Assessment of second-line antiretroviral regimens for HIV therapy in Africa.

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).

Improving adherence to antiretroviral treatment in Uganda with a low-resource facility-based intervention.

Objective: To assess the effects of facility-based interventions using existing resources to improve overall patient attendance and adherence to antiretroviral therapy (ART) at ART-providing facilities in Uganda.

Methods: This was an interventional study which tracked attendance and treatment adherence of two distinct cohorts: experienced patients who had been on treatment for at least 12 months prior to the intervention and patients newly initiated on ART before or during the intervention. The interventions included instituting appointment system, fast-tracking, and giving longer prescriptions to experienced stable patients.

The pharmacokinetics and acceptability of lopinavir/ritonavir minitab sprinkles, tablets, and syrups in african HIV-infected children.

Background: Guidelines recommend lopinavir/ritonavir (LPV/r) as first- and second-line therapy for young and older HIV-infected children, respectively. Available formulations have limitations making their widespread use complex.

Methods: An open-label comparative bioavailability (randomized crossover) study compared a novel twice-daily minitab sprinkle formulation (40 mg/10 mg, Cipla Pharmaceuticals) versus innovator syrup in HIV-infected Ugandan infants aged 3 to <12 months (cohort A) and children aged 1-4 years (cohort B) and versus Cipla tablets (100/25 mg) in children aged 4 to <13 years (cohort C).

Pharmacokinetics of zidovudine dosed twice daily according to World Health Organization weight bands in Ugandan HIV-infected children.

Data on zidovudine pharmacokinetics in children dosed using World Health Organization weight bands are limited. About 45 HIV-infected, Ugandan children, 3.4 (2.

Anthropometric measurements and lipid profiles to detect early lipodystrophy in antiretroviral therapy experienced HIV-infected children in the CHAPAS-3 trial.

Background: Few studies have investigated objective markers of lipodystrophy in African children. We compared body circumferences, skin-fold thickness (SFT) and lipids in antiretroviral therapy (ART)-naive and stavudine (d4T)-exposed children with HIV-uninfected controls.

Methods: In the CHAPAS-3 trial, HIV-infected children (ART-naive or on d4T for ≥2 years without clinical lipodystrophy) were randomized to d4T, abacavir or zidovudine with lamivudine (3TC) plus a non-nucleoside reverse transcriptase inhibitor.

Phenotypic and genotypic analyses to guide selection of reverse transcriptase inhibitors in second-line HIV therapy following extended virological failure in Uganda.

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.

Methods: NORA [Nevirapine OR Abacavir study, a sub-study of the Development of AntiRetroviral Therapy in Africa (DART) trial] randomized 600 symptomatic HIV-infected Ugandan adults (CD4 cell count <200 cells/mm(3)) to receive zidovudine/lamivudine plus abacavir (cABC arm) or nevirapine (cNVP arm). All virological tests were performed retrospectively, including resistance tests on week 96 plasma samples with HIV RNA levels ≥1000 copies/mL.

High level of viral suppression and low switch rate to second-line antiretroviral therapy among HIV-infected adult patients followed over five years: retrospective analysis of the DART trial.

Unlabelled: In contrast to resource-rich countries, most HIV-infected patients in resource-limited countries receive treatment without virological monitoring. There are few long-term data, in this setting, on rates of viral suppression or switch to second-line antiretroviral therapy. The DART trial compared clinically driven monitoring (CDM) versus routine laboratory (CD4/haematology/biochemistry) and clinical monitoring (LCM) in HIV-infected adults initiating therapy.

Elucidating emergence and transmission of multidrug-resistant tuberculosis in treatment experienced patients by whole genome sequencing.

Background: Understanding the emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is crucial for its control. MDR-TB in previously treated patients is generally attributed to the selection of drug resistant mutants during inadequate therapy rather than transmission of a resistant strain. Traditional genotyping methods are not sufficient to distinguish strains in populations with a high burden of tuberculosis and it has previously been difficult to assess the degree of transmission in these settings.

Determinants of clinician knowledge on aging and HIV/AIDS: a survey of practitioners and policy makers in Kampala District, Uganda.

Objective: The HIV/AIDS epidemic has evolved with an increasing burden in older adults. We assessed for knowledge about aging and HIV/AIDS, among clinicians in Kampala district, Uganda.

Methods: A cross-sectional survey of 301 clinicians complemented by 9 key-informant interviews between May and October 2011.

Antiretroviral drug resistance profiles and response to second-line therapy among HIV type 1-infected Ugandan children.

We sought to determine the pattern of resistance-associated mutations (RAMs) among HIV-1-infected children failing first-line antiretroviral therapy (ART) and ascertain their response to second-line regimens in 48 weeks of follow-up. The design involved a cohort study within an HIV care program. We studied records of 142 children on ART with virological failure to first-line ART and switched to second-line ART with prior genotypic resistance testing.

Response to antiretroviral therapy of HIV type 1-infected children in urban and rural settings of Uganda.

From 2006 to 2011, a cohort study was conducted among 1000 children resident in urban and rural settings of Uganda to ascertain and compare the response to antiretroviral therapy (ART) among urban versus rural children and the factors associated with this response. Clinical, immunological, and virological parameters were ascertained at baseline and weeks 24, 48, 96, and 144 after ART initiation. Adherence to ART was assessed at enrollment by self-report (SR) and pill counts (PC).

Therapeutic immunization in HIV infected Ugandans receiving stable antiretroviral treatment: a Phase I safety study.

Therapeutic immunizations in HIV infection may boost immunity during antiretroviral treatment. We report on the first therapeutic vaccine trial in Uganda, Africa. This open label Phase I trial was designed to assess the safety, tolerability and immunogenicity of a therapeutic HIV-1 vaccine candidate.

