Adherence to oral HIV pre-exposure prophylaxis among female sex workers in Kampala, Uganda

Introduction: In Kampala Uganda, female sex workers (FSWs) have high HIV prevalence (33%). Oral PrEP is a novel HIV prevention intervention that offers hope to decrease HIV incidence in key populations especially among FSWs. Studies have shown that with poor adherence, oral PrEP has no efficacy, and therefore adherence to PrEP is critical among FSWs to maximize HIV prevention. However, implementation data on adherence to PrEP among FSWs is limited so this study sought to assess adherence to PrEP. Specifically, we sought to 1) determine the level of adherence to PrEP among FSWs, and 2) determine factors associated with PrEP adherence. Methods: This cross-sectional study was conducted from November to December 2018; 126 FSWs using PrEP were interviewed using a questionnaire. Adherence was categorically defined as high adherence and low adherence. Logistic regression was done. Results: Using long-term contraception methods (OR 0.06, 95% CI: 0.04-0.77) and not using condoms with clients (OR 0.07, 95% CI: 0.01-0.42) were negatively associated with high PrEP adherence. Conclusion: Barriers to PrEP adherence need to be addressed for successful PrEP implementation to improve adherence going forward. Service care providers should reinforce positive behaviors such as use of condoms devotedly during PrEP breaks

Drug susceptibility of Plasmodium falciparum in eastern Uganda: a longitudinal phenotypic and genotypic study

Background: Treatment and control of malaria depends on artemisinin-based combination therapies (ACTs) and is challenged by drug resistance, but thus far resistance to artemisinins and partner drugs has primarily occurred in southeast Asia. The aim of this study was to characterise antimalarial drug susceptibility of Plasmodium falciparum isolates from Tororo and Busia districts in Uganda. Methods: In this prospective longitudinal study, P falciparum isolates were collected from patients aged 6 months or older presenting at the Tororo District Hospital (Tororo district, a site with relatively low malaria incidence) or Masafu General Hospital (Busia district, a high-incidence site) in eastern Uganda with clinical symptoms of malaria, a positive Giemsa-stained blood film for P falciparum, and no signs of severe disease. Ex-vivo susceptibilities to ten antimalarial drugs were measured using a 72-h microplate growth inhibition assay with SYBR Green detection. Relevant P falciparum genetic polymorphisms were characterised by molecular methods. We compared results with those from earlier studies in this region and searched for associations between drug susceptibility and parasite genotypes. Findings: From June 10, 2016, to July 29, 2019, 361 P falciparum isolates were collected in the Busia district and 79 in the Tororo district from 440 participants. Of 440 total isolates, 392 (89%) successfully grew in culture and showed excellent drug susceptibility for chloroquine (median half-maximal inhibitory concentration [IC50] 20·0 nM [IQR 12·0-26·0]), monodesethylamodiaquine (7·1 nM [4·3-8·9]), pyronaridine (1·1 nM [0·7-2·3]), piperaquine (5·6 nM [3·3-8·6]), ferroquine (1·8 nM [1·5-3·3]), AQ-13 (24·0 nM [17·0-32·0]), lumefantrine (5·1 nM [3·2-7·7]), mefloquine (9·5 nM [6·6-13·0]), dihydroartemisinin (1·5 nM [1·0-2·0]), and atovaquone (0·3 nM [0·2-0·4]). Compared with results from our study in 2010-13, significant improvements in susceptibility were seen for chloroquine (median IC50 288·0 nM [IQR 122·0-607·0]; p\u3c0·0001), monodesethylamodiaquine (76·0 nM [44·0-137]; p\u3c0·0001), and piperaquine (21·0 nM [7·6-43·0]; p\u3c0·0001), a small but significant decrease in susceptibility was seen for lumefantrine (3·0 nM [1·1-7·6]; p\u3c0·0001), and no change in susceptibility was seen with dihydroartemisinin (1·3 nM [0·8-2·5]; p=0·64). Chloroquine resistance (IC50\u3e100 nM) was more common in isolates from the Tororo district (11 [15%] of 71), compared with those from the Busia district (12 [4%] of 320; p=0·0017). We showed significant increases between 2010-12 and 2016-19 in the prevalences of wild-type P falciparum multidrug resistance protein 1 (PfMDR1) Asn86Tyr from 60% (391 of 653) to 99% (418 of 422; p\u3c0·0001), PfMDR1 Asp1246Tyr from 60% (390 of 650) to 90% (371 of 419; p\u3c0·0001), and P falciparum chloroquine resistance transporter (PfCRT) Lys76Thr from 7% (44 of 675) to 87% (364 of 417; p\u3c0·0001). Interpretation: Our results show marked changes in P falciparum drug susceptibility phenotypes and genotypes in Uganda during the past decade. These results suggest that additional changes will be seen over time and continued surveillance of susceptibility to key ACT components is warranted. Funding: National Institutes of Health and Medicines for Malaria Venture

