with an estimated 50,000 cases projected to be diagnosed in 1989. The mean latency period between infection and diagnosis of AIDS is estimated to be more than seven years, and 78% to 100% of persons infected with HIV are predicted to develop AIDS within 15 years of onset of infection. Rates of seroconversions have been decreasing since 1984 among cohorts of homosexual HIV-seronegative men, and the proportion of AIDS cases among homosexual men is decreasing. In contrast, the proportion of AIDS cases attributed to intravenous drug use is increasing, with 33% of AIDS cases reported in 1988 occurring among intravenous drug users, their sex partners, or children of women who are intravenous drug users or sex partners of intravenous drug users. Worldwide, the differences in the epidemiology of HIV infection and AIDS are primarily due to differences in the proportions of the modes of transmission and in the time in which HIV infection was introduced.

HIV vaccine development and evaluation: realistic expectations.

As of January 1998, more than 85 vaccines for 24 clinical indications are currently licensed in the United States. From the time of discovery of the etiologic agent to the development of a licensed vaccine, many years have usually been required. Although many vaccines have been licensed on the basis of one efficacy trial, multiple vaccine concepts and multiple efficacy trials (both in the United States and internationally) have at times been necessary. Over a relatively short period of time, there has been remarkable progress in human immunodeficiency virus (HIV) vaccine development, with over 34 different HIV candidate vaccines having been tested in phase 1 trials, and three having been tested in phase 2 trials. In spite of our incomplete understanding of HIV pathogenesis and correlates of protection, the first phase 3 efficacy trial has been initiated in the U.S. and tentative plans have been announced for three other phase 3 efficacy trials with the most advanced HIV candidate vaccines to begin in the next 3 years. Like many previous vaccine development efforts, these initial HIV vaccine efficacy trials could be the first of many large-scale efficacy trials in the future, testing various vaccine design concepts among different high-risk populations in both developed and developing countries. The choice of when and how to proceed to phase 3 trials remains a complex decision, but it is likely that only through such trials will further knowledge be gained to advance this important effort and reach our goal of a safe and effective HIV vaccine.