Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study.

BACKGROUND: The 2NN Study was a randomised comparison of the non-nucleoside reverse-transcriptase inhibitors (NNRTI) nevirapine and efavirenz. METHODS: In this multicentre, open-label, randomised trial, 1216 antiretroviral-therapy-naive patients were assigned nevirapine 400 mg once daily, nevirapine 200 mg twice daily, efavirenz 600 mg once daily, or nevirapine (400 mg) and efavirenz (800 mg) once daily, plus stavudine and lamivudine, for 48 weeks. The primary endpoint was the proportion of patients with treatment failure (less than 1 log(10) decline in plasma HIV-1 RNA in the first 12 weeks or two consecutive measurements of more than 50 copies per mL from week 24 onwards, disease progression [new Centers for Disease Control and Prevention grade C event or death], or change of allocated treatment). Analyses were by intention to treat. FINDINGS: Treatment failure occurred in 96 (43.6%) of 220 patients assigned nevirapine once daily, 169 (43.7%) of 387 assigned nevirapine twice daily, 151 (37.8%) of 400 assigned efavirenz, and 111 (53.1%) of 209 assigned nevirapine plus efavirenz. The difference between nevirapine twice daily and efavirenz was 5.9% (95% CI -0.9 to 12.8). There were no significant differences among the study groups in the proportions with plasma HIV-1 RNA concentrations below 50 copies per mL at week 48 (p=0.193) or the increases in CD4-positive cells (p=0.800). Nevirapine plus efavirenz was associated with the highest frequency of clinical adverse events, and nevirapine once daily with significantly more hepatobiliary laboratory toxicities than efavirenz. Of 25 observed deaths, two were attributed to nevirapine. INTERPRETATION: Antiretroviral therapy with nevirapine or efavirenz showed similar efficacy, so triple-drug regimens with either NNRTI are valid for first-line treatment. There are, however, differences in safety profiles. Combination of nevirapine and efavirenz did not improve efficacy but caused more adverse events.

Efficacy of various drugs for treatment of giardiasis. A comparative study.

A total of 172 patients with giardiasis were treated with four of the drugs most commonly used for this infection. All drugs were used in their usual posologic schedules. The cure rates achieved with furazolidone, nimorazole, metronidazole, and tinidazole were; respectively, 72%, 94%, 87%, and 97%, while in a control group given no medication stools of only 35% of the patients became negative. Side effects were of minor importance in patients treated with nimorazole and metronidazole, and were somewhat more frequent and severe in those treated with furazolidone. Tinidazole produced no side effects.

Exercise testing in the latent phase of Chagas' disease.

Exercise stress testing was performed in 50 completely asymptomatic patients in the latent phase of Chagas' disease. In 32 (64%) abnormalities were found consisting of either abnormal ST depression, exercise-induced arrhythmias, or chronotropic incompetence. The latter was determined by comparing the heart rate response to 50 age- and sex-matched control patients without serologic evidence of Chagas' disease. In the absence of an adequate control population we can only speculate as to the significance of the ST depression and arrhythmias during exercise. However, chronotropic incompetence may be a specific marker for Trypanosomal infestation in an endemic area. It probably is an early manifestation of autonomic dysfunction secondary to Chagas' disease.

Oral ciprofloxacin for treatment of severe infections.

Twenty adult patients with severe infections were treated with oral ciprofloxacin, 500 or 750 mg twice daily. Treatment ranged from 8 to 25 days. Efficacy was good: 14 patients (70%) were cured, four (20%) improved and there were only two (10%) failures. Tolerance was very satisfactory, the most common side-effects being mild gastrointestinal symptoms (three patients). Only one adverse laboratory result was observed: a transient rise in blood urea nitrogen and creatinine levels. None of the adverse effects led to discontinuation of treatment. Thus, ciprofloxacin presents as a promising drug for treatment of severe infections caused by susceptible organisms when ambulatorial therapy, at least during a large part of the treatment, is possible and desirable.

Oral ciprofloxacin for treatment of chronic osteomyelitis.

