Browsing by Author "Kityo, Cissy"

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Assessment of Second-Line Antiretroviral Regimens for HIV Therapy in Africa
(Massachusetts Medical Society., 2014-07-17) Paton, I. Nicholas; Kityo, Cissy; Hoppe, Anne; Reid, Andrew; Kambugu, Andrew; Lugemwa, Abbas; Oosterhout, van J. Joep; Kiconco, Mary; Siika, Abraham; Mwebaze, Raymond; Abwola, Mary; Abongomera, George; Mweemba, Aggrey; Alima, Hillary; Atwongyeire, Dickens; Nyirenda, Rose; Boles, Justine; Thompson, Jennifer; Tumukunde, Dinah; Chidziva, Ennie; Mambule, Ivan; Arribas, R. Jose; Easterbrook, J. Philippa; Hakim, James; Walker, Sarah A.; Mugyenyi, Peter
Background The efficacy and toxic effects of nucleoside reverse-transcriptase inhibitors (NRTIs) are uncertain when these agents are used with a protease inhibitor in second-line therapy for human immunodeficiency virus (HIV) infection in resource-limited settings. Removing the NRTIs or replacing them with raltegravir may provide a benefit. Methods In this open-label trial in sub-Saharan Africa, we randomly assigned 1277 adults and adolescents with HIV infection and first-line treatment failure to receive a ritonavir-boosted protease inhibitor (lopinavir–ritonavir) plus clinician-selected NRTIs (NRTI group, 426 patients), a protease inhibitor plus raltegravir in a superiority comparison (raltegravir group, 433 patients), or protease-inhibitor monotherapy after 12 weeks of induction therapy with raltegravir in a noninferiority comparison (monotherapy group, 418 patients). The primary composite end point, good HIV disease control, was defined as survival with no new World Health Organization stage 4 events, a CD4+ count of more than 250 cells per cubic millimeter, and a viral load of less than 10,000 copies per milliliter or 10,000 copies or more with no protease resistance mutations at week 96 and was analyzed with the use of imputation of data (≤4%). Results Good HIV disease control was achieved in 60% of the patients (mean, 255 patients) in the NRTI group, 64% of the patients (mean, 277) in the raltegravir group (P=0.21 for the comparison with the NRTI group; superiority of raltegravir not shown), and 55% of the patients (mean, 232) in the monotherapy group (noninferiority of monotherapy not shown, based on a 10-percentage-point margin). There was no significant differ ence in rates of grade 3 or 4 adverse events among the three groups (P=0.82). The viral load was less than 400 copies per milliliter in 86% of patients in the NRTI group, 86% in the raltegravir group (P=0.97), and 61% in the monotherapy group (P<0.001). Conclusions When given with a protease inhibitor in second-line therapy, NRTIs retained substantial virologic activity without evidence of increased toxicity, and there was no advantage to replacing them with raltegravir. Virologic control was inferior with protease-inhibitor monotherapy. (Funded by European and Developing Countries Clinical Trials Partnership and others; EARNEST Current Controlled Trials number, ISRCTN 37737787, and ClinicalTrials.gov number, NCT00988039.)
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
(Elsevier, 2018-01) Hakim, G. James; Thompson, Jennifer; Kityo, Cissy; Hoppe, Anne; Kambugu, Andrew; van Oosterhout, J Joep; Lugemwa, Abbas; Siika, Abraham; Mwebaze, Raymond; Mweemba, Aggrey; Abongomera, George; Thomason, J Margaret; Easterbrook, Philippa; Mugyenyi, Peter; Walker, A Sarah
Background Millions 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. Methods 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. Findings 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. Interpretation 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.
Therapeutic Responses to AZT 1 3TC 1 EFV in Advanced Antiretroviral Naive HIV Type 1-Infected Ugandan Patients
(Mary Ann Liebert, Inc., 2004-07-05) Kebba, Anthony; Atwine, Diana; Mwebaze, Raymond; Kityo, Cissy; Nakityo, Rose; Mulenyi, Peter
Convenient, non-food-dependent dosing, low tablet volume, and relatively low cost have made nonnucleoside reverse transcriptase inhibitors a first choice for both clinicians and patients in Uganda. Concerns exist as to their efficacy in patients with viral loads (VL) above 100,000 copies/ml, a feature common to about 75% of HIV-1-infected patients presenting at the Joint Clinical Research Center (JCRC) in Uganda. Furthermore, there are few data on the response to such therapy of non-B subtypes, A and D, predominant in Uganda. Presented here is a retrospective analysis of therapeutic responses in 11 antiretroviral (ARV) naïve HIV-1-infected Ugandan patients who had been initiated on zidovudine (AZT), lamivudine (3TC), and efavirenz (EFV). Laboratory assessments subsequent to initiation of ARV therapy, done at 11.6 ± 3.9 weeks and 30.6 ± 5.9 weeks, showed 88.9 and 71.4% patients achieved undetectable viral load, respectively. Virological suppression to below detection occurred in 85.7% of patients at 11.6 weeks despite baseline VL ≥ 100,000 copies/ml. At 31 weeks there was a median increment of +183 cells/mm3 in CD4+ T lymphocytes. These findings reflect significant efficacy in the use of AZT + 3TC + EFV in advanced ARV naive non-B subtype HIV-1-infected patients. The therapeutic responses were comparable to those previously described in the western world.