HIV-free survival and morbidity among formula-fed infants in a prevention of mother-to-child transmission of HIV program in rural Haiti

<p>Abstract</p> <p>Background</p> <p>Partners In Health (PIH) works with the Ministry of Health to provide comprehensive health services in Haiti. Between 1994 and 2009, PIH recommended exclusive formula feeding in the prevention of mother-to-child transmission (PMTCT) of HIV program and provided support to implement this strategy. We conducted this study to assess HIV-free survival and prevalence of diarrhea and malnutrition among infants in our PMTCT program in rural Haiti where exclusive formula feeding was supported.</p> <p>Methods</p> <p>We reviewed medical charts of PMTCT mother-infant pairs at PIH between November 2004 and August 2006 through a retrospective longitudinal study and cross-sectional survey. We performed household surveys for each pair and at control households matched by infant's age and gender.</p> <p>Results</p> <p>254 mother-infant pairs were included. 15.3% of infants were low birth weight; most births occurred at home (68.8%). 55.9% of households had no latrine; food insecurity was high (mean score of 18; scale 0-27, SD = 5.3). HIV-free survival at 18 months was 90.6%. Within the cohort, 9 children (3.5%) were HIV-infected and 17 (6.7%) died. Community controls were more likely to be breastfed (P = 0.003) and more likely to introduce food early (P = 0.003) than PMTCT-program households. There was no difference in moderate malnutrition (Z score ≤ 2 SD) between PMTCT and community groups after controlling for guardian's education, marital status, and food insecurity (OR = 1.05; 95% CI: 0.67, 1.64; P = 0.84). Diarrhea was 2.9 times more prevalent among community children than PMTCT infants (30.3% vs. 12.2%; P < 0.0001).</p> <p>Conclusions</p> <p>In a PIH-supported program in rural Haiti that addressed socioeconomic barriers to ill-health, breast milk substitution was safe, acceptable and feasible for PMTCT for HIV-infected women choosing this option.</p

Aggressive Regimens for Multidrug-Resistant Tuberculosis Reduce Recurrence

Background. Recurrent tuberculosis disease occurs within 2 years in as few as 1% and as many as 29% of individuals successfully treated for multidrug-resistant (MDR) tuberculosis. A better understanding of treatmentrelated factors associated with an elevated risk of recurrent tuberculosis after cure is urgently needed to optimize MDR tuberculosis therapy. Methods. We conducted a retrospective cohort study among adults successfully treated for MDR tuberculosis in Peru. We used multivariable Cox proportional hazards regression analysis to examine whether receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion from positive to negative was associated with a reduced rate of recurrent tuberculosis. Results. Among 402 patients, the median duration of follow-up was 40.5 months (interquartile range, 21.2-53.4). Receipt of an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion was associated with a lower risk of recurrent tuberculosis (hazard ratio, 0.40 [95% confidence interval, 0.17-0.96]; P = .04). A baseline diagnosis of diabetes mellitus also predicted recurrent tuberculosis (hazard ratio, 10.47 [95% confidence interval, 2.17-50.60]; P = .004). Conclusions. Individuals who received an aggressive MDR tuberculosis regimen for ≥18 months following sputum conversion experienced a lower rate of recurrence after cure. Efforts to ensure that an aggressive regimen is accessible to all patients with MDR tuberculosis, such as minimization of sequential ineffective regimens, expanded drug access, and development of new MDR tuberculosis compounds, are critical to reducing tuberculosis recurrence in this population. Patients with diabetes mellitus should be carefully managed during initial treatment and followed closely for recurrent disease

Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives: This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB

Comprehensive treatment of extensively drug-resistant tuberculosis

BACKGROUND: Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. METHODS: A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. RESULTS: Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9 vs. 3.2+/-1.6; P\u3c0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P\u3c0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). CONCLUSIONS: Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis

Multivariable, time-varying Cox proportional hazards analysis of aggressive regimen and time to death.

<p>Multivariable, time-varying Cox proportional hazards analysis of aggressive regimen and time to death.</p

Treatment outcomes of 669 patients enrolled in individualized treatment for MDR-TB in Peru between February 1999 and July 2002. (Adapted from Mitnick et al., 2008) [20].

<p>Treatment outcomes of 669 patients enrolled in individualized treatment for MDR-TB in Peru between February 1999 and July 2002. (Adapted from Mitnick et al., 2008) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058664#pone.0058664-Mitnick2" target="_blank">[20]</a>.</p

Distribution of covariates at initiation of ITR.

1<p>Continuous variable, mean (standard deviation) presented.</p>2<p><18.5 in women; <20 in men; or malnutrition established clinically.</p>3<p>≤30% in women; ≤36% in men; when missing, also used hemoglobin ≤10 in women and ≤12 in men.</p>4<p>Dyspnea; resting respiratory rate greater than 26/minute.</p>5<p>Resistance to the following 12 drugs or drug classes was tested: capreomycin, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin or amikacin, PAS, pyrazinamide, rifampicin, streptomycin, first-generation fluoroquinolones (ciprofloxacin, ofloxacin), and later-generation fluoroquinolones (gatifloxacin, levofloxacin, moxifloxacin).</p>6<p>Isolate resistant to at least isoniazid, rifampin, fluoroquinolone, and injectable (kanamycin, capreomycin, or amikacin).</p>7<p>This includes the following comorbidities: cardiovascular disease (12), diabetes mellitus (18), hepatitis or cirrhosis (10), epilepsy/seizures (11), renal insufficiency (7), psychiatric disorder (116), ever smoked (66), ever used/abused alcohol or other substance (52).</p

Univariate, time-varying Cox proportional hazards analysis of aggressive regimen and time to death.

1<p>Continuous variable, mean (standard deviation) presented.</p>2<p><18.5 in women; <20 in men; or malnutrition established clinically.</p>3<p>≤30% in women; ≤36% in men; when missing, also used hemoglobin ≤10 in women and ≤12 in men.</p>4<p>Dyspnea; resting respiratory rate greater than 26/minute.</p>5<p>Resistance to the following 12 drugs or drug classes was tested: capreomycin, cycloserine, ethambutol, ethionamide, isoniazid, kanamycin or amikacin, PAS, pyrazinamide, rifampicin, streptomycin, first-generation fluoroquinolones (ciprofloxacin, ofloxacin), and later-generation fluoroquinolones (gatifloxacin, levofloxacin, moxifloxacin).</p>6<p>Isolate resistant to at least isoniazid, rifampin, fluoroquinolone, and injectable (kanamycin, capreomycin, or amikacin).</p>7<p>This includes the following comorbidities: cardiovascular disease (12), diabetes mellitus (18), hepatitis or cirrhosis (10), epilepsy/seizures (11), renal insufficiency (7), psychiatric disorder (116), ever smoked (66), ever used/abused alcohol or other substance (52).</p