Factors associated with prior engagement in high-risk sexual behaviours among adolescents (10-19 years) in a pastoralist post-conflict community, Karamoja sub-region, North eastern Uganda.

BACKGROUND: Adolescent sexual risky behaviours continue to be significant drivers of the HIV epidemic globally. The objective of this study was to determine factors associated with prior engagement in high-risk sexual behaviours among adolescents (10-19 years) in Karamoja sub-region, a pastoralist and post-conflict community in North-eastern Uganda. METHODS: Between August and September 2016, we conducted a cross-sectional study among 1439 adolescents receiving primary healthcare services at nine public health facilities located in five of the seven districts that make up Karamoja sub-region. High-risk sexual behaviour was defined as engaging in sex with two or more (2+) sexual partners in the 6 months preceding the survey or exchanging sex for money or gifts with no or inconsistent use of condoms over the same period of time. Factors associated with prior engagement in high-risk sexual behaviours were analysed using a modified Poison regression model with log-link and Poisson-family via a generalized linear model. RESULTS: Eighty-two percent (81.8%, n = 1177) of the respondents had ever tested for HIV while 62 % (61.5%, n = 885) had ever had sex. Of those that had ever had sex, 11.4% (n = 101) reported prior engagement in high-risk sexual behaviours. Prior engagement in high-risk sexual behaviours was lower among men than women (adjusted prevalence ratio (adj. PR) = 0.46; 95% Confidence Interval (95% CI): 0.33, 0.62) and those whose sex debut was above 14 years (adj.PR = 0.63; 95% CI: 0.57, 0.69). However, prior engagement in high-risk sexual behaviours was significantly higher in adolescents who were not aware of their recent sexual partner's HIV status (adj.PR = 2.43; 95% CI: 1.68, 3.52) and those who used illicit drugs (adj.PR = 2.76; 95% CI: 1.88, 4.05). CONCLUSION: Prior engagement in high-risk sexual behaviours was significantly associated with having sex with partners of unknown HIV sero-status and use of illicit drugs. These findings suggest a need for targeted interventions to improve mutual HIV status disclosure between sexual partners while minimizing their use of illicit drugs/substances.

Antiretroviral therapy initiation within seven days of enrolment: outcomes and time to undetectable viral load among children at an urban HIV clinic in Uganda.

BACKGROUND: Viral suppression is a critical indicator of HIV treatment success. In the era of test-and-start, little is known about treatment outcomes and time to undetectable viral loads. This study compares treatment outcomes, median times to achieve undetectable viral loads and its predictors under different antiretroviral (ART) treatment initiation schedules (i.e. within seven days of enrolment or later). METHODS: A retrospective cohort of 367 patients <18 years who enrolled in care between January 2010 and December 2015 with a baseline viral load of >5000 copies/ml were followed up for 60 months. Undetectable viral load measurements were based on both Roche (<20copies/ml) and Abbot (<75copies/ml). Clinical treatment outcomes were compared using chi-squared test. Survival experiences between the two cohorts were assessed through incidence rates and Kaplan Meier curves. A cox model with competing risks was used to assess predictors for time to undetectable viral load. RESULTS: Of the 367 patients, 180 (49.1%) initiated ART within seven days from enrolment, 192 (52.3%) attained undetectable viral load of which 133 (69.3%) were children below six years and 101 (52.6%) were females. Among those who initiated ART within seven days 15 (8.3%) died and 6 (3.3%) were lost to follow-up compared to 27 (14.4%) and 16 (8.6%) respectively in the later initiators. The median time to undetectable viral load was 24.9 months (95% CI: 19.7, 28.5) among early ART initiators and 38.5 months (95% CI: 31.1, 44.5) among those initiating beyond seven days. There was a significant difference in failure estimates between those initiating within seven and those that deferred (log rank, p = 0.001). Significant predictors for time to undetectable viral load were; starting ART within seven days (SHR = 2.02, 95% CI: 1.24, 3.28), baseline WHO stage I or II (SHR = 1.59, 95% CI: 1.06, 2.28), inconsistent adherence on three consecutive clinic visits (SHR = 0.44, 95% CI: 0.28, 0.67), and baseline weight (SRH = 1.04, 95% CI: 1.01, 1.07). CONCLUSION: Prompt initiation of ART within the first week of enrolment is associated with better treatment outcomes. Early timing, baseline WHO clinical stage and adherence rates should be major considerations while managing HIV among children.

Availability of Human Immunodeficiency Virus Prevention Services in Secondary Schools in Kabarole District, Uganda.