Seventeen adult patients with chronic osteomyelitis were treated with oral ciprofloxacin, 750 mg twice daily. Treatment ranged from 28 to 254 days. Efficacy was considered to be good, based upon clinical resolution observed in 13 patients (76%). Clinical and microbiological failure was observed in 3 patients (18%), and there was one case of reinfection. Tolerance was very satisfactory, since the adverse reactions were mild and transitory; these occurred in 7 patients (41%), being cutaneous rash in 4 patients and diarrhoea in 3 patients. No patient had to discontinue treatment. Thus, oral ciprofloxacin may be useful option for the prolonged treatment of chronic osteomyelitis, provided that it is always associated with surgical debridement. Due to the probable development of ciprofloxacin resistance in the S. aureus multiresistant strain, already observed in two patients in the present investigation, it is suggested that for the treatment of such infections another drug with antistaphylococcal activity should be associated with the ciprofloxacin.

Etiological drug treatment of human infection by Trypanosoma cruzi.

Forty-nine American Trypanosomiasis (Chagas' disease) patients, with xenodiagnosis proven parasitemia were treated by the authors. Forty-one of these patients were given benznidazole, at dosages ranging from 5mg/kg/day to 8mg/kg/day, during a pre-established period of 60 days. In this group, 17 patients had an undetermined form of the disease, whereas 22 had cardiologic disease and 4 had digestive disease (two patients had a mixed form of the disease). Side effects were frequent, and led to the discontinuation of treatment in 17 patients. The follow-up period ranged from 1 to 20 years (mean follow-up period of 6 yrs. 7 mo). 26 (63.4%) of the patients became parasitemia-negative. The other eight patients were treated with nifurtimox, during 120 days, following a variable dose regime of 5mg/kg/day (initial dose) to 17 mg/kg/day (final dose). Six of them had severe side effects, and only one patient remained parasitemia-negative throughout the observation period (ranging from 1 to 18 years). Benznidazole proved to be better tolerated and more effective in the management of parasitemia when compared to nifurtimox, although more effective and less toxic drugs are still desirable.

[The treatment of cryptosporidiosis in AIDS patients using paromomycin]. / Tratamento da criptosporidíase em pacientes com AIDS, por meio da paromomicina.

The authors treated with paromomycin 25 patients, with AIDS and cryptosporidiosis. The drug was given orally in a doses of 500 mg qid, for a period of 14 days. Tolerance was good, with just two cases of mild side-effects. Clinical improvement was obtained in 19 (76%) patients. Parasitological cure, however, occurred only in a low percentage (25%). In some cases where initial success was observed, recrudescence occurred after some weeks or few months, but with retreatment again clinical improvement was obtained. Even if it does not lead to frequent parasite eradication, the good clinical results and tolerance permit us to consider paromomycin one of the few drugs effective for the treatment of cryptosporidial diarrhea in AIDS patients. Studies with maintainance therapy are indicated.

Behçet's syndrome/AIDS/cerebral toxoplasmosis: an unusual association.

Few cases of AIDS associated to manifestations suggesting Behçet's syndrome have been reported. This case is of a young married woman who presented, during a period of 7 years, clinical manifestations consistent with the late diagnosis of Behçet's syndrome, when she developed recurrent lymphomonocytic meningoencephalitis. At this time, she was found to be infected by HIV-1. Immunosuppressive doses of glucocorticoid produced an unsatisfactory response and she evolved to death due to CNS toxoplasmosis. The latter diagnosis was presumed on the basis of magnetic resonance imaging findings and proved by necropsy after her third hospital stay. One of the factors hindering the appropriate diagnosis was the low level of CD4 and the CD4/CD8 ratio, sometimes observed in active Behçet's syndrome and higher than those observed in patients with this severe opportunistic infection. No information about the exact period of time she had been infected with HIV-1 is available. So, we do not know whether both diseases were overlooked, if the patient, infected by HIV-1, developed an unusual clinical feature consistent with Behçet's Behçet's syndrome, and subsequently evolved to AIDS.