John M. Karon

Estimation of HIV Incidence in the United States

CONTEXT Incidence of human immunodeficiency virus (HIV) in the United States has not been directly measured. New assays that differentiate recent vs long-standing HIV infections allow improved estimation of HIV incidence. OBJECTIVE To estimate HIV incidence in the United States. DESIGN, SETTING, AND PATIENTS Remnant diagnostic serum specimens from patients 13 years or older and newly diagnosed with HIV during 2006 in 22 states were tested with the BED HIV-1 capture enzyme immunoassay to classify infections as recent or long-standing. Information on HIV cases was reported to the Centers for Disease Control and Prevention through June 2007. Incidence of HIV in the 22 states during 2006 was estimated using a statistical approach with adjustment for testing frequency and extrapolated to the United States. Results were corroborated with back-calculation of HIV incidence for 1977-2006 based on HIV diagnoses from 40 states and AIDS incidence from 50 states and the District of Columbia. MAIN OUTCOME MEASURE Estimated HIV incidence. RESULTS An estimated 39,400 persons were diagnosed with HIV in 2006 in the 22 states. Of 6864 diagnostic specimens tested using the BED assay, 2133 (31%) were classified as recent infections. Based on extrapolations from these data, the estimated number of new infections for the United States in 2006 was 56,300 (95% confidence interval [CI], 48,200-64,500); the estimated incidence rate was 22.8 per 100,000 population (95% CI, 19.5-26.1). Forty-five percent of infections were among black individuals and 53% among men who have sex with men. The back-calculation (n = 1.230 million HIV/AIDS cases reported by the end of 2006) yielded an estimate of 55,400 (95% CI, 50,000-60,800) new infections per year for 2003-2006 and indicated that HIV incidence increased in the mid-1990s, then slightly declined after 1999 and has been stable thereafter. CONCLUSIONS This study provides the first direct estimates of HIV incidence in the United States using laboratory technologies previously implemented only in clinic-based settings. New HIV infections in the United States remain concentrated among men who have sex with men and among black individuals.

HIV in the United States at the turn of the century: an epidemic in transition.

OBJECTIVES The current status of and changes in the HIV epidemic in the United States are described. METHODS Surveillance data were used to evaluate time trends in AIDS diagnoses and deaths. Estimates of HIV incidence were derived from studies done during the 1990s; time trends in recent HIV incidence were inferred from HIV diagnoses and seroprevalence rates among young persons. RESULTS Numbers of deaths and AIDS diagnoses decreased dramatically during 1996 and 1997 but stabilized or declined only slightly during 1998 and 1999. Proportional decreases were smallest among African American women, women in the South, and persons infected through heterosexual contact, HIV incidence has been roughly constant since 1992 in most populations with time trend data, remains highest among men who have sex with men and injection drug users, and typically is higher among African Americans than other racial/ethnic groups. CONCLUSIONS The epidemic increasingly affects women minorities, persons infected through heterosexual contact, and the poor. Renewed interest and investment in HIV and AIDS surveillance and surveillance of behaviors associated with HIV transmission are essential to direct resources for prevention to populations with greatest need and to evaluate intervention programs.

Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial

BACKGROUND There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality. METHODS Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjans four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital. FINDINGS Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group. INTERPRETATION In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.

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

ObjectiveTo describe the dynamics of the HIV-1 epidemic in childbearing women in Kinshasa, Zaïre, by estimating incidence from serial seroprevalence studies. MethodsIn 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. ResultsWhile 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 (Cl), 1.4–4.2]. The highest incidence, 5.7 per 100 (95% Cl, 3.5–8.0), was in women aged 20–24 years in 1989. ConclusionDespite 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.

