Lessons Learned From a Large Cross-Border Field Simulation Exercise to Strengthen Emergency Preparedness in East Africa, 2019.

Field simulation exercises (FSXs) require substantial time, resources, and organizational experience to plan and implement and are less commonly undertaken than drills or tabletop exercises. Despite this, FSXs provide an opportunity to test the full scope of operational capacities, including coordination across sectors. From June 11 to 14, 2019, the East African Community Secretariat conducted a cross-border FSX at the Namanga One Stop Border Post between the Republic of Kenya and the United Republic of Tanzania. The World Health Organization Department of Health Security Preparedness was the technical lead responsible for developing and coordinating the exercise. The purpose of the FSX was to assess and further enhance multisectoral outbreak preparedness and response in the East Africa Region, using a One Health approach. Participants included staff from the transport, police and customs, public health, animal health, and food inspection sectors. This was the first FSX of this scale, magnitude, and complexity to be conducted in East Africa for the purpose of strengthening emergency preparedness capacities. The FSX provided an opportunity for individual learning and national capacity strengthening in emergency management and response coordination. In this article, we describe lessons learned and propose recommendations relevant to FSX design, management, and organization to inform future field exercises.

Anti-tuberculosis drug resistance among new and previously treated sputum smear-positive tuberculosis patients in Uganda: results of the first national survey.

BACKGROUND: Multidrug resistant and extensively drug resistant tuberculosis (TB) have become major threats to control of tuberculosis globally. The rates of anti-TB drug resistance in Uganda are not known. We conducted a national drug resistance survey to investigate the levels and patterns of resistance to first and second line anti-TB drugs among new and previously treated sputum smear-positive TB cases. METHODS: Sputum samples were collected from a nationally representative sample of new and previously treated sputum smear-positive TB patients registered at TB diagnostic centers during December 2009 to February 2011 using a weighted cluster sampling method. Culture and drug susceptibility testing was performed at the national TB reference laboratory. RESULTS: A total of 1537 patients (1397 new and 140 previously treated) were enrolled in the survey from 44 health facilities. HIV test result and complete drug susceptibility testing (DST) results were available for 1524 (96.8%) and 1325 (85.9%) patients, respectively. Of the 1209 isolates from new cases, resistance to any anti-TB drug was 10.3%, 5% were resistant to isoniazid, 1.9% to rifampicin, and 1.4% were multi drug resistant. Among the 116 isolates from previously treated cases, the prevalence of resistance was 25.9%, 23.3%, 12.1% and 12.1% respectively. Of the 1524 patients who had HIV testing 469 (30.7%) tested positive. There was no association between anti-TB drug resistance (including MDR) and HIV infection. CONCLUSION: The prevalence of anti-TB drug resistance among new patients in Uganda is low relative to WHO estimates. The higher levels of MDR-TB (12.1%) and resistance to any drug (25.3%) among previously treated patients raises concerns about the quality of directly observed therapy (DOT) and adherence to treatment. This calls for strengthening existing TB control measures, especially DOT, routine DST among the previously treated TB patients or periodic drug resistance surveys, to prevent and monitor development and transmission of drug resistant TB.

The effect of opportunistic illness on HIV RNA viral load and CD4+ T cell count among HIV-positive adults taking antiretroviral therapy.

INTRODUCTION: HIV RNA viral load (VL) has been shown to increase during opportunistic illnesses (OIs), suggesting active HIV replication in response to infection among patients not taking antiretroviral therapy (ART). We assessed the effects of OIs on HIV RNA VL and CD4+ T cell counts among patients on ART with initially suppressed VL. METHODS: Between 2003 and 2007, we enrolled and followed 1094 HIV-1-infected adults who initiated ART and had quarterly blood draws for VL and CD4+ T cell count. In VL/CD4+ T cell measurement intervals following undetectable VL, we compared the elevation in VL to detectable levels and CD4+ T cell count changes between intervals when participants had episodes of OIs and intervals when they did not have OIs. RESULTS: VL was more likely to be detectable if participants had OIs in the prior three months compared to when they did not (OR=4.0 (95% CI=1.9-8.6)). The CD4+ T cell counts declined 24.1 cells/µL per three months in intervals where the participants had OIs compared to an increase of 21.3 cells/µL per three months in intervals where they did not have OIs (adjusted difference in the rate of CD4+ T cell count change of 61.7 cells/µL per three months (95% CI=13.7-109.7), P value=0.012). The rate of CD4+ T cell count increase was 25.6 cells/µL per three months (95% CI=11.6-39.6) higher for females compared to males (p value=<0.001), 1.4 cells/µL per three months lower per one year increase in age (p value=0.046) and 4 cells/µL per three months lower per 10 cells/µL increase in the starting CD4+ T cell count value (p value=<0.001). CONCLUSION: Episodes of opportunistic infections among patients taking ART with undetectable VL were associated with elevation of HIV RNA VL to detectable levels and decline in CD4+ T cell counts. CLINICAL TRIAL NUMBER: NCT00119093.

