Rift valley fever outbreak in Sembabule District, Uganda, December 2020.

BACKGROUND: Rift Valley Fever (RVF) is a viral zoonosis that can cause severe haemorrhagic fevers in humans and high mortality rates and abortions in livestock. On 10 December 2020, the Uganda Ministry of Health was notified of the death of a 25-year-old male who tested RVF-positive by reverse-transcription polymerase chain reaction (RT-PCR) at the Uganda Virus Research Institute. We investigated to determine the scope of the outbreak, identify exposure factors, and institute control measures. METHODS: A suspected case was acute-onset fever (or axillary temperature > 37.5 °C) and ≥ 2 of: headache, muscle or joint pain, unexpected bleeding, and any gastroenteritis symptom in a resident of Sembabule District from 1 November to 31 December 2020. A confirmed case was the detection of RVF virus nucleic acid by RT-PCR or serum IgM antibodies detected by enzyme-linked immunosorbent assay (ELISA). A suspected animal case was livestock (cattle, sheep, goats) with any history of abortion. A confirmed animal case was the detection of anti-RVF IgM antibodies by ELISA. We took blood samples from herdsmen who worked with the index case for RVF testing and conducted interviews to understand more about exposures and clinical characteristics. We reviewed medical records and conducted an active community search to identify additional suspects. Blood samples from animals on the index case's farm and two neighbouring farms were taken for RVF testing. RESULTS: The index case regularly drank raw cow milk. None of the seven herdsmen who worked with him nor his brother's wife had symptoms; however, a blood sample from one herdsman was positive for anti-RVF-specific IgM and IgG. Neither the index case nor the additional confirmed case-patient slaughtered or butchered any sick/dead animals nor handled abortus; however, some of the other herdsmen did report high-risk exposures to animal body fluids and drinking raw milk. Among 55 animal samples collected (2 males and 53 females), 29 (53%) were positive for anti-RVF-IgG. CONCLUSIONS: Two human RVF cases occurred in Sembabule District during December 2020, likely caused by close interaction between infected cattle and humans. A district-wide animal serosurvey, animal vaccination, and community education on infection prevention practices campaign could inform RVF exposures and reduce disease burden.

Transitioning the COVID-19 response in the WHO African region: a proposed framework for rethinking and rebuilding health systems.

The onset of the pandemic revealed the health system inequities and inadequate preparedness, especially in the African continent. Over the past months, African countries have ensured optimum pandemic response. However, there is still a need to build further resilient health systems that enhance response and transition from the acute phase of the pandemic to the recovery interpandemic/preparedness phase. Guided by the lessons learnt in the response and plausible pandemic scenarios, the WHO Regional Office for Africa has envisioned a transition framework that will optimise the response and enhance preparedness for future public health emergencies. The framework encompasses maintaining and consolidating the current response capacity but with a view to learning and reshaping them by harnessing the power of science, data and digital technologies, and research innovations. In addition, the framework reorients the health system towards primary healthcare and integrates response into routine care based on best practices/health system interventions. These elements are significant in building a resilient health system capable of addressing more effectively and more effectively future public health crises, all while maintaining an optimal level of essential public health functions. The key elements of the framework are possible with countries following three principles: equity (the protection of all vulnerable populations with no one left behind), inclusiveness (full engagement, equal participation, leadership, decision-making and ownership of all stakeholders using a multisectoral and transdisciplinary, One Health approach), and coherence (to reduce the fragmentation, competition and duplication and promote logical, consistent programmes aligned with international instruments).

Intention to vaccinate against COVID-19 and adherence to non-pharmaceutical interventions against COVID-19 prior to the second wave of the pandemic in Uganda: a cross-sectional study.

