NRU :: Browsing by Author "Havlir, Diane V."

Browsing by Author "Havlir, Diane V."

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Acceptability and Feasibility of Serial HIV Antibody Testing During Pregnancy/Postpartum and Male Partner Testing in Tororo, Uganda
(AIDS care, 2014) Kim, Lena H.; Arinaitwe, Emmanuel; Nzarubara, Bridget; Kamya, Moses R.; Clark, Tamara D.; Okonge, Pius; Charlebois, Edwin D.; Havlir, Diane V.; Cohan, Deborah
Our objective was to determine whether serial HIV testing during pregnancy and the postpartum period as well as male partner testing are acceptable and feasible in Tororo, Uganda. This was a prospective study of pregnant women at the Tororo District Hospital (TDH) Antenatal Clinic. Patients presenting for routine antenatal care were asked to participate in a serial HIV testing integrated into standard antenatal and postpartum/child immunization visits, and to invite their male partners for HIV testing. Serial testing was defined as ≥2 tests during pregnancy and ≥2 tests within 24 weeks postpartum. Of the 214 enrolled women, 80 (37%) completed serial testing, 176 (82%) had ≥2 tests, and 147 (69%) had ≥3 tests during the study period. One hundred eighty-two women (85%) accepted male partner testing, but only 19 men (10%) participated. One woman seroconverted during the study, for a cumulative HIV incidence of 0.5% (1/214). In multivariable logistic regression analysis, longer distance between home and clinic (aOR 0.87 [95% CI 0.79–0.97]) and not knowing household income (aOR 0.30 [95% CI 0.11–0.84]) were predictive of not completing serial testing. Higher level of education was associated with completing serial testing (linear trend p value = 0.05). In conclusion, partial serial HIV testing was highly acceptable and feasible, but completion of serial testing and male partner testing had poor uptake.
The Age-specific Burden and Household and School-Based Predictors of Child and Adolescent Tuberculosis Infection in Rural Uganda
(PloS one, 2020) Mwangwa, Florence; Charlebois, Edwin D.; Ayieko, James; Olio, Winter; Kwarisiima, Dalsone; Kabami, Jane; Kapogiannis, Bill; Kamya, Moses R.; Havlir, Diane V.; Ruel, Theodore D.
The age-specific epidemiology of child and adolescent tuberculosis (TB) is poorly understood, especially in rural areas of East Africa. We sought to characterize the age-specific prevalence and predictors of TB infection among children and adolescents living in rural Uganda, and to explore the contribution of household TB exposure on TB infection. From 2015–2016 we placed and read 3,121 tuberculin skin tests (TST) in children (5–11 years old) and adolescents (12–19 years old) participating in a nested household survey in 9 rural Eastern Ugandan communities. TB infection was defined as a positive TST (induration ≥10mm or ≥5mm if living with HIV). Age-specific prevalence was estimated using inverse probability weighting to adjust for incomplete measurement. Generalized estimating equations were used to assess the association between TB infection and multi-level predictors. The adjusted prevalence of TB infection was 8.5% (95%CI: 6.9–10.4) in children and 16.7% (95% CI:14.0–19.7) in adolescents. Nine percent of children and adolescents with a prevalent TB infection had a household TB contact. Among children, having a household TB contact was strongly associated with TB infection (aOR 5.5, 95% CI: 1.7–16.9), but the strength of this association declined among adolescents and did not meet significance (aOR 2.3, 95% CI: 0.8–7.0). The population attributable faction of TB infection due to a household TB contact was 8% for children and 4% among adolescents. Mobile children and adolescents who travel outside of their community for school had a 1.7 (95% CI 1.0–2.9) fold higher odds of TB infection than those who attended school in the community. Children and adolescents in this area of rural eastern Uganda suffer a significant burden of TB. The majority of TB infections are not explained by a known household TB contact. Our findings underscore the need for community-based TB prevention interventions, especially among mobile youth.
