Co-trimoxazole as prophylaxis against opportunistic infections in HIV-infected Zambian children (CHAP): a double-blind randomised placebo-controlled trial. Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection. Effect of co-trimoxazole prophylaxis on morbidity, mortality, CD4-cell count, and viral load in HIV infection in rural Uganda. Randomized trial of 2-dose versus monthly sulfadoxine-pyrimethamine intermittent preventive treatment for malaria in HIV-positive and HIV-negative pregnant women in Malawi. Efficacy and safety of Buxus sempervirens L. preparations (SPV(30)) in HIV-infected asymptomatic patients: a multicentre, randomized, double-blind, placebo-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. The efficacy of antimalarial regimens containing sulfadoxine-pyrimethamine and/or chloroquine in preventing peripheral and placental Plasmodium falciparum infection among pregnant women in Malawi. Comparison of single dose with a 5-day course of co-trimoxazole for asymptomatic (covert) bacteriuria of pregnancy. Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, Côte d'Ivoire: a randomised trial. Cotrimo-CI Study Group.
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. A fever case management (CM) approach using sulfadoxine-pyrimethamine (SP) was compared with two presumptive intertmittent SP treatment regimens in the second and third trimesters in pregnant primigravidae and secundigravidae in an area of intense Plasmodium falciparum malaria transmission in western Kenya. The investigation evaluated efficacy of the antimalarial regimens for prevention of placental malaria and examined the effect of human immunodeficiency virus (HIV) infection on antimalarial drug efficacy and adverse drug reactions. Twenty-seven percent (93 of 343) of pregnant women in the CM group had placental malaria compared with 12% (38 of 330; P < 0.001) of women who received two doses of SP and compared with 9% (28 of 316; P < 0.001) of women who received monthly SP. Fourteen percent (49 of 341) of women in the CM group delivered low birth weight (LBW) infants compared with 8% (27 of 325; P=0.118) of women who received two doses of SP and compared with 8% (26 of 331; P=0.078) of women who received monthly SP. Seven percent (7 of 99) of the HIV-negative women on the two-dose SP regimen had placental malaria compared with 25% (10 of 39; P=0.007) of HIV-positive women on the same regimen; the rate of placental malaria in HIV-positive women was reduced to 7% (2 of 28; P=-0.051) for women on the monthly SP regimen. Less than 2% of women reported adverse drug reactions, with no statistically significant differences between HIV-positive and HIV-negative women. Intermittent treatment with SP is safe and efficacious for the prevention of placental malaria in pregnant primigravidae and secundigravidae in sub-Saharan Africa. While a two-dose SP regimen may be effective in areas with low HIV seroprevalence, administration of SP monthly during the second and third trimesters of pregnancy should be considered in areas of high HIV seroprevalence to prevent the effects of maternal malaria on the newborn. 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. Intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) decreases placental malaria parasitemia and associated maternal anemia, premature delivery, and low birth weight. However, the optimal regimen in the setting of a high prevalence of human immunodeficiency virus (HIV) infection remains unclear.
                In Malawi, where the efficacy of SP for the treatment of malaria in children is decreasing, we conducted a randomized, nonblinded study to compare the efficacy of monthly SP IPTp with a 2-dose regimen for the prevention of placental parasitemia in HIV-positive and -negative primigravid and secundigravid women.
                Of HIV-positive women, 7.8% who received monthly SP had placental malaria, compared with 21.5% of those who received 2-dose SP (relative risk [RR], 0.36 [95% confidence interval {CI}, 0.17-0.79]). Of HIV-negative women, 2.3% who received monthly SP and 6.3% who received 2-dose SP had placental malaria (RR, 0.37 [95% CI, 0.11-1.19]). Less than 1% of women reported adverse drug reactions, with no increase in HIV-positive women or those who received monthly SP.
                In HIV-positive pregnant women, monthly SP IPTp is more efficacious than a 2-dose regimen in preventing placental malaria. The study also demonstrates the continued efficacy of SP for the prevention of placental malaria, even in the face of its decreasing efficacy for the treatment of malaria in children. In areas with intense transmission of falciparum malaria and a high prevalence of HIV infection, monthly SP IPTp should be adopted. The objective of the present study was to compare the efficacy and safety of two doses of SPV(30) in HIV asymptomatic patients. The study was designed as a randomized double-blind multicentre trial of two doses of SPV(30) (990 mg/d and 1980 mg/d) versus placebo. 145 previously untreated subjects with asymptomatic HIV infection (CDC group IV) and CD4 cell counts between 250 and 500 × 10(6)/1 were recruited. There was a statistically significant difference in therapeutic failures between groups in favor of SPV(30) 990 mg including decreases of CD4 cell count < 200 × 10(6)/1 and/or number of clinical aggravations (progression to AIDS or AIDS related complex). The treatment groups differed statistically in the rate of disease progression also in favor of SPV(30) 990 mg/d. Fewer patients receiving SPV(30) 990 mg/d had at the end an increase of viral load greater than 0.5 log (P = 0.029). No severe side-effects were reported in the 3 groups. From these results we conclude that SPV(30) 990 mg/d has beneficial effects in HIV asymptomatic patients and appears to delay the progression of HIV disease.
