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ItemEffect of TB/HIV integration on TB and HIV indicators in rural Ugandan health facilities(Lippincott, 2018)Background—WHO recommends integrating services for patients co-infected with TB and HIV. We assessed the effect of TB/HIV integration on ART initiation and TB treatment outcomes among TB/HIV co-infected patients using data collected from 14 rural health facilities during two previous TB and HIV quality of care studies. Methods—A facility was considered to have integrated TB/HIV services if TB/HIV patients had combined treatment for both illnesses by one provider or care team at one treatment location. We analyzed the effect of integration by conducting a cross-sectional analysis of integrated and nonintegrated facility periods comparing performance on ART initiation and TB treatment outcomes. We conducted logistic regression, with the patient as the unit of analysis, controlling for other intervention effects, adjusting for age and gender, and clustering by health facility. Results—From January 2012-June 2014, 996 TB patients were registered, 97% were tested for HIV and 404 (42%) were HIV positive. Excluding transfers, 296 patients were eligible for analysis with 117 and 179 from non-integrated and integrated periods, respectively. Being treated in a facility with TB/HIV integration was associated with lower mortality (adjusted odds ratio [aOR]=0.38, 95% confidence interval [CI]=0.18–0.77), but there was no difference in the proportion initiating ART (aOR=1.34, 95% CI=0.40–4.47), with TB treatment success (aOR=1.43, 95% CI=0.73–2.82), lost to follow-up (aOR=1.64, 95% CI=0.53–5.04), or failure (aOR=1.21, 95% CI=0.34–4.32). Conclusion—TB/HIV service integration was associated with lower mortality during TB treatment even in settings with suboptimal proportions of patients completing TB treatment and starting on ART.
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ItemUtilization of “prevention of mother-tochild transmission” of HIV services by adolescent and young mothers in Mulago Hospital, Uganda(BMC, 2018)Background: Prevention of mother to child transmission (PMTCT) has lowered the incidence of paediatric HIV globally. The risk of mother-to-child transmission of HIV (MTCT) remains high in Africa, where there is a high prevalence of pregnancy and poor health-seeking behaviour among young girls and women. Methods: In this cross-sectional, mixed-methods study, we evaluated the utilization of PMTCT services and associated factors among adolescent and young postpartum mothers aged 15 to 24 years at a public urban referral hospital in Uganda. Both HIV-positive and HIV-negative participants were recruited. Utilization of PMTCT services was defined as use of the PMTCT cascade of services including ever testing for HIV, receiving HIV test results; If tested negative, subsequent retesting up to 14 weeks; If tested positive, Antiretroviral drugs (ARVs) for the mother, ARVs and septrin prophylaxis for infant, safe delivery, safer infant feeding, early infant diagnosis within 6 weeks, and linkage to treatment and care. Optimal utilization of PMTCT was defined as being up to date with utilization of PMTCT services for reported HIV status at the time of being interviewed. The overall proportion of participants who optimally utilized PMTCT services was determined using descriptive statistics. Qualitative data was analyzed manually using the content thematic approach. Results: Of the 418 participants, 65 (15.5%) were HIV positive. Overall, only 126 of 418 participants (30.1%) had optimally utilized PMTCT services. However, utilization of PMTCT services was better among HIV positive mothers, with 83% (54/65) having utilized the services optimally, compared to only 20% (72/353) of the HIV negative mothers (OR 18.2 (95% CI; 9.0–36.7)). The benefits of knowing ones HIV status, health of the unborn child, and counseling and support from health workers and peers, were the major factors motivating adolescent and young mothers to utilize PMTCT services, while stigma, financial constraints, non-disclosure, and lack of partner and family support were key demotivating factors. Conclusion: Utilization of PMTCT services by these adolescent and young mothers was suboptimal. Special consideration should be given to adolescents and young women in the design of elimination of mother to child transmission (EMTCT) programs, to improve the utilization of PMTCT services. Keywords: Adolescents, HIV, PMTCT, Utilization, Uganda
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ItemLow antituberculosis drug concentrations in HIV-tuberculosis-coinfected adults with low body weight: Is it time to update dosing guidelines?(American Society for Microbiology, 2019)Antituberculosis drugs display large pharmacokinetic variability, which may be influenced by several factors, including body size, genetic differences, and drug-drug interactions. We set out to determine these factors, quantify their effect, and determine the dose adjustments necessary for optimal drug concentrations. HIV-infected Ugandan adults with pulmonary tuberculosis treated according to international weight-based dosing guidelines underwent pharmacokinetic sampling (1, 2, and 4 h after drug intake) 2, 8, and 24 weeks after treatment initiation. Between May 2013 and November 2015, we enrolled 268 patients (148 males) with a median weight of 53.5 (interquartile range [IQR], 47.5 to 59.0) kg and a median age of 35 (IQR, 29 to 40) years. Population pharmacokinetic modeling was used to interpret the data and revealed that patients weighing <55 kg achieved lower concentrations than those in higher weight bands for all drugs in the regimen. The models predicted that this imbalance could be solved with a dose increment of one fixed-dose combination (FDC) tablet for the weight bands of 30 to 37 and 38 to 54 kg. Additionally, the concomitant use of efavirenz increased isoniazid clearance by 24.1%, while bioavailability and absorption of rifampin and isoniazid varied up to 30% in patients on different formulations. Current dosing guidelines lead to lower drug exposure in patients in the lower weight bands. Simply adding one FDC tablet to current weight band-based dosing would address these differences in exposure and possibly improve outcomes. Lower isoniazid exposures due to efavirenz deserve further attention, as does the quality of currently used drug formulations of anti-TB drugs. (This study has been registered at ClinicalTrials.gov under identifier NCT01782950.)