Assessing the Quality of Tuberculosis Evaluation for Children with Prolonged Cough Presenting to Routine Community Health Care Settings in Rural Uganda
(PloS one, 2014) Marquez, Carina; Davis, J. Lucian; Katamba, Achilles; Haguma, Priscilla; Ochomi, Emmanuel; Ayakaka, Irene; Chamie, Gabriel; Dorsey, Grant; Kamya, Moses R.; Charlebois, Edwin; Havlir, Diane V.; Cattamanchi, Adithya
Improving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse. Objective: To describe the current practices and quality of TB evaluation for children with cough $2 weeks’ duration presenting to community health centers in Uganda. Methods: Cross-sectional analysis of children (,15 years) receiving care at five Level IV community health centers in rural Uganda for any reason between 2009–2012. Quality of TB care was assessed using indicators derived from the International Standards of Tuberculosis Care (ISTC). Results: From 2009–2012, 1713 of 187,601 (0.9%, 95% CI: 0.4–1.4%) children presenting to community health centers had cough $ 2 weeks’ duration. Of those children, only 299 (17.5%, 95% CI: 15.7–19.3%) were referred for sputum microscopy, but 251 (84%, 95% CI: 79.8–88.1%) completed sputum examination if referred. The yield of sputum microscopy was only 3.6% (95% CI: 1.3–5.9%), and only 55.6% (95% CI: 21.2–86.3%) of children with acid-fast bacilli positive sputum were started on treatment. Children under age 5 were less likely to be referred for sputum examination and to receive care in accordance with ISTC. The proportion of children evaluated in accordance with ISTC increased over time (4.6% in 2009 to 27.9% in 2012, p = 0.03), though this did not result in increased case-detection. Conclusion: The quality of TB evaluation was poor for children with cough $2 weeks’ duration presenting for health care. Referrals for sputum smear microscopy and linkage to TB treatment were key gaps in the TB evaluation process, especially for children under the age of five.
Characteristics of HIV Seroconverters in the Setting of Universal Test and Treat: Results from the SEARCH trial in rural Uganda and Kenya
(PloS one, 2021) Nyabuti, Marilyn N.; Maya, L. Petersen; Bukusi, Elizabeth A.; Kamya, Moses R.; Mwangwa, Florence; Kabami, Jane; Charlebois, Edwin D.; Tamara, D. Clark; Chamie, Gabriel; Havlir, Diane V.; Ayieko, James
Additional progress towards HIV epidemic control requires understanding who remains at risk of HIV infection in the context of high uptake of universal testing and treatment (UTT). We sought to characterize seroconverters and risk factors in the SEARCH UTT trial (NCT01864603), which achieved high uptake of universal HIV testing and ART coverage in 32 communities of adults (≥15 years) in rural Uganda and Kenya. In a pooled cohort of 117,114 individuals with baseline HIV negative test results, we described those who seroconverted within 3 years, calculated gender-specific HIV incidence rates, evaluated adjusted risk ratios (aRR) for seroconversion using multivariable targeted maximum likelihood estimation, and assessed potential infection sources based on self-report. Of 704 seroconverters, 63% were women. Young (15–24 years) men comprised a larger proportion of seroconverters in Western Uganda (18%) than Eastern Uganda (6%) or Kenya (10%). After adjustment for other risk factors, men who were mobile [≥1 month of prior year living outside community] (aRR:1.68; 95%CI:1.09,2.60) or who HIV tested at home vs. health fair (aRR:2.44; 95%CI:1.89,3.23) were more likely to seroconvert. Women who were aged ≤24 years (aRR:1.91; 95%CI:1.27,2.90), mobile (aRR:1.49; 95%CI:1.04,2.11), or reported a prior HIV test (aRR:1.34; 95%CI:1.06,1.70), or alcohol use (aRR:2.07; 95%CI:1.34,3.22) were more likely to seroconvert. Among survey responders (N = 607, 86%), suspected infection source was more likely for women than men to be ≥10 years older (28% versus 8%) or a spouse (51% vs. 31%) and less likely to be transactional sex (10% versus 16%). In the context of universal testing and treatment, additional strategies tailored to regional variability are needed to address HIV infection risks of young women, alcohol users, mobile populations, and those engaged in transactional sex to further reduce HIV incidence rates.
