Browsing by Author "Ssewanyana, Isaac"

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    Factors Associated with Virological Nonsuppression among HIV-Positive Patients on Antiretroviral Therapy in Uganda, August 2014–July 2015
    (BMC infectious diseases, 2017) Bulage, Lilian; Ssewanyana, Isaac; Nankabirwa, Victoria; Nsubuga, Fred; Kihembo, Christine; Pande, Gerald; Ario, Alex R.; Matovu, Joseph K. B.; Wanyenze, Rhoda K.; Kiyaga, Charles
    Despite the growing number of people on antiretroviral therapy (ART), there is limited information about virological non suppression and its determinants among HIV-positive (HIV+) individuals enrolled in HIV care in many resource-limited settings. We estimated the proportion of virologically non-suppressed patients, and identified the factors associated with virological non suppression. Methods: We conducted a descriptive cross-sectional study using routinely collected program data from viral load (VL) samples collected across the country for testing at the Central Public Health Laboratories (CPHL) in Uganda. Data were generated between August 2014 and July 2015. We extracted data on socio-demographic, clinical and VL testing results. We defined virological non-suppression as having ≥1000 copies of viral RNA/ml of blood for plasma or ≥5000 copies of viral RNA/ml of blood for dry blood spots. We used logistic regression to identify factors associated with virological non-suppression. Results: The study was composed of 100,678 patients; of these, 94,766(94%) were for routine monitoring, 3492(4%) were suspected treatment failures while 1436(1%) were repeat testers after suspected failure. The overall proportion of non suppression was 11%. Patients on routine monitoring registered the lowest (10%) proportion of nonsuppressed patients. Virological non-suppression was higher among suspected treatment failures (29%) and repeat testers after suspected failure (50%). Repeat testers after suspected failure were six times more likely to have virological non-suppression (ORadj = 6.3, 95%CI = 5.5–7.2) when compared with suspected treatment failures (ORadj = 3.3, 95%CI = 3.0–3.6). The odds of virological non-suppression decreased with increasing age, with children aged 0–4 years (ORadj = 5.3, 95%CI = 4.6–6.1) and young adolescents (ORadj = 4.1, 95%CI = 3.7–4.6) registering the highest odds. Poor adherence (ORadj = 3.4, 95%CI = 2.9–3.9) and having active TB (ORadj = 1.9, 95%CI = 1.6–2.4) increased the odds of virological non-suppression. However, being on second/third line regimens (ORadj = 0.86, 95%CI = 0.78–0.95) protected patients against virological non-suppression. Conclusion: Young age, poor adherence and having active TB increased the odds of virological non-suppression while second/third line ART regimens were protective against non-suppression. We recommend close follow up and intensified targeted adherence support for repeat testers after suspected failure, children and adolescents.
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    High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort
    (BMC infectious diseases, 2011) Nakanjako, Damalie; Ssewanyana, Isaac; Mayanja-Kizza, Harriet; Kiragga, Agnes; Manabe, Yukari C.; Nabatanzi, Rose; Kamya, Moses R.; Cao, Huyen
    Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated.T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30].Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022].T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.
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    HIV drug resistance among adults initiating antiretroviral therapy in Uganda
    (Journal of Antimicrobial Chemotherapy, 2021) Watera, Christine; Ssemwanga, Deogratius; Namayanja, Grace; Asio, Juliet; Lutalo, Tom; Namale, Alice; Sanyu, Grace; Ssewanyana, Isaac; Gonzalez-Salazar, Jesus Fidel; Nazziwa, Jamirah; Nanyonjo, Maria; Raizes, Elliot; Kabuga, Usher; Mwangi, Christina; Kirungi, Wilford; Musinguzi, Joshua; Mugagga, Kaggwa; Katongole Mbidde, Edward; Kaleebu, Pontiano
    WHO revised their HIV drug resistance (HIVDR) monitoring strategy in 2014, enabling countries to generate nationally representative HIVDR prevalence estimates from surveys conducted using this methodology. In 2016, we adopted this strategy in Uganda and conducted an HIVDR survey among adults initiating or reinitiating ART. Methods: A cross-sectional survey of adults aged 18 years initiating or reinitiating ART was conducted at 23 sites using a two-stage cluster design sampling method. Participants provided written informed consent prior to enrolment. Whole blood collected in EDTA vacutainer tubes was used for preparation of dried blood spot (DBS) specimens or plasma. Samples were shipped from the sites to the Central Public Health Laboratory (CPHL) for temporary storage before transfer to the Uganda Virus Research Institute (UVRI) for genotyping. Prevalence of HIVDR among adults initiating or reinitiating ART was determined.
