Browsing by Author "Kityo, Cissy"
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Item Antiretroviral Therapy and Sexual Behavior: A Comparative Study between Antiretroviral- Naive and -Experienced Patients at an Urban HIV/AIDS Care and Research Center in Kampala, Uganda(AIDS Patient Care & STDs, 2005) Bateganya, Moses; Colfax, Grant; Shafer, Leigh Anne; Kityo, Cissy; Mugyenyi, Peter; Serwadda, David; Mayanja, Harriet; Bangsberg, DavidWe examined whether use of antiretroviral (ARV) therapy is associated with increased sexual risk behavior in a cross-sectional study of patients undergoing ARV therapy (ARV experienced) compared to patients not undergoing ARV therapy (ARV-naïve) attending an urban HIV clinic in Kampala, Uganda. Sexual behavior during the prior 6 months and sexually transmitted disease (STD) treatment was determined by face-to-face structured interviews. Multiple logistic regression was used to identify independent correlates of sexual activity, multiple sexual partners, inconsistent condom use, and STD treatment during the prior 6 months. Three hundred forty-seven (48%) of the 723 respondents reported a history of sexual intercourse in the 6 months prior to the interview (sexually active). Receipt of ARV therapy was not associated with a significantly higher likelihood of being sexually active (adjusted odds ratio [AOR], 2.0 95% confidence interval [CI], 0.3–9.9). Among both ARV-experienced and ARV-naïve persons who were sexually active, 35% (120) reported one or more casual sexual partners in addition to a main partner (no difference by ARV status). Consistent condom use with spouse, regular, casual, and commercial partners was reported by 57%, 65%, 85%, and 85% of the sexually active respondents, respectively. The ARV-experienced respondents were more likely to report consistent condom use with their spouses than were ARV-naïve respondents (OR 2.8295% CI 1.74–4.6). ARV-experienced respondents were more likely than ARV-naïve respondents to have disclosed their HIV status to their spouses (OR 1.57 95% CI 1.07–2.30).The ARV-experienced group was more likely to report STD treatment in the prior 6 months (AOR 2.62 95% CI 1.83.83) than the ARV-naïve group. The findings suggest that in this population, use of ARV therapy was not associated with risky sexual behavior in the prior 6 months. Still, recall and social desirability biases remain important limitations in interpreting these conclusions.Item Barriers to Initiation of Pediatric HIV Treatment in Uganda: A Mixed-Method Study(AIDS research and treatment, 2012) Boender, T. Sonia; Sigaloff, Kim C. E.; Kayiwa, Joshua; Musiime, Victor; Calis, Job C. J.; Katumba, Lillian Nakatudde; Khauda, Elizabeth; Mukuye, Andrew; Ditai, James; Mugyenyi, Peter; Rinke deWit, Tobias F.; Kityo, CissyAlthough the advantages of early infant HIV diagnosis and treatment initiation are well established, children often present late to HIV programs in resource-limited settings. We aimed to assess factors related to the timing of treatment initiation among HIV-infected children attending three clinical sites in Uganda. Clinical and demographic determinants associated with early disease (WHO clinical stages 1-2) or late disease (stages 3-4) stage at presentation were assessed using multilevel logistic regression. Additionally, semistructured interviews with caregivers and health workers were conducted to qualitatively explore determinants of late disease stage at presentation. Of 306 children initiating first-line regimens, 72% presented late. Risk factors for late presentation were age below 2 years old (OR 2.83, ), living without parents (OR 3.93, ), unemployment of the caregiver (OR 4.26, ), lack of perinatal HIV prophylaxis (OR 5.66, ), and high transportation costs to the clinic (OR 2.51, ). Forty-nine interviews were conducted, confirming the identified risk factors and additionally pointing to inconsistent referral from perinatal care, caregivers’ unawareness of HIV symptoms, fear, and stigma as important barriers. The problem of late disease at presentation requires a multifactorial approach, addressing both health system and individual-level factors.Item A Case of Cryptococcal Lymphadenitis in an HIV-Infected Child(AIDS research and human retroviruses, 2011) Natukunda, Eva; Musiime, Victor; Ssali, Francis; Kizito, Hilda; Kityo, Cissy; Mugyenyi, PeterAn 8-year-old HIV-positive