Safety evaluation of nonoxynol-9 gel in women at low risk of HIV infection.

OBJECTIVE: To determine the safety of a vaginal microbicide, COL-1492, containing 52.5 mg nonoxynol-9, applied once daily for 14 days among healthy volunteers. METHODS: A randomized, double-blind controlled trial with three arms, COL-1492 gel versus placebo gel versus no-treatment controls, was conducted. Outcomes of interest were reported genital symptoms, incidence of gynaecological signs, and incidence of genital lesions revealed by colposcopy. Participants were enrolled in four centres (Belgium, The Netherlands, and two in Thailand). RESULTS: A total of 534 women participated in the study: 179 used COL-1492, 178 used placebo, and 177 were no-treatment controls. Study visits were scheduled 1 week prior to enrollment (day -7), day 0 (enrollment), day 8 and day 14. The most frequently reported genital symptom was vaginal discharge in both the COL-1492 and placebo groups. This appeared to be related to leakage of the product out of the vagina. The incidence of lesions associated with epithelial disruption (ulcers and abrasions) was very low (< 2%) and there was no statistically significant difference between the three groups. Of the lesions observed by colposcopy that did not involve epithelial disruption, petechial haemorrhage was the most frequently detected, with an incidence of 20.1, 9.0 and 7.3% in the COL-1492, placebo and control groups, respectively. COL-1492 users had a higher incidence of erythema (8.4 versus 2% in the other groups). CONCLUSION: COL-1492 showed minimal toxicity when applied once daily. A Phase III trial to assess the product's effectiveness in HIV prevention is currently ongoing.

Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection: a randomised, double blind, placebo controlled trial.

BACKGROUND: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but controversy on the efficacy of this treatment persisted. METHODS: We studied 559 adult Ugandan patients with WHO stage 2-4 HIV infection and a Karnofsky performance score of more than 50, who had not received any drugs with antiretroviral activity in the previous 3 months. The patients were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-alpha/day or placebo. The duration of treatment was extended from 28 weeks to 60 weeks 9 months after enrollment had started. At that time 112 subjects had already received 28 weeks of treatment and been discontinued from the study. RESULTS: Both study groups were comparable with respect to all baseline characteristics studied, except that the nHuIFN-alpha group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 x 10(6)/l) than the placebo group (median 85.3 x 10(6)/l) (p = 0.033). Therefore, all analyses were adjusted for CD4+ lymphocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-alpha and placebo had similar mortality, disease progression rates, decline of CD4+ lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms. No patient reverted to HIV-1 seronegative antibody status. Serious adverse events were not seen. Quality control of the study medication documented that the active drug indeed contained IFN-alpha activity. CONCLUSIONS: The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-alpha/day in a population of African patients with symptomatic HIV infection.

Caring for patients with HIV and AIDS in middle income countries.

PIP: Increased access, in middle-income countries, to innovative but costly medical technologies for the treatment of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) raises important policy considerations about how to optimize their use. Realizing the full potential of antiretroviral therapy, for example, requires widespread availability of HIV tests to identify those in the early stage of HIV infection, counseling services to inform people of their test results and explain the therapeutic options, available and affordable drugs, monitoring of drug efficacy and toxicity, mechanisms to ensure long-term compliance, and well functioning psychosocial support systems. In Thailand, a cost-effectiveness study modelling the use of different antiretroviral treatment options demonstrated that investments in antiretroviral therapy and formula feeding to prevent maternal-child HIV transmission were more effective and affordable than providing antiretroviral agents to those with established HIV infection. The cost of preventing vertical HIV transmission amounted to 16% of Thailand's national AIDS budget. The cost of extending access to and compliance with treatment and preventing opportunistic infections would be 129% of the budget, while that of providing antiretroviral drugs to all those with symptomatic HIV infection would be 235-630% of the budget (depending on the complexity of the regimen). More such studies are needed to develop a conceptual framework for policy development.^ieng

Preventive therapy for tuberculosis in HIV infection: the promise and the reality.

