Stephen Asiimwe

Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1–Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda

Background Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings. Methods and Findings Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7–6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0–0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP. Conclusions Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.

Frequency of vital signs monitoring and its association with mortality among adults with severe sepsis admitted to a general medical ward in Uganda.

Introduction Optimal vital signs monitoring of patients with severe sepsis in resource-limited settings may improve outcomes. The objective of this study was to determine the frequency of vital signs monitoring of patients with severe sepsis and its association with mortality in a regional referral hospital in Uganda. Methods We reviewed medical records of patients admitted to Mbarara Regional Referral Hospital in Southwestern Uganda with severe sepsis defined by the presence of infection plus ≥2 of the systemic inflammatory response syndrome criteria, and ≥1 organ dysfunction (altered mental state, hypotension, jaundice, or thrombocytopenia). We recorded frequency of vital signs monitoring in addition to socio-demographic, clinical, and outcome data. We analyzed the data using logistic regression. Results We identified 202 patients with severe sepsis. The median age was 35 years (IQR, 25–47) and 98 (48%) were female. HIV infection and anemia was present in 115 (57%) and 83 (41%) patients respectively. There were 67 (33%) in-hospital deaths. The median monitoring frequency per day was 1.1 (IQR 0.9–1.5) for blood pressure, 1.0 (IQR, 0.8–1.3) for temperature and pulse, and 0.5 (IQR, 0.3–1.0) for respiratory rate. The frequency of vital signs monitoring decreased during the course of hospitalization. Patients who died had a higher frequency of vital signs monitoring (p<0.05). The admission respiratory rate was associated with both frequency of monitoring (coefficient of linear regression 0.6, 95% CI 0.5–0.8, p<0.001) and mortality (AOR 2.5, 95% CI 1.3–5.3, p = 0.01). Other predictors of mortality included severity of illness, HIV infection, and anemia (p<0.05). Conclusions More research is needed to determine the optimal frequency of vital signs monitoring for severely septic patients in resource-limited settings such as Uganda.

Prevalence and predictors of high-risk human papillomavirus infection in a population-based sample of women in rural Uganda:

Summary: High-risk genital human papillomavirus (HPV) infection is aetiologically linked to cervical cancer; however, data on the prevalence and determinants of high-risk HPV infection in Uganda are limited. We conducted a population-based cross-sectional survey among 18-49-year-old women in rural Southwest Uganda. The primary outcome was presence or absence of high-risk HPV DNA (for genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68) in the genital secretions as determined by HPV DNA Hybrid Capture 2 assay (Digene Corp, Beltsville, MD, USA). In 314 women who participated, the prevalence of high-risk HPV was 17.2% (54/314; 95% confidence interval [CI]: 13-21). Older women had a lower proportion of high-risk HPV infection; with a 9% decrease in the odds ratio (OR) of high-risk HPV infection per year increase in age (OR = 0.91; 95% CI: 0.86, 0.96). The odds of detecting high-risk HPV infection was higher among women who were previously tested positive for HIV (OR = 12.1; 95% CI: 2.8, 52.3). In this population of rural Ugandan women, the prevalence of high-risk cervical HPV infection was high. Information on predictors of high-risk HPV infection and intention to receive a vaccine can guide future immunization initiatives for young sexually active women.

Comparison of Traditional and Novel Self-Report Measures to an Alcohol Biomarker for Quantifying Alcohol Consumption Among HIV-Infected Adults in Sub-Saharan Africa