antiretroviral therapy-naive child developed severe headache and generalized lymphadenopathy. The serum cryptococcal antigen (CRAG) test was positive, the histology on the lymph node biopsy revealed budding yeast cells, and Cryptococcus neoformans was isolated on culture of his cerebrospinal fluid. He was treated with intravenous amphotericin B followed by oral fluconazole with a good response. Therefore cryptococcal lymphadenitis should be considered in the differential diagnosis of children presenting with lymphadenopathy and a positive serum CRAG.Item Coronary artery calcium, HIV and inflammation in Uganda compared with the USA(Open Heart, 2019) Alencherry, Ben; Erem, Geoffrey; Mirembe, Grace; Ssinabulya, Isaac; Yun, Chun-Ho; Hung, Chung-Lieh; Siedner, Mark J.; Bittencourt, Marcio; Kityo, Cissy; McComsey, Grace A.; Longenecker, Chris T.To compare the prevalence of detectable coronary artery calcium (CAC) among higher risk, older people living with HIV (PLWH) and uninfected persons in Uganda versus the USA, and second to explore associations of CAC with HIV-specific variables and biomarkers of inflammation. This cross-sectional study of 430 total subjects compared 100 PLWH on antiretroviral therapy and 100 age-matched and sex-matched HIV-uninfected controls in Uganda with 167 PLWH on antiretroviral therapy and 63 uninfected controls in the USA. Multivariable logistic regression was used to examine associations with detectable CAC (CAC >0). Compared with US subjects, Ugandans were older (mean age 56 vs 52 years) and were more likely to have diabetes (36% vs 3%) and hypertension (85% vs 36%), but were less likely to be male (38% vs 74%) or smokers (4% vs 56%). After adjustment for HIV serostatus, age, sex and traditional risk factors, Ugandans had substantially lower odds of CAC >0 (adjusted OR 0.07 (95% CI 0.03 to 0.17), p<0.001). HIV was not associated with CAC >0 in either country (p>0.1). Among all PLWH, nadir CD4 count was associated with the presence of CAC, and among Ugandans soluble intercellular adhesion molecule (p=0.044), soluble CD163 (p=0.004) and oxidised low-density lipoprotein (p=0.043) were all associated with the presence of CAC. Ugandans had a dramatically lower prevalence of any coronary calcification compared with US subjects. The role of HIV infection and inflammation as risk factors for subclinical coronary disease in sub-Saharan Africa merits further investigation.Item Cost Effectiveness Analysis of Clinically Driven versus Routine Laboratory Monitoring of Antiretroviral Therapy in Uganda and Zimbabwe(PloS one, 2012) Lara, Antonieta Medina; Kigozi, Jesse; Amurwon, Jovita; Muchabaiwa, Lazarus; Wakaholi, Barbara Nyanzi; Mota, Ruben E. Mujica; Walker, A. Sarah; Kasirye, Ronnie; Ssali, Francis; Reid, Andrew; Grosskurth, Heiner; Babiker, Abdel G.; Kityo, Cissy; Katabira, Elly; Munderi, Paula; Mugyenyi, Peter; Hakim, James; Darbyshire, Janet; Gibb, Diana M.; Gilks, Charles F.Despite funding constraints for treatment programmes in Africa, the costs and economic consequences of routine laboratory monitoring for efficacy and toxicity of antiretroviral therapy (ART) have rarely been evaluated.Cost-effectiveness analysis was conducted in the DART trial (ISRCTN13968779). Adults in Uganda/Zimbabwe starting ART were randomised to clinically-driven monitoring (CDM) or laboratory and clinical monitoring (LCM); individual patient data on healthcare resource utilisation and outcomes were valued with primary economic costs and utilities. Total costs of first/second-line ART, routine 12-weekly CD4 and biochemistry/haematology tests, additional diagnostic investigations, clinic visits, concomitant medications and hospitalisations were considered from the public healthcare sector perspective. A Markov model was used to extrapolate costs and benefits 20 years beyond the trial.3316 (1660LCM;1656CDM) symptomatic, immunosuppressed ART-naive adults (median (IQR) age 37 (32,42); CD4 86 (31,139) cells/mm3) were followed for median 4.9 years. LCM had a mean 0.112 year (41 days) survival benefit at an additional mean cost of $765 [95%CI:685,845], translating into an adjusted incremental cost of $7386 [3277,dominated] per life-year gained and $7793 [4442,39179] per quality-adjusted life year gained. Routine toxicity tests were prominent cost-drivers and had no benefit. With 12-weekly CD4 monitoring from year 2 on ART, low-cost second-line