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ItemDetrimental outcomes of unmasking cryptococcal meningitis with recent ART initiation(Oxford, 2018)Background. Increased antiretroviral therapy (ART) availability has been associated with more patients developing cryptococ cosis after ART initiation. Despite this changing epidemiology, data regarding cryptococcal meningitis in those already receiving ART are limited. We compared clinical presentations and outcomes among ART-naïve and ART-experienced Ugandans. Methods. We prospectively enrolled 605 HIV-infected persons with first-episode cryptococcal meningitis from August 2013 to May 2017 who received amphotericin-based combination therapy. We classified participants by ART status and ART duration and compared groups for 2-week survival. Results. Overall, 46% (281/605) of participants were receiving ART at presentation. Compared with those not receiving ART, those receiving ART had higher CD4 counts (P < .001) and lower cerebrospinal fluid fungal burdens (P < .001). Of those receiving ART, 56% (156/281) initiated ART within 6 months, and 18% (51/281) initiated ART within 14 days. Two-week mortality did not differ by ART status (27% in both ART-naïve and ART-experienced%; P > .99). However, 47% (24/51) of those receiving ART for ≤14 days died within 2 weeks, compared with 19% (20/105) of those receiving ART for 15–182 days and 26% (32/125) of those receiving ART for >6 months (P < .001). Among persons receiving ART for >6 months, 87% had HIV viral loads >1000 copies/mL. Conclusions. Cryptococcosis after ART initiation is common in Africa. Patients initiating ART who unmask cryptococcal men ingitis are at a high risk of death. Immune recovery in the setting of central nervous system infection is detrimental, and manage ment of this population requires further study. Implementing pre-ART cryptococcal antigen screening is urgently needed to prevent cryptococcal meningitis after ART initiation. Keywords. antiretroviral therapy; cryptococcal meningitis; cryptococcus; HIV; immune reconstitution inflammatory syndrome
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ItemXpert MTB/RIF ultra for tuberculosis testing in children: A mini-review and commentary(Frontiers in Pediatrics, 2019)Tuberculosis (TB) remains a significant, yet under-recognized cause of death in the pediatric population, with a WHO estimate of 1 million new cases of childhood TB in 2016 resulting in 250,000 deaths. Diagnosis is notoriously difficult; manifestations are protean due to the high proportion of cases of extra-pulmonary TB in children, and logistical problems exist in obtaining suitable specimens. These issues are compounded by the paucibacillary nature of disease with the result that an estimated 96% of pediatric TB-associated mortality occurs prior to commencing anti-tuberculous treatment. Further development of sensitive, rapid diagnostic tests and their incorporation into diagnostic algorithms is vital in this population, and central to the WHO End-TB strategy. Initial gains were made with the expansion of nucleic acid amplification technology, particularly the introduction of the GeneXpert fully-automated PCR Xpert MTB/Rif assay in 2010, and more recently, the Xpert MTB/Rif Ultra (Ultra) assay in 2017. Ultra provides increased analytical sensitivity when compared with the initial Xpert assay in vitro; a finding now also supported by six clinical studies to date, two of which included pediatric samples. Here, we review the published evidence for the performance of Ultra in TB diagnosis in children, as well as studies in adults with paucibacillary disease providing results relevant to the pediatric population. Following on from this, we speculate upon future directions for Ultra, with focus on its potential use with alternative diagnostic specimens, which may be of particular utility in children.