HIV-infected ugandan adults taking antiretroviral therapy with CD4 counts >200 cells/µL who discontinue cotrimoxazole prophylaxis have increased risk of malaria and diarrhea.

BACKGROUND: Cotrimoxazole prophylaxis prolongs survival and prevents opportunistic infections, malaria, and diarrhea in persons infected with human immunodeficiency virus (HIV). Many countries recommend that individuals taking antiretroviral therapy (ART) discontinue cotrimoxazole when CD4 counts are >200 cells/µL. However, this practice has not been evaluated in sub-Saharan Africa. METHODS: Patients in the Home-Based AIDS Care program in eastern Uganda initiated ART if they had a CD4 cell count ≤250 cells/µL or World Health Organization stage III or IV HIV disease. In the program's fourth year, patients with CD4 counts >200 cells/µL were randomly assigned, by household, to continue or discontinue cotrimoxazole. Consenting participants were followed for episodes of malaria and diarrhea. RESULTS: At randomization, 836 eligible patients had been receiving ART for a mean of 3.7 years, with a median CD4 count of 489 cells/µL; 94% had a viral load <400 copies/mL. Among those continuing (n = 452) vs discontinuing (n = 384) cotrimoxazole, 0.4 vs 12.2%, respectively, had at least 1 episode of malaria (P < .001), and 14% vs 25%, respectively, had at least 1 episode of diarrhea (P < .001). Compared to those remaining on cotrimoxazole, patients who discontinued had a relative risk of malaria of 32.5 (95% confidence interval [CI], 8.6-275.0; P < .001) and of diarrhea of 1.8 (95% CI, 1.3-2.4; P < .001). CONCLUSIONS: HIV-infected adults on ART with CD4 counts >200 cells/µL who live in a malaria-endemic area of sub-Saharan Africa and who abruptly discontinue cotrimoxazole prophylaxis have an increased incidence of malaria and diarrhea compared with those who continue prophylaxis. Clinical Trials Registration. NCT00119093.

Effect of CD4+ T cell count and antiretroviral treatment on two serological HIV incidence assays.

Serological assays are increasingly being used to measure HIV incidence in cross-sectional studies, but their specificity to determine incident infections remains problematic. We estimated the specificity of the BED assay in a cohort of long-term HIV-infected adults before and during antiretroviral treatment (ART) and evaluated an HIV avidity assay to detect BED-based false-recent results. We used the BED assay to test stored specimens from known long-term HIV-1-infected adult Ugandans before and at 3, 12, and 24 months after ART initiation. We evaluated the frequency of false-recent classifications by ART status and CD4(+) T(+) cell count. Specimens classified as BED false-recent were further tested with an avidity assay. In all, 950 blood specimens from 253 adults were tested with the BED assay. Of these, 149 (15.7%) specimens tested false-recent and 64 (24.9%) individuals tested false-recent at least once. Among all specimens tested, the proportion of false-recent rose with increasing CD4(+) cell count (<250 cells/µl: 11.3%, 250-499: 17.8%, ≥500: 21.4%; p for trend=0.002). Of 197 persons with all four BED results available, 75.6% were classified as long-term infected throughout and 8.1% as false-recent throughout; the remainder changed classification once (12.2%) or twice (4.1%). Of 105 false-recent specimens retested with the avidity assay, 101 (96.2%) were correctly classified as "long-term." The BED assay's specificity varied with CD4(+) cell count and use of ART. Knowledge of these parameters for blood samples could improve incidence estimates using the BED assay. The additional use of an avidity assay may help to minimize the proportion of BED false-recent specimens.