Pharmacokinetics and acceptability of once- versus twice-daily lamivudine and abacavir in HIV type-1-infected Ugandan children in the ARROW Trial.

Background: No data on once-daily dosing of nucleoside analogues in African children currently exist. We compared the pharmacokinetics (PK) of once- versus twice-daily lamivudine and abacavir treatment using the World Health Organization recommended weight band dosing of scored adult tablets.

Methods: HIV type-1 (HIV-1)-infected Ugandan children aged 3-12 years receiving antiretroviral therapy that included lamivudine and abacavir twice daily (total 150+300 mg, 225+450 mg and 225/300+600 mg daily for 12-<20, 20-<25 and ≥25 kg, respectively) were enrolled in a crossover study.

A Case of Cryptococcal Lymphadenitis in an HIV-Infected Child.

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.

Pharmacokinetics of lopinavir-ritonavir with and without nonnucleoside reverse transcriptase inhibitors in Ugandan HIV-infected adults.

We evaluated the pharmacokinetics of lopinavir-ritonavir with and without nonnucleoside reverse transcriptase inhibitors (NNRTIs) in Ugandan adults. The study design was a three-period crossover study (3 tablets [600 mg of lopinavir/150 mg of ritonavir {600/150 mg}], 4 capsules [533/133 mg], and 2 tablets [400/100 mg] twice a day [BD]; n = 40) of lopinavir-ritonavir with NNRTIs and a parallel one-period study (2 tablets BD; n = 20) without NNRTIs. Six-point pharmacokinetic sampling (0, 2, 4, 6, 8, and 12 h) was undertaken after observed intake with a standardized breakfast.

Sexual behaviour among persons living with HIV/AIDS in Kampala, Uganda.

Objective: To identify sexual behaviour and reproductive health needs of people living with HIV/AIDS (PLWHAs).

Design: A cross sectional study.

Setting: Joint Clinical Research Centre, Kampala Uganda.

Response to nonnucleoside reverse transcriptase inhibitor-based therapy in HIV-infected children with perinatal exposure to single-dose nevirapine.

We set out to investigate whether there are clinically significant consequences when children with perinatal exposure to single-dose nevirapine are initiated on a nonnucleoside reverse transcriptase inhibitor (NNRTI) containing a highly active antiretroviral therapy (HAART) regimen. We carried out a chart and database review of 104 HIV-infected children, who had initiated HAART with an NNRTI at JCRC and were less than or equal to 5 years of age, 35 (33.7%) of whom had prior exposure to perinatal single-dose nevirapine.

Enteric bacterial pathogens in HIV-infected children with acute diarrhea in Mulago referral and teaching hospital, Kampala, Uganda.

Objective: HIV-infected children develop severe bacterial infections. We set out to determine the enteric bacterial pathogens in HIV-infected children and HIV-negative controls with acute diarrhea and their antimicrobial sensitivities.

Methods: Children below 5 years of age with acute diarrhea were screened for HIV and their stools were analyzed by culture and use of antisera and the sensitivities of the pathogens were determined using the Kirby Bauer disc diffusion method.

The Distribution and Immune Profile of T Cell Subsets in HIV-Infected Children from Uganda.

Abstract T cell activation is an important mechanism in HIV-associated immune depletion. We have previously demonstrated an association between the hyperactivation of CD4(+) and CD8(+) T cells and low CD4 status in HIV-infected Ugandan children. In this study, we explore differences in activation between naive and memory T cells in HIV-infected Ugandan children.

Orphanhood predicts delayed access to care in Ugandan children.

We aimed to determine patient characteristics, treatment challenges, and adherence outcomes according to orphanhood status in a prospective cohort of 101 HIV+ children in rural Uganda. Orphans were older at antiretroviral initiation (P = 0.0008) and more likely to be WHO stage-4 (P = 0.

Profile of T cell immune responses in HIV-infected children from Uganda.

Human immunodeficiency virus (HIV) immunopathogenesis in children remains poorly understood. We assessed T cell immune activation in antiretroviral therapy-naive children in Uganda (n=154). Increased CD4+ and CD8+ T cell activation strongly correlated with decreased CD4+ T cell percentage.

Pattern of malaria-specific T-cell responses in a cohort of Ugandan children.

Malaria is the leading cause of morbidity and mortality in children in Uganda. The mechanisms whereby malaria parasites are eliminated, or how they may avoid the immune response remain poorly understood. We examined malaria-specific T-cell responses in a well-characterized cohort of African children in an endemic area where malaria transmission occurs throughout the year.

Prevalence, incidence and predictors of severe anaemia with zidovudine-containing regimens in African adults with HIV infection within the DART trial.

Objective: To describe the prevalence, incidence and predictors of severe anaemia in previously untreated symptomatic HIV-infected adults with CD4+ T-cells <200 cells/mm(3) initiating zidovudine-containing regimens in Africa.

Design: DART is a randomized trial comparing two strategies for HIV/AIDS management in Uganda and Zimbabwe.

Methods: We analysed the occurrence of anaemia at weeks 4 and 12, and then every 12 weeks.

Human immunodeficiency virus-specific responses in adult Ugandans: patterns of cross-clade recognition.

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.

HIV vaccines: the Uganda experience.

By late 1980s Uganda was the epicenter of the AIDS epidemic in the world but strong preventive interventions and committed leadership has turned the epidemic round. HIV incidence and prevalence have declined but infection rates remain unacceptably high, making HIV vaccine research a priority. Uganda pioneered the first HIV vaccine trial in Africa but had to overcome ethical, scientific and logistical challenges.