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Being Alive
Tuberculosis and HIV/AIDS: What's New and What You Should Do
Walt Senterfitt, RN, MPH
April 5, 1992
Being Alive 1992 Apr 5: 10

A resurgent tuberculosis (TB) epidemic has gathered increasing attention from the mainstream press over the last few months. The specter of highly contagious and usually fatal "multiple-drug- resistant" (MDR) strains of TB is frightening public health authorities. These new developments are typically linked to the spread of the HIV/AIDS epidemic. Just how serious is the threat, especially to persons living with AIDS or HIV infection? What can and should we do about it? In a punchline, the threat is quite real and serious but it can be effectively fought with specific measures to protect individuals and collective action to protect all of us.

TB is unique among HIV-associated infections because it is at once contagious, readily treatable with standard drugs, and potentially preventable. All of us, and health care providers most especially, must be familiar with HIV-associated TB and its treatment; it is often the first clinical manifestation of immunodeficiency.

BACKGROUND TB is transmitted by tiny airborne droplets, created when a person with active pulmonary TB coughs or sneezes. These infected droplets can then be breathed in by a susceptible person. The initial (primary) infection is contained in most people and does not develop into active disease, though a small number of bacilli may remain dormant in the body for the rest of the host's life. Clinically apparent disease (referred to as reactivation TB) may occur many years later, usually associated with immune system dysfunction. The lifetime probability, without HIV, of latent infection reactivating is about 10%.

Persons with HIV have a much higher probability of having reactivated TB than the general population as much as 8 to 10% a year. Most TB cases in HIV+ people are from reactivation of old infections. However, since it is contagious by casual contact (unlike most OIs), PWAs/PWHIVs can also contract new or primary TB infection. These new infections can go rapidly to active disease, rather than follow the typical course of years of dormancy.

WHO IS AT RISK ? It is often assumed that only those whose HIV infection is associated with injection drug use or debilitating inner-city poverty are at increased risk for active TB. Indeed, epidemiologic data show the greatest concentration of TB/AIDS cases have occurred in such populations. For example, in New Jersey and New York, 82 to 91% of such persons were black or Hispanic (typically, but not always, also poor) and 62 to 69% were heterosexual IDUs. These concentrations are probably due to both higher pre-HIV prevalence of dormant TB infections and to poverty-associated crowded living conditions, homelessness, and physical debilitation which always facilitate TB transmission.

However, it would be a big mistake to assume that traditional poverty, minority group membership and drug use delimit the risk. In California and Texas, for instance, more than 40% of the TB/AIDS cases through 1990 were among non-Hispanic whites and nearly 60% were in gay or bisexual men who had not injected drugs. Group residences and hospices, hospitals and clinics used by PWAs/PWHIVs from diverse backgrounds have been the sites of reported outbreaks and rapid spread of new TB infection. The risk varies in magnitude, but includes all of us.

MANIFESTATION AND DIAGNOSIS Reactivated TB usually occurs at an earlier stage of immunodeficiency than other opportunistic infections. Indeed, it may be the first symptom of HIV-related disease. The median T cell count for appearance of TB symptoms in one study of HIV positive persons was 342. Experts think this is because M. tuberculosis is more virulent than other pathogens such as its relative M. avium complex (MAC) or Pneumocystis carinii (PCP).

New primary TB infections typically occur with more severe immunosuppression, though definitive epidemiologic data are lacking.

A major problem in diagnosis is that the most common symptoms of TB infection fever, weight loss, night sweats, and shortness of breath are also frequent symptoms of several other OIs, especially PCP and MAC. If these symptoms occur in someone without other symptoms of HIV, the odds are greater that it is TB, but it still often requires several diagnostic procedures.

Another problem is that the appearance of reactivated TB on x-rays and in physical exams is usually not typical of non-HIV-associated TB. In general, the more advanced the HIV disease is when TB is recognized, the less typical are the TB manifestations. For one thing, the disease is usually not confined to the upper lobes of the lung, as it is in non-HIV cases. The typical cavitations are rarely seen on x-ray. There is a much greater chance of finding "extrapulmonary" TB disease (outside the lungs), usually with but sometimes without concomitant pulmonary disease.

Another complication is that the tuberculin skin test, an integral part of TB screening and diagnosis, becomes less and less reliable as persons with HIV progressively develop "anergy," or the loss of the ability to react to foreign material injected under the skin.

The definitive diagnosis of TB has rarely ever been simple and straightforward. The bacillus grows only very slowly in laboratory culture, diagnostic ("acid-fast") smears are positive in only a minority of sputum specimens from people known to have active TB and x-rays can be misleading. The particulars of HIV's interaction with TB have just greatly exacerbated these problems.