Utility of routine viral load, CD4 cell count, and clinical monitoring among adults with HIV receiving antiretroviral therapy in Uganda: randomised trial.

OBJECTIVE: To evaluate the use of routine laboratory monitoring in terms of clinical outcomes among patients receiving antiretroviral therapy (ART) in Uganda. DESIGN: Randomised clinical trial SETTING: A home based ART programme in rural Uganda. PARTICIPANTS: All participants were people with HIV who were members of the AIDS Support Organisation. Participants had CD4 cell counts <250 cells × 10(6)/L or World Health Organization stage 3 or 4 disease. INTERVENTIONS: Participants were randomised to one of three different monitoring arms: a viral load arm (clinical monitoring, quarterly CD4 counts, and viral load measurements), CD4 arm (clinical monitoring and CD4 counts), or clinical arm (clinical monitoring alone). MAIN OUTCOME MEASURES: Serious morbidity (newly diagnosed AIDS defining illness) and mortality. RESULTS: 1094 participants started ART; median CD4 count at baseline was 129 cells × 10(6)/L. Median follow-up was three years. In total, 126 participants died (12%), 148 (14%) experienced new AIDS defining illnesses, and 61(6%) experienced virological failure, defined as two consecutive viral loads >500 copies/mL occurring more than three months after the start of ART. After adjustment for age, sex, baseline CD4 count, viral load, and body mass index, the rate of new AIDS defining events or death was higher in the clinical arm than the viral load arm (adjusted hazard ratio 1.83, P = 0.002) or the CD4 arm (1.49, P = 0.032). There was no significant difference between the CD4 arm and the viral load arm (1.23, P = 0.31). CONCLUSION: In patients receiving ART for HIV infection in Uganda, routine laboratory monitoring is associated with improved health and survival compared with clinical monitoring alone. Trial registration Clinical Trials NCT00119093.

CD4 cell count and viral load monitoring in patients undergoing antiretroviral therapy in Uganda: cost effectiveness study.

OBJECTIVE: To examine the cost and cost effectiveness of quarterly CD4 cell count and viral load monitoring among patients taking antiretroviral therapy (ART). DESIGN: Cost effectiveness study. SETTING: A randomised trial in a home based ART programme in Tororo, Uganda. PARTICIPANTS: People with HIV who were members of the AIDS Support Organisation and had CD4 cell counts <250 × 10(6) cells/L or World Health Organization stage 3 or 4 disease. MAIN OUTCOME MEASURES: Outcomes calculated for the study period and projected 15 years into the future included costs, disability adjusted life years (DALYs), and incremental cost effectiveness ratios (ICER; $ per DALY averted). Cost inputs were based on the trial and other sources. Clinical inputs derived from the trial; in the base case, we assumed that point estimates reflected true differences even if non-significant. We conducted univariate and multivariate sensitivity analyses. INTERVENTIONS: Three monitoring strategies: clinical monitoring with quarterly CD4 cell counts and viral load measurement (clinical/CD4/viral load); clinical monitoring and quarterly CD4 counts (clinical/CD4); and clinical monitoring alone. RESULTS: With the intention to treat (ITT) results per 100 individuals starting ART, we found that clinical/CD4 monitoring compared with clinical monitoring alone increases costs by $20,458 (£12,780, €14,707) and averts 117.3 DALYs (ICER = $174 per DALY). Clinical/CD4/viral load monitoring compared with clinical/CD4 monitoring adds $142,458, and averts 27.5 DALYs ($5181 per DALY). The superior ICER for clinical/CD4 monitoring is robust to uncertainties in input values, and that strategy is dominant (less expensive and more effective) compared with clinical/CD4/viral load monitoring in one quarter of simulations. If clinical inputs are based on the as treated analysis starting at 90 days (after laboratory monitoring was initiated), then clinical/CD4/viral load monitoring is dominated by other strategies. CONCLUSIONS: Based on this trial, compared with clinical monitoring alone, monitoring of routine CD4 cell count is considerably more cost effective than additionally including routine viral load testing in the monitoring strategy and is more cost effective than ART.

