NRU :: Browsing by Author "Ssali, Francis"

Browsing by Author "Ssali, Francis"

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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, Peter
An 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.
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.
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.
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.
The effect of AIDS defining conditions on immunological recovery among patients initiating antiretroviral therapy at Joint Clinical Research Centre, Uganda
(AIDS Research and Therapy, 2009) Kigozi, Brian K.; Sumba, Samwel; Mudyope, Peter; Namuddu, Betty; Kalyango, Joan; Karamagi, Charles; Odere, Mathew; Katabira, Elly; Mugyenyi, Peter; Ssali, Francis
Many HIV-infected patients only access health care once they have developed advanced symptomatic disease resulting from AIDS Defining Conditions (ADCs). We carried out a study to establish the effect of ADCs on immunological recovery among patients initiated on antiretroviral therapy (ART). Methods: A retrospective cohort of 427 HIV-1 patients who were initiated on ART between January 2002 and December 2006 was studied. Data on ADCs was retrieved from Joint Clinical Research Centre (JCRC) data base and backed up by chart reviews. We employed Kaplan-Meier survival curves to estimate median time to 50 CD4 cells/μl from the baseline value to indicate a good immunological recovery process. Cox proportional hazard models were used at multivariate analysis. Results: The median time to gaining 50 CD4 cells/μl from the baseline value after ART initiation was longer in the ADC (9.3 months) compared to the non-ADC group (6.9 months) (log rank test, p = 0.027). At multivariate analysis after adjusting for age, sex, baseline CD4 count, baseline HIV viral load, total lymphocyte count and adherence level, factors that shortened the median time to immunological recovery after ART initiation were belonging to the non-ADC group (HR = 1.31; 95% CI: 1.03–1.28, p = 0.028), adherence to ART of ≥ 95% (HR = 2.22; 95% CI: 1.57–3.15, p = 0.001) and a total lymphocyte count ≥ 1200 cells/mm3 (HR = 1.84; 95% CI: 1.22–2.78, p = 0.003). A low baseline CD4 count of ≤ 200 cells/μl (HR = 0.52; 95% CI: 0.37–0.77, p = 0.001) was associated with a longer time to immunological recovery. There was no interaction between low CD4 counts and ADC group. Conclusion: Patients with ADCs take longer to regain their CD4 counts due to the defect in the immune system. This may prolong their risk of morbidity and mortality.
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, William
Convalescent 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.
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, Bruce
Evidence 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.
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, Kazunori
The 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.
Prevalence, Incidence and Predictors of Severe Anaemia with Zidovudine-Containing Regimens in African Adults With HIV Infection within the DART trial
(Antiviral therapy, 2006) Ssali, Francis; Munderi, Paula; Walker, Sarah; Mugyenyi, Peter
To describe the prevalence, incidence and predictors of severe anaemia in previously untreated symptomatic HIV-infected adults with CD4+ T-cells <200 cells/mm3 initiating zidovudine-containing regimens in Africa. DART is a randomized trial comparing two strategies for HIV/AIDS management in Uganda and Zimbabwe.We analysed the occurrence of anaemia at weeks 4 and 12, and then every 12 weeks. We also evaluated sex, age, WHO stage, body mass index (BMI), baseline laboratory measurements and first regimen aspredictors of developing grade 4 anaemia (<6.5 mg/dl) by week 48 using logistic regression. To May 2005, 3,314 participants (65% women, 23% at WHO stage 4, median age=37 years, baseline CD4+ T-cell=86 cells/mm3 and median baseline haemoglobin=11.4 g/dl) had a median 72 weeks follow-up. Prevalence of grade 4 anaemia was 0.7%, 2.0%, 0.5% and <0.5% at weeks 4, 12, 24 and ≥36, respectively. Overall, 219 (6.6%) participants developed grade 4 anaemia by week 48; women and those with lower haemoglobin, CD4+ T-cell count and BMI at baseline were at significantly higher risk (P<0.05), but not those with lower neutrophils or receiving cotrimoxazole at baseline. We observed a higher incidence of grade 4 anaemia than in studies from industrialized countries, which is likely to be due in part to population characteristics and in part to a higher rate of concurrent HIV-related clinical events. Clinical vigilance and haemoglobin measurements 4, 8 and 12 weeks after starting zidovudine could help to manage serious anaemia.