Costs of Streamlined HIV Care Delivery in Rural Ugandan and Kenyan Clinics in the SEARCH Study
(AIDS, 2018) Shade, Starley B.; Osmand, Thomas; Aine, Ronald; Mwebaza, Betty; Owaraganise, Asiphas; Mwangwa, Florence; Kwarisiima, Dalsone; Bukusi, Elizabeth A.; Kamya, Moses R.; Petersenk, Maya L.; Havlir, Diane V.; Jain, Vivek
As antiretroviral therapy (ART) rapidly expands in sub-Saharan Africa using new efficient care models, data on costs of these approaches are lacking. We examined costs of a streamlined HIV care delivery model within a large HIV test-and-treat study in Uganda and Kenya. We calculated observed per-person-per-year (ppy) costs of streamlined care in 17 health facilities in SEARCH Study intervention communities (NCT: 01864603) via micro-costing techniques, time-and-motion studies, staff interviews, and administrative records. Cost categories included salaries, ART, viral load testing, recurring goods/services, and fixed capital/facility costs. We then modeled costs under three increasingly efficient scale-up scenarios: lowest-cost ART, centralized viral load testing, and governmental healthcare worker salaries. We assessed the relationship between community-specific ART delivery costs, retention in care, and viral suppression. Estimated streamlined HIV care delivery costs were $291/ppy. ART ($117/ppy for TDF/3TC/EFV [40%]) and viral load testing ($110/ppy for 2 tests/year [39%]) dominated costs versus salaries ($51/ppy), recurring costs ($5/ppy), and fixed costs ($7/ppy). Optimized ART scale-up with lowest-cost ART ($100/ppy), annual viral load testing ($24/ppy), and governmental healthcare salaries ($27/ppy), lowered streamlined care cost to $163/ppy. We found clinic-to-clinic heterogeneity in retention and viral suppression levels versus streamlined care delivery costs, but no correlation between cost and either retention or viral suppression. In the SEARCH Study, streamlined HIV care delivery costs were similar to or lower than prior estimates despite including viral load testing; further optimizations could substantially reduce costs further. These data can inform global strategies for financing ART expansion to achieve UNAIDS 90–90–90 targets.
Early Adopters of Human Immunodeficiency Virus Pre-exposure Prophylaxis in a Population-based Combination Prevention Study in Rural Kenya and Uganda
(Clinical Infectious Diseases, 2018) Koss, Catherine A.; Ayieko, James; Mwangwa, Florence; Owaraganise, Asiphas; Kwarisiima, Dalsone; Kabami, Jane; Bukusi, Elizabeth A.; Charlebois, Edwin D.; Petersen, Maya L.; Kamya, Moses R.; Havlir, Diane V.; for the SEARCH Collaboration
Global guidelines recommend preexposure prophylaxis (PrEP) for individuals with substantial human immunodeficiency virus (HIV) risk. Data on PrEP uptake in sub-Saharan Africa outside of clinical trials are limited. We report on “early adopters” of PrEP in the Sustainable East Africa Research in Community Health (SEARCH) study in rural Uganda and Kenya. After community mobilization and PrEP education, population-based HIV testing was conducted. HIV-uninfected adults were offered PrEP based on an empirically derived HIV risk score or self-identified HIV risk (if not identified by score). Using logistic regression, we analyzed predictors of early PrEP adoption (starting PrEP within 30 days vs delayed/no start) among adults identified for PrEP. Of 21212 HIV-uninfected adults in 5 communities, 4064 were identified for PrEP (2991 by empiric risk score, 1073 by self-identified risk). Seven hundred and thirty nine individuals started PrEP within 30 days (11% of those identified by risk score; 39% of self-identified); 77% on the same day. Among adults identified by risk score, predictors of early adoption included male sex (adjusted odds ratio 1.53; 95% confidence interval, 1.09–2.15), polygamy (1.92; 1.27–2.90), serodiscordant spouse (3.89; 1.18–12.76), self-perceived HIV risk (1.66; 1.28–2.14), and testing at health campaign versus home (5.24; 3.33–8.26). Among individuals who self-identified for PrEP, predictors of early adoption included older age (2.30; 1.29–4.08) and serodiscordance (2.61; 1.01–6.76). Implementation of PrEP incorporating a population-based empiric risk score, self-identified risk, and rapid initiation, is feasible in rural East Africa. Strategies are needed to overcome barriers to PrEP uptake, particularly among women and youth.
Efficacy and Safety of Three Regimens for the Prevention of Malaria in Young HIV-Exposed Ugandan Children: A Randomized Controlled Trial
(AIDS, 2014) Kamya, Moses R.; Kapisi, James; Bigira, Victor; Tamara, D. Clark; Kinara, Stephen; Mwangwa, Florence; Muhindo, Mary K.; Kakuru, Abel; Aweeka, Francesca T.; Achan, Jane; Havlir, Diane V.; Rosenthal, Philip J.; Dorsey, Grant
Trimethoprim-sulfamethoxazole (TS) prophylaxis is recommended for HIV-exposed infants until breastfeeding ends and HIV infection has been excluded. Extending prophylaxis with a focus on preventing malaria may be beneficial in high transmission areas. We investigated three regimens for the prevention of malaria in young HIV-exposed children. Tororo, Uganda, a rural area with intense, year-round, malaria transmission. 200 infants aged 4-5 months enrolled and 186 randomized after cessation of breastfeeding and confirmed to be HIV uninfected (median 10 months of age). No chemoprevention, monthly sulfadoxine-pyrimethamine (SP), daily TS, or monthly dihydroartemisinin-piperaquine (DP) given from randomization to 24 months of age. The primary outcome was the incidence of malaria during the intervention period. Secondary outcomes included the incidence of hospitalization, diarrheal illness, or respiratory tract infection; prevalence of anemia and asymptomatic parasitemia; measures of safety; and incidence of malaria over 1 year after the intervention was stopped. During the intervention, the incidence of malaria in the no chemoprevention group was 6.28 episodes per person-year at risk. Protective efficacy was 69% (95% CI, 53-80%, p<0.001) for DP, 49% (95% CI, 23-66%, p=0.001) for TS, and 9% for SP (95% CI, −35 to 38%, p=0.65). There were no significant differences in any secondary outcomes, with the exception of a lower prevalence of asymptomatic parasitemia in the DP arm. Monthly chemoprevention with DP was safe and associated with a significant reduction in malaria in young HIV-exposed children.
