Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial. Routinely available cotrimoxazole prophylaxis and occurrence of respiratory and diarrhoeal morbidity in infants born to HIV-infected mothers in South Africa. Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal. Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. A controlled trial of lambda-cyhalothrin-impregnated bed nets and/or dapsone/pyrimethamine for malaria control in Sierra Leone. Effect of nitazoxanide on morbidity and mortality in Zambian children with cryptosporidiosis: a randomised controlled trial. 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. A cluster-randomized trial of provider-initiated (opt-out) HIV counseling and testing of tuberculosis patients in South Africa. Cotrimoxazole prophylaxis in patients with leukemia and prolonged granulocytopenia.
No trials of co-trimoxazole (trimethoprim-sulfamethoxazole) prophylaxis for HIV-infected adults or children have been done in areas with high levels of bacterial resistance to this antibiotic. We aimed to assess the efficacy of daily co-trimoxazole in such an area.
                We did a double-blind randomised placebo-controlled trial in children aged 1-14 years with clinical features of HIV infection in Zambia. Primary outcomes were mortality and adverse events possibly related to treatment. Analysis was by intention to treat.
                In October, 2003, the data and safety monitoring committee recommended early stopping of the trial. 541 children had been randomly assigned; seven were subsequently identified as HIV negative and excluded. After median follow-up of 19 months, 74 (28%) children in the co-trimoxazole group and 112 (42%) in the placebo group had died (hazard ratio [HR] 0.57 [95% CI 0.43-0.77], p=0.0002). This benefit applied in children followed up beyond 12 months (n=320, HR 0.48 [0.27-0.84], test for heterogeneity p=0.60) and across all ages (test for heterogeneity p=0.82) and baseline CD4 counts (test for heterogeneity p=0.36). 16 (6%) children in the co-trimoxazole group had grade 3 or 4 adverse events compared with 18 (7%) in the placebo group. These events included rash (one placebo), and a neutrophil count on one occasion less than 0.5x10(9)/L (16 [6%] co-trimoxazole vs seven [3%] placebo, p=0.06). Pneumocystis carinii was identified by immunofluorescence in only one (placebo) of 73 nasopharyngeal aspirates from children with pneumonia.
                Our results suggest that children of all ages with clinical features of HIV infection should receive co-trimoxazole prophylaxis in resource-poor settings, irrespective of local resistance to this drug. To examine the influence of cotrimoxazole (CTM) prophylaxis on incidence of lower respiratory tract infections (LRTIs) and diarrhoea.
                A prospective observational cohort study. Morbidity and feeding data on infants born to HIV-infected mothers were collected routinely at clinic visits at 1 week, 6 weeks and 3 months, and 3-monthly thereafter, with blood drawn for determining HIV status.
                Two hospitals in Durban, South Africa. In one hospital (King Edward VIII Hospital), infants born to HIV infected mothers received CTM prophylaxis and in the other (McCord Hospital) infants did not receive CTM prophylaxis.
                Infants born to HIV-infected mothers. Outcome measures. Incidence of LRTI and diarrhoea.
                In multivariate analysis controlling for breast-feeding status, number of clinic visits and HIV infection status, HIV infected infants with access to CTM prophylaxis had a significantly lower incidence of LRTI (82%) than those without access to prophylaxis. However in HIV-uninfected infants, this was not the case. CTM prophylaxis was associated with a non-significant increased risk for diarrhea in both infected (odds ratio (OR) 1.58, p = 0.45) and uninfected infants (OR 1.52, p = 0.10).
                This observational study confirms current thinking that CTM prophylaxis is protective against LRTIs in HIV-infected children. However, because of a possible association between CTM prophylaxis and an increased risk of diarrhoea, HIV status of infants should be determined as early as possible in order to prevent unnecessary exposure of uninfected infants to CTM prophylaxis, while further studies to quantify both beneficial and adverse effects of CTM prophylaxis are undertaken. To assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV-1-infected adults.
                Randomized, double-blind, placebo-controlled clinical trial in the urban community of Dakar, Senegal.
                Eligibility criteria were age greater than 15 years, HIV-1 or HIV-1 and HIV-2 dual seropositivity, CD4 cell count lower than 400 copies/mm3, no progressive infection, no previous history of intolerance to sulphonamide, lack of severe anemia or neutropenia, and renal or hepatic failure. Written informed consent was obtained. Recruited patients received 80 mg of trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The main outcomes were survival and the occurrence of clinical events defined as Pneumocystis carinii pneumonia, cerebral toxoplasmosis, bacterial pneumonia, infectious enteritis, bacterial meningitis, urinary tract infection, bacterial otitis and sinusitis, and pyomyositis.