OBJECTIVES: The resurgence in cases and deaths due to COVID-19 in many countries suggests complacency in adhering to COVID-19 preventive guidelines. Vaccination, therefore, remains a key intervention in mitigating the impact of the COVID-19 pandemic. This study investigated the level of adherence to COVID-19 preventive measures and intention to receive the COVID-19 vaccine among Ugandans. DESIGN, SETTING AND PARTICIPANTS: A nationwide cross-sectional survey of 1053 Ugandan adults was conducted in March 2021 using telephone interviews. MAIN OUTCOME MEASURES: Participants reported on adherence to COVID-19 preventive measures and intention to be vaccinated with COVID-19 vaccines. RESULTS: Overall, 10.2% of the respondents adhered to the COVID-19 preventive guidelines and 57.8% stated definite intention to receive a SARS-CoV-2 vaccine. Compared with women, men were less likely to adhere to COVID-19 guidelines (Odds Ratio (OR)=0.64, 95% CI 0.41 to 0.99). Participants from the northern (4.0%, OR=0.28, 95% CI 0.12 to 0.92), western (5.1%, OR=0.30, 95% CI 0.14 to 0.65) and eastern regions (6.5%, OR=0.47, 95% CI 0.24 to 0.92), respectively, had lower odds of adhering to the COVID-19 guidelines than those from the central region (14.7%). A higher monthly income of ≥US$137 (OR=2.31, 95% CI 1.14 to 4.58) and a history of chronic disease (OR=1.81, 95% CI 1.14 to 2.86) were predictors of adherence. Concerns about the chances of getting COVID-19 in the future (Prevalence Ratio (PR)=1.26, 95% CI 1.06 to 1.48) and fear of severe COVID-19 infection (PR=1.20, 95% CI 1.04 to 1.38) were the strongest predictors for a definite intention, while concerns for side effects were negatively associated with vaccination intent (PR=0.75, 95% CI 0.68 to 0.83). CONCLUSION: Behaviour change programmes need to be strengthened to promote adherence to COVID-19 preventive guidelines as vaccination is rolled out as another preventive measure. Dissemination of accurate, safe and efficacious information about the vaccines is necessary to enhance vaccine uptake.

Treatment Failure and Associated Factors among Individuals on Second Line Antiretroviral Therapy in Eastern Uganda: A Retrospective Cohort Study.

BACKGROUND: ART failure is a growing public health problem and a major threat to the progress of HIV/AIDS control. In Uganda however, little is documented on treatment outcomes and their associated factors among individuals on second line ART regimen. The rapid scale-up of ART over the past has resulted in substantial reductions in morbidity and mortality. However, as millions of people must be maintained on ART for life, individuals with ART treatment failure are increasingly encountered and the numbers are expected to rise. This could be attributed to factors such as sub-standard regimens, limited access to routine viral load monitoring, treatment interruptions, suboptimal adherence, among others. The purpose of this study was to estimate 5-year cumulative treatment failure and the associated factors among individuals on second line ART regimen Eastern Uganda. MATERIALS AND METHODS: A retrospective analysis of 541 records of HIV positive individuals, switched to second line ART regimen from January 2012 to December 2017. Inferential statistics including the Chi square test and multivariable logistic regression analysis was applied to determine associations of treatment failure against of the selected demographic, laboratory and clinical factors was performed. Associations between treatment failure and the predictors was based on a P-value of less than 5% and confidence intervals level of 95%. RESULTS: We reviewed 541 records of individuals on second line ART regimen, of which 350 (64.7%) were female, 226 (41.8%) were married, and 197 (36.4%) were older than 35 years. The mean age at ART initiation was 30 years (SD = 14.8), while the mean weight at ART initiation was 47 kg (SD = 18.6), (range 4-97 kg). The overall proportion of treatment failure was 23%. The cumulative mortality risk for 5 years was 12.4% and the mortality rate was 2.5 deaths per 100 individuals per year. The odds of developing treatment failure among individuals switched to ATV/r-based regimen were 44% lower as compared to individuals who were switched to LPV/r (ORadj0.56, 95% CI 0.35-0.90, P = .016). while the odds of experiencing treatment failure among individuals that used AZT at ART initiation were 43% lower as compared to individuals that used a TDF based regimen at ART initiation (ORadj0.57, 95% CI 0.33-0.98, P = .041). CONCLUSION: The 5 year cumulative incidence of treatment failure in a cohort of 541 individuals was 23%. The type of protease inhibitor (PI) used in second line regimen and use of AZT at ART initiation were significantly associated with treatment failure. Our study also shows that the cumulative mortality risk while on second line ART regimen was 12.4% while the mortality rate was 2.5 deaths per 100 individuals per year. Given the high level of treatment failure among individuals on second line ART regimen, yet the current ART protocols limits the use of third line ART regimens to only regional referral hospitals, the Ministry of Health should strengthen the surveillance systems for identifying individuals failing on second line ART regimen even at district hospitals and lower health facilities to facilitate timely switch to optimal regimen. The Ministry of health through the Quality Improvement Division should conduct routine onsite support supervision to sites offering ART to ensure that treatment guides and other standard of care like timely switch to appropriate regimens among others are being adhered to. Knowledge gaps identified can also be addressed through onsite Continuous Medical Educations.

