[Show abstract][Hide abstract] ABSTRACT: Medical male circumcision (MC) of HIV-infected men may increase plasma HIV viral load and place female partners at risk of infection. We assessed the effect of MC on plasma HIV viral load in HIV-infected men in Rakai, Uganda.
195 consenting HIV-positive, HAART naïve men aged 12 and above provided blood for plasma HIV viral load testing before surgery and weekly for six weeks and at 2 and 3 months post surgery. Data were also collected on baseline social demographic characteristics and CD4 counts. Change in log10 plasma viral load between baseline and follow-up visits was estimated using paired t tests and multivariate generalized estimating equation (GEE).
Of the 195 men, 129 had a CD4 count ≧350 and 66 had CD4 <350 cells/mm3. Men with CD4 counts <350 had higher baseline mean log10 plasma viral load than those with CD4 counts ≧350 cells/mm3 (4.715 vs 4.217 cps/mL, respectively, p = 0.0005). Compared to baseline, there was no statistically significant increase in post-MC HIV plasma viral loads irrespective of CD4. Multivariate analysis showed that higher baseline log10 plasma viral load was significantly associated with reduction in mean log10 plasma viral load following MC (coef. = -0.134, p<0.001).
We observed no increase in plasma HIV viral load following MC in HIV-infected, HAART naïve men.
PLoS ONE 11/2014; 9(11):e110382. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: War-related violence in Northern Uganda is well documented and may be accelerating HIV spread. We studied the differences in prevalence and risk factors for HIV infection between men and women in this post-conflict region.
Methods: The “Cango Lyec Project” is a prospective cohort study in Northern Uganda. We randomly selected study communities and mapped and enumerated the entire population. 2448 residents aged 13-59 consented to participate in the survey. Trauma, depression and sociodemographic-behavioural surveys and HIV testing were conducted.
Results: Of 2448 participants, 58.2% were females; 24% had been abducted, and 23% sexually-assaulted in captivity. HIV prevalence was 14.4% in women vs. 7.9% in men (p< 0.001), reaching 19.77% among women in one community. PTSD was observed in 13.9% of women compared to 8.6% of men and depression was reported by 19.9% and 8.2% respectively (p< 0.001). Among sexually-active men, HIV positivity was associated with never using condoms with most recent sex partner (AOR: 2.03, 95% CI: 1.09-3.78); history of genital ulcers in last year (4.64, [2.2-9.4]); and residing in Gulu district (1.83, [0.98-3.42]). For sexually active women, HIV positivity was associated with never use of condoms with most recent sex partner in last year (1.83, [1.28-2.62]), history of genital ulcers in last year (2.51, [1.65-3.82]), war-related sexual violence (1.80 [1.19-2.73]), depression (1.82, [1.26-2.64]) and residing in Gulu district (1.45, [1.04-2.04])
Conclusions: Women are disproportionately impacted by HIV, trauma and depression in this conflict-affected population. Trauma-informed HIV prevention and culturally safe mental health care initiatives are urgently required.
142nd APHA Annual Meeting and Exposition 2014; 11/2014
[Show abstract][Hide abstract] ABSTRACT: Background: Abduction by the Lords Resistance Army profoundly impacts the physical and psychosocial wellbeing of those surviving the conflict in Northern Uganda. It is estimated that more than 66,000 were abducted between 1986-2006. It is important to understand the HIV related vulnerabilities of this ‘at risk’ population.
Methods: The Cango Lyec Project is a prospective cohort of 2448 participants aged 13-49 in Northern Uganda. Participants consented to HIV testing and completed surveys on socio-demographics, PTSD (HTQ), and depression (HSCL-25). Multivariable logistic regression models were used to assess HIV vulnerability.
Results: Of formerly-abducted participants 319 (54.1%) were women and 271 (45.9%) were men. HIV prevalence was 20.4% and 11.8% respectively (p=0.005). Males were abducted more times (2.1 vs. 1.6 times; p=0.006). 34.2% of women and 3.3% of men experienced war related sexual violence. 26.3% of abducted women were given as a wife to LRA commanders. Of those with HIV, 9.4% of men and 24.6% of women screened positively for PTSD, while 21.8% and 43.1% screened positively for depression. There is difference in levels of PTSD or depression between those with and without HIV. In the multi-variable logistic regression, being female (AOR: 1.68; 95%CI: 1.03-2.80), one-year increase in age (1.04; 1.01-1.07), genital ulcers in the past year (3.77; 2.15-6.58), and living in the Gulu (2.34; 1.25-4.20) or Nwoya (2.25; 1.10-4.67) compared to Amuru district were associated with HIV positivity.
