HIV-1 seroconversion in United States Army active duty personnel, 1985-1999.

OBJECTIVE: To monitor HIV-1 infection trends among United States Army personnel, a predominantly young population group, tested between 1985 and 1999 for HIV-1 infection. DESIGN: Demographic correlates of HIV-1 infection were assessed in the cohort via epidemiologic analysis. METHODS: Annual seroconversion incidence rates were calculated per 1000 person-years (PY) of follow-up. Poisson regression was used to assess demographic correlates of HIV-1 seroconversion risk. RESULTS: There were 1275 seroconverters among 2 004 903 active duty Army personnel accounting for 7 700 231 PY of follow-up. The HIV-1 incidence rate (IR) was 0.17/1000 PY [95% confidence interval (CI), 0.16-0.17]. The highest IR was observed in the first year of testing (IR, 0.43/1000 PY; 95% CI, 0.33-0.52). The IR for male and female soldiers was 0.18/1000 PY and 0.08/1000 PY, respectively. HIV-1 incidence declined with age. Significant risk of HIV-1 seroconversion was associated with age [> 30 years old relative risk (RR), 1.51], race (Black RR, 4.61; Hispanic RR, 2.76), gender (male RR, 3.12), marital status (unmarried RR, 2.01) and rank (enlisted RR, 2.50). CONCLUSIONS: HIV-1 seroconversions in the US Army have been low and stable since the early 1990s. Continued HIV-1 incidence surveillance in the US Army provides information on the status of the epidemic in the Army, as well as important corroborative data on HIV-1 infections throughout the US.

Declining prevalence of HIV-1 infection in young Thai men.

OBJECTIVE: To evaluate trends in HIV-1 seroprevalence in Thailand. DESIGN: HIV-1 serosurvey of successive cohorts of young Thai men entering service with the Royal Thai Army (RTA) between November 1989 and November 1994. METHODS: In November 1989, the RTA Medical Department began routine HIV-1-antibody screening of men who were selected by lottery for conscription. Between November 1989 and November 1994, 311,108 young men were screened at induction. Demographic data were collected between November 1991 and May 1993 and again in November 1994. RESULTS: The seroprevalence of HIV-1 among conscripts nationwide increased rapidly from 0.5% in 1989 to 3.5% in 1992 and reached 3.7% in 1993. In 1994, the overall prevalence decreased to 3.0%. The decrease was greatest in the upper North (from 12.4% in 1992 to 7.9% in 1994), where the prevalence has been the highest. However, decreases were observed in men from all regions of residence in the country, from both rural and urban areas, and at all educational levels. CONCLUSIONS: The decline in prevalence suggests declining incidence and that HIV control programs in Thailand are having an impact on the HIV epidemic.

PIP: Since 1989, the Royal Thai Army has screened new conscripts for human immunodeficiency virus (HIV)-1 infection. An analysis of HIV test results for the 311,108 young men entering the Army between November 1989 and November 1994 indicates that the Thailand Government's acquired immunodeficiency syndrome (AIDS) prevention program has had a positive impact on high-risk behaviors. The HIV seroprevalence increased from 0.5% in 1989 to 3.5% in 1992 and 3.7% in 1993, but then fell to 3.0% in 1994. The prevalence in the North--the region with the highest rate--peaked at 7.5% in 1992, then declined to 5.1% in 1994. This pattern of decline was observed in all regions of residence and at all educational levels. The only exception was a slight increase (from 4.1% in 1992 to 5.0% in 1994) in seroprevalence among the 4.2% of conscripts aged 22-29 years. Condom use, less frequent visits to commercial sex workers, and decreasing rates of sexually transmitted diseases are assumed to be the factors contributing to the decline in HIV infection.

Risk factors for prevalent human immunodeficiency virus (HIV) infection in active duty Army men who initially report no identified risk: a case-control study.