The increasing frequency of heterosexually acquired AIDS in the United States, 1983-88

Of 88,510 cases of acquired immunodeficiency syndrome (AIDS) reported in adults in the United States from 1983 through 1988, the percentage attributed to reported heterosexual contact with persons known to be infected or at increased risk of infection with human immunodeficiency virus (HIV) has increased steadily from 0.9 percent in the first quarter of 1983 to 4.0 percent in the fourth quarter of 1988, from 0.1 (in 1983) to 1.4 percent (in 1988) among men, and from 13 (in 1983) to 28 percent (in 1988) among women. Among women, the cumulative incidence of AIDS attributable to heterosexual contact per million population is over 11 times greater for Blacks and Hispanics than for Whites. Among men, this incidence is over 10 times greater for Blacks and four times greater for Hispanics than for Whites. The pattern of distribution of heterosexually acquired AIDS parallels the distribution of other heterosexually transmitted diseases, which are also more frequent in Black and Hispanic inner-city populations. Drug use, exchange of sex for drugs or money, and early onset of sexual activity in adolescents are increasingly associated with heterosexually transmitted infections and are likely to be very important in heterosexual transmission of HIV in inner-city US populations.

Safety and acceptability of the candidate microbicide Carraguard in Thai Women: findings from a Phase II Clinical Trial

Objective:To determine the safety and acceptability of vaginal application of Carraguard, a carrageenan-derived candidate microbicide gel. Design:A randomized, placebo-controlled, triple-blinded clinical trial was conducted in Chiang Rai, northern Thailand. Methods:Women were asked to insert one applicator of study gel vaginally at least three times per week (with or without sex) and to use gel with condoms every time they had sex. Safety was assessed by visual inspection of the vagina and cervix, changes in vaginal flora and self-reported symptoms at day 14, month 1 and then monthly for up to 1 year. Acceptability was assessed through reported use of the gel, return of used and unused applicators, and quarterly interviews. Results:One hundred sixty-five women were randomized: 83 to Carraguard and 82 to the placebo (methylcellulose gel) group. Study gel use was similarly high in both groups throughout the trial with an average of four applicators per week. Carraguard use was not associated with abnormal genital clinical findings, abnormal vaginal flora, Pap smear abnormalities or other abnormal clinical signs or symptoms. Adverse events were mostly mild, not attributed to gel use, and similarly distributed between groups. Participants in both groups reported high acceptability. Conclusions:Carraguard can safely be used an average of four times per week with or without sex and is acceptable to Thai women. A Phase III efficacy trial of Carraguard is warranted and is currently ongoing in South Africa.

Trends in AIDS incidence and survival among racial/ethnic minority men who have sex with men, United States, 1990-1999.

Objectives: We describe trends in AIDS incidence, survival, and deaths among racial/ethnic minority men who have sex with men (MSM). Methods: We examined AIDS surveillance data for men diagnosed with AIDS from 1990 through 1999, survival trends from 1993 through 1997, and trends in AIDS incidence and deaths from 1996 to 1999, when highly active antiretroviral therapy (HAART) was introduced. Results: The percentage of racial/ethnic minority MSM with AIDS increased from 33% of 26.930 men in 1990 to 54% of 17,162 men in 1999. From 1996 through 1998, declines in AIDS incidence were smallest among black MSM (25%, from 66.2 to 49.5 per 100,000) and Hispanic MSM (29%, from 39.3 to 27.8), compared with white MSM (41%, from 17.9 to 10.5). Declines in deaths of MSM with AIDS were also smallest among black MSM (53%, from 39.7 to 18.6 deaths per 100.000) and Hispanic MSM (61%, 21.6 to 8.4), compared with white MSM (63%, 12.3 to 4.5). Survival improved each year for all racial/ethnic groups but was poorest for black MSM in all years. Conclusions: Since the introduction of HAART, a combination of factors that include relatively higher infection rates in more recent years and differences in survival following AIDS diagnosis contribute to observed differences in trends in AIDS incidence and deaths among racial/ethnic minority MSM. Increased development of culturally sensitive HIV prevention services, and improved access to testing and care early in the course of disease are needed to further reduce HIV‐related morbidity in racial/ethnic minority MSM.

HIV infection in disadvantaged out-of-school youth: prevalence for U.S. Job Corps entrants, 1990 through 1996.