Therefore, extra vigilance and diligence are required. Providers should identify those at risk for reactivated TB. This is most easily done by administering the tuberculin skin test. At early stages of HIV infection, this is a highly accurate marker of past TB infection. Even with advanced HIV disease, it still identifies half or more of those at risk, especially if the criterion for a positive test is reduced from the standard 10 mm diameter to 5 mm (as the CDC and TB experts now recommend). After a negative test, the provider should ascertain whether the person ever had a positive skin test, or if other aspects of a person's background indicate a likelihood of having been exposed in the past. People thus identified as at risk should probably take anti-TB prophylaxis, and the possibility of active TB should always be kept in mind.

Diligence is required to seek out TB as a possible cause of any suspicious symptoms. It may require an eye for the unusual x-ray presentation, repeated sputum and blood cultures and smears, and sometimes more invasive tests like lymph node biopsy (needle or excision) and bronchoscopy. This diligence, and a modicum of test-related discomfort and annoyance, can pay off not only in starting effective TB treatment early enough but also in avoiding unnecessarily treating another suspect cause.

Finally, the drugs to treat TB can be started on the basis of likelihood and good empirical reasons, even without a definitive diagnosis. Though these drugs have potentially serious side effects, in general they have been found to be less toxic than most.

TREATMENT, SIDE EFFECTS AND RESISTANCE Fortunately, most strains of TB found in persons with HIV or AIDS have been quite susceptible to the standard therapy for TB in all people. The vast majority of HIV positive persons with documented TB who take the appropriate standard regimen demonstrate complete recovery from their TB symptoms and laboratory evidence of active disease vanishes. The only changes to the standard regimens are to continue treatment longer, and to be especially watchful for side effects and drug interactions.

Since drug resistance is always a concern with TB, the baseline recommended treatment is a three-drug regimen: isoniazid or INH (300 mg per day), rifampin (600 mg per day), and pyrazinamide or PZA (30 mg per kg per day) for the first two months, followed by isoniazid and rifampin for 7 more months, or for 6 months after sputum cultures become TB-negative, whichever is longer. If a possibly drug resistant strain is suspected, therapy should include a fourth drug, ethambutol. There are individual reasons for modifying standard regimens, eg. intolerable side effects or development of resistance, so particular therapy should be carefully discussed with and prescribed by one's provider.

It is critical to take the medications very regularly and for the entire duration of indicated treatment. Failure to do so albeit often for understandable reasons associated with poverty, multiple life problems, and inequitable access to health care is the major proximate cause of the development of drug-resistant strains.

The most threatening form of resistance is the recent emergence of the so-called MDR strains. In the past two years, at least six outbreaks of MDR TB have been reported to the CDC, totalling 200 cases. About 90% of these cases have been in persons with HIV, and some of the remaining 10% have been in other persons in close association with HIV/TB patients. The mortality rate from this extremely virulent form of the disease has ranged from 70 to 90% with a median of 4 to 16 weeks from diagnosis to death. It is probable that this horrifying mortality rate can be reduced by earlier identification of TB in general and resistant strains in particular.

Much more research needs to be done on the incidence and severity and preventability of adverse reactions to anti-TB drugs, the long term effects of their use, and their interaction with other medications. Preliminary studies have shown that rifampin may cause untoward side effects in about 12% of people who take it, somewhat similar to those caused by sulfa drugs in some people usually rashes and fevers but life-threatening in a rare case or two. Less frequently, there has been intolerance to INH, PZA, and ethambutol.

When these reactions have occurred, it has almost always been early on, within the first two months of therapy. In terms of interaction, there has been none reported with antiretroviral drugs, but there are reports of interaction of INH and rifampin with antifungal agents ketoconazole and fluconazole. Both INH and rifampin reduce serum levels of both of these antifungals, so the antifungal doses need to be increased. Ketoconazole, at least, can also inhibit the absorption of rifampin, resulting in its failure to work against TB.

PROPHYLAXIS AND PREVENTION OF TRANSMISSION Effective prevention of reactivated TB is possible in more than 90% of persons with healthy immune systems by taking 300 mg a day of isoniazid (INH) for 9 months. Studies are underway by NIH to confirm that this prophylactic regimen is as effective among HIV-infected people, but it's reasonable to assume so in the meantime given the documented similarity in response to treatment regimens. The CDC recommends that prophylaxis with HIV seropositivity be extended to 12 months. Some providers and experts think it should continued for life. There is also some controversy about when to start prophylaxis. Some say when T cell counts first drop under 500, others say whenever evidence of HIV seropositivity is first discovered. Finally, there is debate about how widely to cast the prophylactic net. Certainly, anyone with a current or past positive tuberculin skin test should take prophylaxis at some chosen point. When tuberculin reactivity cannot be determined, it's a judgement call, depending on an estimate of one's demographic and individual risk.