Gendered dimensions of population mobility associated with HIV across three epidemics in rural Eastern Africa
(Theoretical Medicine and Bioethics, 2008) Camlin, Carol S.; Akullian, Adam; Neilands, Torsten B.; Getahun, Monica; Bershteyn, Anna; Ssali, Sarah; Geng, Elvin; Gandhi, Monica; Cohen, Craig R.; Maeri, Irene; Eyul, Patrick; Petersen, Maya L.; Havlir, Diane V.; Kamya, Moses R.; Bukusi, Elizabeth A.; Charlebois, Edwin D.
Mobility in sub-Saharan Africa links geographically-separate HIV epidemics, intensifies transmission by enabling higher-risk sexual behavior, and disrupts care. This population-based observational cohort study measured complex dimensions of mobility in rural Uganda and Kenya. Survey data were collected every 6 months beginning in 2016 from a random sample of 2308 adults in 12 communities across three regions, stratified by intervention arm, baseline residential stability and HIV status. Analyses were survey-weighted and stratified by sex, region, and HIV status. In this study, there were large differences in the forms and magnitude of mobility across regions, between men and women, and by HIV status. We found that adult migration varied widely by region, higher proportions of men than women migrated within the past one and five years, and men predominated across all but the most localized scales of migration: a higher proportion of women than men migrated within county of origin. Labor-related mobility was more common among men than women, while women were more likely to travel for non-labor reasons. Labor-related mobility was associated with HIV positive status for both men and women, adjusting for age and region, but the association was especially pronounced in women. The forms, drivers, and correlates of mobility in eastern Africa are complex and highly gendered. An in-depth understanding of mobility may help improve implementation and address gaps in the HIV prevention and care continua.
High Levels of Retention in Care with Streamlined Care and Universal Test-and-Treat in East Africa
(AIDS, 2016) Brown, Lillian B.; Havlir, Diane V.; Ayieko, James; Mwangwa, Florence; Owaraganise, Asiphas; Kwarisiima, Dalsone; Tamara, Clark; Bukusi, Elizabeth A.; Kamya, Moses R.; Petersen, Maya L.; Charlebois, Edwin D.; The Search Collaboration
We sought to measure retention in care and identify predictors of non-retention among patients receiving ART with streamlined delivery during the first year of the ongoing SEARCH “test-and-treat” trial (NCT 01864603) in rural Uganda and Kenya. Prospective cohort of patients in the intervention arm of the SEARCH Study. We measured retention in care at 12 months among HIV-infected adults who linked to care and were offered ART regardless of CD4 cell count, following community-wide HIV-testing. Kaplan-Meier estimates and Cox proportional hazards modeling were used to calculate the probability of retention at one year and identify predictors of non-retention. Among 5,683 adults (age ≥ 15) who linked to care, 95.5% (95% CI: 92.9 – 98.1%) were retained in care at 12 months. The overall probability of retention at one year was 89.3% (95% CI: 87.6 – 90.7%) among patients newly linking to care and 96.4% (95% CI: 95.8 – 97.0%) among patients previously in care. Younger age and pre-ART CD4 below country treatment initiation guidelines were predictors of non-retention among all patients. Among those newly linking, taking more than 30 days to link to care after HIV diagnosis was additionally associated with non-retention at one year. HIV viral load suppression at 12 months was observed in 4,227/4736 (89%) of patients retained with valid viral load results. High retention in care and viral suppression after 1 year were achieved in a streamlined HIV care delivery system in the context of a universal test-and-treat intervention.