Evaluation of the Ebola Virus Disease (EVD) preparedness and readiness program in Uganda: 2018 to 2019.

INTRODUCTION: the Democratic Republic of Congo (DRC) declared its 10thoutbreak of Ebola virus disease (EVD) in 42 years on August 1st 2018. The rapid rise and spread of the EVD outbreak threatened health security in neighboring countries and global health security. The United Nations developed an EVD preparedness and readiness (EVD-PR) plan to assist the nine neighboring countries to advance their critical preparedness measures. In Uganda, EVD-PR was implemented between 2018 and 2019. The World Health Organization commissioned an independent evaluation to assess the impact of the investment in EVD-PR in Uganda. Objectives: i) to document the program achievements; ii) to determine if the capacities developed represented good value for the funds and resources invested; iii) to assess if more cost-effective or sustainable alternative approaches were available; iv) to explore if the investments were aligned with country public health priorities; and v) to document the factors that contributed to the program success or failure. METHODS: during the EVD preparedness phase, Uganda's government conducted a risk assessment and divided the districts into three categories, based on the potential risk of EVD. Category I included districts that shared a border with the DRC provinces where EVD was ongoing or any other district with a direct transport route to the DRC. Category II were districts that shared a border with the DRC but not bordering the DRC provinces affected by the EVD outbreak. Category III was the remaining districts in Uganda. EVD-PR was implemented at the national level and in 22 category I districts. We interviewed key informants involved in program design, planning and implementation or monitoring at the national level and in five purposively selected category I districts. RESULTS: Ebola virus disease preparedness and readiness was a success and this was attributed mainly to donor support, the ministry of health's technical capacity, good coordination, government support and community involvement. The resources invested in EVD-PR represented good value for the funds and the activities were well aligned to the public health priorities for Uganda. CONCLUSION: Ebola virus disease preparedness and readiness program in Uganda developed capacities that played an essential role in preventing cross border spread of EVD from the affected provinces in the DRC and enabled rapid containment of the two importation events. These capacities are now being used to detect and respond to the COVID-19 pandemic.

Effect of a 72 Hour Stroke Care Bundle on Early Outcomes after Acute Stroke: A Non Randomised Controlled Study.

BACKGROUND: Integrated care pathways (ICP) in stroke management are increasingly being implemented to improve outcomes of acute stroke patients. We evaluated the effect of implementing a 72 hour stroke care bundle on early outcomes among patients admitted within seven days post stroke to the national referral hospital in Uganda. METHODS: In a one year non-randomised controlled study, 127 stroke patients who had 'usual care' (control group) were compared to 127 stroke patients who received selected elements from an ICP (intervention group). Patients were consecutively enrolled (controls first, intervention group second) into each group over 5 month periods and followed to 30-days post stroke. Incidence outcomes (mortality and functional ability) were compared using chi square test and adjusted for potential confounders. Kaplan Meier survival estimates and log rank test for comparison were used for time to death analysis for all strokes and by stroke severity categories. Secondary outcomes were in-hospital mortality, median survival time and median length of hospital stay. RESULTS: Mortality within 7 days was higher in the intervention group compared to controls (RR 13.1, 95% CI 3.3-52.9). There was no difference in 30-day mortality between the two groups (RR 1.2, 95% CI 0.5-2.6). There was better 30-day survival in patients with severe stroke in the intervention group compared to controls (P = 0.018). The median survival time was 30 days (IQR 29-30 days) in the control group and 30 days (IQR 7-30 days) in the intervention group. In the intervention group, 41patients (32.3%) died in hospital compared to 23 (18.1%) in controls (P < 0.001). The median length of hospital stay was 8 days (IQR 5-12 days) in the controls and 4 days (IQR 2-7 days) in the intervention group. There was no difference in functional outcomes between the groups (RR 0.9, 95% CI 0.4-2.2). CONCLUSIONS: While implementing elements of a stroke-focused ICP in a Ugandan national referral hospital appeared to have little overall benefit in mortality and functioning, patients with severe stroke may benefit on selected outcomes. More research is needed to better understand how and when stroke protocols should be implemented in sub-Saharan African settings. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201510001272347.

