Randomised trial of isoniazid versus rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection.

BACKGROUND: Tuberculosis is a common complication of HIV-1 infection, especially in developing countries. Practical and effective chemoprophylaxis regimens for HIV-1-related tuberculosis are needed. Our aim was to test the efficacy of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1-positive individuals. METHODS: We compared the efficacy of 6 months of isoniazid with 2 months of rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1-seropositive individuals. Eligible participants were aged 16-77 years, HIV-1 seropositive, had a positive purified-protein derivative (PPD) skin test reaction of at least 5 mm, and had a normal chest radiograph. Participants were randomly assigned partially supervised twice weekly isoniazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks. Participants were followed up for up to 4 years for the development of tuberculosis and survival. FINDINGS: Tuberculosis developed in 14 (3.8%) of 370 participants assigned isoniazid and 19 (5.0%) of 380 participants assigned rifampicin and pyrazinamide (Cox model rate ratio 1.3 [95% CI 0.7-2.7]). The Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months after entry was 3.7% among participants who received rifampicin and pyrazinamide compared with 1.0% (p=0.03) among participants who received isoniazid, and 5.4% versus 5.1%, respectively (p=0.9) at 36 months after entry. Higher rates of tuberculosis were observed in people with baseline CD4 percentages (of total lymphocytes) of less than 20 (rate ratio 4.0 [95% CI 1.8-9.0]). There were no significant differences in total mortality at any time. INTERPRETATION: Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected, PPD-positive adults. The better protection among recipients of isoniazid during the first 10 months was most likely secondary to the longer duration of chemoprophylaxis. Preventive therapy for HIV-1-seropositive, PPD-positive individuals could be practical in developing countries with a once weekly clinic visit, but optimum duration of chemoprophylaxis has not been determined.

Widespread HIV counseling and testing linked to a community-based tuberculosis control program in a high-risk population.

The aim of the work reported here was to evaluate community-wide screening for HIV infection that was linked to a tuberculosis control program in a population at high risk for both infections. Between May 1990 and August 1992, adults in Cité Soleil, Haiti, were recruited by community health workers at their homes and in clinics for individual, clinic-based counseling and testing for HIV and tuberculosis. All of the screened subjects were offered post-test HIV counseling. Those with active tuberculosis received treatment, while those with latent tuberculosis and HIV infection were offered an opportunity to participate in a trial of antituberculosis chemoprophylaxis. The 10,611 individuals screened for HIV represented 10.0% of the adult population in Cité Soleil. HIV infection was detected in 1,629 (15.4%) and active tuberculosis in 242 (2.3%). Latent M. tuberculosis infection was found in 4,800 (67.5%) of 7,309 community residents who completed tuberculosis screening, 781 (16.3%) of whom were coinfected with HIV. The high prevalence of HIV infection found in this screened population, as compared to other groups undergoing HIV screening in the same community, suggests that people at high risk for HIV infection selectively sought or accepted tuberculosis clinic screening. Also, many people with active tuberculosis were identified earlier in the course of their disease than they would have been in the absence of a screening program. Overall, the results indicate that community-based screening for HIV infection within a tuberculosis control program can result in effective targeting of screening for both infections.

PIP: Findings are reported from an evaluation of community-wide screening for HIV infection linked to a tuberculosis (TB) control program in a population at high risk for both infections. Between May 1990 and August 1992, adults in Cite Soleil, Haiti, were recruited by community health workers at their homes and in clinics for individual, clinic-based counseling and testing for HIV and TB. All screened subjects were offered post-test HIV counseling. Those with active TB received treatment, while those with latent TB and HIV infection were offered an opportunity to participate in a trial of anti-TB chemoprophylaxis. The 10,611 individuals screened for HIV represented 10.0% of the adult population in Cite Soleil. HIV infection was detected among 1629 (15.4%) and active TB in 242 (2.3%). Latent M. tuberculosis infection was found in 4800 (67.5%) of 7309 community residents who completed TB screening, 781 (16.3%) of whom were coinfected with HIV. The high prevalence of HIV infection in this screened population, compared to other groups screened in the same community, suggests that people at high risk for HIV infection selectively sought or accepted TB clinic screening. Also, many people with active TB were identified earlier in the course of their disease than they would have been in the absence of a screening program. Overall, these results indicate that community-based screening for HIV infection within a TB control program can result in the effective targeting of screening for both infections.

Suboptimal response following intradermal hepatitis B vaccine in infants.

Two hundred and twenty-five infants were randomly assigned to receive 2 micrograms of plasma-derived hepatitis B vaccine (Heptavax) intradermally (ID-2), 10 micrograms intramuscularly (IM-10), or 2 micrograms intramuscularly (IM-2) in the deltoid region at birth, 2 and 4 months. At 6 months, ID-2 infants were less likely to have developed > or = 10 mIU ml-1 of antibody to hepatitis B surface antigen (anti-HBs) than IM-10 infants (91 versus 100%; p = 0.02) and had a lower geometric mean concentration of anti-HBs (312 mIU ml-1 versus 2248 mIU ml-1; p < 0.01). At 6 months IM-10 infants had significantly lower mean weights and lengths than infants receiving 2 micrograms doses of vaccine. Intramuscular administration of 2 micrograms and 10 micrograms doses of Heptavax in the deltoid of young infants was well tolerated and effective; however, intradermal administration of Heptavax provided no immunological benefit over intramuscular administration and resulted in significantly higher rates of induration and persistent hyperpigmentation. Intramuscular immunization at birth, 2 and 4 months is an acceptable, effective alternative schedule for immunizing infants.