PIP: An increasing incidence of tuberculosis has been recorded in areas where both human immunodeficiency virus (HIV) and Mycobacterium tuberculosis are prevalent. 98% of HIV-associated tuberculosis cases occur in developing countries, most notably sub-Saharan Africa. This trend has led to the consideration of tuberculosis prevention therapy for HIV-infected patients. The efficacy of isoniazid for this purpose has been demonstrated in numerous clinical trials, but its application has been limited by concerns about hepatotoxicity, non-adherence, drug resistance, and costs. Recommended is the approach adopted in the US of providing a six-month course of isoniazid to those with a positive tuberculin skin test reaction and epidemiologic risk factors; for those already infected with HIV, 12 months of treatment is suggested. Rifampicin preventive therapy is recommended for those infected by isoniazid-resistant bacilli. Needed are studies to assess operational feasibility, cost-benefits, the use of life-long isoniazid preventive therapy in areas of high tuberculosis transmission, and alternative regimens such as short-course multidrug treatment.^ieng

Frequent use of menfegol spermicidal vaginal foaming tablets associated with a high incidence of genital lesions.

Menfegol is a spermicide with in vitro activity against human immunodeficiency virus (HIV). A randomized placebo-controlled safety study covered the use of menfegol foaming tablets for 14 days at increasing frequencies of insertion by 125 prostitutes in Dakar, Senegal. The frequencies of colposcopically diagnosed genital lesions were 5.0%, 11.8%, 27.8%, 49.7%, and 29.4% among menfegol recipients when tablets were used once every other day or 1, 2, 4, or 8 times a day, respectively (P < .05). Among placebo recipients, frequencies were 11.1% and 23.5% when tablets were used < 8 times daily and 8 times daily, respectively. There was no association between subjective genital symptoms and the incidence of colposcopically detected lesions. The high incidence of genital lesions when menfegol foaming tablets were used more than once daily suggests that their frequent use should not be recommended to prevent HIV transmission. In use at low frequency, the tablets' toxicity might be balanced by anti-HIV properties. Safety studies on vaginal microbicides should use objective methods, such as colposcopy, to assess the incidence of lesions.

Pulmonary tuberculosis in HIV-infected patients in Zaire. A controlled trial of treatment for either 6 or 12 months.

BACKGROUND: We studied the efficacy of a short-course regimen of chemotherapy for pulmonary tuberculosis in Kinshasa, Zaire. We also assessed whether, among patients with human immunodeficiency virus (HIV) infection, treatment should be extended from 6 to 12 months. METHODS: HIV-seropositive and HIV-seronegative outpatients with pulmonary tuberculosis were treated with rifampin, isoniazid, pyrazinamide, and ethambutol daily for two months, followed by rifampin plus isoniazid twice weekly for four months. The HIV-positive patients who had no evidence of tuberculosis were then randomly assigned to receive either rifampin plus isoniazid or placebo twice weekly for a further six months. We also followed a comparison group of HIV-seronegative patients who received no further treatment for tuberculosis after six months. RESULTS: After six months, 260 of 335 HIV-seropositive and 186 of 188 HIV-seronegative participants could be evaluated, and their rates of treatment failure were similar: 3.8 and 2.7 percent, respectively. At 24 months, the HIV-seropositive patients who received extended treatment had a relapse rate of 1.9 percent, as compared with 9 percent among the HIV-seropositive patients who received placebo for the second 6 months (P < 0.01). Extended treatment did not improve survival, however. Among the HIV-seronegative patients, 5.3 percent relapsed. CONCLUSIONS: Among HIV-seropositive patients with pulmonary tuberculosis, extending treatment from 6 to 12 months reduces the rate of relapse but does not improve survival. The six-month program of partly intermittent antituberculous treatment may be an acceptable alternative when resources are limited.

