Richard E. Chaisson

Seropositivity for HIV and the development of AIDS or AIDS related condition: three year follow up of the San Francisco General Hospital cohort

The three year actuarial progression rate to the acquired immune deficiency syndrome (AIDS) in a cohort of men in San Francisco who were seropositive for the human immuno-deficiency virus (HIV) was 22%. An additional 26 (19%) developed AIDS related conditions. β2 Microglobulin concentration, packed cell volume, HIV p24 antigenaemia, and the proportion and number of T4 lymphocytes each independently predicted progression to AIDS. β2 Microglobulin was the most powerful predictor. The 111 subjects tested who were normal by all predictors (40%) had a three year progression rate of 7%, and the 68 subjects who were abnormal by two or more predictors (24%) had a progression rate of 57%. Two thirds of all men who progressed to AIDS were in the last group. The median T4 lymphocyte count in subjects who did not progress to AIDS fell from 626 × 106 to 327 × 106/1. HIV p24 antigenaemia developed in 7% of the subjects per year. The proportion who were abnormal by two or more predictive variables rose to 41%. At three years an estimated two thirds of the seropositive subjects showed clinical AIDS, an AIDS related condition, or laboratory results that were highly predictive of AIDS. It is concluded from the observed rates and the distribution of predictive variables at three years that half of the men who were seropositive for HIV will develop AIDS by six years after the start of the study, and three quarters will develop AIDS or an AIDS related condition.

Treatment of Tuberculosis in Patients with Advanced Human Immunodeficiency Virus Infection

BACKGROUND AND METHODSnInfection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988.nnnRESULTSnAt the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3.nnnCONCLUSIONSnTuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.

Human immunodeficiency virus infection in heterosexual intravenous drug users in San Francisco.

To investigate the risk of infection with the human immunodeficiency virus (HIV) in San Francisco, the prevalence of antibodies to HIV was determined in 281 heterosexual intravenous drug users recruited from community-based settings. Ten per cent of subjects had ELISA and Western blot confirmed seropositivity for antibodies (95 per cent CI 6.8-14.2 per cent). Analysis of behavioral factors revealed an increased risk of seropositivity in addicts who reported regularly sharing needles when injecting, particularly those sharing with two or more persons (odds ratio = 5.43; 95 per cent CI 1.08-52.5). Blacks and Latinos also had a greater prevalence of seropositivity than Whites, and this finding persisted after adjustment for needle sharing (adjusted odds ratio = 2.8; 95 per cent CI .84-8.59). Seropositivity was not associated with age, sex, duration of drug use, or history of prostitution. These data indicate that a new epidemic of AIDS (acquired immunodeficiency syndrome) in intravenous drug users, similar to that which has occurred among homosexuals in San Francisco, is possible. The relatively low seroprevalence in 1985 provides health officials an important opportunity to intervene and attempt to prevent widespread infection of drug users with HIV.

Surrogate markers for survival in patients with AIDS and AIDS related complex treated with zidovudine.

OBJECTIVE--To determine whether early effects of zidovudine treatment on CD4+ lymphocyte count and concentrations of beta 2 microglobulin, neopterin, or HIV p24 antigen or antibody are correlated with survival in patients with AIDS or AIDS related complex. DESIGN--Retrospective study of changes in laboratory markers and survival. SETTING--Multicentre trial at university hospital clinics. SUBJECTS--90 Patients with AIDS or AIDS related complex. INTERVENTION--Patients started zidovudine 200 mg orally every four hours. Fifty six of the patients died a median 17 months after starting zidovudine; the remaining 34 patients were followed up for a median 25.5 months. MAIN OUTCOME MEASURES--Changes in CD4+ lymphocyte count and serum concentrations of p24 antigen and antibody, beta 2 microglobulin, and neopterin; survival of the patient. RESULTS--The pretreatment characteristics that independently predicted poor survival were determined using a multivariate proportional hazards model: a diagnosis of AIDS (v AIDS related complex), age over 45 years, and the logarithm of serum neopterin concentration. When these baseline characteristics were controlled for the logarithm of CD4+ lymphocyte count at weeks 8-12 of treatment (p = 0.007) and an increase in serum beta 2 microglobulin concentration at weeks 8-12 (p = 0.05) also independently correlated with survival. In the 38 patients with a better pretreatment prognosis, 24 month survival estimated by the product-limit method was 88% for those with a good response on both surrogate markers during early treatment compared with only 50% for those with a poor response on either marker. In the 38 with a worse pretreatment prognosis, 24 month survival was estimated to be 49% for those with a good response on both surrogate markers compared with only 18% for those with a poor response on either. CONCLUSION--These data suggest that CD4+ lymphocyte count at 8-12 weeks and, perhaps, change in serum beta 2 microglobulin concentration could be surrogate end points for clinical outcome in trials of antiretroviral drugs for patients with HIV disease.

Rectal Leishmaniasis in a patient with acquired immunodeficiency syndrome

A severe rectal lesion due to Leishmania infection is described in an American-born homosexual man with the acquired immunodeficiency syndrome. The infection, which may have been venereally transmitted, responded to treatment with amphotericin B. There was no evidence of visceral leishmaniasis. The contribution of the patients immunodeficiency to the development of the atypical cutaneous leishmanial lesion is unclear. The case may foretell increasing problems with protozoan infections in AIDS as the epidemic spreads to areas with endemic protozoan diseases.

Time of exposure and risk of HIV infection in homosexual partners of men with AIDS.

We interviewed, and tested for HIV antibody, 117 homosexual men who had been regular sexual partners of men who developed acquired immunodeficiency syndrome (AIDS); 85 tested seropositive. Receptive anal intercourse with the index AIDS case and number of different sexual partners with whom subjects were anally receptive were both risk factors. Controlling for the number of partners with whom subjects were anally receptive, we found that the odds ratio of receptive anal intercourse with the case was infinite (95% confidence intervals, 3.3-infinity) if sexual contact continued up to or beyond the time of diagnosis, while the odds ratio was 1.0 (95% CI 0.3-3.2) if contact ceased before the cases AIDS diagnosis. Risk was not associated with the duration or frequency of contact. Our data suggest that the potential for sexual transmission from an HIV-infected person may be greater close to or after the onset of disease.