BACKGROUND In Sub-Saharan Africa (SSA), HIV-infected patients may underreport alcohol consumption. We compared self-reports of drinking to phosphatidylethanol (PEth), an alcohol biomarker. In particular, we assessed beverage-type-adjusted fractional graduated frequency (FGF) and quantity frequency (QF) measures of grams of alcohol, novel nonvolume measures, and the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). METHODS We analyzed cohort entry data from the Biomarker Research of Ethanol Among Those with HIV cohort study (2011 to 2013). Participants were HIV-infected past-year drinkers, newly enrolled into care. Self-report measures included FGF and QF grams of alcohol, the AUDIT-C, number of drinking days, and novel adaptations of FGF and QF methods to expenditures on alcohol, time spent drinking, and symptoms of intoxication. PEth levels were measured from dried blood spots. We calculated Spearmans rank correlation coefficients of self-reports with PEth and bias-corrected bootstrap 95% confidence intervals (CIs) for pairwise differences between coefficients. RESULTS A total of 209 subjects (57% men) were included. Median age was 30; interquartile range (IQR) 25 to 38. FGF grams of alcohol over the past 90 days (median 592, IQR 43 to 2,137) were higher than QF grams (375, IQR 33 to 1,776), p < 0.001. However, both measures were moderately correlated with PEth: ρ = 0.58, 95% CI 0.47 to 0.66 for FGF grams and 0.54, 95% CI 0.43 to 0.63 for QF grams (95% CI for difference -0.017 to 0.099, not statistically significant). AUDIT-C, time drinking, and a scale of symptoms of intoxication were similarly correlated with PEth (ρ = 0.35 to 0.57). CONCLUSIONS HIV-infected drinkers in SSA likely underreport both any alcohol consumption and amounts consumed, suggesting the need to use more objective measures like biomarkers when measuring drinking in this population. Although the FGF method may more accurately estimate drinking than QF methods, the AUDIT-C and other nonvolume measures may provide simpler alternatives.

How home HIV testing and counselling with follow-up support achieves high testing coverage and linkage to treatment and prevention: a qualitative analysis from Uganda

The successes of HIV treatment scale‐up and the availability of new prevention tools have raised hopes that the epidemic can finally be controlled and ended. Reduction in HIV incidence and control of the epidemic requires high testing rates at population levels, followed by linkage to treatment or prevention. As effective linkage strategies are identified, it becomes important to understand how these strategies work. We use qualitative data from The Linkages Study, a recent community intervention trial of community‐based testing with linkage interventions in sub‐Saharan Africa, to show how lay counsellor home HIV testing and counselling (home HTC) with follow‐up support leads to linkage to clinic‐based HIV treatment and medical male circumcision services.

A simple prognostic index based on admission vital signs data among patients with sepsis in a resource-limited setting

IntroductionIn sub-Saharan Africa, vital signs are a feasible option for monitoring critically ill patients. We assessed how admission vital signs data predict in-hospital mortality among patients with sepsis. In particular, we assessed whether vital signs data can be incorporated into a prognostic index with reduced segmentation in the values of included variables.MethodsSubjects were patients with sepsis hospitalized in Uganda, who participated in two cohort studies. Using restricted cubic splines of admission vital signs data, we predicted probability of in-hospital death in the development cohort and used this information to construct a simple prognostic index. We assessed the performance of the index in a validation cohort and compared its performance to that of the Modified Early Warning Score (MEWS).ResultsWe included 317 patients (167 in the development cohort and 150 in the validation cohort). Based on how vital signs predicted mortality, we created a prognostic index giving a score of 1 for: respiratory rates ≥30 cycles/minute; pulse rates ≥100 beats/minute; mean arterial pressures ≥110/<70 mmHg; temperatures ≥38.6/<35.6°C; and presence of altered mental state defined as Glasgow coma score ≤14; 0 for all other values. The proposed index (maximum score = 5) predicted mortality comparably to MEWS. Patients scoring ≥3 on the index were 3.4-fold (95% confidence interval (CI) 1.6 to 7.3, P = 0.001) and 2.3-fold (95% CI 1.1 to 4.7, P = 0.031) as likely to die in hospital as those scoring 0 to 2 in the development and validation cohorts respectively; those scoring ≥5 on MEWS were 2.5-fold (95% CI 1.2 to 5.3, P = 0.017) and 1.8-fold (95% CI 0.74 to 4.2, P = 0.204) as likely to die as those scoring 0 to 4 in the development and validation cohorts respectively.ConclusionAmong patients with sepsis, a prognostic index incorporating admission vital signs data with reduced segmentation in the values of included variables adequately predicted mortality. Such an index may be more easily implemented when triaging acutely-ill patients. Future studies using a similar approach may develop indexes that can be used to monitor treatment among acutely-ill patients, especially in resource-limited settings.