Associations between Varied Susceptibilities to PfATP4 Inhibitors and Genotypes in Ugandan Plasmodium falciparum Isolates.

Among novel compounds under recent investigation as potential new antimalarial drugs are three independently developed inhibitors of the Plasmodium falciparum P-type ATPase (PfATP4): KAE609 (cipargamin), PA92, and SJ733. We assessed ex vivo susceptibilities to these compounds of 374 fresh P. falciparum isolates collected in Tororo and Busia districts, Uganda, from 2016 to 2019. Median IC50s were 65 nM for SJ733, 9.1 nM for PA92, and 0.5 nM for KAE609. Sequencing of pfatp4 for 218 of these isolates demonstrated many nonsynonymous single nucleotide polymorphisms; the most frequent mutations were G1128R (69% of isolates mixed or mutant), Q1081K/R (68%), G223S (25%), N1045K (16%), and D1116G/N/Y (16%). The G223S mutation was associated with decreased susceptibility to SJ733, PA92, and KAE609. The D1116G/N/Y mutations were associated with decreased susceptibility to SJ733, and the presence of mutations at both codons 223 and 1116 was associated with decreased susceptibility to PA92 and SJ733. In all of these cases, absolute differences in susceptibilities of wild-type (WT) and mutant parasites were modest. Analysis of clones separated from mixed field isolates consistently identified mutant clones as less susceptible than WT. Analysis of isolates from other sites demonstrated the presence of the G223S and D1116G/N/Y mutations across Uganda. Our results indicate that malaria parasites circulating in Uganda have a number of polymorphisms in PfATP4 and that modestly decreased susceptibility to PfATP4 inhibitors is associated with some mutations now present in Ugandan parasites

Improving livelihoods outcomes for forcibly displaced populations: a Rapid Review

Globally, the number of forcibly displaced individuals has surpassed 100 million, with approximately80 percent situated in low- or middle-income countries. In these resource-constrained settings the magnitude and protracted nature of displacement poses an increasing challenge. Recent policy discourse has begun to shift away from emergency response interventions towards those that promote investments inthe human capital and self-reliance of displaced populations. This paper reviews evidence of the impacts and costs of eleven interventions designed to improve the livelihoods of forcibly displaced people in low-and middle-income settings. The study team finds suggestive evidence that graduation-style approaches and cash transfers can improve people’s self-employment, wages, engagement in paid work and wellbeing. However, too few studies have been conducted among the exact populations and settings of interest to discern clear strategies for adapting interventions for success in every context. To address this gap, the authors introduce a primitive taxonomy of contextual factors, which encourages more robust discussion of how context impacts interventions. It will be important for future research to both evaluate a broader range of interventions, and to more systematically identify the effects of context to advance our understanding of how to improve the economic wellbeing of displaced people

Effect and implementation experience of intensive adherence counseling in a public HIV care center in Uganda : a mixed-methods study