Anti-A60 immunoglobulin G in the serodiagnosis of tuberculosis in HIV-seropositive and seronegative patients.

OBJECTIVE: A60 is a high molecular weight mycobacterial antigen complex. The detection of immunoglobulin (Ig) G antibodies to A60 has been advocated as a reasonably sensitive and specific test for active tuberculosis (TB). We aimed to compare the sensitivity of this test among HIV-seropositive and HIV-seronegative patients with pulmonary TB. METHODS: The presence and concentration of anti-A60 IgG antibodies was assessed by enzyme-linked immunosorbent assay in 208 HIV-seropositive and 91 HIV-seronegative Zaïrian patients with smear-positive pulmonary TB. The relationship between anti-A60 IgG levels and HIV serostatus, CD4+ lymphocyte counts, presence of clinical AIDS, and tuberculin skin test results was verified. RESULTS: Only 36.5% of the HIV-seropositive, compared with 69.2% of the HIV-seronegative patients had a positive anti-A60 IgG test (P < 0.00001). Among HIV-seropositive patients, anti-A60 IgG levels did not differ according to CD4+ lymphocyte counts, presence of clinical AIDS, or tuberculin skin test results. CONCLUSIONS: Among patients with pulmonary TB, the sensitivity of testing for anti-A60 IgG was much lower among HIV-seropositive than among HIV-seronegative patients, even from the early stages of HIV-related immunodeficiency. This limits the utility of anti-A60 IgG-antibody testing in the diagnosis of TB among HIV-infected patients.

A clinical and pathological comparison of the WHO and CDC case definitions for AIDS in Kinshasa, Zaïre: is passive surveillance valid?

OBJECTIVES: To compare the specificity of the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) case definitions for AIDS in autopsy cases from Zaïre. SETTING: Mama Yemo Hospital and University Hospital morgues in Kinshasa, and Karawa Hospital in Equateur Region, Zaïre. METHODS: Autopsy cases with a clinical diagnosis of AIDS on the death certificate or chart were studied. Evaluation included post-mortem HIV-1 serology, chart review for specific AIDS-related symptoms and signs, and application of WHO and CDC case criteria to the clinical and autopsy diagnoses. RESULTS: Of the 68 diagnosed AIDS cases, 98% fulfilled WHO criteria for AIDS and 93% fulfilled both WHO and CDC criteria. All cases fulfilling both criteria were HIV-1-seropositive. Opportunistic infections accounted for 84% of CDC AIDS-defining conditions. Disseminated tuberculosis was the most frequent (41%) specific diagnosis; Pneumocystis carinii pneumonia was rare (< 2%). CONCLUSIONS: There was good concordance between WHO and CDC case definitions. A diagnosis of AIDS on the chart or death certificate is adequate for surveillance purposes in this population.

Mycobacterium tuberculosis in household contacts of human immunodeficiency virus type 1-seropositive patients with active pulmonary tuberculosis in Kinshasa, Zaire.

Rates of infection with Mycobacterium tuberculosis were compared in Kinshasa, Zaire, in 521 household contacts of 74 human immunodeficiency virus type 1 (HIV-1)-seropositive index patients and in 692 household contacts of 95 HIV-1-seronegative [corrected] index patients with sputum smear-positive pulmonary tuberculosis: No difference was noted between contacts of HIV-1-seropositive and -seronegative patients. The increasing prevalence of M. tuberculosis infection with increasing age was similar in household contacts of seropositive and seronegative patients; by age 16 years, 75% were purified protein derivative-positive. The similarly low rates of M. tuberculosis infection in household contacts of HIV-1-seropositive and -seronegative index patients with sputum smear-positive pulmonary tuberculosis indicates that HIV-1-seropositive patients with pulmonary tuberculosis are not more infectious than HIV-1-seronegative patients with pulmonary tuberculosis.

Spectrum of immunodeficiency in HIV-1-infected patients with pulmonary tuberculosis in Zaire.

