Download Article PDF/SlidesThe impact that HIV has on the pathogenesis of tuberculosis (TB) is clear. It is one of the most important risk factors associated with an increased risk of latent TB infection (LTBI) progressing to active TB disease. HIV-infected people have an annual risk of 5% to 15% of developing active TB once infected (Rieder, 1999). TB is the most common opportunistic infection in people living with HIV worldwide. It is also the most common cause of death in HIV-positive adults living in developing countries, despite being a preventable and treatable disease (Corbett, 2003).
Dr. Sonal Munsiff began her April 2006 PRN lecture describing the global epidemiology of TB and HIV coinfection and emphasized its relevance to New York City’s large immigrant population. Following a discussion of the current status of TB and HIV coinfected patients in New York City, she focused on the diagnosis and treatment challenges in these patients.
The estimated incidence of TB remains high in both Asia and Africa, with the highest estimated incidence in sub-Saharan Africa (300 new cases per 100,000 population). “The main reason for the markedly high rates of TB in sub-Saharan Africa is the high prevalence of HIV infection,” Dr. Munsiff pointed out. “In fact, more than half of TB cases in many sub-Saharan African countries are in HIV-infected persons. The AIDS epidemic has caused marked acceleration of the TB epidemic worldwide and in sub-Saharan Africa, in particular” (see Figure 1).
The Stop TB Partnership recently released a ten year plan to address the global TB epidemic (Stop TB Partnership, 2006). While this plan aims to reduce the global burden of TB, Dr. Munsiff noted that even if all aspects of the plan are implemented and fully funded, a decrease in TB incidence in African countries with high HIV prevalence in the next ten years is probably unlikely based on current trends.
While TB and HIV co-infection remains a major public health problem in many parts of the world, the number of TB cases coinfected with HIV in the United States has been decreasing. The number of TB cases has been declining since 1992, and the prevalence of TB and HIV coinfection has reached a somewhat steady state. According to the U.S. Centers for Disease Control and Prevention (CDC), approximately 10% of all TB cases in the US are also co-infected with HIV (CDC, 2004).
Figure 1.Estimated HIV Prevalence in TB Cases, 15–49 years (%), 2003
| Table 1. Demographic and Clinical Characteristics of TB patients by HIV status in New York City, 2000–20051 | ||||||
| Variable | HIV-infected patients (n=1,113) | HIV-uninfected patients (n=3,580) | OR | P value | ||
| N | % | N | % | |||
| Age | ||||||
| 0 –18 | 8 | 0.7 | 264 | 7.4 | 0.09 | <.0001 |
| 19–44 | 671 | 60.3 | 2,085 | 58.2 | 1.09 | .226 |
| 45–65 | 412 | 37.0 | 881 | 24.6 | 1.80 | <.0001 |
| 65 and over | 22 | 2.0 | 350 | 9.8 | 0.19 | <.0001 |
| US-born | 707 | 63.5 | 962 | 26.9 | 4.74 | <.0001 |
| Homeless | 203 | 18.2 | 167 | 4.7 | 4.56 | <.0001 |
| History of Substance Abuse | 593 | 53.3 | 640 | 17.9 | 5.24 | <.0001 |
| Race/ Ethnicity | ||||||
| Non-Hispanic White | 62 | 5.6 | 264 | 7.4 | 0.74 | .039 |
| Non-Hispanic Black | 708 | 63.6 | 1,046 | 29.2 | 4.23 | <.0001 |
| Hispanic | 308 | 27.7 | 1,226 | 34.2 | 0.73 | <.0001 |
| Asian | 34 | 3.1 | 1,030 | 28.8 | 0.08 | <.0001 |
| Culture Positive | 879 | 79.0 | 2,769 | 77.4 | 1.10 | .254 |
| Respiratory Smear Positive | 522 | 47.0 | 1,549 | 43.3 | 1.16 | .033 |
| Tuberculin Skin Test Positive2 | 313 | 52.8 | 1,929 | 80.0 | 0.28 | <.0001 |
| Site of Disease | ||||||
| Pulmonary Only | 632 | 56.8 | 2,482 | 69.3 | 0.58 | <.0001 |
| Extrapulmonary Only | 202 | 18.2 | 808 | 22.6 | 0.76 | .002 |
| Both | 279 | 25.1 | 290 | 8.1 | 3.80 | <.0001 |
| Chest Radiograph Status | ||||||
| Normal | 261 | 23.5 | 587 | 16.4 | 1.56 | <.0001 |
| Abnormal/Cavitary3 | 74 | 11.7 | 635 | 25.6 | 0.39 | <.0001 |
| Abnormal/Non-cavitary2 | 476 | 75.3 | 1,776 | 71.6 | 1.21 | .059 |
| Multidrug-resistant TB | 33 | 3.0 | 83 | 2.3 | 1.29 | .225 |
| Other Drug Resistance | 99 | 8.9 | 363 | 10.1 | 0.87 | .223 |
1 hiv-status was unknown in 2,079 patients. 2 Among those that were tst tested. 3 Among pulmonary tb patients only. |