Determinants of early and late mortality among HIV-infected individuals receiving home-based antiretroviral therapy in rural Uganda.

BACKGROUND: Up to 20% of people initiating antiretroviral therapy (ART) in sub-Saharan Africa die during the first year of treatment. Understanding the clinical conditions associated with mortality could potentially lead to effective interventions to prevent these deaths. METHODS: We examined data from participants aged ≥18 years in the Home-Based AIDS Care project in Tororo, Uganda, to describe mortality over time and to determine clinical conditions associated with death. Survival analysis was used to examine variables associated with mortality at baseline and during follow-up. RESULTS: A total of 112 (9.4%) deaths occurred in 1132 subjects (73% women) during a median of 3.0 years of ART. Mortality was 15.9 per 100 person-years during the first 3 months and declined to 0.3 per 100 person-years beyond 24 months after ART initiation. Tuberculosis (TB) was the most common condition associated with death (21% of deaths), followed by Candida disease (15%). In 43% of deaths, no specific clinical diagnosis was identified. Deaths within 3 months after ART initiation were associated with World Health Organization clinical stage III or IV at baseline, diagnosis of TB at baseline, a diagnosis of a non-TB opportunistic infection in follow-up and a body mass index ≤17 kg/m² during follow-up. Mortality after 3 months of ART was associated with CD4 cell counts <200 cells per microliter, a diagnosis of TB or other opportunistic infection, adherence to therapy <95%, and low hemoglobin levels during follow-up. CONCLUSION: Potentially remediable conditions and preventable infections were associated with mortality while receiving ART in Uganda.

Human herpesvirus 8 infection in children and adults in a population-based study in rural Uganda.

BACKGROUND: Human herpesvirus 8 (HHV-8) infection is endemic in sub-Saharan Africa. We examined sociodemographic, behavioral, and biological factors associated with HHV-8 infection in children and adults to determine HHV-8 seroprevalence and potential routes of transmission. METHODS: Participants were 1383 children and 1477 adults from a population-based sample in a rural community in Uganda. Serum samples were tested for HHV-8 antibodies with use of an enzyme immunoassay against K8.1. RESULTS: HHV-8 seroprevalence increased from 16% among children aged 1.5-2 years to 32% among children aged 10-13 years (P <.001) and from 37% among participants aged 14-19 years to 49% among adults aged ≥ 50 years (P <.05). HHV-8 seropositivity in children was independently associated with residing with a seropositive parent (P < .001) and residing with ≥ 1 other seropositive child aged <14 years (P < .001). History of sharing food and/or sauce plates was marginally associated with HHV-8 infection in children (P = .05). Among 1404 participants aged ≥ 15 years , there was no association between correlates of sexual behavior (eg, number of lifetime sex partners and HIV infection) and HHV-8 seropositivity (P > .10). CONCLUSIONS: Our data suggest that HHV-8 is acquired primarily through horizontal transmission in childhood from intrafamilial contacts and that transmission continues into adulthood potentially through nonsexual routes.

The cost effectiveness of home-based provision of antiretroviral therapy in rural Uganda.

BACKGROUND: Highly active antiretroviral therapy (HAART) provides dramatic health benefits for HIV-infected individuals in Africa, and widespread implementation of HAART is proceeding rapidly. Little is known about the cost and cost effectiveness of HAART programmes. OBJECTIVE: To determine the incremental cost effectiveness of a home-based HAART programme in rural Uganda. METHODS: A computer-based, deterministic cost-effectiveness model was used to assess a broad range of economic inputs and health outcomes. From the societal perspective, the cost effectiveness of HAART and cotrimoxazole prophylaxis was compared with cotrimoxazole alone, and with the period before either intervention. Data for 24 months were derived from a trial of home-based HAART in 1045 patients in the Tororo District in eastern Uganda. Costs and outcomes were projected out to 15 years. All costs are in year 2004 values. The main outcome measures were HAART programme costs, health benefits accruing to HAART recipients, averted HIV infections in adults and children and the resulting effects on medical care costs. The first-line HAART regimen consisted of standard doses of stavudine, lamivudine, and either nevirapine or, for patients with active tuberculosis, efavirenz. Second-line therapy consisted of tenofovir, didanosine and lopinavir/ritonavir. For children, first-line HAART consisted of zidovudine, lamivudine and nevirapine syrup; second-line therapy was stavudine, didanosine and lopinavir/ritonavir. RESULTS: The HAART programme, standardized for 1000 patients, cost an incremental $US1.39 million in its first 2 years. Compared with cotrimoxazole prophylaxis alone, the programme reduced mortality by 87%, and averted 6861 incremental disability-adjusted life-years (DALYs). Benefits were accrued from reduced mortality in HIV-infected adults (67.5% of all benefits), prevention of death in HIV-negative children (20.7%), averted HIV infections in adults (9.1%) and children (1.0%), and improved health status (1.7%). The net programme cost, including the medical cost implications of these health benefits, was $US4.10 million. The net cost per DALY averted was $US597 compared with cotrimoxazole alone. Many HIV interventions have a cost-effectiveness ratio in the range of $US1-150 per DALY averted. CONCLUSIONS: This study suggests that a home-based HAART programme in rural Africa may be more cost effective than most previous estimates for facility-based HAART programmes, but remains less cost effective than many HIV prevention and care interventions, including cotrimoxazole prophylaxis.

