Objectives: We investigated phenotypic and genotypic resistance after 2 years of first-line thera... more Objectives: We investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring.
Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 1995
This pilot study was conducted at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda, w... more This pilot study was conducted at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda, where tuberculosis (TB) is an epidemic health problem aggravated by the HIV-1 pandemic. To evaluate the feasibility of a larger phase III trial utilizing rifabutin as a substitute for rifampicin in short-course therapy for pulmonary TB. Single-blind randomized trial in 50 patients with new onset smear- and culture-positive pulmonary tuberculosis and HIV-1 infection. Comparison of daily, intermittently supervised 6-month treatment regimens of rifabutin versus rifampicin, together with isoniazid, ethambutol and pyrazinamide. Rifabutin- and rifampicin-containing regimens had comparable efficiency. However, rifabutin-treated patients had significantly more rapid clearance of acid-fast bacilli from sputum at 2 months (P < 0.05, Fisher exact test) and over the entire study period (P < 0.05, logrank test) than rifampicin-treated patients. The presence of cavitary disease was associated wit...
objectives To describe associations between different summaries of adherence in the first year on... more objectives To describe associations between different summaries of adherence in the first year on antiretroviral therapy (ART) and the subsequent risk of mortality, to identify patients at high risk because of early adherence behaviour.
Human immunodeficiency virus (HIV) or AIDS is currently the leading cause of death in Uganda, wit... more Human immunodeficiency virus (HIV) or AIDS is currently the leading cause of death in Uganda, with at least three HIV clades (subtypes) accounting for most new infections. Whether an effective vaccine formulated on viruses from a single clade will be able to protect against infection from other local clades remains unresolved. We examined the T-cell immune responses from a cohort of HIV-seropositive individuals in Uganda with predominantly clade A and D infections. Surprisingly, we observed similar frequencies of cross-clade T-cell responses to the gag, env, and nef regions. Our data suggest that the level of viral sequence variability between distinct HIV strains does not predict the degree of cross-clade responses. High sequence homologies were also observed between consensus peptides and sequences from viral isolates, supporting the use of consensus amino acid sequences to identify immunogenic regions in studies of large populations.
With NNRTI, the recommended dose of lopinavir/r (LPV/ r) is 4 capsules (533/133 mg) BD. With LPV/... more With NNRTI, the recommended dose of lopinavir/r (LPV/ r) is 4 capsules (533/133 mg) BD. With LPV/r tablets, the closest doses are 2 tablets (400/100 mg) BD or 3 tablets [tabs] (600/150 mg) BD. Improved bioavailability of the tablet suggests that 2 tabs BD should be sufficient, but PK data are few and generally from Caucasians.
Objectives: Depression is common among persons living with HIV/AIDS in sub-Saharan Africa, yet fe... more Objectives: Depression is common among persons living with HIV/AIDS in sub-Saharan Africa, yet few studies in the region have assessed the relationship of depression to economic wellbeing and risk-reduction behavior. Among HIV clients in Uganda, we examined whether depression is directly related to self-efficacy, work status, and condom use, as well as indirectly through its interaction with physical health functioning. Methods: Baseline data from a prospective longitudinal cohort of 602 clients entering HIV care were examined. In separate multivariate analyses, we examined whether depression [both depressive severity and clinical depression, as measured by the nine-item Patient Health Questionnaire (PHQ-9)], physical health functioning, and their interaction were predictors of current work status, consistent condom use, and general self-efficacy, controlling for measures of social support, stigma, and demographics. Results: Mean PHQ-9 score was 5.2 (S.D.=3.9; range=0-24) and 13% had scores ≥10 (indicator of clinical depression). Not being depressed, better physical health, and their interaction were predictors of working, while lower depressive severity, lower physical health, and their interaction were associated with always using condoms. Better physical health was predictive of greater self-efficacy, but not depression; general self-efficacy was predictive of both work status and condom use. Conclusions: Effective diagnosis and treatment of depression may be critical to maximizing the benefits of HIV treatment with regard to both HIV prevention and restoring the social and economic health of persons living with HIV.