Tuberculosis (TB) is the most common opportunistic infection in African patients who die from AIDS, yet the stage of immunodeficiency at which TB develops is uncertain. We studied the immune status of HIV-infected outpatients with pulmonary TB in relation to their clinical presentation in a cross-sectional study of 216 HIV-seropositive and 146 HIV-seronegative ambulatory incident cases of smear-positive and culture-positive pulmonary TB in Kinshasa, Zaire. HIV-seropositive and seronegative patients had median CD4 lymphocyte counts of 316.5/microL and 830.5/microL, respectively. Of the HIV-seropositive patients, 32.9% had less than 200 CD4 lymphocytes/microL, 37% between 200 and 499, and 30.1% 500 or more. Clinical AIDS, as defined by the WHO clinical case-definition or a modified version, was of similar limited use as a predictor of immunodeficiency. Among HIV-seropositive patients, oral candidosis, lymphopenia, a negative tuberculin purified protein derivative test, and cutaneous anergy were strongly associated with CD4 counts of less than 200/microL, and seemed to be better markers of immune dysfunction. We conclude that pulmonary TB develops across a broad spectrum of HIV-induced immunodeficiency and that a diagnosis of pulmonary TB is of limited use as a marker of stage of HIV disease in African HIV-infected outpatients.

PIP: Between March 1989 and September 1991, physicians compared CD4 lymphocyte counts of 216 HIV-seropositive patients whose sputum smears tested positive for pulmonary tuberculosis (TB) with those of 146 HIV- negative patients who also tested positive for TB at a TB screening center in Kinshasa, Zaire. The researchers wanted to investigate the immune status of HIV-infected outpatients with pulmonary TB in relation to clinical criteria. HIV seropositive patients had much lower CD4 lymphocyte counts than did HIV seronegative patients (total CD4 count, 316.5/mcl vs. 830.5/mcl; CD4 count, 13% vs. 36%; p .001). 90.4% of HIV-positive patients had CD4 counts 800 compared with 48% of HIV- negative patients. 32.9% of HIV-positive patients had CD4 counts 200 while just 1.4% of HIV-negative patients did. As CD4 counts fell, weight loss, diarrhea during the previous month, past or present herpes zoster, and oral candidosis occurred more frequently (p = .004 for oral candidosis and p = .02 for the rest). Negative purified protein derivative RT23 (PPD) tests and cutaneous anergy occurred more often as immunodeficiency rose (p .001). Increased immunosuppression was also characterized by no detectable cavitation on chest radiography, anemia, and low total lymphocyte counts (p = .02 for absence of cavitation and p .001 for the others). These results suggested that pulmonary TB occurred along the continuum of immunodeficiency as defined by CD4 counts. Thus, it is not likely to be a marker of the severity of HIV infection. Instead weight loss, diarrhea during the previous month, past or present herpes zoster, oral candidosis, negative PPD test and cutaneous anergy, absence of detectable cavitation on chest radiography, anemia, and low total lymphocyte appeared to be better markers of the severity of HIV-related immunodeficiency.

Low and stable HIV seroprevalence in pregnant women in Shaba province, Zaire.

Sentinel serosurveillance for HIV infection has been carried out in Shaba province, Zaire, among consecutive pregnant women attending antenatal clinics from 1989 to 1991. There were four surveillance sites (three urban and one semiurban), at which a total of 13 surveillance studies were made of 4,205 women. Overall, 3.1% were HIV seropositive. There were no significant differences in HIV seroprevalence between surveillance sites, and HIV seroprevalence did not increase at any of the surveillance sites during the 2-year period of study. Since changes in the population studied did not occur between surveillance studies, it is believed that the observed stable trend reflects stable HIV seroprevalence rates in the general adult population of the surveillance sites. Collateral HIV seroprevalence data were available from 8,725 blood donors at 20 sites (six urban, 14 rural) in the province, who had an overall HIV seroprevalence of 4.6%. The higher HIV seroprevalence rate among blood donors was probably due to selection bias, since HIV seroprevalence rates in two blood banks, which relied nearly exclusively on replacement donors, were 2.7 and 2.8%, our best estimate for HIV seroprevalence in the three cities where blood banks exist and where no surveillance studies were carried out. The stable and relatively low HIV seroprevalence rates in Shaba province are in sharp contrast with the rapidly increasing and much higher rates in neighboring Zambia and other East African cities. Reasons for this discrepancy are unclear, and their eludication may yield critical information for HIV prevention programs.

