Assessing eosinophil count as a marker of immune activation among human immunodeficiency virus-infected persons in sub-Saharan Africa.

In 611 human immunodeficiency virus-infected persons who had not yet begun to receive antiretroviral therapy, we evaluated the linear association between absolute eosinophil count (as a surrogate for immune response to helminthic infection) and CD4+ T cell count, and between absolute eosinophil count and log virus load. Overall, no significant correlations were observed between eosinophil count and CD4+ T cell count, or between eosinophil count and log virus load.

High prevalence of genotypic and phenotypic HIV-1 drug-resistant strains among patients receiving antiretroviral therapy in Abidjan, Côte d'Ivoire.

To describe prevalence of antiretroviral (ARV) drug-resistant HIV-1 strains among patients with a history of earlier treatment with ARV drugs in Abidjan, Côte d'Ivoire, we determined mutations that confer HIV-1 ARV drug resistance by sequencing the viral reverse-transcriptase and protease genes derived from plasma viral RNA of 68 individuals consecutively enrolled in the Joint United Nations Program on AIDS Drug Access Initiative (UNAIDS-DAI) with a history of earlier ARV drug treatment in Abidjan between August 1998 and April 1999. Phenotypic ARV drug resistance was assessed using a recombinant virus assay. Primary mutations associated with ARV drug resistance to at least one of the reverse-transcriptase inhibitors or protease inhibitors were detected in 39 (57.4%) of the 68 patients. The prevalence of mutations associated with resistance to ARV drugs was: 29 (42.6%) to zidovudine, 10 (14.7%) to lamivudine, one (1.5%) to didanosine, one K103N mutation (associated with resistance to delavirdine, nevirapine, and efavirenz), one Y181C mutation (associated with resistance to delavirdine and nevirapine), two to both indinavir (M46I/L and V82A) and saquinavir (G48V and L90M), and one each to ritonavir (V82A) and nelfinavir (D30N). Phenotypic resistance to at least one nucleoside reverse transcriptase inhibitor (RTI) was seen in 25 (39.7%) patients, to nonnucleoside RTIs in 5 (8%) patients, and to protease inhibitors in 4 (6%) patients. The high prevalence we observed in this study may limit in future the effectiveness of ARV programs in the Côte d'Ivoire.

Efficacy of trimethoprim-sulphamethoxazole prophylaxis to decrease morbidity and mortality in HIV-1-infected patients with tuberculosis in Abidjan, Côte d'Ivoire: a randomised controlled trial.

BACKGROUND: There is a high incidence of opportunistic infection among HIV-1-infected patients with tuberculosis in Africa and, consequently, high mortality. We assessed the safety and efficacy of trimethoprim-sulphamethoxazole 800 mg/160 mg (co-trimoxazole) prophylaxis in prevention of such infections and in decrease of morbidity and mortality. METHODS: Between October, 1995, and April, 1998, we enrolled 771 HIV-1 seropositive and HIV-1 and HIV-2 dually seroreactive patients who had sputum-smear-positive pulmonary tuberculosis (median age 32 years [range 18-64], median CD4-cell count 317 cells/microL) attending Abidjan's four largest outpatient tuberculosis treatment centres. Patients were randomly assigned one daily tablet of co-trimoxazole (n=386) or placebo (n=385) 1 month after the start of a standard 6-month tuberculosis regimen. We assessed adherence to study drug and tolerance monthly for 5 months and every 3 months thereafter, as well as rates of admission to hospital. FINDINGS: Rates of laboratory and clinical adverse events were similar in the two groups. 51 patients in the co-trimoxazole group (13.8/100 person-years) and 86 in the placebo group (25.4/100 person-years) died (decrease In risk 46% [95% CI 23-62], p<0.001). 29 patients on co-trimoxazole (8.2/100 person-years) and 47 on placebo (15.0/100 person-years) were admitted to hospital at least once after randomisation (decrease 43% [10-64]), p=0.02). There were significantly fewer admissions for septicaemia and enteritis in the co-trimoxazole group than in the placebo group. INTERPRETATION: In HIV-1-infected patients with tuberculosis, daily co-trimoxazole prophylaxis was well tolerated and significantly decreased mortality and hospital admission rates. Our findings may have important implications for improvement of clinical care for such patients in Africa.