Isoniazid Preventive Therapy Completion in the Era of Differentiated HIV Care
(Journal of acquired immune deficiency syndromes, 2017) Tram, Khai Hoan; Mwangwa, Florence; Atukunda, Mucunguzi; Owaraganise, Asiphas; Ayieko, James; Plenty, Albert; Kwariisima, Dalsone; Tamara, D. Clark; Maya, L. Petersen; Charlebois, Edwin D.; Kamya, Moses R.; Chamie, Gabriel; Havlir, Diane V.; Marquez, Carina; The Search Collaboration
Isoniazid preventive therapy (IPT) reduces incidence of TB by up to 60% and reduces mortality among people living with HIV (PLWH),1–4 but implementation of IPT remains poor. In East Africa, use of IPT by patients in HIV care ranges from 0.5% in Uganda to 19% in Kenya.5 Even where IPT programs are implemented, completion rates in East Africa range between 36–98%.6–11 Countries in sub-Saharan Africa are scaling up both IPT and differentiated HIV care, but there is little data to guide optimal integration of IPT into differentiated HIV care models. In differentiated HIV care stable patients typically receive quarterly ART refills either in a clinic or via community adherence groups to enhance retention in care and to decongest clinics.12,13 This less frequent scheduling is at odds with guideline recommended monthly IPT visit frequencies and could challenge successful IPT completion. To our knowledge, there are no studies assessing IPT treatment completion in the setting of well-engaged patients receiving differentiated HIV care. As such, we sought to characterize (1) baseline IPT completion rates and (2) predictors of IPT completion among HIV-infected adults, with a high rate of virologic suppression, who were receiving differentiated HIV care in 5 rural clinics in Uganda. These patients were accustomed to quarterly visits for ART refills, but to receive IPT, had to increase their visit frequency to monthly.
Mycobacterium tuberculosis Microbiologic and Clinical Treatment Outcomes in a Randomized Trial of Immediate versus CD4+ -Initiated Antiretroviral Therapy in HIV-Infected Adults with a High CD4+ Cell Count
(Clinical infectious diseases, 2010) Chamie, Gabriel; Charlebois, Edwin D.; Walusimbi-Nanteza, Maria; Mugerwa, Roy D.; Mayanja, Harriet; Okwera, Alphonse; Whalen, Christopher C.; Havlir, Diane V.
In a prospective randomized, controlled trial in Uganda comparing the efficacy of antiretroviral therapy during tuberculosis therapy with the efficacy of tuberculosis therapy alone in HIV-infected patients with tuberculosis who have a CD4+ cell count >350 cells/µL, it was found that antiretroviral therapy did not accelerate microbiologic, radiographic, or clinical responses to tuberculosis therapy: 18% of participants had sputum smears positive for Mycobacterium tuberculosis after 5 months of tuberculosis therapy, despite having had negative culture results.
Neurocognitive and Motor Deficits in HIV-Infected Ugandan Children With High CD4 Cell Counts
(Clinical Infectious Diseases, 2012) Ruel,Theodore D.; Boivin, Michael J.; Boal, Hannah E.; Bangirana, Paul; Charlebois,Edwin; Havlir, Diane V.; Rosenthal, Philip J.; Dorsey,Grant; Achan, Jane; Akello, Carolyne; Kamya, Moses R.; Wong, Joseph K.
Background. Human immunodeficiency virus (HIV) infection causes neurocognitive or motor function deficits in children with advanced disease, but it is unclear whether children with CD4 cell measures above the World health Organization (WHO) thresholds for antiretroviral therapy (ART) initiation suffer significant impairment
Predictors of Isoniazid Preventive Therapy Completion Among HIV-Infected Patients Receiving Differentiated and non-Differentiated HIV Care in Rural Uganda
(AIDS care, 2020) Tram, Khai Hoan; Mwangwa, Florence; Chamie, Gabriel; Atukunda, Mucunguzi; Owaraganise, Asiphas; Ayieko, James; Jain, Vivek; Tamara, D. Clark; Kwarisiima, Dalsone; Maya, L. Petersen; Kamya, Moses R.; Charlebois, Edwin D.; Havlir, Diane V.; Marquez, Carina; SEARCH collaboration
Rates of Isoniazid Preventive Therapy (IPT) completion remain low in programmatic settings in sub-Saharan Africa. Differentiated HIV care models may improve IPT completion by addressing joint barriers to IPT and HIV treatment. However, the impact of differentiated care on IPT completion remains unknown. In a cross-sectional study of people with HIV on antiretroviral therapy in 5 communities in rural Uganda, we compared IPT completion between patients receiving HIV care via a differentiated care model versus a standard HIV care model and assessed multi-level predictors of IPT completion. A total of 103/144 (72%) patients received differentiated care and 85/161 (53%) received standard care completed IPT (p < 0.01). Adjusting for age, gender and community, patients receiving differentiated care had higher odds of completing IPT (aOR: 2.6, 95% CI: 1.5–4.5, p < 0.01). Predictors of IPT completion varied by the care model, and differentiated care modified the positive association between treatment completion and the belief in the efficacy of IPT and the negative association with side-effects. Patients receiving a multi-component differentiated care model had a higher odds of IPT completion than standard care, and the model’s impact on health beliefs, social support, and perceived side effects to IPT may underlie this positive association.