ART, but without toxicity monitoring, CD4 test costs need to fall below $3.78 to become cost-effective (<3xper-capita GDP, following WHO benchmarks). CD4 monitoring at current costs as undertaken in DART was not cost-effective in the long-term.There is no rationale for routine toxicity monitoring, which did not affect outcomes and was costly. Even though beneficial, there is little justification for routine 12-weekly CD4 monitoring of ART at current test costs in low-income African countries. CD4 monitoring, restricted to the second year on ART onwards, could be cost-effective with lower cost second-line therapy and development of a cheaper, ideally point-of-care, CD4 test.Item Defining total-body AIDS-virus burden with Implications for Curative Strategies(Nature medicine, 2017) Estes, Jacob D.; Kityo, Cissy; Ssali, Francis; Beilman, Gregory J.; Schacker, Timothy W.In the quest for a functional cure or the eradication of HIV infection, it is necessary to know the sizes of the reservoirs from which infection rebounds after treatment interruption. Thus, we quantified SIV and HIV tissue burdens in tissues of infected nonhuman primates and lymphoid tissue (LT) biopsies from infected humans. Before antiretroviral therapy (ART), LTs contained >98% of the SIV RNA+ and DNA+ cells. With ART, the numbers of virus (v) RNA+ cells substantially decreased but remained detectable, and their persistence was associated with relatively lower drug concentrations in LT than in peripheral blood. Prolonged ART also decreased the levels of SIV- and HIV-DNA+ cells, but the estimated size of the residual tissue burden of 108 vDNA+ cells potentially containing replication-competent proviruses, along with evidence of continuing virus production in LT despite ART, indicated two important sources for rebound following treatment interruption. The large sizes of these tissue reservoirs underscore challenges in developing 'HIV cure' strategies targeting multiple sources of virus production.Item Differences in body circumference, skin fold thickness and lipid profile measurements among HIV-infected children on and not on stavudine-based therapy in Uganda and Zambia in the CHAPAS-3 clinical trial(Joint Clinical Research Centre, 2013) Musiime, Victor; Cook, Adrian.; Kayiwa, Joshua; Zangata, Dorothy; Gibb, Diana M.; Kityo, Cissy; Kekitiinwa, Adeodata; Mulenga, Veronica; Nansubuga, Carol; Arach, Beatrice; Kenny, Julia; Wavamunno, Priscilla; Kabamba, Desiree; Asiimwe, Alice R.; Abongomera, GeorgeLipodystrophy is a major side effect of antiretroviral therapy (ART) especially in adults, and although there have been some reports among HIV-infected children [1,2], paediatric data are limited Stavudine (d4T) has particularly been associated with lipodystrophy among HIVinfected adults owing to intracellular accumulation of the drug and its metabolites In HIV-infected children, d4T clearance is enhanced, potentially protecting them from these effects [3]. In addition, the relative d4T dose in paediatric fixed dosecombination “baby” tablets is lower than used in adults, and is also lower compared to the 4mg/kg licensed dose for children [4] Features of lipodystrophy have been observed to reverse when children have been switched from d4T-containing regimens [5]; however, clinical lipodystrophy ismore difficult to diagnose in growing children than in adults We compared body circumferences, skin-fold thickness (SFT) and lipid levels, as objective measures of lipodystrophy, among HIV-infected ART naïve vs experienced children at enrolment into the CHAPAS-3 trial, and in HIV-uninfectedItem Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA pharmacogenetic substudy of DART(Tropical medicine & international health, 2011) Munderi, Paula; Snowden, Wendy B.; Kityo, Cissy; Kabuye, Geoffrey; Thoofer, Navdeep K.; Ssali, Francis; Gilks, Charles F.; Hughes, Arlene R.To determine the frequencies of HLA-B alleles in Ugandan patients in the NORA substudy of the DART trial and to compare HLA-B allele frequencies in those with and without clinically diagnosed hypersensitivity reaction (HSR). DNA-based HLA-B genotyping was used to determine HLA alleles in 247 participants who received abacavir, including all six participants (‘cases’) with clinically diagnosed abacavir HSR. The incidence of clinical abacavir HSR in this double-blinded study was 2.0% (6/300) in the abacavir group. As