Early mortality and functional outcome after acute stroke in Uganda: prospective study with 30 day follow-up.

Identification of early outcomes post stroke and their predictors is important in stroke management strategies. We prospectively analysed 30-day outcomes (mortality and functional ability) after stroke and their predictors among patients admitted within 7 days post event to a national referral hospital in Uganda. This was a prospective study of acute stroke patients consecutively enrolled between February and July 2014. Social demographics, clinical, laboratory, imaging characteristics, outcomes (all through 30 days), time of death were assessed using standardised questionnaires. Multiple regression was used to analyse the independent influence of factors on outcomes. Of 127 patients, 88 (69.3 %) had ischemic stroke and 39 (30.7 %) had hemorrhagic stroke. Eight (6.3 %) died within 7 days, 34 (26.8 %) died within 30 days, with 2/3 of deaths occurring in hospital. Two were lost to follow up. Of 91 survivors, 49 (53.9 %) had satisfactory outcome, 42 (46.1 %) had poor functional outcome. At multivariate analysis, independent predictors of mortality at 30 days were unconsciousness (GCS <9), severe stroke at admission and elevated fasting blood sugar. None of the patients with functional independence (Barthel index ≥60) at admission died within 30 days. Inverse independent predictors of satisfactory outcome at 30 days were older age, history of hypertension and severe stroke at admission. Acute stroke patients in Uganda still have high rates of early mortality and poor functional outcomes. Independent predictors of mortality and poor functional outcome were severe stroke at admission, unconsciousness, high fasting blood sugar, old age and history of hypertension.

Stroke-Risk Factors Differ between Rural and Urban Communities: Population Survey in Central Uganda.

BACKGROUND: Socioeconomic transition is changing stroke risk factors in Sub-Saharan Africa. This study assessed stroke-risk factors and their associated characteristics in urban and rural Uganda. METHODS: We surveyed 5,420 urban and rural participants and assessed the stroke-risk factor prevalence and socio-behavioural characteristics associated with risk factors. RESULTS: Rural participants were older with higher proportions of men and fewer poor compared to urban areas. The most prevalent modifiable stroke-risk factors in all areas were hypertension (27.1% rural and 22.4% urban, p = 0.004), overweight and obesity (22.0% rural and 42% urban, p < 0.0001), and elevated waist hip ratio (25.8% rural and 24.1% urban, p = 0.045). Diabetes, smoking, physical inactivity, harmful alcohol consumption were found in ≤5%. Age, family history of hypertension, and waist hip ratio were associated with hypertension in all, while BMI, HIV were associated with hypertension only in urban dwellers. Sex and family history of hypertension were associated with BMI in all, while age, socio-economic status and diabetes were associated with BMI only in urban dwellers. CONCLUSIONS: The prevalence of stroke-risk factors of diabetes, smoking, inactivity and harmful alcohol consumption was rare in Uganda. Rural dwellers belonging to a higher age group tended to be with hypertension and elevated waist hip ratio. Unlike high-income countries, higher socioeconomic status was associated with overweight and obesity.

Knowledge and Perception of Stroke: A Population-Based Survey in Uganda.