                Between September 1996 and March 1998, 297 patients were screened, and 100 were randomized in the study. Demographic, clinical, and biological characteristics of the two groups were similar as was the mean length of follow-up (7.7 months for the cotrimoxazole group vs. 8.0 months for the placebo group). There was no significant difference between the two groups in survival (hazard ratio = 0.84; 95% confidence interval [CI]: 0.36-1.94) in the probability of severe event occurrence, defined as death or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13), or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55-2.59). Adjustment for initial CD4 cell count did not change these results. A low dose of cotrimoxazole was tolerated well clinically as well as biologically; only one treatment interruption occurred as the result of a moderate cutaneous eruption (grade 2).
                Our study does not show a beneficial effect of chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of opportunistic or nonopportunistic infections for HIV-1-infected patients in Dakar, Senegal. Prophylaxis with co-trimoxazole (trimethoprim-sulphamethoxazole) is recommended for people with HIV infection or AIDS but is rarely used in Africa. We assessed the effect of such prophylaxis on morbidity, mortality, CD4-cell count, and viral load among people with HIV infection living in rural Uganda, an area with high rates of bacterial resistance to co-trimoxazole.
                Between April, 2001, and March, 2003, we enrolled, and followed up with weekly home visits, 509 individuals with HIV-1 infection and their 1522 HIV-negative household members. After 5 months of follow-up, HIV-positive participants were offered daily co-trimoxazole prophylaxis (800 mg trimethoprim, 160 mg sulphamethoxazole) and followed up for a further 1.5 years. We assessed rates of malaria, diarrhoea, hospital admission, and death.
                Co-trimoxazole was well tolerated with rare (<2% per person-year) adverse reactions. Even though rates of resistance in diarrhoeal pathogens were high (76%), co-trimoxazole prophylaxis was associated with a 46% reduction in mortality (hazard ratio 0.54 [95% CI 0.35-0.84], p=0.006) and lower rates of malaria (multivariate incidence rate ratio 0.28 [0.19-0.40], p<0.0001), diarrhoea (0.65 [0.53-0.81], p<0.0001), and hospital admission (0.69 [0.48-0.98], p=0.04). The annual rate of decline in CD4-cell count was less during prophylaxis than before (77 vs 203 cells per microL, p<0.0001), and the annual rate of increase in viral load was lower (0.08 vs 0.90 log(10) copies per mL, p=0.01).
                Daily co-trimoxazole prophylaxis was associated with reduced morbidity and mortality and had beneficial effects on CD4-cell count and viral load. Co-trimoxazole prophylaxis is a readily available, effective intervention for people with HIV infection in Africa. A randomized controlled trial investigated the impact of community-wide use of mosquito nets impregnated with lambda-cyhalothrin alone or with dapsone/pyrimethamine (d/p) prophylaxis on clinical malaria due to perennially transmitted Plasmodium falciparum in children in the Bo district of Sierra Leone. The 17 study communities were pair-matched and randomly allocated to receive treated mosquito nets or no nets and the children (age range = 3 months-6 years) in each community were randomly allocated to receive d/p or placebo individually every two weeks. This resulted in each of the approximately 2,000 children recruited being in one of four study groups (impregnated mosquito nets and d/p prophylaxis, impregnated mosquito nets, d/p prophylaxis, and controls). The intervention phase of the study lasted 12 months. A total of 1,800 children attended more than 25% of the 48 total weekly morbidity surveillance surveys and were included in the analysis. The effects of the exclusive use of either treated mosquito nets or d/p prophylaxis on protection against clinical malaria due to P. falciparum was significantly similar (49% and 42%, respectively), while in combination this protective efficacy was significantly increased to 72% (95% confidence interval = 67-76%). Children in the control group had an average of 1.3 clinical malaria episodes per child annually compared with 0.65 episodes or 0.78 episodes for those using treated mosquito nets and d/p, respectively. Children using both treated mosquito nets and d/p prophylaxis had an average of 0.37 episodes per child. The interventions significantly reduced spleen rates and increased hematocrit values, and reduced the duration of episodes of clinical malaria. Cryptosporidiosis in children in developing countries causes persistent diarrhoea and malnutrition and is associated with increased mortality, but there is no effective treatment. We aimed to assess the effect of nitazoxanide-a new broad-spectrum antiparasitic drug-on morbidity and mortality in Zambian children with diarrhoea due to Cryptosporidium parvum.