D-dimer levels and traditional risk factors are associated with incident hypertension among HIV-infected individuals initiating antiretroviral therapy in Uganda.

Objectives:We sought to describe blood pressure (BP) changes after antiretroviral therapy (ART) initiation and evaluate the association of markers of inflammation with incident hypertension in a cohort of HIV-infected individuals in Uganda. Methods:We used mixed effects linear regression to model changes in systolic BP over time among a cohort of HIV-infected individuals initiating ART in Uganda. After exclusion of participants with preexisting hypertension, we identified participants with normal BP throughout follow-up (controls) and those with elevated BP on ≥3 consecutive visits (cases). Before ART initiation, participants had testing for interleukin 6, kynurenine/tryptophan ratio, lipopolysaccharide, soluble CD14, soluble CD163, and D-dimer and those with viral suppression at 6 months during ART had repeat tests. We fit logistic regression models to estimate associations between biomarkers and risk of incident hypertension. Results:In the entire cohort, systolic BP increased by 9.6 mm Hg/yr (95% CI: 7.3 to 11.8) in the first 6 months of ART, then plateaued. Traditional factors: male gender (adjusted odds ratio (AOR) 2.76, 95% CI: 1.34 to 5.68), age (AOR 1.09, 95% CI: 1.04 to 1.13), overweight (AOR 4.48, 95% CI: 1.83 to 10.97), and a CD4 count <100 cells (AOR 3.08, 95% CI: 1.07 to 8.89) were associated with incident hypertension. After adjusting for these, D-dimer levels at month 6 were inversely associated with incident hypertension (AOR 0.61, 95% CI: 0.37 to 0.99). Although not significant, similar associations were seen with sCD14 and kynurenine/tryptophan ratio. Conclusion:BP increases early after ART initiation in Ugandans. Traditional risk factors, rather than immune activation, were associated with incident hypertension in this population.

Factors influencing use of long-acting versus short-acting contraceptive methods among reproductive-age women in a resource-limited setting.

BackgroundUnplanned pregnancy remains a common problem in many resource-limited settings, mostly due to limited access to modern family planning (FP) services. In particular, use of the more effective long-acting reversible contraceptive (LARC) methods (i.e., intrauterine devices and hormonal implants) remains low compared to the short-acting methods (i.e., condoms, hormonal pills, injectable hormones, and spermicides). Among reproductive-age women attending FP and antenatal care clinics in Uganda, we assessed perceptions and practices regarding the use of modern contraceptive methods. We specifically aimed to evaluate factors influencing method selection.MethodsWe performed a mixed-methods cross-sectional study, in which we administered structured interviews to 180 clients, and conducted 4 focus group discussions (FGDs) with 36 clients and 8 in-depth personal qualitative interviews with health service providers. We summarized quantitative data and performed latent content analysis on transcripts from the FGDs and qualitative interviews.ResultsThe prevalence of ever use for LARC methods was 23%. Method characteristics (e.g., client control) appeared to drive method selection more often than structural factors (such as method availability) or individual client characteristics (such as knowledge and perceptions). The most common reasons for choosing LARC methods were: longer protection; better child-spacing; and effectiveness. The most common reasons for not choosing LARC methods included requiring a client-controlled method and desiring to conceive in the near future. The most common reasons for choosing short-acting methods were ease of access; lower cost; privacy; perceived fewer side effects; and freedom to stop using a method without involving the health provider. The personal characteristics of clients, which appeared to be important were client knowledge and number of children. The structural factor which appeared to be important was method availability.ConclusionsOur results suggest that interventions to improve uptake of LARC among reproductive age women in this setting should consider: incorporating desired method-characteristics into LARC methods; targeted promotion and supply of LARC; and increased counselling, sensitization, and education.