Discussion: Culturally safe HIV programming addressing these specific HIV related vulnerabilities of people surviving abduction and war in Northern Uganda are urgently required.
142nd APHA Annual Meeting and Exposition 2014; 11/2014
[Show abstract][Hide abstract] ABSTRACT: An effective HIV vaccine is still elusive. Of the 9 HIV preventive vaccine efficacy trials conducted to-date, only one reported positive results of modest efficacy. More efficacy trials need to be conducted before one or more vaccines are eventually licensed. We assessed the suitability of fishing communities in Uganda for future HIV vaccine efficacy trials.
BMC Public Health 09/2014; 14(1):986. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Methods. We compared responses to YF-17D in 50 volunteers in Entebbe, Uganda, and 50 volunteers in Lausanne, Switzerland. We measured the CD8+ T cell and B cell responses induced by YF-17D and correlated them with immune parameters analyzed by flow cytometry prior to vaccination. Results. We showed that YF-17D-induced CD8+ T cell and B cell responses were substantially lower in immunized individuals from Entebbe compared with immunized individuals from Lausanne. The impaired vaccine response in the Entebbe cohort associated with reduced YF-17D replication. Prior to vaccination, we observed higher frequencies of exhausted and activated NK cells, differentiated T and B cell subsets and proinflammatory monocytes, suggesting an activated immune microenvironment in the Entebbe volunteers. Interestingly, activation of CD8+ T cells and B cells as well as proinflammatory monocytes at baseline negatively correlated with YF-17D-neutralizing antibody titers after vaccination. Additionally, memory T and B cell responses in preimmunized volunteers exhibited reduced persistence in the Entebbe cohort but were boosted by a second vaccination. Conclusion. Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity. Trial registration. Registration is not required for observational studies. Funding. This study was funded by Canada's Global Health Research Initiative, Defense Threat Reduction Agency, National Institute of Allergy and Infectious Diseases, Bill & Melinda Gates Foundation, and United States Agency for International Development.
Journal of Clinical Investigation 06/2014; · 13.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: High HIV-1 incidence rates were reported among persons in fisherfolk communities (FFC) in Uganda who were selected for high risk behaviour. We assessed the incidence of HIV-1 and associated risk factors in a general population FFC to determine population-wide HIV rates.
PLoS ONE 05/2014; 9(5):e94932. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite growing knowledge of the dynamics of HIV infection during conflict, far less is known about the period that follows cessation of hostilities and its implications for population health. This study sought to fill a lacuna in epidemiological evidence by examining HIV infection and related vulnerabilities of young people living in resource-scarce, post-emergency transit camps that are now home to thousands of displaced people following two decades of war in northern Uganda. In 2010, a cross-sectional demographic and behavioural survey was conducted with 384 transit camp residents aged 15-29 years old in Gulu District. Biological specimens were collected for rapid and confirmatory HIV testing. Separate multivariable logistic regression models by sex identified risk factors for HIV infection. HIV prevalence was 15.6% (95% confidence interval [CI]: 10.8%, 21.6%) among females and 9.9% (95% CI: 6.1%, 15.0%) among males. The strongest correlate of HIV infection among men was a non-consensual sexual debut (adjusted odds ratio [AOR] 3.24; 95% CI: 1.37-7.67), and having practiced dry sex (AOR 7.62; 95% CI: 1.56-16.95) was the strongest correlate among women. Conflict-affected men and women experience vulnerability to HIV infection in different ways than may have originally been understood. Post-conflict programme planners must therefore design and implement contextualised, evidence-based responses to HIV that are sensitive to gender and cultural issues.
Global Public Health 02/2014; · 0.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Little is known about HIV infection and the related vulnerabilities of young people living in resource-scarce, post-emergency transit camps that are now home to thousands of Internally Displaced Persons (IDPs) following two decades of war in northern Uganda. The objective of this analysis was to assess the prevalence and correlates of HIV infection among young people living in post-conflict transition in Gulu District, northern Uganda.
In 2010, a cross-sectional demographic and behavioural survey was conducted in two of Gulu District's sub-counties with 384 purposively selected transit camp residents aged 15 to 29 years. Biological specimens were collected for rapid HIV testing in the field and confirmatory laboratory testing. Multivariable logistic regression identified independent determinants of HIV infection.