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| I. TB and HIV Coinfection in New York City | Top of page |
In New York City, we had a very large TB epidemic,” Dr. Munsiff recounted. “Case rates reached about 52 per 100,000 at the height of our recent epidemic in 1992, at which time, at least a third of all patients with TB were HIV-infected. We think it was closer to 40% because there was a lot of underreporting and underestimation.” Over the past 15 years, the percentage of TB cases who are also HIV infected has dropped and now hovers around 15% to 18% of all cases (New York City Department of Health and Mental Hygiene, 2005). While the percentage of TB patients with an unknown HIV status has also decreased from 51% in 1992, it still remains quite high at 28% in 2005. The Bureau of Tuberculosis Control (BTBC) is trying to increase counseling and testing of coinfected patients by offering rapid and conventional HIV testing at all its TB chest centers. For known HIV-infected TB cases, the BTBC has also increased efforts to get high-risk contacts tested for HIV infection.
Data from the Bureau of HIV/AIDS Prevention and Control indicate that in 2000, TB was second to only Pneumocystis pneumonia (PCP) as the most common opportunistic infection in HIV/AIDS patients in New York City.
In New York City, the prevalence of HIV infection among TB patients is higher in men than women. Over the past 5 years, 18% of all male TB cases were HIV-infected, compared to 11% of all female TB cases. Dr. Munsiff explained, “It used to be that the disparity was much greater with almost half the US-born men having HIV infection versus women but the disparity has gone down.” A demographic review of the past six years of TB cases in NYC by HIV status shows that 97% of HIV-infected TB cases are between 19 and 65 years of age, and 64% are US-born (see Table 1).
Compared to the HIV-negative TB patients, HIV-infected TB cases are more likely to be homeless and have history of substance abuse, emphasizing that these patients are often disenfranchised from the community. Dr. Munsiff explained, “It’s a population that’s very hard to reach. Part of the reason why we continue to see a lot of TB is that the patients are not staying in care and receiving treatment, especially for latent TB infection, which could prevent this opportunistic infection.” BTBC’s Homeless Services Unit continues to assess barriers to TB screening at homeless shelters and implement methods to improve screening and treatment of LTBI. They are working to improve programs to conduct contact investigations of infectious cases in the Department of Homeless Services (DHS) shelters, and provide more directly observed therapy (DOT) for LTBI. They also offer TB education for medical providers working in DHS shelters.
Figure 2. HIV-Infected TB Cases by Country of Birth, New York City
While US-born TB cases have decreased by 90% since 1994, Dr. Munsiff went on to say “the percentage of US-born people with TB who have HIV infection really hasn’t changed that much in the past years.” The percentage of US-born TB cases infected with HIV has only dropped 13%, from 43% in 1994 to 30% in 2005 (see Figure 2). “A lot of this reflects the extensive transmission that occurred in the late eighties and early nineties in New York,” Dr. Munsiff said. “There is also ongoing transmission among HIV-infected persons in some congregate residential settings for AIDS patients now. HIV-infected persons living in these facilities are at a greater risk for becoming infected with TB, and onceinfected, are more likely to develop active TB disease due to theirimmunocompromised state.”
There is also a high risk of re-infection and developing active TB once exposed, even if LTBI treatment was completed in the past (CDC, 1998). TB diagnostic tests, such as the tuberculin skin test, do not always indicate if infection is present in immunosuppressed individuals. The BTBC conducts contact investigations and screenings in congregate facilities where TB exposures have occurred. In 2004 and 2005, nineteen such investigations were conducted. Despite these efforts, there have been several outbreaks in residential facilities for HIV-infected persons where extensive transmission occurred. (See Sidebar: Evidence of Recent Transmission in TB and HIV-infected Populations).