The aim of this study was to assess the level of availability of HIV prevention strategies in secondary schools in Kabarole district, Uganda in order to inform the design of interventions to strengthen HIV Prevention and psychosocial support. Quantitative and qualitative research methods were used in eight secondary schools in Kabarole district to establish available HIV prevention and psychosocial support services. Questionnaires were administered to 355 students 12-24 years old. In addition, 20 Key Informant interviews were held with education service providers. Quantitative data was analyzed using Epi-data and qualitative data were analyzed by thematic content analysis. Seven of the eight schools had at least one HIV prevention strategy. Two teachers in each of the five schools had been trained in HIV prevention. No school had a nurse trained in HIV prevention, care and support. Education service providers had limited knowledge of HIV prevention support and care of students living with HIV. We found out that students had knowledge on how one can acquire HIV. HIV prevention services reported by students in schools included: talks from teachers and guests (19%), drama with HIV prevention related messages (16%), peer education clubs (15%), workshops and seminars on HIV (8%), sensitization about HIV/AIDS (7%), guidance and counseling (6%), talking compounds- (5%), abstinence talks (6%), keeping students busy in sports (4%), straight talk (4%). Sixty three percent reported receiving HIV reading materials from various sources. Preventing HIV infection among students in schools is still demanding with limited interventions for students. Efforts to support school interventions should focus on including HIV Prevention in the school curriculum, working with peer educators as well as education service providers who spend much of the time with the students while at school.

Virologic, immunologic and clinical response of infants to antiretroviral therapy in Kampala, Uganda.

BACKGROUND: Antiretroviral therapy (ART) is known to save lives. Among HIV-infected infants living in resource constrained settings, the short and long term benefits of ART are only partially known. This study was designed to determine the virologic, immunologic and clinical outcomes of antiretroviral therapy in a cohort of HIV-infected infants receiving care from an outpatient clinic in Kampala, Uganda. METHODS: A prospective cohort of HIV-infected infants receiving treatment at the Baylor-Uganda clinic was analyzed. Patients were diagnosed, enrolled and followed up at the clinic. HIV viral load, CD4 cell counts and clinical progress were assessed during follow-up. Descriptive statistical analysis and logistic regression modeling to determine predictors of treatment success were conducted. RESULTS: Of 91 HIV-infected infants enrolled into the cohort, 53 (58.2%) infants were female; 43 (47.3%) were 6 months of age or younger, and 50 (55.6%) had advanced HIV/AIDS disease (Clinical stage 3 or 4). Eighty four infants started ART and 78 (92.9%) completed 6 months of treatments. Fifty six (71.8%) infants attained virologic suppression by month-6 of ART, and at month-12 of ART, the cumulative probability of attaining viral suppression was 83.1%. None of the baseline infant factors (age, sex, WHO stage, CD4 cell percent, weight for age, or height for age z-score) predicted treatment success. There was an increase in CD4 cells from a baseline mean of 23% to 30% at month-6 of treatment (p<0.001) and by month-24 of ART, the mean CD4 percent was 36%. A total of 7 patients died while on ART and another 7 experienced adverse events that were related to treatment. CONCLUSION: Our results show that, even among very young patients from resource constrained settings, ART dramatically suppresses HIV replication, allows immune recovery and clinical improvement, and is safe. However, baseline characteristics do not predict recovery in this age group.

The effect of blood storage age on treatment of lactic acidosis by transfusion in children with severe malarial anaemia: a pilot, randomized, controlled trial.

BACKGROUND: Severe malarial anaemia requiring blood transfusion is a life-threatening condition affecting millions of children in sub-Saharan Africa. Up to 40% of children with severe malarial anaemia have associated lactic acidosis. Lactic acidosis in these children is strongly associated with fatal outcomes and is corrected by blood transfusion. However, it is not known whether the storage age of blood for transfusion affects resolution of lactic acidosis. The objective of this pilot study was to evaluate the effect of blood storage age on resolution of lactic acidosis in children with severe malarial anaemia and demonstrate feasibility of conducting a large trial. METHODS: Children aged six to 59 months admitted to Acute Care Unit of Mulago Hospital (Kampala, Uganda) with severe malarial anaemia (haemoglobin ≤ 5 g/dL) and lactic acidosis (blood lactate ≥5 mmol/L), were randomly assigned to receive either blood of short storage age (one to 10 days) or long storage age (21-35 days) by gravity infusion. Seventy-four patients were enrolled and randomized to two equal-sized study arms. Physiological measurements, including blood lactate, oxygen saturation, haemoglobin, and vital signs, were taken at baseline, during and after transfusion. The primary outcome variable was the proportion of children whose lactic acidosis resolved by four hours after transfusion. RESULTS: Thirty-four of 37 (92%) of the children in the short storage treatment arm compared to 30/37 (81%) in the long storage arm achieved a blood lactate <5 mmol/L by four hours post transfusion (p value = 0.308). The mean time to lactic acidosis resolution was 2.65 hours (95% CI; 2.25-3.05) in the short storage arm, compared to 3.35 hours (95% CI; 2.60-4.10) in the long storage arm (p value = 0.264). CONCLUSION: Pilot data suggest that among children with severe malarial anaemia and lactic acidosis transfused with packed red blood cells, the storage age of blood does not affect resolution of lactic acidosis. The results support a larger and well-powered study which is under way. TRIAL REGISTRATION: clinicaltrials.gov NCT01580111.

