trimethoprim--sulfamethoxazole-drug-combination and efavirenz

Human immunodeficiency virus (HIV)-infected pregnant women are at increased risk of malaria and its complications. In vitro and in vivo data suggest that the HIV protease inhibitors lopinavir/ritonavir may have potent antimalarial activity. We sought to evaluate whether lopinavir/ritonavir-based antiretroviral therapy (ART) reduced the risk of placental malaria.. HIV-infected, ART-naive pregnant women were enrolled between gestational weeks 12 and 28 and randomly assigned to receive lopinavir/ritonavir-based or efavirenz-based ART. Women received daily trimethoprim-sulfamethoxazole prophylaxis and insecticide-treated bed nets at enrollment and were followed up to 1 year after delivery. The primary outcome was placental malaria, defined by the detection of malaria parasites, using microscopy or polymerase chain reaction (PCR) analysis of placental blood specimens. Secondary outcomes included placental malaria, defined by histopathologic results; adverse birth outcomes; incidence of malaria; and prevalence of asymptomatic parasitemia. Analyses were done using an intention-to-treat approach.. Of 389 subjects randomly assigned to a treatment group, 377 were followed through to delivery. There was no significant difference in the risk of placental malaria, as defined by thick smear or PCR findings, between the lopinavir/ritonavir-based and efavirenz-based ART arms (7.4% vs 9.8%; P = .45). Similarly, there were no differences in secondary outcomes between the 2 treatment arms.. Lopinavir/ritonavir-based ART did not reduce the risk of placental or maternal malaria or improve birth outcomes, compared with efavirenz-based ART.. NCT00993031.

Topics: Adolescent; Adult; Alkynes; Anti-HIV Agents; Antimalarials; Antiretroviral Therapy, Highly Active; Benzoxazines; Cyclopropanes; Female; HIV Infections; Humans; Infant, Newborn; Lopinavir; Malaria; Pregnancy; Pregnancy Complications, Infectious; Ritonavir; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-associated tuberculous meningitis is unknown.. We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses.. A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81-1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87-1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04).. Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration. ISRCTN63659091.

Topics: Adult; Alkynes; Anti-HIV Agents; Anti-Inflammatory Agents; Antiretroviral Therapy, Highly Active; Antitubercular Agents; Benzoxazines; Cyclopropanes; Dexamethasone; Double-Blind Method; Female; HIV Infections; Humans; Lamivudine; Male; Placebos; Time Factors; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Tuberculosis, Meningeal; Zidovudine

Stevens-Johnson syndrome (SJS) can be a severe and life-threatening reaction with many potential causes, including multiple medications used in HIV care and treatment. Specific risk factors, especially in children, are not currently well-understood.. We describe a series of cases of SJS that occurred from 2006 to 2010 in an HIV-focused clinic in Mbabane, Swaziland. The electronic medical and pharmacy records of all pediatric patients <20 years old were reviewed to identify cases of SJS. Patient demographic, immunosuppression and outcome data were also collected.. A total of 19 cases of SJS were documented. Eighty-four percent of cases were attributed to nevirapine (NVP) exposure whereas the remaining cases were caused by cotrimoxazole (11%) and efavirenz (5%). Median symptom onset was 22 days after initiation of the offending medication (interquartile range = 14-25 days). At time of SJS, 84% had advanced or severe immunosuppression. Forty-two percent of patients required hospitalization, and no SJS-associated deaths were known to occur. Use of efavirenz was attempted in 8 NVP-associated cases after SJS resolution and was successful in all except 1.. SJS occurrence was rare in this population, with the majority of cases being associated with NVP. All occurred within 32 days of medication initiation, providing a target window for intensified monitoring and anticipatory guidance. SJS can occur in children at any age, with any level of immunosuppression, and can occur during the lead-in dosing period of NVP.

Topics: Adolescent; Alkynes; Anti-HIV Agents; Benzoxazines; CD4 Lymphocyte Count; Child; Child, Preschool; Cyclopropanes; Eswatini; Female; HIV Infections; Hospitalization; Humans; Infant; Male; Nevirapine; Retrospective Studies; Stevens-Johnson Syndrome; Trimethoprim, Sulfamethoxazole Drug Combination; Young Adult

We report the case of an HIV-infected woman, who presented with chronic and productive cough without sign of hypersensitivity (fever, cutaneous eruption, gastrointestinal disorders), while taking abacavir. All complementary exams being negative, the involvement of abacavir has been suspected. So the drug was stopped leading to a rapid disappearance of cough. It is the first report of chronic cough with abacavir apart of a context of hypersensitivity reaction.

Topics: Alkynes; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Benzoxazines; Chronic Disease; Cough; Cyclopropanes; Dideoxynucleosides; Female; HIV Infections; HIV Protease Inhibitors; Humans; Lamivudine; Middle Aged; Nelfinavir; Oxazines; Reverse Transcriptase Inhibitors; Rhinitis; Sputum; Stavudine; Trimethoprim, Sulfamethoxazole Drug Combination