PURPOSE: This study, designed to complement a large population survey on prevalence of stroke risk factors, assessed knowledge and perception of stroke and associated factors. METHODS: A population survey was conducted in urban Nansana and rural Busukuma, Wakiso district, central Uganda. Adult participants selected by multistage stratified sampling were interviewed about selected aspects of stroke knowledge and perception in a pretested structured questionnaire. RESULTS: There were 1616 participants (71.8% urban; 68.4% female; mean age: 39.6 years ± 15.3). Nearly 3/4 did not know any stroke risk factors and warning signs or recognize the brain as the organ affected. Going to hospital (85.2%) was their most preferred response to a stroke event. Visiting herbalists/traditional healers was preferred by less than 1%. At multivariable logistic regression, good knowledge of stroke warning signs and risk factors was associated with tertiary level of education (OR 4.29, 95% CI 2.13-8.62 and OR 5.96, 95% CI 2.94-12.06), resp.) and self-reported diabetes (OR 1.97, 95% CI 1.18-3.32 and OR 1.84, 95% CI 1.04-3.25), resp.). CONCLUSION: Knowledge about stroke in Uganda is poor although the planned response to a stroke event was adequate. Educational strategies to increase stroke knowledge are urgently needed as a prelude to developing preventive programmes.

Free HIV antiretroviral therapy enhances adherence among individuals on stable treatment: implications for potential shortfalls in free antiretroviral therapy.

OBJECTIVE: To estimate the population-level causal effect of source of payment for HIV medication on treatment adherence using Marginal Structural Models. METHODS: Data were obtained from an observational cohort of 76 HIV-infected individuals with at least 24 weeks of antiretroviral therapy treatment from 2002 to 2007 in Kampala, Uganda. Adherence was the primary outcome and it was measured using the 30-day visual analogue scale. Marginal structural models (MSM) were used to estimate the effect of source of payment for HIV medication on adherence, adjusting for confounding by income, duration on antiretroviral therapy (ART), timing of visit, prior adherence, prior CD4⁺ T cell count and prior plasma HIV RNA. Traditional association models were also examined and the results compared. RESULTS: Free HIV treatment was associated with a 3.8% improvement in adherence in the marginal structural model, while the traditional statistical models showed a 3.1-3.3% improvement in adherence associated with free HIV treatment. CONCLUSION: Removing a financial barrier to treatment with ART by providing free HIV treatment appears to significantly improve adherence to antiretroviral therapy. With sufficient information on confounders, MSMs can be used to make robust inferences about causal effects in epidemiologic research.

Longitudinal antiretroviral adherence in HIV+ Ugandan parents and their children initiating HAART in the MTCT-Plus family treatment model: role of depression in declining adherence over time.

We conducted a study to assess the effect of family-based treatment on adherence amongst HIV-infected parents and their HIV-infected children attending the Mother-To-Child-Transmission Plus program in Kampala, Uganda. Adherence was assessed using home-based pill counts and self-report. Mean adherence was over 94%. Depression was associated with incomplete adherence on multivariable analysis. Adherence declined over time. Qualitative interviews revealed lack of transportation money, stigma, clinical response to therapy, drug packaging, and cost of therapy may impact adherence. Our results indicate that providing ART to all eligible HIV-infected members in a household is associated with excellent adherence in both parents and children. Adherence to ART among new parents declines over time, even when patients receive treatment at no cost. Depression should be addressed as a potential barrier to adherence. Further study is necessary to assess the long-term impact of this family treatment model on adherence to ART in resource-limited settings.

Steady state bioequivalence of generic and innovator formulations of stavudine, lamivudine, and nevirapine in HIV-infected Ugandan adults.

BACKGROUND: Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune) or the corresponding brand formulations (Epivir, Zerit, and Viramune). METHODOLOGY/PRINCIPAL FINDINGS: An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received lamivudine (150 mg), stavudine (40 mg), and nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC(0-12h) and C(max). Bioequivalence was defined as a geometric mean ratio between the generic and brand name within the 90% confidence interval of 0.8-1.25. The geometric mean ratios and the 90% confidence intervals were: stavudine C(max), 1.3 (0.99-1.71) and AUC(0-12h), 1.1 (0.87-1.38); lamivudine C(max), 0.8 (0.63-0.98) and AUC(0-12h), 0.8 (0.65-0.99); and nevirapine C(max), 1.1 (0.95-1.23) and AUC(0-12h), 1.1 (0.95-1.31). The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters. CONCLUSIONS/SIGNIFICANT FINDINGS: These findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical.

Circumcision and HIV infection: assessment of causality.