Predictors of Retention in HIV Care among Youth (15–24) in a Universal Test-and-Treat Setting in Rural Kenya
(Journal of acquired immune deficiency syndromes, 2017) Brown, Lillian B.; Ayieko, James; Mwangwa, Florence; Owaraganise, Asiphas; Kwarisiima, Dalsone; Bukusi, Elizabeth A.; Kamya, Moses R.; Petersen, Maya L.; Charlebois, Edwin D.; Havlir, Diane V.
n 2013, 4 million youth age 15–24 years were living with HIV and 85% of HIV-infected youth live in sub-Saharan Africa1, where AIDS is the number-one cause of death of adolescents2. The magnitude of the HIV epidemic among youth in sub-Saharan Africa is expected to increase as demographic projections predict a “youth bulge”, increasing the population at risk for new infections, and leading to a doubling of the 15–24 year old HIV-infected cohort in sub-Saharan Africa by 20203. Retention in HIV care among this age group is essential to maximizing the benefits of antiretroviral therapy (ART), including improved quality of life, greater life expectancy, and prevention of new infections. Prior to guidelines for universal treatment, HIV-infected youth who started ART were more likely to be lost to follow-up4–6, report lower adherence4,6, and were more likely to have detectable viral loads than older age groups4,5,7. After two years of universal HIV testing and treatment in rural east Africa as part of the Sustainable East Africa Research in Community Health (SEARCH) trial, 82% of all adults with HIV in intervention communities were virally suppressed compared to only 67% of those age 15–248. These data suggest that even when high levels of viral suppression are achieved at the population level, current disparities could be exacerbated under universal treatment unless engagement in care among youth is specifically addressed. Understanding factors associated with retention in care, including any unique predictors, among this vulnerable age group will help develop additional interventions. We describe predictors of 12-month retention in HIV care among youth (15–24 years) who are linking to HIV care for the first time in rural Kenya as part of the ongoing SEARCH universal test-and-treat trial and compare these to young adults (25–29 years) and older adults (≥30 years).
Protective Efficacy and Safety of Three Antimalarial Regimens for the Prevention of Malaria in Young Ugandan Children: A Randomized Controlled Trial doi:10.1371/journal.pmed.1001689
(PLoS medicine, 2014) Bigira, Victor; Kapisi, James; Clark, Tamara D.; Kinara, Stephen; Mwangwa, Stephen; Muhindo, Mary K.; Osterbauer, Beth; Aweeka, Francesca T.; Huang, Liusheng; Achan, Jane; Havlir, Diane V.; Rosenthal, Philip J.; Kamya, Moses R.; Dorsey, Grant
Chemoprevention offers a promising strategy for prevention of malaria in African children. However, the optimal chemoprevention drug and dosing strategy is unclear in areas of year-round transmission and resistance to many antimalarial drugs. To compare three available regimens, we conducted an open-label randomized controlled trial of chemoprevention in Ugandan children. Methods and Findings: This study was conducted between June 28, 2010, and September 25, 2013. 400 infants were enrolled and 393 randomized at 6 mo of age to no chemoprevention, monthly sulfadoxine-pyrimethamine (SP), daily trimethoprim-sulfamethoxazole (TS), or monthly dihydroartemisinin-piperaquine (DP). Study drugs were administered at home without supervision. Piperaquine (PQ) levels were used as a measure of compliance in the DP arm. Participants were given insecticide-treated bednets, and caregivers were encouraged to bring their child to a study clinic whenever they were Chemoprevention was stopped at 24 mo of age, and participants followed-up an additional year. Primary outcome was the incidence of malaria during the intervention period. During the intervention, the incidence of malaria in the no chemoprevention arm was 6.95 episodes per person-year at risk. Protective efficacy was 58% (95% CI, 45%–67%, p,0.001) for DP, 28% (95% CI, 7%–44%, p = 0.01) for TS, and 7% for SP (95% CI, 219% to 28%, p = 0.57). PQ levels were below the detection limit 52% of the time when malaria was diagnosed in the DP arm, suggesting non-adherence. There were no differences between the study arms in the incidence of serious adverse events during the intervention and the incidence of malaria during the 1-y period after the intervention was stopped.Conclusions: For preventing malaria in children living in an area of high transmission intensity, monthly DP was the mostefficacious and safe, although adherence may pose a problem.Monthly SP and daily TS may not be appropriate in areas with high transmission intensity and frequent resistance to antifolates.