HLA-B*5701 was absent throughout the entire cohort, including the six HSR ‘cases’, an association could not be established between HLA-B*5701 and clinically diagnosed abacavir HSR. No other HLA-B*57 alleles were present among the six ‘cases’. HLA-B*5703 was the most frequent HLA-B*57 allele among the abacavir-tolerant participants. The rate of clinical HSR was low, which may reflect the expected 2–3% clinical false-positive rate seen in previous double-blind randomized studies. The presumption that these cases may be false-positive abacavir HSR is supported by the fact that no HLA-B*5701 alleles were found in the abacavir group. Implementation of prospective HLA-B*5701 screening must be based on benefit/risk considerations within local practice. Clinical risk management remains paramount.Item Efficacy and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Females Living With HIV: An Integrated Analysis of 5 Trials(Journal of Acquired Immune Deficiency Syndromes, 1999) Orkin, Chloe; Ajana, Faiza; Kityo, Cissy; Koenig, Ellen; Natukunda, Eva; Gandhi-Patel, Bhumi; Wang, Hui; Liu, Yapei; Wei, Xuelian; White, Kirsten; Makadzange, Tariro; Pikora, Cheryl; McNicholl, Ian; Collins, Sean E.; Brainard, Diana; Chuck, Susan K.We characterized the efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in a broad population of pediatric/adolescent/adult/elderly females living with HIV (FWH). Setting: Integrated analysis. Methods: Available data from 5 trials were integrated. Week 48 virologic suppression (HIV-1 RNA ,50 copies/mL), resistance, adverse events (AEs), and laboratory parameters were assessed. Results: Three hundred and seventy-three FWH [304 virologically suppressed; 69 antiretroviral therapy (ART)-naive] received B/F/TAF [data from comparator regimens available for 306 individuals (236 virologically suppressed and 70 ART-naive participants)]. Virologic suppression rates with B/F/TAF at week 48 were high regardless of age in participants virologically suppressed at baseline ($95%) and in ART-naive participants ($87%). Virologic suppression rates were similar in B/F/TAF and comparator regimens (both virologically suppressed and ART-naive groups). Treatment-emergent resistance was not detected in the B/F/TAF group. AEs considered related to study drugs were experienced by 9.2% (B/F/TAF) and 5.5% (comparator regimen) of virologically suppressed participants and 15.9% (B/F/TAF) and 31.4% (comparator regimen) of ART-naive participants. For virologically suppressed and ART-naive FWH combined, only 1 of the 373 B/F/TAF–treated and 2 of the 306 comparator-regimen participants discontinued because of AEs (none were bone/renal/hepatic AEs); grade 3/4 AEs were experienced by 5.1% (B/F/TAF) and 7.8% (comparator regimen); and grade 3/4 elevation of low-density lipoprotein/total cholesterol occurred in 2.7%/ 0.3% (B/F/TAF) and 5.9%/2.0% (comparator regimen). At week 48, median changes from baseline estimated glomerular filtration rate in adults were ,5 mL/min; results were similar in B/F/TAF and comparator-regimen groups. Conclusion: B/F/TAF treatment was effective and well tolerated over 48 weeks, confirming B/F/TAF as an option for a broad population of FWH.Item Efficacy and Safety of Dolutegravir or Darunavir in Combination with Lamivudine plus either Zidovudine or Tenofovir for second-line Treatment of HIV Infection (NADIA): week 96 results from a Prospective, Multicentre, Open-label, Factorial, Randomised, Non-inferiority trial(The Lancet HIV, 2022) Paton, Nicholas I.; Musaazi, Joseph; Kityo, Cissy; Walimbwa, Stephen; Hoppe, Anne; Balyegisawa, Apolo; Mirembe, Grace; Lugemwa, Abbas; Ategeka, Gilbert; Mugerwa, Henry; Kambugu, AndrewWHO guidelines recommend dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) for second-line HIV therapy, with NRTI switching from first-line tenofovir to zidovudine. We aimed to examine whether dolutegravir is non-inferior to darunavir, the best-in-class protease inhibitor drug, and whether maintaining tenofovir in second-line therapy is non-inferior to switching to zidovudine. In this prospective, multicentre, open-label, factorial, randomised, non-inferiority trial (NADIA), participants with confirmed HIV first-line treatment failure (HIV-1 RNA ≥1000 copies per mL) were recruited at seven clinical sites in Kenya, Uganda, and Zimbabwe. Following a 2 × 2 factorial design and stratified by site and screening