BackgroundAttrition during the period from HIV testing to antiretroviral therapy (ART) initiation is high worldwide. We assessed whether same-day HIV testing and ART initiation improves retention and virologic suppression.Methods and findingsWe conducted an unblinded, randomized trial of standard ART initiation versus same-day HIV testing and ART initiation among eligible adults ≥18 years old with World Health Organization Stage 1 or 2 disease and CD4 count ≤500 cells/mm3. The study was conducted among outpatients at the Haitian Group for the Study of Kaposi’s Sarcoma and Opportunistic infections (GHESKIO) Clinic in Port-au-Prince, Haiti. Participants were randomly assigned (1:1) to standard ART initiation or same-day HIV testing and ART initiation. The standard group initiated ART 3 weeks after HIV testing, and the same-day group initiated ART on the day of testing. The primary study endpoint was retention in care 12 months after HIV testing with HIV-1 RNA <50 copies/ml. We assessed the impact of treatment arm with a modified intention-to-treat analysis, using multivariable logistic regression controlling for potential confounders. Between August 2013 and October 2015, 762 participants were enrolled; 59 participants transferred to other clinics during the study period, and were excluded as per protocol, leaving 356 in the standard and 347 in the same-day ART groups. In the standard ART group, 156 (44%) participants were retained in care with 12-month HIV-1 RNA <50 copies, and 184 (52%) had <1,000 copies/ml; 20 participants (6%) died. In the same-day ART group, 184 (53%) participants were retained with HIV-1 RNA <50 copies/ml, and 212 (61%) had <1,000 copies/ml; 10 (3%) participants died. The unadjusted risk ratio (RR) of being retained at 12 months with HIV-1 RNA <50 copies/ml was 1.21 (95% CI: 1.04, 1.38; p = 0.015) for the same-day ART group compared to the standard ART group, and the unadjusted RR for being retained with HIV-1 RNA <1,000 copies was 1.18 (95% CI: 1.04, 1.31; p = 0.012). The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain.ConclusionsSame-day HIV testing and ART initiation is feasible and beneficial in this setting, as it improves retention in care with virologic suppression among patients with early clinical HIV disease.Trial registrationThis study is registered with ClinicalTrials.gov number NCT01900080
We report outcomes for a cohort of patients with multidrug-resistant tuberculosis who received high-dose isoniazid in Haiti. Patients who received high-dose isoniazid had a faster time to culture conversion and higher odds of successful outcome, despite high-level isoniazid resistance. This suggests high-dose isoniazid may have effectiveness even with phenotypic resistance.
More than 1 in 10 females (13%) reported being a victim of sexual assault in the 2012 Mortality, Morbidity, and Service Utilization Survey conducted in Haiti. This study aimed to describe the characteristics of sexual assault and its psychological consequences among female victims of sexual assault (patients) who presented to the Group for the Study of Kaposi's Sarcoma and Opportunistic Infections (GHESKIO) clinic in Port-au-Prince, Haiti, and determine which characteristics impact seeking medical evaluation or follow-up care. We conducted comparisons of the characteristics of sexual assault and psychological impact among female patients in Haiti by age stratification using chi-square or analysis of variance tests. Logistic regressions were used to assess the determinants of receiving medical evaluation within 72 h or returning for follow-up. A total of 4092 female patients presented from January 2006 to December 2015. Patients aged £10 years had significantly higher rates of assault by known assailants and a single assailant (p < 0.001). A total of 2650 (64.8%) patients reported at least one psychological condition, and 2458 patients (60.1%) returned within 6 months for follow-up. The adjusted odds ratio of returning for follow-up among patients exhibiting a psychological condition at first visit was 0.20 (0.17-0.24; p < 0.001), indicating that patients exhibiting a psychological condition were 80% less likely to return for follow-up. There are significant differences in sexual assault characteristics between child and adult patients. Psychological assessments could help predict the likelihood of return for follow-up. Health care workers should be trained to recognize psychological trauma as a risk factor for loss to follow-up.
Multidrug-resistant tuberculosis (MDR-TB) outcomes are poor partly because of the long treatment duration; the World Health Organization conditionally recommends a shorter course regimen to potentially improve treatment outcomes. Here, we describe the drug susceptibility patterns of a cohort of MDR-TB patients in Haiti and determine the number of likely effective drugs if they were treated with the recommended shorter course regimen. We retrospectively examined drug susceptibility patterns of adults initiating MDR-TB treatment between 2008 and 2015 at the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections in Port-au-Prince, Haiti. First-and second-line drug susceptibility testing (DST) was analyzed and used to determine the number of presumed effective drugs. Of the 239 patients analyzed, 226 (95%), 183 (77%), 135 (57%), and 38 (16%) isolates were resistant to high-dose isoniazid, ethambutol, pyrazinamide, and ethionamide, respectively. Eight patients (3%) had resistance to either a fluoroquinolone or a second-line injectable and none had extensively resistant TB. Of the 239 patients, 132 (55%) would have fewer than five likely effective drugs in the intensive phase of the recommended shorter course regimen and 121 (51%) would have two or fewer likely effective drugs in the continuation phase. Because of the high rates of resistance to first-line TB medications, about 50% of MDR-TB patients would be left with only two effective drugs in the continuation phase of the recommended shorter course regimen, raising concerns about the effectiveness of this regimen in Haiti and the importance of using DST to guide treatment.