Redemption of the “spoiled identity:” the role of HIV-positive individuals in HIV care cascade interventions
(Journal of the International AIDS Society, 2017) Camlin, Carol S.; Geng, Elvin; Semitala, Fred; Wallenta, Jeanna; Kampiire, Leatitia; Bukusi, Elizabeth A.; Kwarisiima, Dalsone; Clark, Tamara D.; Kamya, Moses R.; Havlir, Diane V.
The concept of “therapeutic citizenship” has drawn attention to ways in which public testimony, the “story-telling in the public sphere” undertaken by people living with HIV (PLHIV), has shaped the global response to the epidemic. This paper presents qualitative findings from two large studies in eastern Africa that reveal how the advent of population-based HIV testing campaigns and efforts to accelerate antiretroviral “treatment for all” has precipitated a rapidly expanding therapeutic citizenship “project,” or social movement. The title of this paper refers to Goffman's original conceptualization of stigma as a social process through which a person's identity is rendered “spoiled.”
Two or More Significant Life-Events in 6-Months are Associated with Lower Rates of HIV Treatment and Virologic Suppression among Youth with HIV in Uganda and Kenya
(AIDS care, 2022) Mwangwa, Florence; Ayieko, James; Olio, Winter; Peng, James; Kwarisiima, Dalsone; Kabami, Jane; Kapogiannis, Bill; Kamya, Moses R.; Havlir, Diane V.; Ruel, Theodore D.
Youth living with HIV in sub-Saharan Africa have poor HIV care outcomes. We determined the association of recent significant life-events with HIV antiretroviral treatment (ART) initiation and HIV viral suppression in youth aged 15–24 years living with HIV in rural Kenya and Uganda. This was a cross-sectional analysis of 995 youth enrolled in the SEARCH Youth study. At baseline, providers assessed recent (within 6 months) life-events, defined as changes in schooling/employment, residence, partnerships, sickness, incarceration status, family strife or death, and birth/pregnancy, self-reported alcohol use, being a parent, and HIV-status disclosure. We examined the frequencies of events and their association with ART status and HIV viral suppression (<400 copies/ul). Recent significant life-events were prevalent (57.7%). Having >2 significant life-events (aOR = 0.61, 95% CI:0.45-0.85) and consuming alcohol (aOR = 0.61, 95% CI:0.43-0.87) were associated with a lower odds of HIV viral suppression, while disclosure of HIV-status to partner (aOR = 2.39, 95% CI:1.6-3.5) or to family (aOR = 1.86, 95% CI:1.3-2.7), being a parent (aOR = 1.8, 95% CI:1.2-2.5), and being single (aOR = 1.6, 95% CI:1.3-2.1) had a higher odds. This suggest that two or more recent life-events and alcohol use are key barriers to ART initiation and achievement of viral suppression among youth living with HIV in rural East Africa.
Understanding Demand for PrEP and Early Experiences of PrEP Use Among Young Adults in Rural Kenya and Uganda: A Qualitative Study
(AIDS and Behavior, 2020) Camlin, Carol S.; Koss, Catherine A.; Owino, Lawrence; Akatukwasa, Cecilia; Bakanoma, Robert; Onyango, Anjeline; Atwine, Frederick; Ayieko, James; Kabami, Jane; Mwangwa, Florence; Atukunda, Mucunguzi; Owaraganise, Asiphas; Kwarisiima, Dalsone; Bukusi, Elizabeth A.; Kamya, Moses R.; Maya, L. Petersen; Cohen, Craig R.; Charlebois, Edwin D.; Havlir, Diane V.