Use of a rapid test and an ELISA for HIV antibody screening of pooled serum samples in Lubumbashi, Zaire.

Pools with a size of 3 and 5 were prepared by mixing one HIV confirmed HIV-1 seropositive serum with either 2 or 4 HIV seronegative sera at the Regional HIV Laboratory in Lubumbashi, Zaire. These pools were assessed in a blind fashion by ELISA (Vironostika anti-HTLV-III microELISA system, Organon Technika). Similarly constituted pools of 3 samples were assayed by a rapid test with visual reading (HIVCHEK 1 + 2, Dupont de Nemours). With the HIVCHEK, pooling was achieved on the test device itself by dropping consecutively 3 different serum samples on the devices's membrane. After the last serum was soaked in, wash fluid and conjugate were added. Results of the pooling experiments were compared with testing sera individually. The ELISA results from pools and from individual tested samples matched completely if, and only if, the final dilution of individual samples in the reagent medium was the same as recommended by the manufacturer for testing of individual samples. With the HIVCHEK a sensitivity of 99-100% was obtained with pooled sera. Both approaches seemed sensitive enough to enable their use for screening of blood donors and patient management, but a prospective study to validate these preliminary results is necessary.

Treatment, prophylaxis and research priorities for developing countries.

PIP: An estimated two million new adult and pediatric HIV infections occurred worldwide during 1992, more than 50% of them in sub-Saharan Africa, 25% in Asia, and one-eighth in Latin America and the Caribbean. The remaining infections occurred in Europe, North America, and the industrialized countries of the Pacific Rim. Transmission by sexual intercourse and from an infected woman to her fetus/child remain major routes of transmission. The World Health Organization estimates that there will be a cumulative total of 30-40 million people infected with HIV by the year 2000. Over time, increasing numbers of people already infected with HIV and soon to be infected will develop AIDS and require higher levels of care. Obstacles to increasing access to cost-effective drugs for HIV/AIDS in developing countries, however, include weak drug distribution systems, the improper prescribing of available drugs by health workers, and the improper use of these drugs by patients who have not been appropriately educated by prescribing health workers. Currency shortages and lack of political will underlie these obstacles. This paper considers cost-effective prophylaxis and treatment of HIV-related infections including tuberculosis, candidiasis, penicilliosis, combined chemoprophylaxis, pruritus and diarrhea with wasting, and HIV infection. The prevention of HIV transmission is discussed under headings on heterosexual and perinatal transmission, followed by a discussion on increasing access to cost-effective drugs.^ieng

Prevention of blood-borne HIV transmission using a decentralized approach in Shaba, Zaire.

OBJECTIVE: To prevent blood transfusion-acquired HIV infection with a decentralized approach to HIV screening of blood donors, using an instrument-free rapid test. SETTING: Shaba province, Zaire (496,877 km2). METHODS: The programme consisted of training health-care workers, distribution of a rapid HIV-antibody test (DuPont's HIVCHEK) for screening of all blood donations, and quality control of testing by a regional reference centre. RESULTS: Over a 2-year period, 11,940 rapid tests were distributed to 37 hospitals, covering 75% of all hospital beds outside the copper mine's health system in Shaba. Eighty-five per cent of the tests were used to screen blood donors (5.4% positive test rate) and 13% to test patients (39.7% positive test rate). At least 265 cases of HIV-positive blood donation were prevented, at an estimated cost of 137-279 ECU per case. Only 26% of initially positive specimens reached the central laboratory for supplemental testing, and sterile transfusion equipment and blood-grouping reagents were frequently unavailable. The lack of transport and communications and a deteriorating health system were major constraints. CONCLUSIONS: District hospitals in Africa are often long distances from major cities, difficult to reach for most of the year, and perform a small number of transfusions. In this context a classical centralized regional blood bank may not be a feasible option to ensure safe blood transfusions. However, safe blood transfusion can be achieved with a decentralized approach using a rapid test, provided that minimum standards of health-care services are available.