In some countries, but not the US, a partially-effective vaccine, known as BCG, is used to prevent primary infection with TB. Some studies are underway to help determine if the net benefits of this approach would be helpful in the context of HIV, but it is not currently recommended.

The most effective measures to prevent transmission, and thus new cases of primary TB infection among those not previously exposed are 1) the rapid identification and appropriate treatment of all possible cases of active TB, whether primary or reactivated; 2) rigorous adherence to recommended infection control procedures in health care settings (including having hospitalized patients with active TB stay only in rooms with external or negative-pressure ventilation and having anyone with even suspected active TB wear protective hospital masks when around their visitors, fellow patients, or health care personnel); 3) in living and social situations, asking people with active coughs to wear protective hospital masks until it is known that the cause of the cough is NOT TB or until treatment has been underway two weeks if it IS TB.

GOVERNMENT AND MEDICAL ESTABLISHMENT RESPONSE The usual suspects were caught flat-footed and initially responded to the new tuberculosis epidemic with palpable, even criminal, negligence. Both research and public health control measures have been ill-funded for years because officialdom thought TB had been largely conquered. Unstated, but likely in the eyes of most of us, is a further reason: the perceived primary affected groups were drug users and the inner-city minority and/or immigrant poor. Who cares? Even within the HIV-affected communities, TB was for a time given scant attention for similar class-related reasons.

Concretely, some key anti-TB drugs were allowed to become unavailable. According to CDC Director William Roper and chief TB expert Dixie Snider, "Streptomycin and aminosalicylic acid are currently unavailable, and supplies of isoniazid [sic!], cycloserine, and ethionamide are erratic." Why? These drugs are not profitable for pharmaceutical companies because patents have expired and demand for generic forms is comparatively low. The authority and responsibility is the government's, to arrange that production and availability nevertheless continue. They fell down on the job.

Furthermore, Roper and Snider acknowledge, "treatment strategies for persons with drug-resistant tuberculosis and those exposed to such persons have not been evaluated." This is part of the larger problem of inattention to detection, prevention, and conquest of resistance. Immediate steps must be taken to speed research in developing faster and more accurate resistance assays, more drugs, and more rapid diagnostic tests for all forms of TB. Funds must be found to enable hospitals and clinics to retrofit sufficient patient and procedure rooms with proper ventilation. And, again quoting Roper and Snider, "we must reevaluate the need for an effective tuberculosis vaccine." Roper and Snider are comparatively enlightened. They have just established a federal Tuberculosis Task Force, albeit belatedly and perhaps under goading from ACT UP's national TB Working Group, established last fall to fight the general paralysis. We hope the good doctors will be able to get the attention of their Bush Administration superiors and the less-awake among their peers, but you can pardon our "wait-and-see" stance and determination to keep a very close eye on them.

WHAT CAN YOU DO ? First, make sure you choose and follow a smart strategy toward your own individual risk of TB infection. If you are tuberculin-positive, consider INH prophylaxis if you haven't already. If you don't know whether you are or not, try to find out or estimate your risk in consultation with your provider. Discuss TB with your provider the next chance you get, and whenever some symptoms arise that could conceivably involve TB.

Second, spread the word. Urge others to become "TB-aware," including especially awareness of the need to keep taking prophylactic or treatment medication for the whole damn time.

Third, get in the habit of having around or asking for a few hospital masks at regular PWA/PWHIV meeting places. Persons actively coughing can be encouraged to use them, or others can if they wish, so that it becomes common and routine. We may well be reluctant at first, because of past bad experience with groundless isolation precautions by others, but this one's for us. The risk is probably not very high for situations of relatively brief exposure, as in a two-hour support group. Most transmission of primary infection to PWAs, including the MDR strains, has been in situations of repeated close exposure such as prison, hospital, hospice, or group home. However, given that TB can be TOTALLY nasty and given that, for a change, we can prevent transmission of this one, why not err on the side of caution? Fourth, support calls for more research, drug development/availability, and adequate public health measures. I'm the local contact for the national ACT UP TB Working Group, and would like to see one established for LA County (and in every locality). You can reach me through the Being Alive office or at 310.657.6176.

(The references from medical journals which underpin this article are available at the Being Alive office.)