Seroprevalence of human immunodeficiency virus type 1 among pregnant women.

Five (0.74%) of 678 women delivering in 1985 at a tertiary referral hospital for high-risk pregnancies and 16 (1.34%) of 1198 women visiting an urban prenatal obstetrics clinic in 1986-1987 had serologic evidence of human immunodeficiency virus type 1 (HIV-1) infection. Unlinked testing (removal of personal identifiers from the blood specimen and the epidemiologic data sheet) of residual serum from hepatitis B virus serologic testing was used. Neither age, marital status, payor status, nor serologic markers of hepatitis B virus infection was useful in identifying women at risk for HIV-1 infection. As a result of these data, we have initiated a program in which counseling is offered to all women and testing for those who consent. Unlinked testing of women who refuse consent is performed for epidemiologic purposes. This will allow us to continue to plan for health care resource needs and to track the course of the epidemic in various subgroups of pregnant women.

Tuberculin skin test reactivity among adults infected with human immunodeficiency virus.

Infection with the human immunodeficiency virus type 1 (HIV-1) results in decreased cell-mediated immunity, which includes decreased delayed hypersensitivity to skin test antigens. HIV-1 seropositivity and skin test reactivity to purified protein derivative (PPD) were determined among 2042 healthy Haitian adults with normal chest radiographs. Among HIV-1-seropositive individuals, 52.3% (146/279) had PPD reactions greater than or equal to 10 mm compared with 67.2% (1184/1763) of the seronegative adults (P less than .001). However, the percentage of HIV-1-seropositive individuals with PPD reactions greater than or equal to 5 mm was similar to the percentage of seronegative adults with PPD reactions greater than or equal to 10 mm (180/279 [64.5%] vs. 1184/1763 [67.2%]). Assuming that the rate of prior infection with Mycobacterium tuberculosis was similar for HIV-1-seronegative and -seropositive populations, these data provide support for the recent recommendations to use induration of greater than or equal to 5 mm as evidence of past infection with M. tuberculosis in HIV-1 seropositive adults.

Sexual behavior, smoking, and HIV-1 infection in Haitian Women.

OBJECTIVE: To determine whether a previously observed association between human immunodeficiency virus type 1 (HIV-1) infection and smoking in Haitian women could be explained by confounding high-risk behaviors. DESIGN AND SETTING: A nested case-control study at a primary care health clinic in Cité Soleil, Haiti. PARTICIPANTS: Women who reported having smoked (n = 89) and randomly selected nonsmokers (n = 329) who had participated in a survey 1 to 12 months earlier evaluating risk factors for HIV-1 infection. MAIN OUTCOME MEASURES: Lifetime sexual practices, smoking, health beliefs and practices, and other factors potentially confounding the relationship between smoking and HIV-1 infection. RESULTS: Compared with nonsmokers, smokers reported higher rates of high-risk behaviors, including more lifetime sex partners (P less than .001), being less likely to be married (P less than .01), and being more likely to have visited folk healers (P less than .01). No intravenous drug use was reported, and no significant differences were noted between smokers and nonsmokers in numbers of past surgical or dental procedures or injections. Adjustment for all factors associated with HIV-1 infection and smoking in regression analyses revealed an independent association between smoking and HIV-1 infection (odds ratio [OR], 3.4; 95% confidence interval [Cl], 1.6 to 7.5). Other factors associated with HIV-1 infection included having more than two life-time sex partners (OR, 3.4; 95% Cl, 1.7 to 6.8) and lower socioeconomic status as reflected by a dirt floor in the home (OR, 8.6; 95% Cl, 3.3 to 22.0). CONCLUSIONS: Smoking is a marker for high-risk sexual behavior and is associated with an increased risk of HIV-1 infection in this population. The persistent association between smoking and HIV-1 infection after adjustment for all known risk factors suggests the possibility of a biologic effect of smoking that warrants further evaluation in other populations.

Transmission of HIV-1 infections from mothers to infants in Haiti. Impact on childhood mortality and malnutrition. The CDS/JHU AIDS Project Team.

Of 4588 pregnant women in a high-risk Haitian population, 443 (9.7%) were serologically positive for the human immunodeficiency virus type 1 (HIV-1). Infants born to women who were HIV-1 seropositive were more likely to be premature, of low birth weight, and malnourished at 3 and 6 months of age than were infants born to women who were HIV-1 seronegative. Increased mortality was observed in infants born to women who were HIV-1 seropositive by 3 months of age. At 12 months of age, 23.4% of the infants born to women who were HIV-1 seropositive had died compared with 10.8% of the infants born to women who were HIV-1 seronegative; at 24 months of age, the mortality rates were 31.3% and 14.2%, respectively. Maternal HIV-1 infections resulted in an 11.7% increase in the overall infant mortality rate in this population. The estimated mother-to-infant HIV-1 transmission rate in these breast-fed infants was 25%, similar to the rates reported for non-breast-fed populations in the United States and Europe.