PIP: This program aimed at preventing blood transfusion-acquired HIV infection with a decentralized approach to HIV screening of blood donors using an instrument free raid test was initiated in Shaba province in Zaire (496,877 sq. km and included training of health care workers, distribution of a rapid HIV-antibody test (DuPont's HIVCHEK) for screening of all blood donations, and quality control of testing by a regional reference center. Over a 2-year period, 11,940 rapid tests were distributed to 37 hospitals, covering 75% of all hospital beds outside the copper mine's health system in Shaba. 85% of the tests were used to screen blood donors (5.4% positive test rate) and 13% to test patients (39.7% positive test rate). At least 265 cases of HIV-positive blood donation were prevented at an estimated cost of 137-279 ECU per case. Only 26% of initially positive specimens reached the central laboratory for supplemental testing, and sterile transfusion equipment and blood-grouping reagents were frequently unavailable. The lack of transport and communications and a deteriorating health system were major constraints. District hospitals in Africa are often long distances from major cities, difficult to reach for most of the year, and perform a small number of transfusions. In this context, a classical centralized regional blood bank may not be a feasible option to ensure safe blood transfusions. However, safe blood transfusion can be achieved with a decentralized approach using a rapid test, provided that minimum standards of health care services, are available.

High-dose cyclophosphamide and dexamethasone in paraquat poisoning: a prospective study.

Between March 1986 and March 1988, 47 consecutive patients, whose paraquat intoxication was confirmed by urine testing, were enrolled in a prospective study on the treatment of paraquat poisoning. Fourteen received a standard treatment regimen consisting of fluid replacement and oral absorbents, and 33 received high-dose cyclophosphamide and dexamethasone, in addition to standard therapy. The case fatality rate in both treatment groups (63 and 61%) was similar. In addition, all 26 patients whose paraquat serum concentrations were measured and who had a probability of survival of less than 65% according the survival curve of Hart et al. died, regardless of therapy. These included four in the cyclophosphamide/dexamethasone group and two in the standard treatment group who had prior survival probabilities between 50 and 65%. This indicated that the cut-off curve relating mortality and paraquat serum concentrations was similar in both treatment groups. High-dose cyclophosphamide/dexamethasone treatment is unlikely to improve the prognosis of paraquat poisoning.

Gentian violet, ketoconazole and nystatin in oropharyngeal and esophageal candidiasis in Zairian AIDS patients.

A randomized un-blinded study on the treatment of oropharyngeal and esophageal candidiasis was conducted in Kinshasa (Zaire), among 141 inpatients with AIDS and oropharyngeal candidiasis, of whom 136 also had esophageal candidiasis. The study compared the efficacy of gentian violet mouth washes (1.5 ml 0.5% aqueous solution b.i.d.), oral ketoconazole (200 mg/day, after a meal) and nystatin mouth washes (200.000 U oral suspension q.i.d.). Patients treated with mouth washes swallowed their medication after mouth washing. Patients enrolled in this study had a very high mortality (probability of death: 41.6% after 14 days). After 14 days, 72 patients could be evaluated. At that time, oropharyngeal lesions had disappeared in similar proportions of patients treated with gentian violet (11/26, 42%) and ketoconazole (10/23, 43%), and in a lower proportion of patients treated with nystatin (2/23, 9%; p less than 0.05). In esophageal candidiasis, ketoconazole seemed more efficient than both other treatments: esophageal lesions had disappeared in 5 (24%) of the 21 patients on ketoconazole, compared to less than 10% of patients on both other treatments (p = 0.07). The suboptimal results observed with all 3 treatments could be explained by the profound immunosuppression of patients enrolled in the study. This study suggests that gentian violet is effective treatment for oropharyngeal candidiasis. As it is very cheap (0.5 US$/treatment course in Kinshasa), we suggest that its use should be assessed in larger studies.

