Experiences in implementation of routine human immunodeficiency virus testing in a US tuberculosis clinic.

SETTING: Rhode Island Tuberculosis (RI TB) Clinic, The Miriam Hospital, Providence, RI, USA. BACKGROUND: Human immunodeficiency virus (HIV) status is a critical factor in the management of both patients with latent TB infection (LTBI) and active TB. Since 2006, the Centers for Disease Control and Prevention has recommended routine, opt-out HIV testing in all health care settings, including TB clinics. However, implementation of HIV testing in LTBI patients has been limited. DESIGN: A policy for HIV assessment of all new patients was instituted at the RI TB Clinic. Patients who reported no HIV testing in the preceding year were offered opt-out HIV testing. Patient records (June 2010-June 2011) were retrospectively reviewed. Structured nursing interviews assessed staff acceptance. RESULTS: A total of 821 (77.5%) first-visit TB patients underwent HIV status assessment: 96.3% of those not tested in the previous year agreed to testing; 65.9% of tests were performed at point of care. There was one new HIV diagnosis. CONCLUSION: Implementing routine opt-out HIV testing in the RI TB Clinic is feasible, with high staff acceptance rates and low patient refusal rates. Perceived health systems barriers can be overcome. Incorporating opt-out HIV testing for LTBI patients expands testing opportunities to individuals unaware of their HIV status, and can identify HIV-infected patients early in the course of infection.

Cultural feasibility studies in preparation for clinical trials to reduce maternal-infant HIV transmission in Haiti.

A cultural feasibility study is defined as one that investigates scientific as well as ethical, behavioral, and social issues in the design of clinical trials. The value of such a broadly defined assessment is illustrated through the presentation of two case studies conducted to prepare for clinical trials to reduce maternal-infant HIV transmission on Cité Soleil, Haiti. The first study addressed issues surrounding a trial of breast-feeding and exclusive bottle-feeding among HIV seropositive mothers. The second study focused on the implementation of a double-blind trial of HIV immune globulin and standard immune globulin to be administered to infants of seropositive mothers shortly after birth. Both cases used focus group interviews with mothers and in-depth interviews with key informants to investigate AIDS-related beliefs, acceptability of trial participation, risks to subjects, and community reactions and repercussions to the trial. Findings point to the difficulties posed by attempts to conduct trial involving complex research designs in socially disadvantaged populations. Recommendations highlight the need to consider the community-wide impact of a trial, and the need to undertake extensive educational preparation of participants to ensure informed consent and adherence to protocols.

PIP: Cultural feasibility studies use ethnographic methods to explore ethical, behavioral, and social issues inherent in the design of proposed clinical trials. This approach was applied in advance of clinical trials aimed at reducing maternal-infant HIV transmission in Cite Soleil, Haiti. The first focused on conditions that would be necessary to conduct a trial of breast feeding versus exclusive bottle feeding by HIV-positive mothers; the second investigated the feasibility of a double-blind trial of administration of a high- titer antibody preparation--HIV immune globulin (HIVIG)--to infants of seropositive mothers shortly after birth. Study methods included focus group discussions with mothers and in-depth interviews with key informants about AIDS-related beliefs, acceptability of trial participation, risks to subjects, and community repercussions. Concerns identified included the potential negative effect on breast feeding promotion efforts in Haiti, the scarcity of economic means to sustain safe bottle feeding, the risk of being labeled HIV-positive by virtue of study participation, the potential for the HIVIG trial to reinforce the misconception that a vaccine effective against AIDS exists, and problems explaining the concept of a double-blind study and accepting random assignment to treatment and control groups. As a result of these studies, it was decided to conduct the infant feeding study in a community with higher rates of exclusive bottle feeding and lower infant mortality than exist in Cite Soleil. The HIVIG trial could be conducted, but only after extensive community education to ensure informed consent. An objective assessment of subject comprehension was developed for this purpose.

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.

Prevalence of HIV-1 DNA and p24 antigen in breast milk and correlation with maternal factors.

Breast milk specimens from human immunodeficiency virus type 1 (HIV-1)-seropositive and HIV-1-seronegative women were examined for the presence of HIV-1 p24 antigen by the antigen capture method and for viral DNA using the polymerase chain reaction. HIV-1 DNA was present in 70% of milk specimens collected from 47 HIV-seropositive women 0-4 days after delivery and in approximately 50% of specimens collected 6 and 12 months postpartum. p24 antigen, present in 24% of milk specimens collected from 37 seropositive women within the first 4 days postpartum, was not detected in any of the subsequent specimens. The presence of HIV-1 DNA or p24 antigen in milk was not significantly associated with maternal CD4 lymphocyte count, beta 2-microglobulin level, or fulfillment of the AIDS clinical case definition. Although the correlation of either HIV-1 proviral DNA or p24 antigen with the presence of infectious virus is not known, these data indicate the need for additional studies examining the role of breastfeeding in maternal-infant transmission of HIV-1.

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.