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    Impact of CD8R T-cell activation on CD4R T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy
    (AIDS (London, England), 2011) Hunt, Peter W.; Caoa, Huyen L.; Muzoora, Conrad; Ssewanyana, Isaac; Bennett, John; Emenyonu, Nneka; Kembabazi, Annet; Neilands, Torsten B.; Bangsberg, David R.; Deeks, Steven G.; Martin, Jeffrey N.
    To assess whether T-cell activation independently predicts the extent of CD4þ T-cell recovery and mortality in HIV-infected Ugandans initiating antiretroviral therapy (ART). Prospective cohort study. HIV-infected adults starting ART and achieving a plasma HIV RNA level (VL) less than 400 copies/ml by month 6 were sampled from the Uganda AIDS Rural Treatment Outcomes (UARTO) cohort in Mbarara, Uganda. CD4 count, VL, and the percentage-activated (CD38þHLA-DRþ) T cells were measured every 3 months. Of 451 HIV-infected Ugandans starting ART, most were women (70%) with median pre-ART values: age, 34 years; CD4 count, 135 cells/ml; and VL, 5.1 log10 copies/ml. Of these, 93% achieved a VL less than 400 copies/ml by month 6 and were followed for a median of 24 months, with 8% lost to follow-up at 3 years. Higher pre- ART CD8þ T-cell activation was associated with diminished CD4 recovery after year 1, after adjustment for pre-ART CD4 count, VL, and sex (P¼0.017). Thirty-four participants died, 15 after month 6. Each 10% point increase in activated CD8þ T cells at month 6 of suppressive ART was associated with a 1.6-fold increased hazard of subsequent death after adjusting for pretherapy CD4 count (P¼0.048). Higher pre-ART CD8þ T-cell activation independently predicts slower CD4þ T-cell recovery and higher persistent CD8þ T-cell activation during ART mediated viral suppression independently predicts increased mortality among HIV infected Ugandans. Novel therapeutic strategies aimed at preventing or reversing immune activation during ART are needed in this setting.
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    Short-Term Risk of HIV-Disease Progression and Death in Ugandan Children Not Eligible for Antiretroviral Therapy
    (Journal of acquired immune deficiency syndromes, 2010) Charlebois, Edwin D; Ruel, Theodore D; Gasasira, Anne F.; Achan, Jane; Kateera, Frederick; Akello, Caroline; Cao, Huyen; Dorsey, Grant; Rosenthal, Philip J; Ssewanyana, Isaac; Kamya, Moses R; Havlir, Diane V
    Background—Increasing numbers of HIV-infected children not yet eligible for antiretroviral therapy (ART) are entering health care in Africa. We sought to characterize the risk of short-term disease progression in this population. Methods—In a cohort of HIV-infected ART-naive and -ineligible Ugandan children >1 year old, the rates of clinical/immunologic progression within 2 years were assessed using Kaplan–Meier survival analysis and multivariate Cox proportional-hazards modeling. Results—Among 192 children (mean age: 6.4 years, CD4%:25), 19% progressed within 2 years by WHO-stage 3/4 event(n=22), death (n=3), or WHO-defined CD4 threshold for ARTinitiation( n=12). Significant univariate predictors were CD4%(HR=2.0 per 10% decrease, p=0.005), HIV-RNA level(HR=2.4 per log10 increase, p=0.002), male gender (HR:2.0, p=0.04), age < 3 years (HR=3.7, p=0.001), CD4-activation [%CD4+CD38+HLADR+] (HR=1.6 per 10% increase, p=0.05) and CD8-activation [%CD8+CD38+HLADR+](HR=1.3 per 10% increase, p=0.05] (HR=1.3, p=0.5). In multivariate analysis, CD4%(HR=2.0, p=0.034), HIV-RNA level(HR=1.8, p=0.013) and age < 3 years (HR:3.0, p=0.008) were independently predictive. Children with HIV-RNA >105 copies/ml and CD4% <25 had progression rates of 29% (1 year) and 34% (2 years). Conclusions—Even with frequent CD4 monitoring, HIV-infected Ugandan children experienced significant clinical events while ineligible for ART. Alternate strategies for monitoring or ART-initiation may be needed to improve outcomes