Simplifications of the mini nutritional assessment short-form are predictive of mortality among hospitalized young and middle-aged adults

OBJECTIVE Measuring malnutrition in hospitalized patients is difficult in all settings. I evaluated associations of items in the mini nutritional assessment short-form (MNA-sf), a nutritional-risk screening tool previously validated in the elderly, with malnutrition among hospitalized patients in Uganda. I used results to construct two simplifications of this tool that may be applicable to young and middle-aged adults. METHODS I assessed the association of each MNA-sf item with the mid-upper arm circumference (MUAC), a specific measure of malnutrition at appropriate cut-offs. I incorporated only malnutrition-specific items into the proposed simplifications scoring each item according to its association with malnutrition. I assessed numbers classified to different score-levels by the simplifications and, via proportional hazards regression, how the simplifications predicted in-hospital mortality. RESULTS I analyzed 318 patients (median age 37, interquartile range 27 to 56). Variables making it into the simplifications were: reduced food intake, weight loss, mobility, and either BMI in kg/m(2) (categorized as <16, 16 to 16.9, and ≥17) or MUAC in centimeters (categorized as <16 or <17, 16 to 18.9 or 17 to 19.9, and ≥19 or ≥20 for females and males respectively). Compared to the traditional MNA-sf, the simplifications classified fewer patients as malnourished, yet remained strongly predictive of in-hospital mortality. In the MUAC-incorporating simplification, malnourished patients had 3.8-fold (95% CI 1.9 to 7.8) higher risk of in-hospital death than those not malnourished; adjusting for age, sex, and HIV status. CONCLUSION The MNA-sf simplifications described may provide an improved measure of malnutrition in hospitalized young and middle-aged adults.

Use of Modern Family Planning Methods in Fishing Communities of Lake Victoria, Uganda.

Introduction Fishing communities (FCs) in Uganda have high HIV infection rates but poor access to health services including family planning (FP). Although FP is a cost-effective public health intervention, there is a paucity of data on knowledge and use of modern FP in FCs. This study determined knowledge and use of modern FP methods in FCs of Uganda. Methods Data were accrued from a 12-month follow up of 1,688 HIV-uninfected individuals, 18–49 years from 8 FCs along Lake Victoria, between September 2011 and March 2013. Data on knowledge and use of modern FP were collected through a semi-structured questionnaire. Prevalence Risk Ratios with corresponding 95% CIs were used to determine factors associated with Modern FP knowledge and use. Results The mean age was 31.4 years, with nearly half (48.8%) being females while more than half (58.6%) had attained up to primary education level. Knowledge of modern FP was high, 87.5% (1477/1688); significantly higher among females [adj. PRR = 4.84 (95% CI; 3.08, 7.61)], among older respondents (25–29 years) [adj. PRR = 1.83 (95% CI; 1.12, 2.99)] compared to younger ones (18–24 years) and among those conducting business [adj. PRR = 2.42(95% CI; 1.02, 5.74)] relative to those primarily in fishing. Just over a third (35.2%, 595/1688) reported use of at least one modern FP method. Use of modern FP methods was significantly higher among females [adj. PRR = 2.04 (95% CI; 1.56, 2.65, and among those reporting multiple sexual partnerships [adj. PRR = 2.12, 95% CI; 1.63, 2.76)]. Nonuse of modern methods was mostly due to desire for more children (30.6%), fear of side effects (12.2%) and partner refusal (5.2%). Conclusion Despite their high knowledge of FP, FCs have low use of modern FP methods. Key barriers to use of modern FP methods were high fertility desires, fear of perceived side effects and partner refusal of methods.