A large proportion of human immunodeficiency virus antibody (HIV-Ab) positive male soldiers are considered to be at no identified risk (NIR) because they do not disclose histories of sexual activity with other men, intravenous drug use, blood transfusions, or sexual activity with persons at known high risk for HIV infection. A case-control study involving personal interviews with 26 NIR cases and 74 controls was conducted to determine if lifestyle information that might jeopardize a soldier's military career could be obtained from an Army population and to evaluate risk factors for prevalent HIV infection. Subjects consented to a voluntary, anonymous, and confidential interview containing information on demographic characteristics, medical history, drug use, and sexual behavior. Of 26 cases interviewed, 20 (76.9%) reported behaviors defined by the Centers for Disease Control (CDC) as risk factors for HIV infection, while 11 of 74 (14.9%) controls also reported such behaviors. This proportion of reclassified NIR cases was similar to that reported from the NIR case series study conducted by the CDC. Of the six (23.1%) cases who remained at NIR, all reported at least one of the following risks: a history of sexually transmitted diseases, sexual contact with prostitutes, or sexual activity with female partners which caused bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for spread of the human immunodeficiency virus epidemic into low prevalence areas of the United States.

Reports of an increased proportion of AIDS cases occurring in small and medium-sized cities suggest that the HIV epidemic may be spreading into locations that were previously characterized by their low HIV antibody prevalences. Studying the question of the geographic spread of the HIV infection epidemic (rather than the AIDS epidemic) has been difficult largely because most serial seroprevalence data have been gathered from cohorts of high risk individuals (e.g., homosexual/bisexual cohorts) in New York City, San Francisco, and other geographically circumscribed areas. The U.S. military applicant HIV screening data were used in the current report to examine rates and 24 month temporal trends in geographic areas characterized by their HIV endemicities. The data examined concern the seven most populous states and four hyperendemic metropolitan areas located within those states (New York City, Miami, Houston, and San Francisco). In the nonepidemic regions, seroprevalence rates increased among black and white applicants. In the four epidemic urban areas, only young black applicants had higher HIV seroprevalence rates during the second 12 month period. Six of the seven nonepidemic regions had positive HIV seroprevalence trends, and these trends were significant in Florida, California, Texas, Illinois, and Ohio. The increases in these regions were greater for young blacks (30% excess for year 2 vs. year 1) compared to young whites (12% excess for year 2 vs. year 1). These data provide evidence of birth year specific increases in seroprevalence over time occurring in presumed low HIV prevalence areas. These increases cannot be due to, but are observed in spite of, biases associated with increasing self-selection over time.

Incidence of HIV-1 infection among young men in Thailand.

Royal Thai Army (RTA) enlistees were tested for HIV-1 seropositivity prospectively in order to explore their feasibility as a cohort in an HIV-1 preventive vaccine efficacy trial. The 17,615 seronegative enlistees, virtually all 21-year-old men, contributed 10,409 person-years (p-y) of follow-up. Cohorts were enlisted in November 1991 and May 1992 from northern Thailand and Bangkok. The follow-up rate was 50%, with loss to follow-up significantly associated with location of the base, marital status, and educational level. Seroincidence was 0.5/100 p-y for recruits stationed in Bangkok, 1.0/100 p-y in the lower north, and 3.2/100 p-y in the upper north. In a multiple regression model, the young man's birthplace was strongly associated with risk of infection, suggesting that transmission occurred during leave as well as during duty. Incidence rates were significantly lower in those who were married at the time of enlistment and in those with > or = 10 years of education. The seroincidence rates among recruits stationed in the upper north support vaccine trial feasibility, but follow-up rates need to be improved.

Tracking the spread of the HIV infection epidemic among young adults in the United States: results of the first four years of screening among civilian applicants for U.S. military service.

Because the period from infection to clinically apparent disease is long, variable, and changing as new therapies are developed and applied, AIDS data are inadequate for tracking current values of critical parameters of HIV infection epidemics: prevalence of infection, rate of acquisition of new infections (incidence rate), and direction and rate of change of infection incidence over time (acceleration). These "vital signs" of infection epidemics can be tracked using serial cross-sectional seroprevalence data, however. From October 1985 through September 1989, more than 2.3 million applicants for U.S. military service were screened for antibody to HIV. The overall seroprevalence was 1.31 per 1,000 (3,014/2,300,675). Seroprevalences were highest near urban centers of the AIDS epidemic and were independently associated with age, race/ethnicity, and gender. Based on age seroprevalence trends, it was crudely estimated that at least one of 2,000 young men and one of 7,000 young women are infected with HIV annually in the U.S. Infection incidence rates, estimated from age and temporal trends, were estimated to be highest among black males (1.40/1,000/year) and lowest among white females (0.03/1,000/year). Poisson regression analysis of seroprevalence trends suggested that infection incidence rates accelerated among black females during the first 3 years of screening. Since selection factors undoubtedly changed over the period, estimates based on these data probably underestimate actual values in the general population, particularly near urban AIDS epicenters. Nonetheless, even crude estimates of these critical values, particularly among adolescents and young adults, are useful to guide policy development, to allocate resources, and to monitor program effects.