Fixed-dose combination scored dispersible stavudine, lamivudine, and nevirapine minitablets (Trio... more Fixed-dose combination scored dispersible stavudine, lamivudine, and nevirapine minitablets (Triomune Baby and Junior; Cipla Ltd) are simpler and cheaper than liquid formulations and have correct dose ratios for human immunodeficiency virus-infected children. However, they cannot be used for dose escalation (DE) of nevirapine. Children were randomized to initiate antiretroviral therapy with full-dose (FD) nevirapine (Triomune Baby or Junior in the morning and evening) versus DE (half-dose nevirapine for 14 days [Triomune in the morning and stavudine-lamivudine {Lamivir-S} in the evening], then FD), in accordance with World Health Organization weight-band dosing tables. The primary end point was nevirapine-related clinical or laboratory grade 3 or 4 adverse events (AEs). In total, 211 children (median [interquartile range {IQR}] age, 5 [ 2-9 ] years; median [IQR] CD4 cell percentage, 13% [8%-18%]) were enrolled and followed up for a median (IQR) of 92 (68-116) weeks. There were 31 grade 3 or 4 AEs that were definitely/probably or uncertainly related to nevirapine in the FD group (18.0 per 100 child-years), compared with 29 in the DE group (16.5 per 100 child-years) (incidence rate ratio, 1.09; 95% confidence interval, 0.63&amp;amp;amp;#x2013;1.87; P = .74). All were asymptomatic; 11 versus 3 were single grade 3 or 4 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, all of which resolved without a change in nevirapine dose or interruption. Thirteen (12%) FD versus 2 (2%) DE children had grade 1 (2 in FD) or grade 2 (11 in FD and 2 in DE) rashes. Three (2 in FD and 1 in DE) substituted efavirenz, 3 (FD) continued FD nevirapine, and 9 (8 in FD and 1 in DE) temporarily interrupted nevirapine, followed by successful DE. Predictors of nevirapine rash were older age (P = .003) and higher CD4 cell count for age (P = .03). Twenty-two children died (12 in FD and 10 in DE), 1 FD and 5 DE children at &amp;amp;lt;4 weeks; none were considered to be drug related by independent review. Rash was more frequent with FD nevirapine, but 88% had no clinical toxicity; elevated AST or ALT levels were transient and resolved spontaneously, suggesting that routine laboratory monitoring has limited value. Dual pediatric stavudine-lamivudine minitablets are preferred for safe and simple DE; if unavailable, initiating FD Triomune requires timely review for rash, which could be managed by temporary reduction to half-dose Triomune or efavirenz substitution. Current Controlled Trials identifier: ISRCTN31084535 .
Structured treatment interruption (STI) of antiretroviral therapy (ART) could potentially reduce ... more Structured treatment interruption (STI) of antiretroviral therapy (ART) could potentially reduce cost and toxicity, but clinical efficacy requires evaluation. An assessment of fixed-duration STI was nested in DART, a multicentre trial comparing strategies for monitoring ART in Uganda and Zimbabwe (ISCRTN 13968779). Of 3316 ART-naive symptomatic adults with CD4 cell count &lt; 200 cells/microl at ART initiation, 813 with &gt; or = 300 cells/microl after 48 or 72 weeks underwent a second randomization to either STI, cycles of 12 weeks on/off (408), or continuous ART (CT; 405). Median age at STI/CT randomization was 37 years (range, 19-67) and CD4 cell count 358 cells/microl (range, 300-1054). A second review terminated the STI/CT randomisation on 15 March 2006, and participants changed to CT. Median follow-up was 51 weeks (range, 0-85): 99% and 50% of time was spent on ART in CT and STI, respectively. First new World Health Organization (WHO) stage 4 events or death occurred more frequently in STI (24; 6.4/100 person-years) than CT (9; 2.4/100 person-years) (hazard ratio, 2.73; 95% confidence interval, 1.27-5.88; P = 0.007); oesophageal candidiasis being the most frequent event (STI, 13; CT, 3). Nine (1%) participants died (STI, 5; CT, 4). There was no difference in time to first serious adverse event (P = 0.78), although ART change owing to toxicity occurred more with CT (10; 2.6/100 person-years) than with STI (2; 0.5/100 person-years) (P = 0.02). Although absolute rates of WHO stage 4 events/death were low, 12 week STIS initiated at a CD4 cell count &gt;/= 300 cells/microl resulted in a greater than twofold increased relative rate of disease progression compared with continuous therapy in adult Africans initiating ART with advanced disease, and cannot be recommended.