Whether the observed association between male circumcision and HIV infection is causal or not has not been verified. We did a meta-analysis of published data and applied Hill's criteria for causality on all available evidence to assess presence of a causal association. Analysis was by the random effects method. Summary estimates were calculated for all studies combined and for sub groups stratified by type of study population, study design, and method of ascertaining circumcision status. Thirteen studies were included. Circumcised men had a reduced risk for HIV infection (adjusted RRoverall = 0.42, 95% CI 0.33-0.53; RR(RCT) = 0.43 95% CI 0.32-0.59, RRobservational = 0.39, 95% CI 0.27-0.56). Available evidence satisfies six of Hill's criteria: strength of association, consistency, temporality, coherence, biological plausibility, and experiment. These results provide unequivocal evidence that circumcision plays a causal role in reducing the risk of HIV infection among men.

Adherence to antiretroviral therapy in children attending Mulago Hospital, Kampala.

BACKGROUND: Non-adherence reduces the effectiveness of antiretroviral therapy in children attending the paediatric HIV/AIDS clinic at Mulago Hospital, Kampala. AIM: To determine the levels of adherence to HAART and identify factors associated with non-adherence. METHODS: A cross-sectional study of 170 children aged 2-18 years. Adherence to HAART was defined as taking > or =95% of prescribed medication. It was determined using three measures: a 3-day self-report by the caregivers, clinic-based pill counts at enrolment and home-based unannounced pill counts 2-3 weeks later. RESULTS: The 3-day self-reported > or =95% adherence was 89.4% (n=170). Using clinic-based pill counts, 94.1% (n=170) had > or =95% adherence to treatment compared with only 72% (n=164) by unannounced pill counts. When the primary caregiver was the only one who knew the child's serostatus, he/she was three times more likely to be non-adherent (p=0.02, OR 3.34, 95% CI 1.14-9.82). Those who had been hospitalised twice or more before starting HAART were more likely to have > or =95% adherence (p=0.02, OR 0.44, 95% CI 0.20-0.92). CONCLUSION: The majority of children had good adherence levels when estimated by unannounced pill counts. Disclosing the child's HIV serostatus only to the primary caregiver and having been hospitalised only once or not at all were associated with poor adherence.

Hepatotoxicity during nevirapine-based fixed-dose combination antiretroviral therapy in kampala, Uganda.

BACKGROUND: Generic, low-cost, nevirapine (NVP)-based antiretroviral therapy (ART) has improved survival in HIV-infected individuals living in resource-limited settings. However, there is concern about the potential hepatotoxicity of these regimens. METHODS: The authors conducted a prospective study of persons initiating self-pay Triomune or Maxivir therapy in Kampala, Uganda. RESULTS: The 97 study participants were predominantly women (64%), median age was 35 (interquartile range [IQR] 30-40), median CD4 at baseline was 56 cells/mm(3) (IQR 8-138), and 19% had lifetime alcohol problems (CAGE >/= 2). Severe liver enzyme elevations (LEEs) of grade 3-4 were rare (2.2%); however, 1 patient died in the setting of grade 4 LEEs. Grade 1-4 LEEs occurred among 22.2% of participants, and 9.8% had new grade 1-4 LEEs after the initiation of treatment. DISCUSSION: The authors found that LEEs were common but that severe hepatotoxicity in persons initiating NVP-based ART was infrequent yet potentially life-threatening. Monitoring for NVP-related severe hepatic toxicity should be part of expanding antiretroviral treatment programs in resource-limited settings.

Discontinuation and modification of highly active antiretroviral therapy in HIV-infected Ugandans: prevalence and associated factors.