HIV-1 RNA concentration, participants were randomly assigned (1:1:1:1) to receive a 96-week regimen containing either dolutegravir (50 mg once daily) or ritonavir-boosted darunavir (800 mg of darunavir plus 100 mg of ritonavir once daily) in combination with either tenofovir (300 mg once daily) plus lamivudine (300 mg once daily) or zidovudine (300 mg twice daily) plus lamivudine (150 mg twice daily). The NRTI drugs allocated by randomisation were administered orally in fixed-dose combination pills; other drugs were administered orally as separate pills. The previously reported primary outcome was the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 48 weeks. Here, we report the main secondary outcome: the proportion of participants with a plasma HIV-1 RNA concentration of less than 400 copies per mL at 96 weeks (non-inferiority margin 12%). We analysed this outcome and safety outcomes in the intention-to-treat population, which excluded only those who were randomly assigned in error and withdrawn before receiving trial drugs. This study was registered at ClinicalTrials.gov, NCT03988452, and is complete.Item Efficacy of convalescent plasma for treatment of COVID-19 in Uganda(BMJ Open Resp Res, 2021) Kirenga, Bruce; Byakika-Kibwika, Pauline; Muttamba, Winters; Kayongo, Alex; Namakula, Olive Loryndah,; Mugenyi, Levicatus; Kiwanuka, Noah; Lusiba, John; Atukunda, Angella; Mugume, Raymond; Ssali, Francis; Ddungu, Henry; Katagira, Winceslaus; Sekibira, Rogers; Kityo, Cissy; Kyeyune, Dorothy; Acana, Susan; Aanyu-Tukamuhebwa, Hellen; Kabweru, Wilberforce; Nakwagala, Fred; Sentalo Bagaya, Bernard; Kimuli, Ivan; Nantanda, Rebecca; Buregyeya, Esther; Byarugaba, Baterana; Olaro, Charles; Mwebesa, Henry; Lutaakome Joloba, Moses; Siddharthan, Trishul; Bazeyo, WilliamConvalescent plasma (CCP) has been studied as a potential therapy for COVID-19, but data on its efficacy in Africa are limited. Objective In this trial we set out to determine the efficacy of CCP for treatment of COVID-19 in Uganda. Measurements Patients with a positive SARS-CoV- 2 reverse transcriptase (RT)-PCR test irrespective of disease severity were hospitalized and randomized to receive either COVID-19 CCP plus standard of care (SOC) or SOC alone. The primary outcome was time to viral clearance, defined as having two consecutive RT-PCR- negative tests by day 28. Secondary outcomes included time to symptom resolution, clinical status on the modified WHO Ordinal Clinical Scale (≥1-point increase), progression to severe/ critical condition (defined as oxygen saturation <93% or needing oxygen), mortality and safety.Item Feasibility of collecting and processing of COVID-19 convalescent plasma for treatment of COVID-19 in Uganda(PLoS ONE, 2021) Muttamba, Winters; Lusiba, John; Namakula, Loryndah Olive; Byakika-Kibwika, Pauline; Ssali, Francis; Ddungu, Henry; Mugenyi, Levicatus; Kiwanuka, Noah; Sekibira, Rogers; Kityo, Cissy; Keyune, Dorothy; Acana, Susan; Musinguzi, Ambrose; Masasi, Ayub; Byamugisha, Joseph; Mpanju, David; Musoki, Walter Jack; Tukamuhebwa, Hellen Aanyu; Nakwagala, Fred; Sentalo Bagaya, Bernard; Kayongo, Alex; Kimuli, Ivan; Nantanda, Rebecca; Katagira, Winceslaus; Buregyeya, Esther; Byanyima, Rosemary; Byarugaba, Baterana; Siddharthan, Trishul; Mwebesa, Henry; Charles, Olaro; Lutaakome Joloba, Moses; Bazeyo, William; Kirenga, BruceEvidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda. Methods In a cross-sectional study, persons with documented evidence of recovery from COVID-19 in Uganda were contacted and screened for blood donation via telephone calls. Those found eligible were asked to come to the blood donation centre for further screening and consent. Whole blood collection was undertaken from which plasma was processed. Plasma was tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers. SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors.Item High Rate of HIV Resuppression After Viral Failure on First-line Antiretroviral Therapy in the Absence of Switch to Second-line Therapy(Clinical infectious diseases, 2014) Gupta, Ravindra K.; Goodall, Ruth L.; Kityo, Cissy; Munderi, Paula; Lyagoba, Fred; Mugarura, Lincoln; Kaleebu, Pontiano; Pillay, DeenanIn a randomized comparison of nevirapine or abacavir with zidovudine plus lamivudine, routine viral load monitoring was not performed, yet 27% of individuals with viral failure at week 48 experienced