Neurological complications of HIV-1-seropositive internal medicine inpatients in Kinshasa, Zaire.

Because little was known about the prevalence of neurological complications of human immunodeficiency virus type 1 (HIV-1) infection in Africa, we conducted a cross-sectional study among consecutive admissions to the internal medicine wards of Mama Yemo Hospital in Kinshasa, Zaire. Of the 196 patients studied, 104 (53%) were HIV-1 seropositive, of whom 50 (48%) had stage 3 and 49 (47%) had stage 4 HIV-1 infection according to the provisional WHO staging criteria for HIV infection. Neuropsychiatric abnormalities were present in 43 (41%) of 104 HIV-1-seropositive patients. Of the HIV-1-seropositive patients, 9 (8.7%; 95% confidence interval, 4-16%) were diagnosed as having possible HIV-1-associated dementia complex, 1 (1%) as having possible HIV-1 myelopathy, and 3 (2.7%) as having possible HIV-1-associated minor cognitive/motor disorder. Definitive diagnoses could not be made because there were no facilities for neuroimaging and neuropathology. Meningitis caused by cryptococcus was diagnosed in six (5.6%) and by Mycobacterium avium in two (2%) of the HIV-1 seropositive patients. Acute onset hemiplegia, believed to be due to stroke, was present in four (4%) of the HIV-1-seropositive patients. The prevalence of other central nervous system opportunistic infections and mass lesions, especially toxoplasmic encephalitis, could not be assessed. In this population of Zairian inpatients, the prevalence of neurological complications of HIV-1 infection was similar to that observed in industrialized countries among patients with advanced HIV disease.

Increased mortality and tuberculosis treatment failure rate among human immunodeficiency virus (HIV) seropositive compared with HIV seronegative patients with pulmonary tuberculosis treated with "standard" chemotherapy in Kinshasa, Zaire.

To evaluate their treatment outcomes 170 human immunodeficiency virus (HIV) seropositive and 597 HIV seronegative patients with active pulmonary tuberculosis (TB) treated for 1 yr with "standard" chemotherapy, including streptomycin, isoniazid, and, in most cases, thiacetazone, were traced at completion of therapy. All 582 survivors were invited for reevaluation, and 385 patients, of whom 82 (21.3%) were HIV seropositive, were evaluated. Of those, 325 consenting patients, of whom 67 (20.6%) were HIV seropositive, were followed for 12 months. One year after TB had been diagnosed 47 (31.3%) of the 150 HIV seropositive and 22 (4.4%) of the 501 HIV seronegative patients traced had died (p = 10(-6]. During the subsequent year the mortality of 67 HIV seropositive patients (26.3/100 patient-years) was higher than that of the 303 HIV seronegative patients (2.2/100 patients-years, p = 10(-6]. HIV seropositive patients had a higher overall TB therapy failure rate 24 months after the diagnosis of TB than did HIV seronegative patients (21.1/100 patient-years versus 8.1/100 patient-years, p = 0.002), mainly because their relapse rate of pulmonary TB (18.1/100 patient-years) was higher than that of HIV seronegative patients (6.0/100 patient-years, p = 0.03). Given their higher relapse rate after 1 yr of "standard" chemotherapy, the public health impact of routine maintenance therapy in HIV seropositive patients with pulmonary TB who complete such therapy should be assessed in comparison to the introduction of rifampicin-based short-course antituberculosis chemotherapy in developing countries.