BACKGROUND: Data on discontinuation and modification of highly active antiretroviral therapy (HAART) are scarce among sub-Saharan African populations. We sought to estimate the prevalence and to identify factors associated with these phenomena in our resource-limited setting. METHODS: Patients were recruited into this cross-sectional study from 2 treatment centers in Kampala, Uganda. Discontinuation and modification were assessed by self-report using semistructured quantitative and unstructured qualitative interviews. Discontinuation was defined as the simultaneous stopping of all antiretrovirals for at least 1 month, and modification as the changing of at least 1 antiretroviral used in an initial HAART regimen. Factors independently associated with each outcome were assessed using multivariate logistic regression. RESULTS: Of 686 subjects evaluated, 94 (13.7%) had ever discontinued therapy, whereas 175 (25.5%) had ever modified their regimen. The median CD4 count was 175 (interquartile range: 66-297) cells/microL. Factors associated with discontinuation were HAART experience before starting the current regimen (odds ratio [OR] = 3.70, 95% confidence interval [CI]: 2.13 to 6.25), use of alternative medicines (OR = 2.18, 95% CI: 1.06 to 4.47), hospitalization (OR = 2.36, 95% CI: 1.32 to 4.20), and 1 year or less on HAART (OR = 11.11, 95% CI: 5.00 to 25.00). Modification was associated with more than 3 months' duration on HAART (OR = 3.13, 95% CI: 1.16 to 8.33) and being unmarried (OR = 1.64, 95% CI: 1.02 to 2.70). CONCLUSIONS: The proportions of discontinuation and modification of antiretroviral therapy (ART) observed in our resource-poor setting pose a challenge to the limited treatment options presently available. Drug cost as a major reason for discontinuation of HAART has major implications for ART programs that charge fees in resource-limited settings.

Treatment interruptions predict resistance in HIV-positive individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda.

OBJECTIVE: To evaluate adherence, treatment interruptions, and outcomes in patients purchasing antiretroviral fixed-dose combination (FDC) therapy. DESIGN: Ninety-seven participants were recruited into a prospective 24-week observational cohort study of HIV-positive, antiretroviral-naive individuals initiating self-pay Triomune or Maxivir therapy in Kampala, Uganda. Adherence was measured by monthly structured interview, unannounced home pill count, and electronic medication monitors (EMM). Treatment interruptions were measured as continuous intervals greater than 48 h without opening the EMM. The primary outcomes were survival with viral suppression below 400 copies/ml, CD4 cell increases, and genotypic drug resistance at 24 weeks. RESULTS: The median baseline CD4 cell count was 56 cells/microl and median log10 copies RNA/ml was 5.54; mean adherence ranged from 82 to 95% for all measures but declined significantly over time. In an intent-to-treat analysis, 70 (72%) patients had an undetectable plasma HIV-RNA level at week 24. Sixty-two of 95 (65%) individuals with continuous EMM data had a treatment interruption of greater than 48 h. Treatment interruptions accounted for 90% of missed doses. None of 33 participants who did not interrupt treatment for over 48 h had drug resistance, whereas eight of 62 (13%) participants who did interrupt therapy experienced drug resistance. Antiretroviral resistance was seen in 8% of individuals and overall mortality was 10% at 24 weeks. CONCLUSION: HIV-positive individuals purchasing generic FDC antiretroviral therapy have high rates of adherence and viral suppression, low rates of antiretroviral resistance, and robust CD4 cell responses. Adherence is an important predictor of survival with full viral suppression. Treatment interruptions are an important predictor of drug resistance.

Multiple validated measures of adherence indicate high levels of adherence to generic HIV antiretroviral therapy in a resource-limited setting.

BACKGROUND: There are no validated measures of adherence to HIV antiretroviral therapy in resource-poor settings. Such measures are essential to understand the unique barriers to adherence as access to HIV antiretroviral therapy expands. METHODS: We assessed correspondence between multiple measures of adherence and viral load suppression in 34 patients purchasing generic Triomune antiretroviral therapy (coformulated stavudine, lamivudine, and nevirapine; CIPLA, Ltd., Mumbai, India) in Kampala, Uganda. Measures included 3-day patient self-report, 30-day visual analog scale, electronic medication monitoring, and unannounced home pill count. HIV-1 load was determined at baseline and 12 weeks. RESULTS: Mean adherence was 91%-94% by all measures. Seventy-six percent of subjects had a viral load of <400 copies/mL at 12 weeks. All measures were closely correlated with each other (R = 0.77-0.89). Each measure was also significantly associated with 12-week HIV load. There was no significant difference between patient-reported and objective measures of adherence. CONCLUSIONS: This sample of patients purchasing generic HIV antiretroviral therapy has among the highest measured adherence reported to date. Patient-reported measures were closely associated with objective measures. The relative ease of administration of the 30-day visual analog scale suggests that this may be the preferred method to assess adherence in resource-poor settings.