Hematologic changes associated with Zidovudine following single-drug substitution from stavudine in a home-based AIDS care program in rural Uganda.

BACKGROUND: The authors evaluated hematologic changes associated with zidovudine (ZDV) following single-drug substitution from stavudine (D4T) in HIV-infected persons in Uganda. METHODS: From May 2003 through February 2007, the authors evaluated incidence rates (IR) of hematologic abnormalities from quarterly blood draws among adults prescribed highly active antiretroviral therapy (HAART) before and after single-drug substitution of D4T to ZDV. RESULTS: A total of 1089 adults received D4T-containing HAART (median observation time, 35.9 months), and 290 (27%) had ZDV substituted for D4T. While taking D4T, IR for anemia was 0.35/100 person-months (PMs), leukopenia was 0.29/100 PM, and thrombocytopenia was 0.32/100 PM. While taking ZDV, IR for anemia was 0.44/100 PM, leukopenia was 1.05/100 PM, and thrombocytopenia was 0.30/100 PM. CONCLUSIONS: Patients had a higher incidence of anemia and leukopenia after substitution from D4T to ZDV, but hematologic toxicity was not a major complication in this population. Patients on ZDV-containing HAART regimens are still at risk for anemia and need close monitoring.

CD4+ T-cell count monitoring does not accurately identify HIV-infected adults with virologic failure receiving antiretroviral therapy.

BACKGROUND: CD4 T-lymphocyte (CD4) counts are widely used to monitor response to antiretroviral therapy (ART) in resource-limited settings. However, the utility of such monitoring in terms of predicting virologic response to therapy has been little studied. METHODS: We studied participants aged 18 years and older who initiated ART in Tororo, Uganda. CD4 counts, CD4 percentages, and viral load (VL) were examined at 6-monthly intervals. Various definitions of immunologic failure were examined to identify individuals with VLs>or=50, >or=500, >or=1000, or >or=5000 copies per milliliter at 6, 12, and 18 months after treatment initiation. RESULTS: One thousand sixty-three ART-naive persons initiated ART. The proportion of individuals with virologic failure ranged between 1.5% and 16.4% for each time point. The proportion with no increase in CD4 count from baseline did not differ between those with suppressed or unsuppressed VLs at 6, 18, and 24 months after ART initiation. No increase in CD4 cell counts at 6 months had a sensitivity of 0.04 [95% confidence interval (CI) 0.00 to 0.10] and a positive predictive value of 0.03 (95% CI 0.00 to 0.09) for identifying individuals with VL>or=500 copies per milliliter at 6 months. The best measure identified was an absolute CD4 cell count<125 cells per microliter at 21 months for predicting VL>or=500 copies per milliliter at 18 months which had a sensitivity of 0.13 (95% CI 0.01 to 0.21) and a positive predictive value of 0.29 (95% CI 0.10 to 0.44). CONCLUSIONS: CD4 cell count monitoring does not accurately identify individuals with virologic failure among patients taking ART.

Liver enzymes improve over twenty-four months of first-line non-nucleoside reverse transcriptase inhibitor-based therapy in rural Uganda.