Prospective long-term outcomes of a cohort of Ugandan children with laboratory monitoring during antiretroviral therapy.

BACKGROUND: Treatment of HIV-1 infected Ugandan children with antiretroviral therapy (ART) is increasing, but few prospective long-term studies evaluating the treatment process have been reported. In this study, we sought to determine prospectively how consistent monitoring of HIV-1 RNA levels affects the ART treatment process. METHODS: One hundred eight children initiating ART were enrolled into this study. These children had comprehensive laboratory monitoring, including HIV-1 RNA level determination and genotype analysis (where appropriate), CD4% plus absolute counts and safety laboratory measurements performed before starting therapy and at regular intervals after receiving ART. Kaplan-Meier statistics were used to examine predictors of survival and virologic failure. Viral genotype analysis was performed on samples obtained from children having virologic failure to determine the emergence of mutations. RESULTS: Clinically, there was no difference in the 3-year survival between our cohort receiving consistent laboratory monitoring and a matched historical clinic cohort not routinely receiving laboratory monitoring. However, 34% of children receiving ART demonstrated virologic failure. Eleven of these children received second-line ART, and all responded with an undetectable HIV-1 RNA level and an increase in CD4 count. Children remaining on a failing antiretroviral regimen accumulated resistance mutations. CONCLUSIONS: Our prospective long-term findings support the general use of monitoring HIV-1 RNA levels for the management of children on ART and the adoption of a clearer definition for virologic failure and better guidelines for managing children with unsuppressed HIV-1 RNA levels.

Safety and tolerability of antiretroviral therapy among HIV-infected children and adolescents in Uganda.

BACKGROUND: Antiretroviral therapy (ART) is known to cause a number of adverse effects. The objective of this study was to determine the frequency and outcome of ART-related adverse events among patients aged 6 weeks to 18 years. METHODS: We followed up a cohort of 378 HIV-infected children and adolescents who started ART at the Baylor-Uganda Clinic during the period July 2004 to July 2009. Patients were started on zidovudine or stavudine, plus lamivudine, and efavirenz or nevirapine. Adverse events were recorded as they occurred. Descriptive analyses and Kaplan-Meier survival analysis were carried out. RESULTS: Of 126 adverse events reported among 107 (28.3%) patients, dizziness (17.5%), diarrhea (13.5%), and nausea and vomiting (14.3%) were the most frequent. Anxiety/night mares, skin rashes, nail discoloration, and lipodystrophy each contributed between 5% and 10%; whereas anorexia, abdominal pain, hepatitis, and somnolence contributed 1%-5%. Amnesia, lactic acidosis, gynaecomastia, cardiomyopathy, and peripheral neuropathy were rare, each contributing less than 1% of the total events. The overall probability of remaining free of adverse events was 77.1% (95% confidence interval: 72.38 to 81.13) at month 6 of ART.Among infants and young children, neurologic events could not be determined. Laboratory abnormalities were present at baseline and during follow-up, and hemoglobin levels increased significantly during the first 6 months of ART. There was no association between adverse events and baseline patient characteristics. CONCLUSION: Close to one-third of children on ART experience adverse events. Most events occur within the first 3 months of ART and are not associated with baseline patient characteristics.

Prevention messages and AIDS risk behavior in Kampala, Uganda.

Uganda was one of the first countries to substantially reduce HIV rates through behavior change, but these gains have not continued in recent years. Little is known about what messages Ugandans are currently hearing about AIDS prevention, what they themselves believe to be important prevention strategies, and how these beliefs are associated with behavior. We interviewed men and women aged between 20 and 39 in two poor peri-urban areas of Kampala, using a random sample, cross-sectional household survey design. Respondents provided detailed reports of sexual behavior over the past six months, the main prevention message they are currently hearing about AIDS, and their own ranking of the importance of prevention strategies. Condom use was the main AIDS prevention message that respondents reported hearing, followed by getting tested. These were also what respondents themselves considered most important, followed closely by faithfulness. Abstinence was the lowest ranked strategy, but a higher ranking for this prevention strategy was the only one consistently associated with less risky behavior. A higher ranking for condoms was associated with higher levels of risk behavior, while the ranking of testing made no difference in any behavior. These results present challenges for AIDS prevention strategies that rely primarily on promoting condoms and testing. HIV prevention programs need to assess their impact on behavior.