Background: The current standard induction therapy for de novo Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) is a tyrosine kinase inhibitor (TKI) in combination with chemotherapy or corticosteroids. Three generations of TKIs are currently available for the treatment of Ph+ ALL. Ponatinib, a third generation multi-targeted TKI, is a more potent inhibitor of BCR/ABL than previous generations. It also is effective in cases where there is a threonine-to-isoleucine substitution at position 315 (T315I mutation), which confers resistance to all first- and second-generation TKIs (i.e., imatinib, dasatinib, and nilotinib). However, evidence on the comparative effectiveness of front-line combination therapy with ponatinib relative to other TKIs in de novo Ph+ ALL has not been well-established. Aims: The purpose of this study is to evaluate the effectiveness, as measured by complete molecular response (CMR) and 2- and 3-year overall survival (OS), of front-line treatment combinations with ponatinib versus first- and second-generation TKIs in de novo Ph+ ALL. Methods: Twenty-six studies of front-line Ph+ ALL treatment with TKI in combination with chemotherapy or corticosteroids (18 studies of imatinib, 5 of dasatinib, 2 of nilotinib, and 1 of ponatinib) were identified from published targeted literature reviews and recently published trials. These consisted of 25 phase 2 through 4 trials and 1 retrospective analysis. Study arms in which patients received chemotherapy or corticosteroids only, a single TKI agent, or in which they received autologous stem cell transplant exclusively were excluded. Data on aggregated patient characteristics were extracted and summarized using the median (range). The proportions of patients achieving CMR (following induction or consolidation therapy) and 2- and 3-year OS were also extracted from all study arms and summarized by TKI group (ponatinib versus all other first and second generation TKIs) using pooled estimates with 95% confidence intervals (CIs) from a random-effects meta-analysis. A binomial distribution was assumed to calculate the 95% CIs for the ponatinib trial. Multivariate logistic meta-regressions were conducted to examine the association between each TKI treatment group and CMR rates, 2-year OS, and 3-year OS, separately, adjusting for age and gender. Results: A total of 32 TKI treatment arms were included in the analysis. The median (range) of age across trial arms was 46 years (36-69 years) and proportion of male patients was 53% (42-67%). The pooled proportion of patients achieving CMR with ponatinib was higher than that with first and second generation TKIs (79% versus 34%). The pooled 2- and 3-year OS with ponatinib were also higher than those with other TKIs (2-year: 83% versus 58%; 3-year: 79% versus 50%). Relative to other TKIs, ponatinib was associated with a statistically significant 6.09-fold increase in the odds of achieving CMR (N=25) [odds ratio=6.09 (95% CI: 1.16-31.90), p=0.034]. While ponatinib was not significantly associated with an increase in the odds of 2-year OS (N=27) [odds ratio=3.70 (95% CI: 0.93-14.73), p=0.062], it was associated with a statistically significant 4.49-fold increase in the odds of 3-year OS (N=19) [odds ratio=4.49 (95% CI: 1.00-20.13), p=0.050] compared to earlier generation TKIs. Conclusion: Frontline treatment with ponatinib in combination with chemotherapy or corticosteroids was associated with significantly better odds of CMR and 3-year OS in patients newly diagnosed with Ph+ ALL than combination therapy with earlier generations of TKIs. In particular, ponatinib was associated with a 6-fold increase in CMR, the most important factor in predicting long-term survival outcomes. The improved efficacy of ponatinib in Ph+ ALL may be particularly important for patients who are ineligible to undergo stem cell transplantation due to lack of suitably matched donors, advanced age, or significant comorbidities. In such cases, combination therapy with TKI may be a suitable alternative. Though the number of studies included was small and few covariates could be used to adjust for heterogeneity across trials, the results suggest that ponatinib in combination with chemotherapy may represent an effective front-line treatment option for patients with Ph+ ALL. Prospective head-to-head clinical trials are needed to confirm these results. Sponsor: ARIAD Pharmaceuticals, Inc. Disclosures Jabbour: ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. DerSarkissian:ARIAD: Research Funding. Duh:Allergan: Consultancy; Abbvie: Consultancy; Novartis: Research Funding; GSK: Research Funding; Bayer: Research Funding; Janssen: Research Funding; Eisai: Research Funding; Pfizer: Research Funding; Medtronic: Research Funding; Takeda: Research Funding; Novo Nordisk: Research Funding; Sanofi: Research Funding; Ariad: Research Funding. McCormick:ARIAD: Research Funding. Cheng:ARIAD: Research Funding. McGarry:ARIAD: Employment, Equity Ownership. Souroutzidis:ARIAD: Research Funding. Huang:ARIAD: Employment, Equity Ownership. Kantarjian:Bristol-Myers Squibb: Research Funding; ARIAD: Research Funding; Amgen: Research Funding; Pfizer Inc: Research Funding; Delta-Fly Pharma: Research Funding; Novartis: Research Funding.
Patients with multidrug-resistant tuberculosis (MDR-TB) who received regimens containing high dose isoniazid (INHHD) had similar time to culture conversion and treatment outcomes as patients who received regimens with bedaquiline (BDQ). INHHD is an inexpensive and safe medication which may contribute additive efficacy in combination regimens.
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