HIV prevalence was alarmingly high at 12.8% (95% CI: 9.6%, 16.5%). The strongest determinant of HIV infection among young people was a non-consensual sexual debut (adjusted odds ratio [AOR], 9.88; 95% CI: 1.70-18.06). Residing in Awach sub-county (AOR, 2.93; 95% CI: 1.28-6.68), experiencing STI symptoms in the previous 12 months (AOR, 2.36; 95% CI: 1.43-6.17), and practicing dry sex (AOR, 2.31; 95% CI: 1.04-5.13) were other key determinants of HIV infection.
Study findings contribute to filling an important gap in epidemiological evidence and are useful for planning public health interventions in northern Uganda that effectively target young people in post-conflict transition and support them in the resettlement process. Findings serve to recommend reaching beyond traditional prevention programming in a way more effectively beneficial to young people in post-conflict settings by developing population-specific responses sensitive to local contexts and sufficient to address the underlying causes of the complex risk factors influencing the spread of HIV.
PLoS ONE 02/2014; 9(2):e89786. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have previously shown that in successful pregnancies increased arginase activity is a mechanism that contributes to the suppression of the maternal immune system. We identified the main type of arginase-expressing cells as a population of activated low-density granulocytes (LDGs) in peripheral blood mononuclear cells and in term placentae. In the present study, we analyzed the phenotype of LDGs and compared it to the phenotype of normal density granulocytes (NDGs) in maternal peripheral blood, placental biopsies and cord blood. Our data reveal that only LDGs but no NDGs could be detected in placental biopsies. Phenotypically, NDGs and LDGs from both maternal and cord blood expressed different levels of maturation, activation and degranulation markers. NDGs from the maternal and cord blood were phenotypically similar, while maternal, cord and placental LDGs showed different expression levels of CD66b. LDGs present in cord blood expressed higher levels of arginase compared to maternal and placental LDGs. In summary, our results show that in maternal and cord blood, two phenotypically different populations of neutrophils can be identified, whereas in term placentae, only activated neutrophils are present.
PLoS ONE 02/2014; 9(2):e85696. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To assess completed wound healing after medical male circumcision (MMC) among human immunodeficiency virus (HIV)-negative and HIV-positive men with cluster of differentiation 4 (CD4) counts of <350 and ≥350 cells/mm3, as minimal data are available on the safety of MMC among HIV-positive men with low CD4 counts. Patients and Methods
In all, 262 HIV-negative and 177 HIV-positive consenting males aged ≥12 years accepted MMC using the dorsal slit procedure and were enrolled in the study.Socio-demographic and behavioural data and blood for HIV testing and CD4 counts were collected at baseline.Participants were followed weekly to collect information on resumption of sex, condom use and both self-reported and clinically assessed wound healing.The proportions healed among HIV-positive men were compared with HIV-negative men. Time to complete wound healing was assessed by Kaplan–Meier survival analysis. ResultsThere were no statistically significant differences in the proportion of men healed by HIV status.At 4 weeks, the proportions healed were 85.9% in HIV-negative men, 77.4% in HIV-positive men with a CD4 count of ≥350 cells/mm3 and 87.1% in HIV-positive men with a CD4 count of <350 cells/mm3.The median time to healing was 4 weeks and did not vary by HIV or CD4 status.All men had certified complete wound healing at 6 weeks after MMC. In all, 1.4% of HIV-positive men with a CD4 count of <350 cells/mm3 resumed sex before healing, compared with 8.5% among HIV-positive men with a CD4 count of ≥350 cells/mm3 (P = 0.052) and 7.8% (P = 0.081) among HIV-negative men. Conclusion
Inclusion of HIV-positive men with low CD4 counts in MMC services is not deleterious to postoperative wound healing.
BJU International 01/2014; 113(1). · 3.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the safety of medical male circumcision (MMC) among human immunodeficiency virus (HIV)-infected men with CD4 levels <350 cells/mm(3), CD4 counts ≥350 cells/mm(3), and HIV-negative men.
Two hundred forty-two HIV-infected men and a sample of 262 HIV-negative consenting men aged 12 years or older who requested free MMC were enrolled in a prospective study. Blood for HIV testing and a CD4 count were collected before surgery. During weekly follow-up over 6 weeks, data were collected on wound healing and adverse events (AEs) by examination, and resumption of sex and condom use ascertained by interview. Surgery-related AEs were characterized by type, severity, management, and resolution. Chi-square and Fisher's exact tests were used to test for differences in AE proportions.
Overall, only 2 of the 453 men experienced moderate AEs, a rate of 0.44 per 100 surgeries. No AE occurred among HIV-negative men, whereas the AE rate among HIV-infected men with CD4 counts ≥350 cells/mm(3) was 0.79 per 100 surgeries, and among men with CD4 counts <350 cells/mm(3) the rate was 1.19 per 100 surgeries (P = .214). AE rates were comparable for all characteristics (P >.05).