A Randomized, Controlled, Trial of Short Cycle Intermittent Compared to Continuous Antiretroviral Therapy for the Treatment of HIV Infection in Uganda
(PLoS One, 2010) Reynolds, Steven J.; Kityo, Cissy; Kabuye, Geoffrey; Atwiine, Diana; Mbamanya, Frank; Ssali, Francis; Davey, Richard T.; Mugyenyi, Peter; Fauci, Anthony S.; Dybul, Mark R.
Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs. A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count $125 cells/mm3 and HIV RNA plasma levels ,50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection. Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39). Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapy
Uptake of family planning methods and unplanned pregnancies among HIV-infected individuals: a cross-sectional survey among clients at HIV clinics in Uganda
(Journal of the International AIDS Society, 2011) Wanyenze, Rhoda K.; Tumwesigye, Nazarius M.; Kindyomunda, Rosemary; Beyeza-Kashesya, Jolly; Atuyambe, Lynn; Kansiime, Apolo; Neema, Stella; Ssali, Francis; Akol, Zainab; Mirembe, Florence
Prevention of unplanned pregnancies among HIV-infected individuals is critical to the prevention of mother to child HIV transmission (PMTCT), but its potential has not been fully utilized by PMTCT programmes. The uptake of family planning methods among women in Uganda is low, with current use of family planning methods estimated at 24%, but available data has not been disaggregated by HIV status. The aim of this study was to assess the utilization of family planning and unintended pregnancies among HIV-infected people in Uganda. Methods: We conducted exit interviews with 1100 HIV-infected individuals, including 441 men and 659 women, from 12 HIV clinics in three districts in Uganda to assess the uptake of family planning services, and unplanned pregnancies, among HIV-infected people. We conducted multivariate analysis for predictors of current use of family planning among women who were married or in consensual union and were not pregnant at the time of the interview.
Validation of World Health Organisation HIV/AIDS Clinical Staging in Predicting Initiation of Antiretroviral Therapy and Clinical Predictors of Low CD4 Cell Count in Uganda
(PLoS ONE, 2011) Baveewo, Steven; Ssali, Francis; Karamagi, Charles; Kalyango, Joan N.; Hahn, Judith A.; Ekoru, Kenneth; Mugyenyi, Peter; Katabira, Elly
The WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4,200cells/mm3, it has not been evaluated at for CD4 cut-offs of ,250cells/mm3 or ,350 cells/mm3. Objective: To validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda. Results: Data was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3%) were classified as in stages 1 and 2 and 262 (68%) were females. Participants had a mean age of 36.8 years (SD 8.5). We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm3 and 350cells/mm3 was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2. Conclusion: The WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda.
Women, economic hardship and the path of survival: HIV/AIDS risk behavior among women receiving HIV/AIDS treatment in Uganda
(Psychological and Socio-medical Aspects of AIDS/HIV, 2014) MacLachlan, Ellen; Neema, Stella; Luyirika, Emmanuel; Ssali, Francis; Juncker, Margrethe; Rwabukwali, Charles; Harvey, Marie; Duncan, Terry
The results are presented from a 2005 survey of 377 women in four HIV/AIDS treatment programs in Uganda. The aim of the study was to explore women’s economic hardships and the association with four sexual risk behaviors: whether a woman was sexually active in the last 12 months, whether a condom was used during the last sex act, whether she reported having had a sexual partner in the last six months who she suspected had multiple partners and report of forced, coercive or survival sex in the last six months. Few women were sexually active (34%), likely due to the high proportion of widows (49%). Married women were likely to report forced, coercive or survival sex (35%). Eighty-four percent of women reported condom used at last sex act. Forced, coercive or survival sex was associated with number of meals missed per week (AOR 1.125, 95% CI 1.11, 1.587, pB0.05). Sex with a partner in the last six months who a woman suspected had multiple partners was also associated with number of missed meals per week (AOR 2.080, 95% CI 1.084, 3.992). Currently women in Ugandan antiretroviral therapy programs are not likely to be sexually active, except for married women. Many women need to find food and other support, which may put them at risk of forced, coercive or survival sex due to dependency on men.

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