resuppression by week 96 without switching. This supports World Health Organization recommendations that suspected viral failure should trigger adherence counseling and repeat measurement before a treatment switch is considered.Item HIV and Pericardial Fat are Associated with Abnormal Cardiac Structure and Function among Ugandans(Heart, 2020) Buggey, Jonathan; Yun, Chun-Ho; Hung, Chung-Lieh; Kityo, Cissy; Mirembe, Grace; Erem, Geoffrey; Ssinabulya, Isaac; McComseya, Grace A.; Longenecker, Chris T.To examine the relationship between pericardial fat (PCF) and cardiac structure and function among HIV-infected patients in the sub-Saharan African country of Uganda. People living with HIV (PLHIV) have altered fat distribution and an elevated risk for heart failure. Whether altered quantity and radiodensity of fat surrounding the heart relates to cardiac dysfunction in this population is unknown. One hundred HIV-positive Ugandans on antiretroviral therapy were compared with 100 age and sex-matched HIV-negative Ugandans; all were >45 years old with >1 cardiovascular disease risk factor. Subjects underwent ECG-gated non-contrast cardiac CT and transthoracic echocardiography with speckle tracking strain imaging. Multivariable linear and logistic regression models were used to explore the association of PCF with echocardiographic outcomes. Median age was 55% and 62% were female. Compared with uninfected controls, PLHIV had lower body mass index (27 vs 30, p=0.02) and less diabetes (26% vs 45%, p=0.005). Median left ventricular (LV) ejection fraction was 67%. In models adjusted for traditional risk factors, HIV was associated with 10.3 g/m2 higher LV mass index (LVMI) (95% CI 3.22 to 17.4; p=0.005), 0.87% worse LV global longitudinal strain (GLS) (95% CI −1.66 to −0.07; p=0.03) and higher odds of diastolic dysfunction (OR 1.96; 95% CI 0.95 to 4.06; p=0.07). In adjusted models, PCF volume was significantly associated with increased LVMI and worse LV GLS, while PCF radiodensity was associated with worse LV GLS (all p<0.05). In Uganda, HIV infection, PCF volume and density are associated with abnormal cardiac structure and function.Item Identification of gaps for implementation science in the HIV prevention, care and treatment cascade; a qualitative study in 19 districts in Uganda(BMC research notes, 2016) Bajunirwe, Francis; Tumwebaze, Flora; Abongomera, George; Akakimpa, Denis; Kityo, Cissy; Mugyenyi, Peter N.Over the last 20 years, countries in sub Saharan Africa have made significant strides in the implementation of programs for HIV prevention, care and treatment. Despite, the significant progress made, many targets set by the United Nations have not been met. There remains a large gap between the ideal and what has been achieved. There are several operational issues that may be responsible for this gap, and these need to be addressed in order to achieve the targets. Therefore, the aim of this study was to identify gaps in the HIV prevention, care and treatment cascade, in a large district based HIV implementation program. We aimed to identify gaps that are amenable for evaluation using implementation science, in order to improve the delivery of HIV programs in rural Uganda.We conducted key informant (KI) interviews with 60 district health officers and managers of HIV/AIDS clinics and organizations and 32 focus group discussions with exit clients seeking care and treatment for HIV in the 19 districts. The data analysis process was guided using a framework approach. The recordings were transcribed verbatim. Transcripts were read back and forth and codes generated based on the framework.Nine emerging themes that comprise the gaps were identified and these were referral mechanisms indicating several loop holes, low levels of integration of HIV/TB services, low uptake of services for PMTCT services by pregnant women, low coverage of services for most at risk populations (MARPs), poor HIV coordination structures in the districts, poor continuity in the delivery of pediatric HIV/AIDS services, limited community support for orphans and vulnerable (OVC’s), inadequate home based care services and HIV services and support for discordant couples. The themes indicate there are plenty of gaps that need to be covered and have been ignored by current programs.Our study has identified several gaps and suggested several interventions that should be tested before large scale implementation. The implementation of these programs should be adequately evaluated in order to provide field evidence of effectiveness and replicability in similar areas.Item Induction of opsonophagocytic killing activity with pneumococcal conjugate vaccine in human immunodeficiency virus-infected Ugandan adults(Vaccine, 2008) Chena, Meng; Ssali, Francis; Mulungi, Maureen; Awio, Peter; Furumoto, Akitsugu; Kityo, Cissy; Mugyenyi, Peter; Oishi, KazunoriThe levels of IgG determined by ELISA may have limited relevance in human immunodeficiency virus (HIV)-infected adults because of non-functional antibodies. 