Profound immunosuppression across the spectrum of opportunistic disease among hospitalized HIV-infected adults in Abidjan, Côte d'Ivoire.

OBJECTIVES: To describe the spectrum of opportunistic disease in HIV-infected patients admitted to hospital in Abidjan, Côte d'Ivoire, and to describe the level of immunosuppression at which these diseases occur. DESIGN: Cross-sectional study. SETTING: In-patient wards of the University Hospital Infectious Diseases Unit. PATIENTS: A total of 250 adult patients recruited by systematic sampling at the point of hospital admission. MAIN MEASURES: HIV status; CD4 count; diagnoses, confirmed by microbiological/radiological investigations whenever possible; and outcome of hospitalization (death or discharge). RESULTS: Overall, 79% patients were HIV-positive. The most frequent diagnoses in HIV-positive patients were septicaemia (20%, with non-typhoid salmonellae, Escherichia coli and Streptococcus pneumoniae the most common organisms), HIV wasting (16%), meningitis (14%), tuberculosis (TB; 13%), isosporiasis (10%), cerebral toxoplasmosis (7%) and bacterial enteritis (7%). Most HIV-positive patients had evidence of severe immunosuppression: 39% had CD4 counts < 50 x 10(6)/l, 17% had 50-99 x 10(6)/l, and 20% had 100-199 x 10(6)/l. In-hospital mortality among HIV-positive patients was 38% compared with 27% among HIV-negative patients [age-adjusted odds ratio (OR), 1.5; 95% confidence interval (CI), 0.7-2.9]. Among HIV-positive patients, the highest case-fatality rates were among patients with meningitis, toxoplasmosis and TB: in a multivariate analysis the strongest independent risk factors for death were an abnormal level of consciousness (OR, 9.3; 95% CI, 3.5-24.6), a haemoglobin concentration below 8 g/dl (OR, 4.2; 95% CI, 1.4-12.8) and age > 40 years (OR, 3.9; 95% CI, 1.5-10.2). CONCLUSIONS: Our data show that, as in industrialized countries, most HIV-infected individuals admitted to and dying in hospital in Abidjan are profoundly immunosuppressed. Potentially preventable infections are the main causes of in-hospital morbidity and mortality among HIV-infected persons in Abidjan, and the evaluation of appropriate primary prophylactic regimes is a priority.

Natural history and spectrum of disease in adults with HIV/AIDS in Africa.

Progression from seroconversion to the development of AIDS in Africa may be shorter than in industrialized countries, but there are insufficient data to be certain. Although the data are not always directly comparable, survival after an AIDS diagnosis appears to be substantially shorter in African countries and this may be partly because of later diagnosis of AIDS in Africa, but may also be because of environmental factors such as increased exposure to pathogens of high virulence and lack of access to care. Tuberculosis and bacterial infections are the most important causes of morbidity and mortality among hospitalized patients. Bacteraemia is frequent, particularly due to non-typhoid salmonellae and S. pneumoniae. Cryptosporidia and I. belli are the most frequently isolated pathogens in patients with diarrhoea; non-typhoid salmonellae and Shigella species are also commonly isolated when stool cultures are performed. Cerebral toxoplasmosis, and meningitis due to Cryptococcus, tuberculosis and bacterial pathogens are the most frequent neurological infections and cognitive changes are frequently identified when specifically looked for. Infections with atypical mycobacteria and Pneumocystis carinii are rare, as is CMV retinitis. In women, HIV infection is associated with cervical human papillomavirus and with SIL, although there is currently no evidence for an association with invasive cervical cancer. Individuals infected with HIV-2 progress to AIDS and to death more slowly than those infected with HIV-1, but seem to experience the same spectrum of opportunistic disease when they reach the stage of advanced disease. The limited data available suggest that HIV-infected individuals in Africa develop opportunistic disease at broadly the same level of immunosuppression as do individuals in industrialized countries, but death occurs at a higher range of CD4 counts, although still in the range consistent with advanced disease. Data are still lacking concerning the aetiology of common clinical presentations of HIV disease and the relative frequencies of specific opportunistic diseases in different regions, particularly from southern Africa. Tuberculosis is the single most important HIV-related opportunistic infection in African countries, but diagnosis, particularly of extrapulmonary disease, remains difficult. The lack of laboratory facilities makes the diagnosis of bacterial infections difficult in many parts of the continent and, since this situation is unlikely to change in the near future, clinical algorithms for syndromic management need to be evaluated. More information is needed about gynaecological disease in HIV-infected women. The most important research questions concern the development and evaluation of cost-effective regimes for prophylaxis and treatment of opportunistic disease in order to prolong healthy life in HIV-infected individuals.