                Copyright © 1998 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved. 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 define an effective and deliverable antimalarial regimen for use during pregnancy, pregnant women at highest risk of malaria (those in their first or second pregnancy) in an area of Malawi with high transmission of chloroquine (CQ)-resistant Plasmodium falciparum were placed on CQ and/or sulfadoxine-pyrimethamine (SP). Of 38 pregnant women who received CQ treatment followed by weekly CQ prophylaxis (CQ/CQ) for at least 45 days prior to delivery, 32% had placental malaria infection, compared with 26% of 50 pregnant women who received a treatment dose of SP followed by weekly CQ prophylaxis (SP/CQ), and only 9% of 71 pregnant women who received a two-dose SP regimen (SP/SP; given once during the second trimester and repeated at the beginning of the third trimester) (P = 0.006, by chi-square test). During the peak transmission season from April to July, 47% of the women who received CQ/CQ had placental malaria infection at delivery, as compared with 37% of the women who received SP/CQ, and 10% of women who received SP/SP (P = 0.004, by chi-square test). Among women in their first or second pregnancy, two treatment doses of SP were highly effective in decreasing the proportion of women with placental malaria infection at delivery. Forty-four pregnant women with covert (asymptomatic) bacteriuria proven by suprapubic bladder aspiration were randomly allocated to treatment with either a single 1.92g dose or a standard 5-day course of co-trimoxazole. Twenty-one of 24 women were cured with a single dose. Seven of these 21 women were reinfected later in the pregnancy. All 20 women treated with a 5-day course of co-trimoxazole were cured, and 2 became reinfected later in the pregnancy. There were no side-effects of treatment, and no detrimental effects on the outcome of pregnancy. Single dose therapy should be considered as the treatment of choice for covert bacteriuria in pregnancy. In sub-Saharan Africa, various bacterial diseases occur before pneumocystosis or toxoplasmosis in the course of HIV-1 infection, and are major causes of morbidity and mortality. We did a randomised, double blind, placebo-controlled clinical trial at community-health centres in Abidjan, Côte d'Ivoire, to assess the efficacy of trimethoprim-sulphamethoxazole (co-trimoxazole) chemoprophylaxis at early stages of HIV-1 infection.
                843 HIV-infected patients were screened and 545 enrolled in the study. Eligible adults (with HIV-1 or HIV-1 and HIV-2 dual seropositivity at stages 2 or 3 of the WHO staging system) received co-trimoxazole chemoprophylaxis (trimethoprim 160 mg, sulphamethoxazole 800 mg) daily or a matching placebo. The primary outcome was the occurrence of severe clinical events, defined as death or hospital admission irrespective of the cause. Analyses were by intention to treat.
                Four of the randomised patients were excluded (positive for HIV-2 only). 120 severe events occurred among 271 patients in the co-trimoxazole group and 198 among 270 in the placebo group. Significantly fewer patients in the co-trimoxazole group than in the placebo group had at least one severe event (84 vs 124); the probability of remaining free of severe events was 63.7% versus 45.8% (hazard ratio 0.57 [95% CI 0.43-0.75], p=0.0001) and the benefit was apparent in all subgroups of initial CD4-cell count. Survival did not differ between the groups (41 vs 46 deaths, p=0.51). Co-trimoxazole was generally well tolerated though moderate neutropenia occurred in 62 patients (vs 26 in the placebo group).
                Patients who might benefit from co-trimoxazole could be recruited on clinical criteria in community clinics without knowing the patients CD4-cell count. This affordable measure will enable quick public-health intervention, while monitoring bacterial susceptibility and haematological tolerance.
Three or more doses of SP may have some advantages over the standard two doses in HIV-positive pregnant women, but larger trials would be necessary to confirm an effect on patient important outcomes. However, since SP cannot be administered concurrently with co-trimoxazole - a drug often recommended for infection prophylaxis in HIV-positive pregnant women, new drugs and research is needed to address needs of HIV-positive pregnant women.