58 HIV-1-infected and 29 HIV-uninfected Ugandan adults were immunized with conjugate vaccine (CV) followed by polysaccharide vaccine (PV) after a 2-month interval, and the opsonophagocytic killing (OPK) titers against serotype 4 or 14 pneumococcal strains as well as the levels of serotype-specific IgG in sera were determined. Significant increases were found in the OPK titers and IgG levels for both serotypes after CV vaccination irrespective of HIV status. Increases in IgG levels and OPK titers were largely dependent on the CD4+ cell counts, except for increases in the IgG levels for serotype 4. The proportions with serum OPK titer equal to or greater than 8 were 0–4.3% for serotype 4 and 26.7–42.9% for serotype 14 before vaccination, but the proportions increased up to 43.3–86.2% for serotype 4 and 63.3–96.6% for serotype 14 in all three groups 2 months after CV vaccination. The serum OPK titers remained at levels higher than the pre-vaccination level for at least 8 months after CV vaccination. A single dose of CV could afford some protective immunity in HIV-infected African adults before the introduction of antiretroviral therapy.Item Lopinavir plus nucleoside reverse-transcriptase inhibitors, lopinavir plus raltegravir, or lopinavir monotherapy for second-line treatment of HIV (EARNEST): 144-week follow-up results from a randomised controlled trial(The Lancet Infectious Diseases, 2018) Hakim, James G.; Kityo, Cissy; Kambugu, Andrew; Lugemwa, Abbas; Mwebaze, Raymond; Mugyenyi, PeterMillions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings. We analysed the 144-week outcomes at the completion of the EARNEST trial, a randomised controlled trial done in HIV-infected adults or adolescents in 14 sites in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, Zambia). Participants were those who were no longer responding to non-NRTI-based first-line ART, as assessed with WHO criteria, confirmed by viral-load testing. Participants were randomly assigned to receive a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus two or three clinician-selected NRTIs (protease inhibitor plus NRTI group), protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group), or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group). Randomisation was by computer-generated randomisation sequence, with variable block size. The primary outcome was viral load of less than 400 copies per mL at week 144, for which we assessed non-inferiority with a one-sided α of 0·025, and superiority with a two-sided α of 0·025. The EARNEST trial is registered with ISRCTN, number 37737787. Between April 12, 2010, and April 29, 2011, 1837 patients were screened for eligibility, of whom 1277 patients were randomly assigned to an intervention group. In the primary (complete-case) analysis at 144 weeks, 317 (86%) of 367 in the protease inhibitor plus NRTI group had viral loads of less than 400 copies per mL compared with 312 (81%) of 383 in the protease inhibitor plus raltegravir group (p=0·07; lower 95% confidence limit for difference 10·2% vs specified non-inferiority margin 10%). In the protease inhibitor monotherapy group, 292 (78%) of 375 had viral loads of less than 400 copies per mL; p=0·003 versus the protease inhibitor plus NRTI group at 144 weeks. There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification.Protease inhibitor plus raltegravir offered no advantage over protease inhibitor plus NRTI in virological efficacy or safety. In the primary analysis, protease inhibitor plus raltegravir did not meet non-inferiority criteria. A regimen of protease inhibitor with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings.Item Nucleoside Reverse-Transcriptase Inhibitor Cross-Resistance And Outcomes from Second-Line Antiretroviral Therapy in the Public Health Approach: An Observational Analysis within the Randomised, Open-Label, EARNEST trial(The lancet HIV, 2017) Paton, Nicholas I.; Kityo, Cissy; Thompson, Jennifer; Nankya, Immaculate; Bagenda, Leonard; Kambugu, Andrew; Kiconco, Mary; Mugyenyi, PeterCross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activity, predicted by resistance testing, of the NRTIs used in second-line therapy and treatment outcomes for patients infected with HIV. We did an observational analysis of additional data from a published open-label, randomised trial of second-line ART (EARNEST) in sub-Saharan Africa. 