Isoniazid plus Sulphadoxine-Pyrimethamine Can Reduce Morbidity of HIV-Positive Patients Treated for Tuberculosis in Africa: A Controlled Clinical Trial

Abstract

An annual 20% excess mortality rate is observed in HIV-seropositive patients after treatment for tuberculosis. An affordable secondary prophylaxis against main opportunistic diseases is needed, i.e. against tuberculosis, toxoplasmosis, pneumocystosis and other infections occurring in this target population. This open prospective randomized study assessed morbidity and mortality in 2 cohorts of HIV-seropositive patients having recently recovered from pulmonary tuberculosis: 134 patients assigned to prophylactic treatment with isoniazid (INH, 300 mg once daily) plus sulphadoxine-pyrimethamine (S, 500 mg/P, 25 mg once weekly), and 129 were controls, comparable for sex, age, weight and HIV-serology. Patients were followed-up for up to 2 years: 192 person-years (PY) in the prophylaxis group and 142 PY in the control group. Four patients developed tuberculosis and 20 patients died in the prophylaxis group, compared to 10 and 23 controls, respectively. Sick days were reported by 22 patients in the prophylaxis group and by 77 patients in the control group. This prophylaxis was associated with a moderate decrease of mortality (log rank test: p = 0.1736), a significant decrease of tuberculosis incidence (log rank test: p = 0.0234), a highly significant reduction of adverse events and sick days, and a prevention of wasting (p = 0.008) and anaemia (p = 0.045). No death from toxoplasmosis occurred in the prophylaxis group as compared to 2 possible cases among controls; toxoplasmosis IgG levels declined in treated patients, but increased in controls (p = 0.01). There was no adverse drug reaction due to SP (10,006 doses) or to INH. Compliance with SP intake was good, but moderate as with INH intake. We conclude that a secondary prophylaxis with INH+SP represents a cost-effective measure to improve health conditions of HIV-infected adults in Côte d’Ivoire, following a full treatment course against tuberculosis.

Preventing opportunistic infections among human immunodeficiency virus-infected adults in African countries.

“…In an open randomized controlled trial, daily isoniazid plus weekly sulfadoxine-pyrimethamine was compared with no treatment among 263 HIV-infected patients who had completed treatment for pulmonary TB in Abidjan. 39 Symptoms were less frequent in the intervention group (rate ratio ϭ 0.35, 95% CI ϭ 0.31-0.4) as were ''sick days'' (rate ratio ϭ 0.21, 95% CI ϭ 0.13-0.34), although the reduction in mortality rates was not statistically significant (rate ratio ϭ 0.64, 95% CI ϭ 0. 35-1.17).…”

“…38 In an open trial among HIV-infected adults who had completed treatment for pulmonary TB in Abidjan, Côte d'Ivoire, the incidence of TB in the isoniazid plus sulphadoxine-pyrimethamine group versus the untreated group was 2.1 versus 7.0 per 100 person years (relative risk [RR] ϭ 0.3, 95% CI ϭ 0.09-0.94). 39 In a study in Haiti, individuals completing short course TB treatment were randomly assigned to receive 12 months of isoniazid as post-treatment prophylaxis or placebo. 40 Among HIV-infected participants, the incidence of TB was lower in the group receiving isoniazid compared with controls (1.4 versus 7.8 per 100 person years, RR ϭ 0.18, 95% CI ϭ 0.04-0.83); it was noted that recurrent TB occurred only in individuals who had symptomatic HIV disease before their initial diagnosis of TB.…”

Experimental in vitro Efficacy Study on the Interaction of Epiroprim plus Isoniazid against <i>Mycobacterium tuberculosis</i>

“…Hence, there is a compelling need for new prophylactic treatments against tuberculosis, toxoplasmosis and other bacterial infections. Isoniazid (INH) has been proven to be effective for secondary prophylaxis against tuberculosis [5]. There is also firm evidence of the usefulness of co-trimoxazole for the prophylaxis of toxoplasmosis and bacterial infections, particularly in patients with low CD4 counts [6].…”

Resistance in Uropathogens among HIV-Positive Kenyan and Cambodian Children in Comparison to an HIV-Negative Population in South Sudan

“…In Kenya, norfloxacin, ciprofloxacin and cefuroxime axetil are used in addition to TMP/SMX. In contrast, HIVpositive children with many opportunistic infections showed an extremely large proportion of different patterns of resistance, especially in Cambodia (84.4%), probably due to the large number of antimicrobial drugs given because of opportunistic infections (quinolones, penicillins, secondgeneration cephalosporins) or prophylaxis (co-trimoxazole) [5] . …”