Objectives: We investigated phenotypic and genotypic resistance after 2 years of first-line thera... more Objectives: We investigated phenotypic and genotypic resistance after 2 years of first-line therapy with two HIV treatment regimens in the absence of virological monitoring.
Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 1995
This pilot study was conducted at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda, w... more This pilot study was conducted at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda, where tuberculosis (TB) is an epidemic health problem aggravated by the HIV-1 pandemic. To evaluate the feasibility of a larger phase III trial utilizing rifabutin as a substitute for rifampicin in short-course therapy for pulmonary TB. Single-blind randomized trial in 50 patients with new onset smear- and culture-positive pulmonary tuberculosis and HIV-1 infection. Comparison of daily, intermittently supervised 6-month treatment regimens of rifabutin versus rifampicin, together with isoniazid, ethambutol and pyrazinamide. Rifabutin- and rifampicin-containing regimens had comparable efficiency. However, rifabutin-treated patients had significantly more rapid clearance of acid-fast bacilli from sputum at 2 months (P < 0.05, Fisher exact test) and over the entire study period (P < 0.05, logrank test) than rifampicin-treated patients. The presence of cavitary disease was associated wit...
objectives To describe associations between different summaries of adherence in the first year on... more objectives To describe associations between different summaries of adherence in the first year on antiretroviral therapy (ART) and the subsequent risk of mortality, to identify patients at high risk because of early adherence behaviour.
Human immunodeficiency virus (HIV) or AIDS is currently the leading cause of death in Uganda, wit... more Human immunodeficiency virus (HIV) or AIDS is currently the leading cause of death in Uganda, with at least three HIV clades (subtypes) accounting for most new infections. Whether an effective vaccine formulated on viruses from a single clade will be able to protect against infection from other local clades remains unresolved. We examined the T-cell immune responses from a cohort of HIV-seropositive individuals in Uganda with predominantly clade A and D infections. Surprisingly, we observed similar frequencies of cross-clade T-cell responses to the gag, env, and nef regions. Our data suggest that the level of viral sequence variability between distinct HIV strains does not predict the degree of cross-clade responses. High sequence homologies were also observed between consensus peptides and sequences from viral isolates, supporting the use of consensus amino acid sequences to identify immunogenic regions in studies of large populations.
With NNRTI, the recommended dose of lopinavir/r (LPV/ r) is 4 capsules (533/133 mg) BD. With LPV/... more With NNRTI, the recommended dose of lopinavir/r (LPV/ r) is 4 capsules (533/133 mg) BD. With LPV/r tablets, the closest doses are 2 tablets (400/100 mg) BD or 3 tablets [tabs] (600/150 mg) BD. Improved bioavailability of the tablet suggests that 2 tabs BD should be sufficient, but PK data are few and generally from Caucasians.
Objectives: Depression is common among persons living with HIV/AIDS in sub-Saharan Africa, yet fe... more Objectives: Depression is common among persons living with HIV/AIDS in sub-Saharan Africa, yet few studies in the region have assessed the relationship of depression to economic wellbeing and risk-reduction behavior. Among HIV clients in Uganda, we examined whether depression is directly related to self-efficacy, work status, and condom use, as well as indirectly through its interaction with physical health functioning. Methods: Baseline data from a prospective longitudinal cohort of 602 clients entering HIV care were examined. In separate multivariate analyses, we examined whether depression [both depressive severity and clinical depression, as measured by the nine-item Patient Health Questionnaire (PHQ-9)], physical health functioning, and their interaction were predictors of current work status, consistent condom use, and general self-efficacy, controlling for measures of social support, stigma, and demographics. Results: Mean PHQ-9 score was 5.2 (S.D.=3.9; range=0-24) and 13% had scores ≥10 (indicator of clinical depression). Not being depressed, better physical health, and their interaction were predictors of working, while lower depressive severity, lower physical health, and their interaction were associated with always using condoms. Better physical health was predictive of greater self-efficacy, but not depression; general self-efficacy was predictive of both work status and condom use. Conclusions: Effective diagnosis and treatment of depression may be critical to maximizing the benefits of HIV treatment with regard to both HIV prevention and restoring the social and economic health of persons living with HIV.