Predictors of HIV-1 disease progression in early- and late-stage patients: the U.S. Army Natural History Cohort. Military Medical Consortium for Applied Retrovirology.

HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2, N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the initial clinical evaluation. Progression was defined as the occurrence of Stage 5 disease or beyond for the early cohort and Stage 6 disease or beyond for the late cohort. The cumulative incidence of progression was 15.7% (137 events) for the early-stage cohort, and 53.7% (85 events) for the late-stage cohort. Baseline CD4+ T lymphocyte (T4) count was the most significant marker of progression: 26% of WR Stage 1 or 2 patients with T4 lymphocytes below 500/mm3 progressed, compared with 12% with T4 lymphocytes at or above 500/mm3. In late-stage individuals, 83% with T4 lymphocytes under 200/mm3 progressed, compared with 27% with T4 lymphocytes at or above 200/mm3. Older age was associated with progression in both early- and late-stage groups. Differences in the rates of disease progression were not significant between blacks and whites or between men and women. Two-year rates of progression among the late-stage patients dropped from 78 to 47% between 1986 and 1988. This contrasted with progression rates in the early-stage cohort, which remained stable: 18% for those entering follow-up in 1986 and 17% for those entering follow-up in 1988. These data indicate a significant slowing of HIV disease progression rates and mortality rates among individuals with late-stage disease that is temporally associated with the increased availability and use of therapies. With control of T4 lymphocyte count, age, and calendar time, neither gender nor race was significantly associated with progression in either early- or late-stage patients.

A comparative study of the impact of HIV infection on natural killer cell number and function in Thais and North Americans.

Innate immunity may play a role in preventing HIV infection and progression to AIDS. Most studies of natural killer (NK) cell function have been conducted in populations with different HLA allele frequencies and HIV subtypes than those found in Southeast Asia. NK cell number and function, defined as CD3- cells expressing CD16+/CD56+ and the ability to lyse K562 cells, were enumerated in 42 HIV-seronegative Thais and 20 HIV-seronegative North Americans. The number and percentage of NK cells were similar for both groups, but cytotoxicity function expressed as lytic units (LU20) of NK cells was significantly greater in the Thai subjects compared with the North American subjects (p = 0.004). Comparisons were also conducted between the HIV-seronegative groups and HIV-infected subjects from both Thailand and North America. NK cell number and function were not significantly different between the Thai HIV-seronegative and -seropositive groups. However, the comparison between the North American HIV-seronegative and -seropositive subjects demonstrated profound impairment of NK cell number, percentage, and function (p < 0.001). Matching the Thai and North American HIV-infected subjects on CD4+ cell count revealed higher NK number and function in the Thai subjects (p < 0.001). The study indicates that NK function in both HIV-seronegative and -seropositive Thais is elevated relative to similar groups in North America.

Diversity of envelope glycoprotein from human immunodeficiency virus type 1 of recent seroconverters in Thailand.

The envelope-coding sequence of human immunodeficiency virus type 1 (HIV-1) was determined for 11 Thai seroconverters between 1995 and 1996. On the basis of the env sequences, all subjects were infected with HIV subtype E. Compared with the interpatient protein diversity among HIV-1 Thai reference sequences from 1990 to 1992 (4.4%), the diversity among the 1995-1996 seroconverters was approximately double (9.5%). The tetrapeptide tip of the V3 loop was invariant for 10 of the 11 seroconverters, and identical to that observed in sequences derived from the 1990-1992 group. However, in the V3 region, sequences from 2 of the 11 subjects demonstrated more than 5 amino acid changes relative to the reference strains. This may represent the "aging" of the HIV epidemic seen in other endemic regions. These findings may have substantial implications for vaccine development and evaluation for both HIV antibody and cytotoxic T lymphocyte repertoire recognition.