The impact of maternal highly active antiretroviral therapy and short-course combination antiretrovirals for prevention of mother-to-child transmission on early infant infection rates at the Mulago national referral hospital in Kampala, Uganda, January 2007 to May 2009.

BACKGROUND: Early HIV infant diagnosis and treatment have been shown to dramatically improve survival in infants. Despite these findings, infants accessing HIV diagnosis and treatment remain low in Uganda. We describe the antiretroviral (ARV) drugs given in the Mulago Hospital prevention of mother-to-child transmission (PMTCT) program from January 2007 to May 2009 and its impact on early infant HIV infection rates. METHODS: Pregnant women identified as HIV infected in the Mulago antenatal clinics received one of the following regimens: short-course ARV prophylaxis plus single-dose nevirapine (sdNVP) in labor, highly active antiretroviral therapy (HAART), or sdNVP if they presented in labor. Infants received sdNVP and zidovudine (ZDV) for 1 week. Infants HIV diagnosis was done from 6 weeks after delivery. RESULTS: 62.3% of HIV-infected women received combination ARVs, including HAART. Early infection rates were highest among infants with no maternal ARV [36.4; 95% confidence interval (CI): 17.2 to 59.3] or only sdNVP (11.2; 95% CI: 8.1 to 14.8). Similar rates were observed for the group that took short-course ARVs, ZDV/sdNVP (4.6; 95% CI: 3.2 to 6.4), and ZDV/lamivudine/sdNVP (4.9; 95% CI: 3.1 to 7.2) and lowest rates for those that took HAART (1.7: 95% CI: 0.8 to 2.8). Overall infection rate was 5.0% (95% CI: 4.1 to 5.9). CONCLUSIONS: Findings indicate low rates of infant infection for mothers receiving combination ARVs. These findings demonstrate that provision of combination ARV for PMTCT is feasible and effective in busy referral hospital's PMTCT programs in resource-limited settings.

Clinical characteristics and outcome of children with Burkitt lymphoma in Uganda according to HIV infection.

BACKGROUND: Characteristics of children with Burkitt lymphoma (BL) and HIV infection have not been described in Uganda before. PROCEDURE: We reviewed records at Uganda Cancer Institute (UCI) for years 1994-2004, to compare clinical features and outcome of BL in children who are HIV positive and negative (HIV+, HIV-). As statistical methods we used Student's t-test, Chi-square and Kaplan-Meier's to compare both groups. RESULTS: Of 1,462 records of children retrieved, 228 met the eligibility criteria and were reviewed (158 HIV-, 70 HIV+). There were 139 (61%) males and 89 (39%) females. The mean age was 6.9 years (HIV+ 6.7, HIV- 7.1). One hundred seventy-one cases (75%) had facial tumor (HIV+ 71.4%, HIV- 76.6%). HIV positive children presented significantly with extrafacial disease (lymphadenopathy 67%, hepatic masses 51%, and thoracic masses 10%). Presentation with advanced stage disease occurred more frequently in HIV positive patients compared to HIV negative patients. Treatment response rates to chemotherapy were similar irrespective of HIV status. However, overall survival was poorer in HIV positive patients with a median survival of 11.79 months (P-value < 0.000, 95% CI 8.65-14.92). CONCLUSIONS: BL in Uganda presents frequently with facial disease irrespective of HIV status. However HIV+ BL also presents commonly with extra facial sites, mainly lymphadenopathy. There is no difference in response to treatment with chemotherapy, but HIV+ BL patients have poorer survival. There is need for further characterization of BL in Uganda to understand the role of HIV in disease process and outcome.

Differences in factors associated with initial growth, CD4, and viral load responses to ART in HIV-infected children in Kampala, Uganda, and the United Kingdom/Ireland.