Fixed-dose combination scored dispersible stavudine, lamivudine, and nevirapine minitablets (Trio... more Fixed-dose combination scored dispersible stavudine, lamivudine, and nevirapine minitablets (Triomune Baby and Junior; Cipla Ltd) are simpler and cheaper than liquid formulations and have correct dose ratios for human immunodeficiency virus-infected children. However, they cannot be used for dose escalation (DE) of nevirapine. Children were randomized to initiate antiretroviral therapy with full-dose (FD) nevirapine (Triomune Baby or Junior in the morning and evening) versus DE (half-dose nevirapine for 14 days [Triomune in the morning and stavudine-lamivudine {Lamivir-S} in the evening], then FD), in accordance with World Health Organization weight-band dosing tables. The primary end point was nevirapine-related clinical or laboratory grade 3 or 4 adverse events (AEs). In total, 211 children (median [interquartile range {IQR}] age, 5 [ 2-9 ] years; median [IQR] CD4 cell percentage, 13% [8%-18%]) were enrolled and followed up for a median (IQR) of 92 (68-116) weeks. There were 31 grade 3 or 4 AEs that were definitely/probably or uncertainly related to nevirapine in the FD group (18.0 per 100 child-years), compared with 29 in the DE group (16.5 per 100 child-years) (incidence rate ratio, 1.09; 95% confidence interval, 0.63&amp;amp;amp;#x2013;1.87; P = .74). All were asymptomatic; 11 versus 3 were single grade 3 or 4 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, all of which resolved without a change in nevirapine dose or interruption. Thirteen (12%) FD versus 2 (2%) DE children had grade 1 (2 in FD) or grade 2 (11 in FD and 2 in DE) rashes. Three (2 in FD and 1 in DE) substituted efavirenz, 3 (FD) continued FD nevirapine, and 9 (8 in FD and 1 in DE) temporarily interrupted nevirapine, followed by successful DE. Predictors of nevirapine rash were older age (P = .003) and higher CD4 cell count for age (P = .03). Twenty-two children died (12 in FD and 10 in DE), 1 FD and 5 DE children at &amp;amp;lt;4 weeks; none were considered to be drug related by independent review. Rash was more frequent with FD nevirapine, but 88% had no clinical toxicity; elevated AST or ALT levels were transient and resolved spontaneously, suggesting that routine laboratory monitoring has limited value. Dual pediatric stavudine-lamivudine minitablets are preferred for safe and simple DE; if unavailable, initiating FD Triomune requires timely review for rash, which could be managed by temporary reduction to half-dose Triomune or efavirenz substitution. Current Controlled Trials identifier: ISRCTN31084535 .
Structured treatment interruption (STI) of antiretroviral therapy (ART) could potentially reduce ... more Structured treatment interruption (STI) of antiretroviral therapy (ART) could potentially reduce cost and toxicity, but clinical efficacy requires evaluation. An assessment of fixed-duration STI was nested in DART, a multicentre trial comparing strategies for monitoring ART in Uganda and Zimbabwe (ISCRTN 13968779). Of 3316 ART-naive symptomatic adults with CD4 cell count &lt; 200 cells/microl at ART initiation, 813 with &gt; or = 300 cells/microl after 48 or 72 weeks underwent a second randomization to either STI, cycles of 12 weeks on/off (408), or continuous ART (CT; 405). Median age at STI/CT randomization was 37 years (range, 19-67) and CD4 cell count 358 cells/microl (range, 300-1054). A second review terminated the STI/CT randomisation on 15 March 2006, and participants changed to CT. Median follow-up was 51 weeks (range, 0-85): 99% and 50% of time was spent on ART in CT and STI, respectively. First new World Health Organization (WHO) stage 4 events or death occurred more frequently in STI (24; 6.4/100 person-years) than CT (9; 2.4/100 person-years) (hazard ratio, 2.73; 95% confidence interval, 1.27-5.88; P = 0.007); oesophageal candidiasis being the most frequent event (STI, 13; CT, 3). Nine (1%) participants died (STI, 5; CT, 4). There was no difference in time to first serious adverse event (P = 0.78), although ART change owing to toxicity occurred more with CT (10; 2.6/100 person-years) than with STI (2; 0.5/100 person-years) (P = 0.02). Although absolute rates of WHO stage 4 events/death were low, 12 week STIS initiated at a CD4 cell count &gt;/= 300 cells/microl resulted in a greater than twofold increased relative rate of disease progression compared with continuous therapy in adult Africans initiating ART with advanced disease, and cannot be recommended.
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Papers by C. Kityo