Human immunodeficiency virus type 1 neutralizing antibody serotyping using serum pools and an infectivity reduction assay.

Classification of human immunodeficiency virus type 1 (HIV-1) by neutralization serotype may be important for the design of active and passive immunization strategies. Neutralizing antibody serotyping is hindered by the lack of standard reagents and assay format, and by the weak activity of many individual sera. To facilitate cross-clade neutralization analysis, we used an infectivity reduction assay (IRA) and selected clade-specific serum (or plasma) pools from subjects infected with clade B and E HIV-1, respectively. Several serum pools were utilized; some were selected for strong neutralizing activity against intraclade viruses and others were derived from conveniently available samples. Against a panel of 51 clade B and E viruses, serum pools displayed strong neutralization of most intraclade viruses and significantly diminished cross-clade neutralization. Results were confirmed against a blinded panel of 20 viruses. The data indicate that the phylogenetic classification of virus subtypes B and E corresponds to two distinct neutralization serotypes. This approach to neutralizing antibody serotyping may be useful in defining the antigenic relationship among viruses from other clades.

HIV vaccine development: a subtype E-specific strategy.

The pandemic of HIV/AIDS consists of multiple foci with distinct epidemiological characteristics. Among the approximately one million Southeast Asians infected with HIV, subtype (clade) E infections predominate. This subtype, a recombinant virus comprised of a clade A core (gag) gene and a mosaic clade A/clade E envelope (env) gene, became broadly epidemic in Thailand beginning in 1989. Since then, subtype E HIV has become increasingly prevalent throughout Southeast Asia. Consistent with the recent introduction of clade E HIV, the diversity of Southeast Asian subtype E viruses is narrow (6% nucleotide diversity across env). Since neutralizing antibodies may play a protective role against HIV infection, and are relatively clade specific for genotype E viruses, a subtype E-derived candidate vaccine tested in Southeast Asia would provide an optimal test of vaccine concept. It would also provide, for the first time to a developing region of the world, a non-B clade candidate vaccine designed specifically for the local epidemic. A consortium of industry (Chiron Vaccines and Pasteur Merieux Connaught), academic (Mahidol and Chiang Mai Universities) and military (United States and Royal Thai Army Medical Departments) medicine is working together to develop and test HIV vaccines for the genotype E epidemic. A genotype B recombinant glycoprotein (rgp)120 candidate vaccine has undergone phase I/II testing in Thailand and confirmed to be safe and immunogenic in this ethnic group. An rgp120 (E) has been produced and a phase I/II trial of the bivalent product (B/E) is in the final stages of approval. This vaccine construct is designed to elicit humoral immune responses. To augment these antibody responses with CD8+ CTL responses, an E-specific, live-vectored vaccine is being developed which will be used in conjunction with rgp120 in a second vaccine approach. Canarypox (ALVAC) constructs containing multiple HIV genes (gag/pol/env) currently designed for the subtype B epidemics will be modified to contain a clade E env gene sequence. After predetermined milestones have been met, these two subtype E-specific candidate vaccines will be assessed for protection in a large collaborative efficacy trial. Since neither animal models nor laboratory assays are validated as predictive of HIV vaccine efficacy, it must be through such a phase III trial that vaccine-induced protection and immunologic correlates will be determined.

HIV infection: military occupational sequelae.

The military experience of 573 soldiers found to be HIV seropositive and their 2,262 matched seronegative controls were compared to determine if differences exist. Examination of personnel records for study members showed an expected difference in assignment changes, with seropositives being moved significantly more often to other units in compliance with a regulation prohibiting their presence in special operations units and units located overseas. Otherwise, there was no statistically significant difference at the 0.05 level when comparing changes in education, military occupational specialty code, promotion, or demotion. Seropositive individuals were less likely to marry, but no more likely to divorce. Seropositives were more likely to be separated from active service and barred from reenlistment for medical reasons.

A brief review of the epidemiology of HIV in the U.S. Army.

The Department of Defense has conducted extensive HIV testing for over 5 years. We summarize the epidemiology of the HIV infection in the total Army. While screening of civilian applicants effectively ensures seronegativity of enlistees, there are approximately 220 new HIV infections each year among active duty soldiers. High-risk demographic groups in the Army include single soldiers, males, those age 25-35, blacks, and Hispanics (including black and Hispanic females). While preventive efforts in the Army should reflect the higher risk experienced by these groups, all soldiers should be made aware of their susceptibility as the epidemic evolves to include more women and heterosexual men.