BACKGROUND: Few studies have directly compared response to antiretroviral therapy (ART) between children living in well-resourced and resource-limited settings. In resource-limited settings non-HIV contributors could reduce the beneficial effects of ART. We compare predictors of short-term immunological, virological, and growth response to ART in HIV-infected children in the United Kingdom/Ireland and Kampala. METHODS: We analyzed prospective cohort data from 54 UK/Irish hospitals (the Collaborative HIV Paediatric Study) and Mulago Hospital, Kampala, Uganda. Six- and 12-month responses are described among children initiating combination ART (> or = 3 drugs, > or = 2 classes). Six months post-ART, predictors of viral load (VL) suppression <400 copies/mL, CD4% increases > 10%, and height- and weight-for-age z-score increases > or = +0.5 were investigated using logistic regression. RESULTS: In all, 582 UK/Irish children (76% black African) were younger than 876 Kampala children at ART initiation (median 5.0 vs 7.6 years), with higher CD4% (14%, 8%), lower VL (172,491 and 346,809 copies/mL), and less stunting (-0.8, -2.8) and wasting (-0.6, -2.8). Post-ART, median 12-month changes in the United Kingdom/Ireland and Kampala in CD4% (+12%, +13%) and weight (+0.4, +0.5) were similar, but growth was less in Kampala (+0.20, +0.06, P < 0.001). Younger children in both cohorts had better immunological, weight, and growth responses (all P < 0.001). However, lower pre-ART CD4% predicted better immunological response in the United Kingdom/Ireland but poorer response in Kampala (heterogeneity P = 0.004). Although 70% children in both cohorts had suppressed < 400 copies/mL at 6 months, adolescents starting ART in the United Kingdom/Ireland had somewhat poorer VL responses than those in Kampala (P = 0.15). CONCLUSIONS: Overall immunological and virologic ART responses were similar in children in both cohorts. Poorer CD4 recovery in more immunosuppressed Kampala children and blunted growth responses likely reflect higher background malnutrition and infection rates in Uganda, suggesting the need for earlier HIV diagnosis, nutritional support, cotrimoxazole prophylaxis, and ART.

Life events associated with major depression in Ugandan primary healthcare (PHC) patients: issues of cultural specificity.

OBJECTIVE: The study compared life events experienced by depressed patients seen at primary healthcare (PHC) centres with those among healthy community controls. METHOD: Data was collected from 74 depressed patients and 64 unmatched controls from village locales of patients. Interview instruments included the depression module of the Mini International Neuropsychiatric Interview (MINI) and Interview for Recent Life Events (IRLE). Associations between type of respondent and demographic variables were examined. Statistical comparisons were done for the two groups on other variables. RESULTS: Most depressed patients were single by marital status, lacked formal employment and had less post-primary education.They had experienced more life events; job changes, discomforting working hours, unfavourable working conditions, and job losses; personal health problems; loss of valuables; difficulties with intimate partners and family members' marital problems. Independent life events were more among depressed patients and clustered around work, health, bereavement and marriage. Most events reported by depressed patients had high negative impact ratings compared to controls. CONCLUSION: Compared to healthy community controls, depressed patients reported more undesirable life events. The relationship between life events and depression implies that in PHC settings of poor countries, deploying mental health-oriented workers to manage life events may lessen escalation of distress.

Growth in HIV-infected children receiving antiretroviral therapy at a pediatric infectious diseases clinic in Uganda.

Antiretroviral therapy (ART) improves growth and survival of HIV-infected individuals. We designed a retrospective cohort study to assess clinical factors associated with growth in HIV-infected children on ART in Uganda between July 2003 and March 2006. Height and weight measurements taken pre- and post-ART initiation for at least 6 months were age- and gender-standardized to CDC 2000 reference. We analyzed medical records of 749 children receiving ART. Descriptive and logistic regression analyses were conducted to identify covariates associated with risk of either stunting or being underweight. Longitudinal regression analysis with a mixed model using autoregressive covariance structure was used to compare change in height and weight before and after initiation of ART. The mean age of the study population at first visit was 7.5 years. Mean height-for-age, weight-for-age, and weight-for-height percentiles at first visit were 8.6, 7.7, and 7.9, respectively. At last visit mean height-for-age, weight-for-age, and weight-for-height percentiles were 8.6, 13.3, and 13.8, respectively. Baseline weight-for-age z score of 1 or more was protective against stunting (odds ratio [OR] 0.25, confidence interval [CI] 0.18-0.35) while baseline height-for-age z score of 1 or more was protective against becoming underweight (OR 0.75, CI 0.63-0.88). Children in World Health Organization (WHO) stages II, III, and IV at baseline were 1.5 times more likely to become underweight (OR 1.51, CI 1.07-2.14). Initiation of ART resulted in improvement in mean standardized weight-for-age z score and weight-for-age percentiles (p < 0.001). Weight-for-age percentile and z score improved significantly after initiation of ART. This pediatric population gained weight more rapidly than height after initiation of ART.