To describe HIV infection prevalence and prevalence trends for disadvantaged out-of-school youth in the United States, we analyzed the HIV prevalence for and demographic characteristics of youth, aged 16 through 21 years, who entered the U.S. Job Corps from January 1990 through December 1996. Job Corps is a federally funded jobs training program for socially and economically disadvantaged out-of-school youth. All 357,443 entrants residing at Job Corps centers during their training were tested for HIV infection; 822 (2.3 per 1000) were HIV-positive. HIV prevalence was higher for women than for men (2.8 per 1000 versus 2.0 per 1000; relative risk [RR]=1.4; 95% confidence interval [CI]=1.2-1.6). Among racial/ethnic groups, prevalence was highest for African Americans (3.8 per 1000). Prevalence was higher for African American women (4.9 per 1000) than for any other gender and racial/ethnic group. From 1990 through 1996, standardized HIV prevalence-stratified by age, race/ethnicity, home region, population of home metropolitan statistical area, and year of entry--declined for women and for men: for women, from 4.1 per 1000 in 1990 to 2.1 per 1000 in 1996 (p=.001); and for men, from 2.8 per 1000 in 1990 to 1.4 per 1000 in 1996 (p=.001). These data suggest that HIV prevalence for disadvantaged out-of-school youth declined from 1990 through 1996. However, considering their youth, prevalence was still high, particularly for women and African Americans, most notably African American women. These data support the need for ongoing HIV prevention programs targeting such youth.

Update on the seroepidemiology of human immunodeficiency virus in the United States household population : NHANES III, 1988-1994

To update the estimate of seroprevalence of HIV from the third National Health and Nutrition Examination Survey (NHANES III), data from the second phase of the survey were combined with previously published data to produce a more precise estimate. The testing was performed anonymously on 11,203 individuals 18-59 years of age examined from 1988 to 1994. Fifty-nine individuals were HIV positive, for an overall prevalence of 0.32%. The number of individuals living in households with HIV infection based on this estimate was 461,000, with a 95% confidence interval of 290,000-733,000. Analysis of nonresponse demonstrated that white and black men 40-59 years of age were least likely to participate in the survey. A sensitivity analysis demonstrated that this nonresponse may have biased the NHANES III estimate downward by 190,000 persons. Data from the second phase of the survey were used to analyze the association between drug use and HIV infection. Black women who used cocaine were 12 times more likely to be HIV positive compared with all tested black women (6.5% vs. 0.55%). This survey provides an estimate of HIV prevalence for individuals who reside in households but excludes some persons who are at higher risk for HIV infection, including prisoners and the homeless not residing in shelters.

HIV incidence in the United States, 1978-1999

Context: HIV incidence measurements, which reflect recent or current transmission, are valuable for monitoring the epidemic and evaluating prevention programs. Objectives: To summarize HIV incidence patterns and trends in U.S. population groups. Data Sources: Publications in English from 1980 through mid‐2000. Study Selection and Statistical Methods: We searched the literature for reports of HIV incidence in the United States. Locally weighted scatterplot smoothing was used to generate smooth curves to estimate trends in incidence. Spearman rank correlation was used to estimate the correlation coefficient between prevalence and incidence. Data Synthesis: In 74 eligible reports, HIV incidence varied widely (0.002‐19.8 per 100 person‐years [py]) depending on risk group. Among men who have sex with men (MSM), HIV incidence peaked in the early 1980s (5‐20/100 py) and then declined but remained high during the 1990s (2‐4/100 py). Among injection drug users (IDUs), incidence decreased since the mid‐1980s but differed by geographic area; in the 1990s, incidence remained high in the East (1‐3/100 py) but was lower in the West (<0.5/100 py). Throughout the late 1980s and 1990s, incidence was low and stable in broader populations (blood donors: <0.01/100 py; military personnel: 0.01‐0.07/100 py). The correlation between HIV incidence and prevalence was strong in populations with a prevalence less than 1% (r = 0.94, p < .0001), moderate in populations with a prevalence from 1% to less than 10% (r = 0.57, p < .0001), and weak in populations with a prevalence at least 10% (r = 0.23, p = .09). Conclusions: HIV prevention in the United States should continue to focus on MSM and IDUs. HIV incidence measurements should be considered for monitoring HIV transmission in MSM, IDUs, and other populations in which seroprevalence is high.