We studied hepatic transaminases among rural Ugandans initiating highly active antiretroviral therapy (HAART) and assessed the impact of positive serology for hepatitis B surface antigen (HBsAg) and coadministration of therapy for tuberculosis. From July 2003 to December 2004, persons with symptomatic HIV disease or a CD4 count less than 250 cells/mm(3) and who had alanine transferase (ALT) or aspartate transferase (AST) less than 5 times the upper limit of normal were started on HAART including nevirapine (96%) or efavirenz (4%). Repository sera from a subset of 596 participants were analyzed for hepatic transaminase levels. A transaminase elevation was present before therapy for 249 (42%) of 596, at 3 months for 140 (25%) of 553, 12 months for 59 (11%) of 520, and 24 months for 67 (13%) of 508. In multivariate analyses, a transaminase elevation at 3 months was associated with male gender (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.02-2.35), body mass index less than 18 kg/m(2) (OR, 2.10; 95% CI, 1.34-3.30), transaminase elevation at baseline (OR, 1.97; 95% CI, 1.30-2.99), and treatment for tuberculosis (OR, 4.68; 95% CI, 2.28-9.59). HBsAg status was not associated with transaminase elevations at baseline or while on HAART. The prevalence of hepatic transaminase elevations decreased during non-nucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy in this cohort of HIV-infected persons in rural Uganda.

Antiretroviral therapy improves renal function among HIV-infected Ugandans.

Renal dysfunction is a severe complication of advanced HIV disease. We evaluated the impact of highly active antiretroviral therapy (HAART) on renal function among HIV-infected Ugandans in the Home-Based AIDS Care clinical trial. The patients presented with symptomatic HIV disease or CD4 cell count < or = 250 cells/mm(3) and creatinine clearances above 25 ml/min determined by the Cockcroft-Gault equation. Of the 508 patients at baseline, 8% had a serum creatinine over 133 micromol/l and about 20% had reduced renal function evidenced by a creatinine clearance between 25 and 50 ml/min. After 2 years of HAART, the median serum creatinine was significantly decreased by 16% while the median creatinine clearance significantly increased 21%. The median creatinine clearance of patients with renal dysfunction at baseline, increased by 53% during 2 years of treatment. In multivariable analysis, a baseline creatinine above 133 micromol/l, a weight gain of more than 5 kg over the 2 years, female gender and a WHO stage 4 classification were all associated with greater improvements in creatinine clearance on HAART. Our study shows that renal dysfunction was common with advanced HIV disease in Uganda but this improved following 2 years of HAART.

Changes in lipid profile over 24 months among adults on first-line highly active antiretroviral therapy in the home-based AIDS care program in rural Uganda.

BACKGROUND: Use of highly active antiretroviral therapy (HAART) has been linked to dyslipidemia and increased risk of cardiovascular disease (CVD) in HIV-infected patients in industrialized countries. The effects of HAART on lipid metabolism among sub-Saharan Africans, for whom access to antiretroviral therapy is expanding, remain largely unknown. METHODS: From July 2003 to May 2004, 987 antiretroviral-naive patients with symptomatic HIV disease or a CD4 count <250 cells/mm3 were started on HAART in the Home-Based AIDS Care (HBAC) Program in Tororo, Uganda. The HBAC Program provided weekly drug delivery and field-based clinical monitoring. Nonfasting repository sera from a subset of 374 patients were analyzed for levels of total cholesterol (TC), direct low-density lipoprotein cholesterol (LDL-c), direct high-density lipoprotein cholesterol (HDL-c), and triglycerides (TG) at baseline (before HAART) and after 12 and 24 months of HAART using Randox enzymatic kits (Crumlin, United Kingdom). RESULTS: The 374 patients evaluated (49% women, mean age = 39 years, CD4 count = 124 cells/mm3, body mass index = 19.7 kg/m2) received initial HAART composed of stavudine, lamivudine, and either nevirapine (365 patients [98%]) or efavirenz (9 patients [2%]). During 24 months, 99 (26%) patients had single drug substitutions from stavudine to zidovudine and 27 (7%) had single drug substitutions from nevirapine to efavirenz. At baseline, the mean serum lipid concentrations were 120 mg/dL for TC, 53 mg/dL for LDL-c, 29 mg/dL for HDL-c, and 123 mg/dL for TG; values were generally comparable for men and women. During 24 months of treatment, TC increased by a mean of 31 mg/dL, LDL-c by a mean of 26 mg/dL, and HDL-c by a mean of 19 mg/dL, whereas the TC/HDL-c ratio decreased from a mean of 4.6 to 3.4 (all changes, P < 0.001). TG levels initially decreased and then returned to baseline levels by 24 months. At baseline and 24 months, respectively, TC was > or =200 mg/dL for 2% and 10% of patients, LDL-c was > or =130 mg/dL for 1% and 6%, HDL-c was <40 mg/dL for 88% and 41%, and TG were > or =150 mg/dL for 23% and 20%. CONCLUSIONS: Rural Ugandans with advanced HIV disease initiating nevirapine- or efavirenz-based HAART experienced infrequent elevations in TC, LDL-c, and TG at baseline and after 24 months of therapy. Increases in HDL-c levels were substantial and proportionally greater than increases in TC or LDL-c levels. The risk of CVD and how it is affected by lipid changes in this rural African population are unknown. However, the changes we observed after 24 months of HAART seem unlikely to increase the risk of CVD.