HIV-positive men can be safely included in MMC roll out programs without necessitating presurgery CD4 counts determination.
[Show abstract][Hide abstract] ABSTRACT: Thousands of former child soldiers who were abducted during the prolonged conflict in northern Uganda have returned to their home communities. Programmes that facilitate their successful reintegration continue to face a number of challenges. Although there is increasing knowledge of the dynamics of HIV infection during conflict, far less is known about its prevalence and implications for population health in the post-conflict period. This study investigated the effects of abduction on the prevalence of HIV and HIV-risk behaviours among young people in Gulu District, northern Uganda. An understanding of abduction experiences and HIV-risk behaviours is vital to both the development of effective reintegration programming for former child soldiers and the design of appropriate HIV prevention interventions for all young people.
In 2010, we conducted a cross-sectional study of 2 sub-counties in Gulu District. A demographic and behavioural survey was interview-administered to a purposively selected sample of 384 transit camp residents aged 15--29. Biological specimens were collected for HIV rapid testing in the field and confirmatory laboratory testing. Descriptive statistics were used to describe characteristics of abduction. Additionally, a gender-stratified bivariate analysis compared abductees' and non-abductees' HIV risk profiles.
Of the 384 participants, 107 (28%) were former child soldiers (61% were young men and 39% were young women). The median age of participants was 20 and median age at abduction was 13. HIV prevalence was similar among former abductees and non-abductees (12% vs. 13%; p = 0.824), with no differences observed by gender. With respect to differences in HIV vulnerability, our bivariate analysis identified greater risky sexual behaviours in the past year for former abductees than non-abductees, but there were no differences between the two groups' survival/livelihood activities and food insufficiency experiences, both overall and by gender. The analysis further revealed that young northern Ugandans in general are in desperate need of education, skills development, and support for victims of sexual violence.
This study persuasively demonstrates that all young people in northern Ugandan have been similarly affected by HIV infection during war and displacement. Post-conflict programme planners must therefore abandon rudimentary targeting practices based on abductees as a high-profile category. Instead, they must develop evidence-based HIV interventions that are commensurate with young people's specific needs. As such programmes will be less stigmatizing, more oriented to self-selection, and more inclusive, they will effectively reach the most vulnerable young people in northern Uganda.
[Show abstract][Hide abstract] ABSTRACT: Introduction: HIV epidemics in sub-Saharan Africa are generalized, but high-risk subgroups exist within these epidemics. A recent study among fisher-folk communities (FFC) in Uganda showed high HIV prevalence (28.8%) and incidence (4.9/100 person-years). However, those findings may not reflect population-wide HIV rates in FFC since the study population was selected for high-risk behaviour. Methods: Between September 2011 and March 2013, we conducted a community-based cohort study to determine the population representative HIV rates and willingness to participate (WTP) in hypothetical vaccine trials among FFC, Uganda. At baseline (September 2011-January 2012), a household enumeration census was done in eight fishing communities (one lakeshore and seven islands), after which a random sample of 2200 participants aged 18-49 years was selected from 5360 individuals. Interviewer-administered questionnaire data were collected on HIV risk behaviours and WTP, and venous blood was collected for HIV testing using rapid HIV tests with enzyme-linked immunosorbent assay (EIA) confirmation. Adjusted prevalence proportion ratios (adj.PPRs) of HIV prevalence were determined using log-binomial regression models. Results: Overall baseline HIV prevalence was 26.7% and was higher in women than men (32.6% vs. 20.8%, p<0.0001). Prevalence was lower among fishermen (22.4%) than housewives (32.1%), farmers (33.1%) and bar/lodge/restaurant workers (37%). The adj.PPR of HIV was higher among women than men (adj.PPR =1.50, 95%; 1.20, 1.87) and participants aged 30-39 years (adj.PPR=1.40, 95%; 1.10, 1.79) and 40-49 years (adj.PPR=1.41, 95%; 1.04, 1.92) compared to those aged 18-24 years. Other factors associated with HIV prevalence included low education, previous marriage, polygamous marriage, alcohol and marijuana use before sex. WTP in hypothetical vaccine trials was 89.3% and was higher in men than women (91.2% vs. 87.3%, p=0.004) and among island communities compared to lakeshore ones (90.4% vs. 85.8%, p=0.004). Conclusions: The HIV prevalence in the general fisher-folk population in Uganda is similar to that observed in the "high-risk" fisher folk. FFC have very high levels of willingness to participate in future HIV vaccine trials.