The evidence of recent transmission in these facilities underscores the problem of putting severely immunocompromised individuals in congregate settings. Molecular epidemiologic studies indicate recent transmission among individuals who have TB due to clustered strains. Our data have shown that 60% of HIV-infected TB cases in NYC from 2001 to 2005 were genotypically clustered, compared to 40% of HIV-negative cases. While some clustered TB strains do not indicate recent transmission because they are endemic in NYC and may have been acquired several years earlier, the difference between these two groups is significant and is consistent with evidence of ongoing TB transmission in this population (Driver, 2006).
A review of the clinical characteristics of TB patients who also have HIV infection indicated that most (79%) were culture-positive for TB; 21% were clinically diagnosed. HIV-infected TB cases were more likely to have both pulmonary and extrapulmonary disease compared to HIV-negative TB cases, and among HIV-infected extrapulmonary TB cases, there was a higher percentage of meningeal as well as miliary or disseminated TB (see Table 1). HIV-infected TB cases were also more likely to have a normal chest radiograph and less likely to have a cavitary chest radiograph compared to HIV-negative TB cases. TB cases with unknown HIV status were not included in this analysis.
The prevalence of drug resistance did not differ substantially between HIV-positive and HIV-negative TB cases. Dr. Munsiff stated, “New York City has a moderately high prevalence of drug resistance, which is why an empiric four-drug treatment regimen of isoniazid, rifampin (or rifabutin), pyrazinamide and ethambutol is still the standard treatment until susceptibility results become available.”
Clinical outcomes, however, did differ significantly for HIV-infected TB cases (see Table 2). From 2000 to 2005, 18% of all HIV-infected TB cases died during the course of treatment, compared to 3% of all HIV-negative TB cases. Dr. Munsiff noted, “If they have not died before their TB treatment is over, most remain in care and finish treatment. Overall default rates are very low. And whether the cause of death is from TB is very hard to tease out.” However, of all culture-positive HIV-infected TB cases who died before completing treatment, approximately 50% were still culture positive within thirty days of death. TB likely contributed to death in most of these cases.
Additionally, Dr. Munsiff showed data from two cohorts of HIV-infected TB patients in NYC, one group from 1996 (pre-highly active antiretroviral therapy [HAART]) and another from 2005 (post-HAART). In both groups, approximately 70% of patients knew their HIV positive status at the time of TB diagnosis. Dr. Munsiff indicated, “TB diagnosis is not the time when the initial diagnosis of HIV was made in most of the coinfected patients. They were already known to have HIV infections, but most of them were not in care.” The median CD4+ count was less than 200 cells/mm3 for both groups. Therefore, it is likely that most of these patients were eligible for HAART, and yet, only 18% of the HIV-infected TB cases in 1996 were on a protease inhibitor (PI). In 2005, only 33% of the HIV-infected TB cases were on some type of antiretroviral treatment. These data further identify the gaps in the diagnosis and treatment of TB\ patients with HIV infection.
| Table 2. Treatment Outcomes of TB patients by HIV status in New York City, 2000–2005* | Treatment Outcomes | HIV-infected patients (n=1,113) | HIV-uninfected patients (n=3,580) | or | P value | |
| N | % | N | % | |||
| Completed treatment | 748 | 67.2 | 3,021 | 84.3 | 0.38 | <.0001 |
| Died prior to treatment completion | 201 | 18.1 | 122 | 3.4 | 6.25 | <.0001 |
| Still on treatment as of April 18, 2006 | 106 | 9.5 | 282 | 7.9 | 1.23 | .081 |
| Lost to follow up | 38 | 3.4 | 67 | 1.9 | 1.85 | .002 |
| Refused treatment | 10 | 0.9 | 35 | 1.0 | 0.92 | .813 |
| Moved out of New York City | 10 | 0.9 | 53 | 1.5 | 0.60 | .141 |
| * HIV-status was unknown in 2,079 patients. | ||||||
In March 2006, the BTBC launched a TB Awareness Campaign on World TB Day. The campaign, “Moving Toward a Tuberculosis-Free New York City,” combines local media advertising and partnership efforts with medical providers and community-based organizations to target communities in NYC with high rates of TB infection and disease. Specific outreach is ongoing to HIV providers and AIDS clinics in NYC to ensure testing and treatment for LTBI. While the BTBC offers directly observed therapy (DOT) to all active TB cases on treatment, it is also working to expand DOT for HIV-infected persons on LTBI treatment as well.
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