Clinical spectrum of human immunodeficiency virus disease in children in a west African city. Project RETRO-CI.

OBJECTIVES: To determine the prevalence of HIV infection in children and to compare diagnostic syndromes and outcomes in HIV-positive and HIV-negative children. METHODS: Consecutive children hospitalized in Abidjan's three university hospitals were examined, tested for HIV infection and followed to discharge. Admission or discharge diagnoses and outcome (survived or died) were compared in HIV-positive and HIV-negative children. RESULTS: The prevalence of HIV infection in the 4480 children hospitalized for the first time was 8.2%; the highest age-specific rate (11.2%) was in children ages 15 to 23 months. Six clinical syndromes accounted for more than 80% of admissions in HIV-positive and -negative children (all ages combined): respiratory infection; malnutrition; malaria; anemia; diarrhea; and meningitis. The dominant syndromic diagnoses in HIV-positive children were respiratory infection (26.1%) and malnutrition (25.8%); in HIV-negative children they were malaria (30.4%) and respiratory infection (19.1%). The overall mortality rate in HIV-positive children was 20.8%, compared with 8.7% in HIV-negative children (relative risk, 2.4; 95% confidence interval, 1.9 to 3.1); the highest death rate (28.1%) was in children younger than 15 months. CONCLUSIONS: Clinical syndromes associated with HIV infection in African children are difficult to recognize without access to HIV serology. Respiratory infection and malnutrition were the dominant clinical syndromes in HIV-positive children in Abidjan. Greater overlap exists between the clinical presentations of HIV-associated disease and other common health problems in African children than in adults.

The epidemic of HIV/AIDS in Abidjan, Côte d'Ivoire: a review of data collected by Projet RETRO-CI from 1987 to 1993.

We present a review of epidemiologic data collected by Projet RETRO-CI between 1987 and 1993 on trends in human immunodeficiency virus type 1 (HIV-1) and HIV-2 infections and on cases of AIDS in Abidjan, Côte d'Ivoire. Overall rates of HIV infection in pregnant women had already reached 10% in 1987, and have increased only modestly since then. In contrast, in 1992-1993, rates in men with sexually transmitted diseases and in female commercial sex workers reached 27 and 86%, respectively. The increases in infection rates have been largely due to transmission of HIV-1, whereas rates of HIV-2 have remained stable or have declined. Among persons with tuberculosis and hospitalized patients, rates of 46-71% have been reached, increases in recent years again being largely attributable to HIV-1. Among the 15,245 AIDS cases reported by Projet RETRO-CI, a steady decline in the male:female sex ratio has occurred over time, from 4.8:1 in 1988 to 1.9:1 in 1993. It is likely that AIDS cases were initially concentrated among a core group of female commercial sex workers and their male clients. A substantial proportion of sex workers and their clients originate from neighboring countries, and migration is likely to have contributed to the spread of HIV infection in West Africa. Including HIV-associated pulmonary tuberculosis as an AIDS-defining illness increased AIDS cases reported by Projet RETRO-CI by 13% in 1993. Despite a need for interventional research, careful description of the evolution of HIV/AIDS in this region remains essential.