Few studies have sought to understand factors influencing uptake and continuation of pre-exposure prophylaxis (PrEP) among young adults in sub-Saharan Africa in the context of population-based delivery of open-label PrEP. To address this gap, this qualitative study was implemented within the SEARCH study (NCT#01864603) in Kenya and Uganda, which achieved near-universal HIV testing, and offered PrEP in 16 intervention communities beginning in 2016–2017. Focus group discussions (8 groups, n = 88 participants) and in-depth interviews (n = 23) with young adults who initiated or declined PrEP were conducted in five communities, to explore PrEP-related beliefs and attitudes, HIV risk perceptions, motivations for uptake and continuation, and experiences. Grounded theoretical methods were used to analyze data. Young people felt personally vulnerable to HIV, but perceived the severity of HIV to be low, due to the success of antiretroviral therapy (ART): daily pill-taking was more threatening than the disease itself. Motivations for PrEP were highly gendered: young men viewed PrEP as a vehicle for safely pursuing multiple partners, while young women saw PrEP as a means to control risks in the context of engagement in transactional sex and limited agency to negotiate condom use and partner testing. Rumors, HIV/ART-related stigma, and desire for “proof” of efficacy militated against uptake, and many women required partners’ permission to take PrEP. Uptake was motivated by high perceived HIV risk, and beliefs that PrEP use supported life goals. PrEP was often discontinued due to dissolution of partnerships/changing risk, unsupportive partners/peers, or early side effects/pill burden. Despite high perceived risks and interest, PrEP was received with moral ambivalence because of its associations with HIV/ART and stigmatized behaviors. Delivery models that promote youth access, frame messaging on wellness and goals, and foster partner and peer support, may facilitate uptake among young people.
Understanding uptake of an intervention to accelerate antiretroviral therapy initiation in Uganda via qualitative inquiry
(Journal of the International AIDS Society, 2017) Semitala, Fred C.; Wallenta, Jeanna; Kampiire, Leatitia; Katuramu, Richard; Amanyire, Gideon; Namusobya, Jennifer; Havlir, Diane V.; Kamya, Moses R.; Geng, Elvin H.
The Streamlined Antiretroviral Therapy Initiation Strategy (START-ART) study found that a theory-based intervention using opinion leaders to inform and coach health care providers about the risks of treatment delay, provision of point of care (POC) CD4 testing machines (PIMA) and reputational incentives, led to rapid rise in ART initiation. We used qualitative research methods to explore mechanisms of provider behaviour change.
Uptake and Outcomes of a Novel Community-Based HIV Post-exposure Prophylaxis (PEP) Programme in Rural Kenya and Uganda
(Journal of the International AIDS Society, 2021) Ayieko, James; Petersen, Maya L.; Kabami, Jane; Mwangwa, Florence; Nyabuti, Marilyn; Charlebois, Edwin D.; Bukusi, Elizabeth A.; Kamya, Moses R.; Havlir, Diane V.
Antiretroviral-based HIV prevention, including pre-exposure prophylaxis (PrEP), is expanding in generalized epidemic settings, but additional prevention options are needed for individuals with periodic, high-risk sexual exposures. Non-occupational post-exposure prophylaxis (PEP) is recommended in global guidelines. However, in Africa, awareness of and access to PEP for sexual exposures are limited. We assessed feasibility, acceptability, uptake and adherence in a pilot study of a patient-centred PEP programme with options for facility- or community-based service delivery. After population-level HIV testing with universal access to PrEP for persons at elevated HIV risk (SEARCH Trial:NCT01864603), we conducted a pilot PEP study in five rural communities in Kenya and Uganda between December 2018 and May 2019. We assessed barriers to PEP in the population and implemented an intervention to address these barriers, building on existing in-country PEP protocols. We used community leaders for sensitization. Test kits and medications were acquired through the Ministry of Health supply chain and healthcare providers based at the Ministry of Health clinics were trained on PEP delivery. Additional intervention components were (a)PEP availability seven days/week, (b)PEP hotline staffed by providers and (c)option for out-of-facility medication delivery. We assessed implementation using the Proctor framework and measured seroconversions via repeat HIV testing. Successful “PEP completion” was defined as self-reported adherence over four weeks of therapy with post-PEP HIV testing. Community leaders were able to sensitize and mobilize for PEP. The Ministry of Health supplied test kits and PEP medications; after training, healthcare providers delivered the 28-day regimen with high completion rates. Among 124 persons who sought PEP, 66% were female, 24% were ≤25 years and 42% were fisherfolk. Of these, 20% reported exposure with a serodifferent partner, 72% with a new or existing relationship and 7% from transactional sex. 12% of all visits were conducted at out-of-facility community-based sites; 35% of participants had ≥1 out-of-facility visit. No serious adverse events were reported. Overall, 85% met the definition of PEP completion. There were no HIV seroconversions. Among individuals with elevated-risk exposures in rural East African communities, patient-centred PEP was feasible, acceptable and provides a promising addition to the current prevention toolkit.

Browsing by Author "Havlir, Diane V."

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