Journal of the International AIDS Society 07/2013; 16(1):18621. · 4.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
While PEPFAR investments were associated with HIV-related survival, it has been less clear what the effects of this investment in HIV care have been for health-care use generally, especially in maternal care. Understanding of these effects could have implications for how to organise future global health initiatives for major health problems. Maternal mortality in Uganda remains high (310 per 100 000 livebirths in 2010) and could be reduced by increasing deliveries at health facilities.Methods
We visited all of Uganda's 56 districts to collect maternity care data from Health Management Information System records, between the years 2005 and 2010, including monthly reports from all public and most private facilities. Our unit of analysis was district-month. We fitted a negative binomial mixed effects model, with number of infants delivered in health facilities per district-month as outcome, and three categories (tertiles) of population-adjusted annual number of PEPFAR-supported patients on antiretroviral therapy (ART) as input. We adjusted for regional HIV prevalence and proportion of elementary school-aged children attending school. To adjust for secular and seasonal effects, we included control variables for year and month. Random effects for district and an offset for district population were included in the model.FindingsPeople on ART per district-month per 1000 population grew from 1079 in 2005, to 6485 in 2010. Facility deliveries averaged 709 per district-month, growing from 561 in 2005 to 830 in 2010. The average rate of health facility deliveries increased by 4% (incidence rate ratio [IRR] 1·04, 95% CI 1·008–1·068, p=0·012) in districts with medium-level PEPFAR investment in ART care, compared with lowest PEPFAR investment districts. In higher-level investment districts, deliveries increased by 8% (IRR 1·08, 95% CI 1·037–1·126, p=0·0001), relative to low-investment districts.InterpretationPEPFAR investments in ART scale-up in Uganda appear to be associated with small increases in health facility deliveries.FundingThis research was funded by the US Centers for Disease Control, Division of Public Health Systems and Workforce Development through a cooperative agreement with the University of Washington and through subcontracts with Makerere University and the Uganda Ministry of Health.
The Lancet 06/2013; 381:S74. · 39.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The US President's Emergency Plan for AIDS Relief (PEPFAR) has invested more than $30 billion in the care, treatment and prevention of HIV/AIDS. While many studies show the impact of this program in successfully controlling the HIV epidemic in many low-resource settings, there is a growing interest in understanding the collateral impact of large disease-specific programs on services for other diseases and the country's health system. For example, has the focus on HIV/AIDS helped to improve the competency of health workers in other disease areas? Conversely, has PEPFAR investment shifted health care workers away from care of patients with non-HIV conditions? Using the case study of Uganda, we explore how PEPFAR investments affected utilization of other health services and the broader health system. We collected qualitative and quantitative data from 112 health district offices and 336 health facilities across Uganda, looking for changes in the health system between 2005 (when PEPFAR investments began) and the current time. We describe the variation in PEPFAR investments by district, and associated utilization changes in non-HIV services, especially outpatient, maternity and newborn care. We controlled for confounders and effect modifiers. Findings from this study can inform how future investments in disease-specific interventions can simultaneously strengthen the whole health system.
140st APHA Annual Meeting and Exposition 2012; 10/2012
[Show abstract][Hide abstract] ABSTRACT: Background. A genetic bottleneck is known to exist for human immunodeficiency virus (HIV) at the point of sexual transmission. However, the nature of this bottleneck and its effect on viral diversity over time is unclear. Methods. Interhost and intrahost HIV diversity was analyzed in a stable population in Rakai, Uganda, from 1994 to 2002. HIV-1 envelope sequences from both individuals in initially HIV-discordant relationships in which transmission occurred later were examined using Sanger sequencing of bulk polymerase chain reaction (PCR) products (for 22 couples), clonal analysis (for 3), and next-generation deep sequencing (for 9). Results. Intrahost viral diversity was significantly higher than changes in interhost diversity (P < .01). The majority of HIV-1-discordant couples examined via bulk PCR (16 of 22 couples), clonal analysis (3 of 3), and next-generation deep sequencing (6 of 9) demonstrated that the viral populations present in the newly infected recipient were more closely related to the donor partner's HIV-1 variants found earlier during infection as compared to those circulating near the estimated time of transmission (P = .03). Conclusions. These findings suggest that sexual transmission constrains viral diversity at the population level, partially because of the preferential transmission of ancestral as opposed to contemporary strains circulating in the transmitting partner. Future successful vaccine strategies may need to target these transmitted ancestral strains.
The Journal of Infectious Diseases 09/2012; 206(9):1433-42. · 5.85 Impact Factor