1277 adults or adolescents infected with HIV in whom first-line ART had failed (assessed by WHO criteria with virological confirmation) were randomly assigned to a boosted protease inhibitor (standardised to ritonavir-boosted lopinavir) with two to three NRTIs (clinician-selected, without resistance testing); or with raltegravir; or alone as protease inhibitor monotherapy (discontinued after week 96). We tested genotypic resistance on stored baseline samples in patients in the protease inhibitor and NRTI group and calculated the predicted activity of prescribed second-line NRTIs. We measured viral load in stored samples for all patients obtained every 12–16 weeks. This trial is registered with Controlled-Trials.com (number ISRCTN 37737787) and ClinicalTrials.gov (number NCT00988039). Baseline genotypes were available in 391 (92%) of 426 patients in the protease inhibitor and NRTI group. 176 (89%) of 198 patients prescribed a protease inhibitor with no predicted-active NRTIs had viral suppression (viral load <400 copies per mL) at week 144, compared with 312 (81%) of 383 patients in the protease inhibitor and raltegravir group at week 144 (p=0·02) and 233 (61%) of 280 patients in the protease inhibitor monotherapy group at week 96 (p<0·0001). Compared with results with no active NRTIs, 95 (85%) of 112 patients with one predicted-active NRTI had viral suppression (p=0·3) and 20 (77%) of 26 patients with two or three active NRTIs had viral suppression (p=0·08). Over all follow-up, greater predicted NRTI activity was associated with worse viral load suppression (global p=0·0004). Genotypic resistance testing might not accurately predict NRTI activity in protease inhibitor-based second-line ART. Our results do not support the introduction of routine resistance testing in ART programmes in low-income settings for the purpose of selecting second-line NRTIs.Item Poor immunological recovery among severely immunosuppressed antiretroviral therapy-naïve Ugandans(HIV/AIDS – Research and Palliative Care, 2013) Nanzigu, Sarah; Kiguba, Ronald; Kabanda, Joseph; Mukonzo, Jackson K .; Waako, Paul; Kityo, Cissy; Makumbi, FredWith access to antiretroviral therapy (ART) expanding in resource-limited settings, assessing factors related to clinical, immunological, and virological outcomes of ART is of great importance. Even though ART is loosely referred to as a lifelong treatment, clinical, immunological and virological outcome measures differ among patients on highly active ART (HAART), with differences reported within and across cohorts.1–6 Mortality is among the ART-outcome variables that have been studied extensively, and rates of up to 30% have been reported during the first year of treatment in some sub-Saharan settingsItem Prevalence of latent rheumatic heart disease among HIV-infected children in Kampala, Uganda(Journal of acquired immune deficiency syndromes, 2016) Gleason, Brigette; Mirembe, Grace; Namuyonga, Judith; Okello, Emmy; Lwabi, Peter; Lubega, Irene; Lubega, Sulaiman; Musiime, Victor; Kityo, Cissy; Salata, Robert A.; Longenecker, Chris T.Rheumatic heart disease (RHD) remains highly prevalent in resource-constrained settings around the world, including countries with high rates of HIV/AIDS. Although both are immune-mediated diseases, it is unknown whether HIV modifies the risk or progression of RHD. We performed screening echocardiography to determine the prevalence of latent rheumatic heart disease in 488 HIV-infected children aged 5-18 in Kampala, Uganda. The overall prevalence of borderline/definite RHD was 0.82% (95% CI 0.26% to 2.23%) which is lower than the published prevalence rates of 1.5-4% among Ugandan children. There may be protective factors that decrease the risk of RHD in HIV-infected children.