Background: Intensive adherence counseling (IAC) is an intervention recommended by the World Health Organization to improve anti-retroviral therapy (ART) adherence among people living with HIV on ART with unsuppressed viral load; and in 2016, the intervention was implemented in Uganda. This study evaluated the effect and experiences of providing IAC in an urban HIV care center in Kampala, Uganda. Methods: This was a sequential explanatory mixed-method study that compared viral load suppression during IAC implementation (intervention) to the period before IAC at Kisenyi Health centre IV. Data were abstracted from patient files and viral load register. The effect of IAC on viral load suppression and associated factors were analyzed using modified Poisson regression with robust standard errors. Using in-depth interviews and an inductive analysis approach in Atlas-ti 8. We also explored experiences of providing IAC among healthcare workers. Results: A total of 500 records were sampled: 249 (49.8%) in the intervention period and 251 (51.2%) in the pre-intervention period. The mean age was lower during the intervention period 33.1 (± 12.0) than 36.5 (± 13.4) in the pre- intervention period, p = 0.002. More clients were currently on Protease-based regimen in the pre-intervention period 179 (71.3%) than 135 (54.2%) in the intervention period, p ≤ 0.001. In the intervention period, all eligible clients received IAC [249/249 (100.0%)]. Overall, 325 (65.0%) received IAC and of these, 143 (44.1%) achieved viral load suppression compared to 46 (26.3%) who received regular counseling. Receiving IAC significantly increased viral load suppression by 22% (aPR 1.22, 95% CI 1.01–1.47). Clients on Protease-based regimen were less likely to suppress than those on Efavirenz or Nevirapine-based regimens (aPR 0.11, 95% CI 0.08–0.15). All the interviewed healthcare workers lauded IAC for improving ART adherence. However, patient and health care system related factors hindered adherence during IAC. Conclusions: The full potential of IAC in achieving viral load suppression in this setting has not been reached due to a combination of the patient and health care system related factors. Provision of adequate IAC necessities and use of patient centered approach should be emphasized to obtain the maximum benefit of the intervention

Antiretroviral therapy initiation and outcomes of hospitalized HIV-infected patients in Uganda - An evaluation of the HIV test and treat strategy. Health care worker interview guide

Health care worker interview guid

Antiretroviral therapy initiation and outcomes of hospitalized HIV-infected patients in Uganda-An evaluation of the HIV test and treat strategy. Stata data set

BACKGROUND: Uganda adopted the HIV Test and Treat in 2016. There is paucity of data about its implementation among hospitalized patients. We aimed to determine the proportion of patients initiating anti-retroviral therapy (ART) during hospitalization, barriers and mortality outcome. METHODS: In this mixed methods cohort study, we enrolled hospitalized patients with a recent HIV diagnosis from three public hospitals in Uganda. We collected data on clinical characteristics, ART initiation and reasons for failure to initiate ART, as well as 30 day outcomes. Healthcare workers in-depth interviews were also conducted and data analyzed by sub-themes. RESULTS: We enrolled 234 patients; females 140/234 (59.8%), median age 34.5 years (IQR 29-42), 195/234 (83.7%) had WHO HIV stage 3 or 4, and 74/116 (63.8%) had CD4 ≤ 200 cell/μL. The proportion who initiated ART during hospitalization was 123/234 (52.6%) (95% CI 46.0-59.1), of these 35/123 (28.5%) initiated ART on the same day of hospitalization, while 99/123 (80.5%) within a week of hospitalization. By 30 days 34/234 (14.5%) (95% CI 10.3-19.7) died. Patients residing ≥ 35 kilometers from the hospital were more likely not to initiate ART during hospitalization, [aRR = 1.39, (95% CI 1.22-1.59). Inadequate patient preparation for ART initiation and advanced HIV disease were highlighted as barriers of ART initiation during hospitalization. CONCLUSION: In this high HIV prevalence setting, only half of newly diagnosed HIV patients are initiated on ART during hospitalization. Inadequate pre-ART patient preparation and advanced HIV are barriers to rapid ART initiation among hospitalized patients in public hospitals