                Children with cryptosporidial diarrhoea who were admitted to the University Teaching Hospital, Lusaka, Zambia, between November, 2000, and July, 2001, and whose parents consented to their having an HIV test were randomly assigned nitazoxanide (100 mg twice daily orally for 3 days) or placebo. The primary endpoint was clinical response on day 7 after the start of treatment. Secondary endpoints included parasitological response by day 10 and mortality at day 8. Analysis was by intention to treat, with exclusion of patients subsequently found to be negative for C parvum or co-infected at baseline. The trial was stratified by HIV serology.
                50 HIV-seropositive and 50 HIV-seronegative children were recruited for the study, four of whom were subsequently excluded. In HIV-seronegative children, diarrhoea resolved in 14 (56%) of 25 receiving nitazoxanide and 5 (23%) of 22 receiving placebo (difference 33%, 95% CI 7-59; p=0.037). C parvum was eradicated from stool in 13 (52%) of 25 receiving nitazoxanide and three (14%) of 22 receiving placebo (38%, 95% CI 14-63; p=0.007). Four children (18%) of 22 in the placebo group had died by day 8, compared with none of 25 in the nitazoxanide group (-18%, -34 to 2; p=0.041). HIV-seropositive children did not benefit from nitazoxanide. Nitazoxanide was not significantly associated with adverse events in either stratum.
                A 3-day course of nitazoxanide significantly improved the resolution of diarrhoea, parasitological eradication, and mortality in HIV-seronegative, but not HIV-seropositive, children. 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.
                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.
                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.
                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. To determine whether implementation of provider-initiated human immunodeficiency virus (HIV) counseling would increase the proportion of tuberculosis (TB) patients who received HIV counseling and testing.
                Cluster-randomized trial with clinic as the unit of randomization.
                Twenty, medium-sized primary care TB clinics in the Nelson Mandela Metropolitan Municipality, Port Elizabeth, Eastern Cape Province, South Africa.
                A total of 754 adults (18 years and older) newly registered as TB patients in the 20 study clinics.
                Implementation of provider-initiated HIV counseling and testing.
                Percentage of TB patients HIV counseled and tested. SECONDARY: Percentage of patients with HIV test positive, and percentage of those who received cotrimoxazole and who were referred for HIV care.
                : A total of 754 adults newly registered as TB patients were enrolled. In clinics randomly assigned to implement provider-initiated HIV counseling and testing, 20.7% (73/352) patients were counseled versus 7.7% (31/402) in the control clinics (P = 0.011), and 20.2% (n = 71) versus 6.5% (n = 26) underwent HIV testing (P = 0.009). Of those patients counseled, 97% in the intervention clinics accepted testing versus 79% in control clinics (P = 0.12). The proportion of patients identified as HIV infected in intervention clinics was 8.5% versus 2.5% in control clinics (P = 0.044). Fewer than 40% of patients with a positive HIV test were prescribed cotrimoxazole or referred for HIV care in either study arm.
                Provider-initiated HIV counseling significantly increased the proportion of adult TB patients who received HIV counseling and testing, but the magnitude of the effect was small. Additional interventions to optimize HIV testing for TB patients urgently need to be evaluated. Sixty-three patients with acute nonlymphoid leukemia (ANLL) under cytostatic treatment were investigated in a randomized trial to determine whether oral administration of cotrimoxazole (TMP/STX) would reduce the rate of infection. Four significant differences were observed between the group given TMP/STX (30 patients) and the control group (33 patients): 1) the mean duration of severe granulocytopenia (less than or equal to 500 PMN/mm3) before the first febrile episode was longer in prophylaxis group, 14.26 days versus four in the control group (p less than 0.001); 2) the number of febrile episodes was 37 in TMP/STX group and 69 in control group (p less than 0.01); 3) 23 patients on prophylaxis presented at least one febrile episode versus 33 in the control group (p less than 0.01); 4) deaths due to infection were two in the TMP/STX group versus 11 in control group (p less than 0.05). Prophylaxis with TMP/STX appears to be useful since by reducing the number of febrile episodes and deaths due to infection, it increases the survival of leukemia patients under cytostatic drugs. Nevertheless, further studies on a larger number of patients are necessary in order to confirm the true efficacy of the drug in the reduction of sepsis and death due to infection.
A single trial has shown a beneficial effect from the use of cotrimoxazole prophylaxis in HIV infected children in Zambia. It must be decided whether this can be extrapolated to other resource-poor settings.