A cluster of blister-associated toxic shock syndrome in male military trainees and a study of staphylococcal carriage patterns.

In March-April 1985, toxic shock syndrome (TSS) developed in three male military trainees at one base secondary to infected blisters acquired while marching during basic combat training. One trainee died. Staphylococcus aureus was isolated from the blisters in all three patients, and the two strains available for testing both produced toxic shock syndrome toxin-1 (TSST-1). A culture survey identified carriage of S. aureus in 44% (145/333) of the trainees; carriage rates did not differ between the company with two ill trainees and a control company. Carriage was more frequent in the nose than foot (41% versus 9%, p less than 0.0001). White trainees were more likely to carry S. aureus than black trainees (47% versus 28%, p = 0.013), although the same proportion of strains was positive for TSST-1 in both races. The two strains obtained from the patients had similar but not identical phage typing patterns, but had identical antibiograms, and neither strain carried any plasmids. Based upon phage typing of the TSST-1 positive S. aureus strains isolated in the study, widespread carriage of the case strain(s) in other trainees was not found nor was clustering noted by barrack room. It is possible that differences in carriage rates may partially explain the low rate of TSS in blacks.

Clinical prognosis of patients with early-stage human immunodeficiency virus (HIV) disease: contribution of HIV-1 RNA and T lymphocyte subset quantitation.

Systems for the staging of individuals with human immunodeficiency virus type 1 (HIV-1) infection were developed 15 years ago. Subsequently, assays for quantitating HIV-1 RNA and immunophenotyping of lymphocyte subsets have been developed and validated. The utility of these assays for improved staging in early disease was evaluated in 256 HIV-infected adults (52% minority) with CD4 counts > or = 400 cells/microL followed in U.S. military medical centers before the highly active anti-retroviral therapy era. HIV viral load (RNA) was quantitated; the frequencies of select CD4+ immunophenotypes were determined in 112 subjects. The results were analyzed in relation to three outcome measures: death, first acquired immunodeficiency syndrome-defining opportunistic infection, and CD4 count < or = 200 cells/microL. Serum RNA level and CD4 count were each found to be predictive of all three outcomes. In addition, increases in the T-cell subsets CD28-CD4+ and CD29+CD26-CD4+ were found to be independently predictive of more rapid progression. The classification of early-stage HIV patients is improved by the quantitation of both viral RNA and T-lymphocyte subsets.

Inpatient psychiatric morbidity of HIV-infected soldiers.

To determine differences in inpatient psychiatric morbidity, a total of 573 soldiers seropositive for the human immunodeficiency virus (HIV) were matched with 2,266 seronegative soldiers by age, sex, race, marital status, military rank, length of active service, military occupation, and date of HIV test. An HIV-infected individual was seven times more likely to be hospitalized than an uninfected individual. The rate of total hospitalizations was 16 times higher for the HIV-infected soldiers. The median length of hospital stay was six days for the infected soldiers and four days for the control group. The incidence of psychosis, organic mental disorders, and adjustment disorder in the HIV-infected group was significantly higher.

Broad and persistent effects of benzathine penicillin G in the prevention of febrile, acute respiratory disease.

After an outbreak of acute rheumatic fever at a US Army training installation, a benzathine penicillin G prophylaxis program was instituted. Surveillance data were analyzed to measure rates of febrile, acute respiratory disease (ARD) among trainees before and after prophylaxis was begun. Annual admissions for ARD decreased from 1927 to 690 (-64.2%) after benzathine penicillin G prophylaxis was begun. Admissions with throat cultures positive for Streptococcus pyogenes fell from 595 to 63 (-89.4%), a reduction that accounted only for a minority (43%) of the total 1237 "prevented" admissions. Temporal changes in disease rates at other installations where drug was not administered were also analyzed. Only a small decrease in the number of annual ARD admissions (-6.3%) was observed at other training installations. These findings support a hypothesis that benzathine penicillin G has a broad effect in the prevention of ARD that extends beyond the simple elimination of group A streptococcal infection.