Mortality in HIV-infected Ugandan adults receiving antiretroviral treatment and survival of their HIV-uninfected children: a prospective cohort study.

BACKGROUND: Antiretroviral therapy (ART) is increasingly available in Africa, but physicians and clinical services are few. We therefore assessed the effect of a home-based ART programme in Uganda on mortality, hospital admissions, and orphanhood in people with HIV-1 and their household members. METHODS: In 2001, we enrolled and followed up 466 HIV-infected adults and 1481 HIV-uninfected household members in a prospective cohort study. After 5 months, we provided daily co-trimoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole) prophylaxis to HIV-infected participants. Between May, 2003, and December, 2005, we followed up 138 infected adults who were eligible and 907 new HIV-infected participants and their HIV-negative household members in a study of ART (mainly stavudine, lamivudine, and nevirapine). Households were visited every week by lay providers, and no clinic visits were scheduled after enrolment. We compared rates of death, hospitalisation, and orphanhood during different study periods and calculated the number needed to treat to prevent an outcome. FINDINGS: 233 (17%) of 1373 participants with HIV and 40 (1%) of 4601 HIV-uninfected household members died. During the first 16 weeks of ART and co-trimoxazole, mortality in HIV-infected participants was 55% lower than that during co-trimoxazole alone (14 vs 16 deaths per 100 person-years; adjusted hazard ratio 0.45, 95% CI 0.27-0.74, p=0.0018), and after 16 weeks, was reduced by 92% (3 vs 16 deaths per 100 person-years; 0.08, 0.06-0.13, p<0.0001). Compared with no intervention, ART and co-trimoxazole were associated with a 95% reduction in mortality in HIV-infected participants (5 vs 27 deaths per 100 person-years; 0.05, 0.03-0.08, p<0.0001), 81% reduction in mortality in their uninfected children younger than 10 years (0.2 vs 1.2 deaths per 100 person-years; 0.19, 0.06-0.59, p=0.004), and a 93% estimated reduction in orphanhood (0.9 vs 12.8 per 100 person-years of adults treated; 0.07, 0.04-0.13, p<0.0001). INTERPRETATION: Expansion of access to ART and co-trimoxazole prophylaxis could substantially reduce mortality and orphanhood among adults with HIV and their families living in resource-poor settings.

Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda.

OBJECTIVE: To evaluate the association between a positive serum cryptococcal antigen (CRAG) test at baseline and mortality during the first 12 weeks on antiretroviral therapy (ART). Cryptococcal meningitis is a leading cause of HIV-related mortality in Africa, but current guidelines do not advocate CRAG testing as a screening tool. METHODS: Between May 2003 and December 2004, we enrolled HIV-1 infected individuals into a study of ART monitoring in rural Uganda. CRAG testing was conducted retrospectively on stored pre-ART serum samples of participants whose baseline CD4 cell count was <100 cells/mul and who were without symptoms suggestive of disseminated cryptococcal disease at enrolment. RESULTS: Of 377 participants, 5.8% had serum CRAG titre >/=1:2. Of these, 23% died during follow-up. Controlling for CD4 cell count, HIV-1 viral load, anaemia, active tuberculosis and body mass index, relative risk of death during follow-up among those with asymptomatic cryptococcal antigenemia at baseline was 6.6 [95% confidence interval (CI) 1.86-23.61, P = 0.0036]. The population attributable risk for mortality associated with a positive CRAG at baseline was 18% (CI 2-33%), similar to that associated with active tuberculosis (19%, CI 1-36%). CONCLUSION: Asymptomatic cryptococcal antigenemia independently predicts death during the first 12 weeks of ART among individuals with advanced HIV disease in rural Uganda. Routine screening and provision of azole antifungal therapy prior to or simultaneous with the start of ART should be evaluated for the potential to prevent mortality in this population.