Idiopathic CD4+ T-lymphocyte depletion in a west African population.

OBJECTIVE: To assess the frequency of CD4+ T-lymphocyte depletion in selected populations in West Africa and to determine whether an association exists between AIDS-like illnesses and CD4+ T-lymphocytopenia in HIV-negative individuals. DESIGN: Retrospective review of databases and prospective case-control study. SETTING: Project RETRO-CI, an AIDS research project in Abidjan, Côte d'Ivoire, a University Hospital and tuberculosis treatment and maternal and child health centres in Abidjan. METHODS: We conducted a retrospective review of CD4+ T-lymphocyte counts performed between 1991 and 1992 on hospitalized medical patients, outpatients with tuberculosis, and women participating in a study of HIV-1 and HIV-2 mother-to-child transmission. A prospective case-control study was conducted in 1992 to examine the relationship between HIV-negative CD4+ T-lymphocyte depletion and wasting syndrome (wasting and chronic diarrhoea and/or chronic fever). RESULTS: In the retrospective data review, CD4+ T-lymphocyte counts < 300 x 10(6)/l were found in 9.6% of 115 HIV-negative hospitalized patients, in 4.2% of 312 ambulatory tuberculosis patients, and in 0.4% of 263 healthy women after delivery. In the case-control study, no association was found between CD4+ T-lymphocyte depletion in HIV-negative individuals and the presence of wasting syndrome. Increased mortality in HIV-negative individuals was associated with wasting but not with reduced CD4+ T-lymphocyte counts. In contrast, a trend existed for increased mortality with increasingly severe CD4+ T-lymphocyte depletion in HIV-positive patients. Tuberculosis was the most frequently proven or suspected diagnosis in HIV-negative individuals with wasting and CD4+ T-lymphocytopenia. CONCLUSIONS: In the absence of HIV infection, CD4+ T-lymphocytopenia is uncommon (< 1%) in West African asymptomatic individuals but is more frequent in those with tuberculosis (4%) and hospitalized patients (10%). CD4+ T-lymphocytopenia in HIV-negative individuals was not associated with wasting syndrome or increased mortality. There was no evidence for frequent, clinically relevant immune deficiency other than that associated with HIV infection.

The mortality and pathology of HIV infection in a west African city.

BACKGROUND: HIV disease is epidemic in Africa, but associated mortality, underlying pathology and CD4+ T-lymphocyte counts have not previously been evaluated in a representative study. Such data help to determine the management of HIV-positive people. Both HIV-1 and HIV-2 infections are prevalent in Côte d'Ivoire, and the pathology of HIV-2 infection in Africa is unclear. METHODS: Consecutive adult medical admissions to a large city hospital in Côte d'Ivoire were studied in 1991, and a sample of HIV-positive deaths autopsied. RESULTS: Of 5401 patients evaluated, 50% were HIV-positive; 38% of these died, with a median survival of 1 week. At autopsy (n = 294, including 24% of HIV-positive deaths in hospital), tuberculosis (TB), bacteraemia (predominantly Gram-negative rods) and cerebral toxoplasmosis caused 53% of deaths. TB was seen in 54% of cadavers with AIDS-defining pathology and Pneumocystis pneumonia in 4%. The median CD4+ T-lymphocyte counts in those who died was < 90 x 10(6)/l. Compared with HIV-1-positives, patients with HIV-2-positivity had a greater frequency of severe cytomegalovirus infection, HIV encephalitis and cholangitis. CONCLUSIONS: In this population, HIV-positive adults present to hospital with advanced disease associated with high mortality. The three major underlying pathologies (TB, toxoplasmosis and bacteraemia) are either preventable or treatable. TB is an underestimated cause of the 'slim' syndrome in Africa. The patterns of pathology in HIV-2-positive patients suggest a more prolonged terminal course compared with HIV-1. There is an urgent need for attention towards the issues of therapy and care for HIV disease in developing countries.