Coming back from the dead: living with HIV as a chronic condition in rural Africa.

Scaling-up of anti-retroviral therapy (ART) in resource-poor settings has dramatically reduced mortality and morbidity for those with access, but considerable challenges remain for people who are trying to live with HIV as a manageable chronic condition. A return to 'normal life' for people on ART depends on the assurance of an uninterrupted, affordable and accessible supply of medication. However, many poor people also require economic support to re-establish their livelihoods, particularly where productive and financial assets have been depleted because of long-term illness. ART programmes need to seek convergence with economic programmes that have expertise in livelihood support and promotion, and with social protection initiatives. The future for those on ART depends not only on the provision of medicine but also on economic and social support for rebuilding lives and livelihoods.

Prevalence, incidence and mortality associated with tuberculosis in HIV-infected patients initiating antiretroviral therapy in rural Uganda.

BACKGROUND: Tuberculosis (TB) is the leading cause of death among people with HIV in sub-Saharan Africa. Expanding access to antiretroviral therapy (ART) may reduce the burden of TB, but to what extent is unknown. METHODS: In a study of 1044 adults who initiated home-based ART in Tororo, Uganda between 1 May 2003 and 30 June 2005, participants were screened for active TB at baseline and then monitored at weekly home visits. Participants with TB at baseline or follow-up were compared with those without TB to determine factors associated with mortality in those with TB. RESULTS: At baseline, 75 (7.2%) subjects had TB and a total of 53 (5.5%) were diagnosed with TB over a median of 1.4 years of follow-up (3.90 cases/100 person years). Cumulative mortality was 17.9/100 person-years for those with TB and 3.8/100 person-years for those without TB (P < 0.001). Mortality was associated with low baseline CD4 cell counts [relative hazard (RH), 0.99 per 1 cell/microl increase; P = 0.03] and marginally associated with a body mass index

Clinical toxicity of highly active antiretroviral therapy in a home-based AIDS care program in rural Uganda.

BACKGROUND: We evaluated clinical toxicity in HIV-infected persons receiving antiretroviral therapy (ART) in Uganda. METHODS: From May 2003 through December 2004, adults with a CD4 cell count < or =250 cells/microL or World Health Organization stage 3/4 HIV disease were prescribed ART. We calculated probabilities for time to toxicity and single-drug substitution as well as multivariate-adjusted hazard ratios for development of toxicity. RESULTS: ART (stavudine plus lamivudine with nevirapine [96%] or efavirenz [4%]) was prescribed for 1029 adults, contributing 11,268 person-months of observation. Toxicities developed in 543 instances in 411 (40%) patients (incidence rate = 4.47/100 person-months): 36% peripheral neuropathy (9% severe); 6% rash (2% severe); 2% hypersensitivity reaction; < or =0.5% acute hepatitis, anemia, acute pancreatitis, or lactic acidosis; and 13% other. Probabilities of remaining free from any toxicity at 6, 12, and 18 months were 0.76, 0.59, and 0.47 and from any severe toxicity at 6, 12, and 18 months were 0.92, 0.86, and 0.85, respectively. For 217 patients (21%), 222 single-drug substitutions were made, mostly because of peripheral neuropathy or rash. CONCLUSIONS: Clinical toxicities were common, but no patients discontinued ART because of toxicity. The most common toxicities, peripheral neuropathy and rash, were managed with single-drug substitutions. In resource-limited settings, toxicity from ART regimens containing stavudine or nevirapine is manageable but more tolerable regimens are needed.