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.

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.

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.

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.

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.

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.

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

Adherence to antiretroviral therapy in a home-based AIDS care programme in rural Uganda.

BACKGROUND: Poverty and limited health services in rural Africa present barriers to adherence to antiretroviral therapy that necessitate innovative options other than facility-based methods for delivery and monitoring of such therapy. We assessed adherence to antiretroviral therapy in a cohort of HIV-infected people in a home-based AIDS care programme that provides the therapy and other AIDS care, prevention, and support services in rural Uganda. METHODS: HIV-infected individuals with advanced HIV disease or a CD4-cell count of less than 250 cells per muL were eligible for antiretroviral therapy. Adherence interventions included group education, personal adherence plans developed with trained counsellors, a medicine companion, and weekly home delivery of antiretroviral therapy by trained lay field officers. We analysed factors associated with pill count adherence (PCA) of less than 95%, medication possession ratio (MPR) of less than 95%, and HIV viral load of 1000 copies per mL or more at 6 months (second quarter) and 12 months (fourth quarter) of follow-up. FINDINGS: 987 adults who had received no previous antiretroviral therapy (median CD4-cell count 124 cells per muL, median viral load 217,000 copies per mL) were enrolled between July, 2003, and May, 2004. PCA of less than 95% was calculated for 0.7-2.6% of participants in any quarter and MPR of less than 95% for 3.3-11.1%. Viral load was below 1000 copies per mL for 894 (98%) of 913 participants in the second quarter and for 860 (96%) of 894 of participants in the fourth quarter. In separate multivariate models, viral load of at least 1000 copies per mL was associated with both PCA below 95% (second quarter odds ratio 10.6 [95% CI 2.45-45.7]; fourth quarter 14.5 [2.51-83.6]) and MPR less than 95% (second quarter 9.44 [3.40-26.2]; fourth quarter 10.5 [4.22-25.9]). INTERPRETATION: Good adherence and response to antiretroviral therapy can be achieved in a home-based AIDS care programme in a resource-limited rural African setting. Health-care systems must continue to implement, evaluate, and modify interventions to overcome barriers to comprehensive AIDS care programmes, especially the barriers to adherence with antiretroviral therapy.

Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study.

BACKGROUND: HIV-1 and malaria are common infections in Africa, and cause substantial morbidity and mortality. HIV infection has been associated with an increased incidence of malaria, and more severe disease. Our aim was to assess the effect of antiretroviral treatment (ART) on the frequency of clinical malaria in people with HIV, and to measure the additive effects of co-trimoxazole (trimethoprim and sulfamethoxazole) prophylaxis, ART, and insecticide-treated bednets. METHODS: In 2001, we enrolled 466 HIV-infected individuals aged 18 years or older in Uganda in a prospective cohort study that provided co-trimoxazole prophylaxis to 399 participants after 5 months of no intervention. In 2003, we enrolled 138 survivors from the initial study, and 897 new participants from the same community, to take antiretroviral therapy (ART) in addition to co-trimoxazole prophylaxis. The ART was in most cases a combination of stavudine, lamivudine, and nevirapine or efavirenz. In 2004, we also gave participants insecticide-treated bednets. Households were visited weekly by study staff to record fever, illness, or death in the preceding 7 days. In cases of reported fever in the previous 2 days, we took blood to test for malaria parasites. We compared the frequency of clinical malaria, adjusting for CD4-cell count, age, sex, and season. FINDINGS: 1035 individuals were given co-trimoxazole and ART (median age 38 years, 74% female, and median CD4-cell count 124 cells/microL); 985 of these, plus four new participants, received co-trimoxazole, ART, and bednets. There were 166 cases of clinical malaria in the study. Compared with a baseline malaria incidence of 50.8 episodes per 100 person-years, co-trimoxazole prophylaxis was associated with 9.0 episodes per 100 person-years (adjusted incidence rate ratio [IRR] 0.24, 95% CI 0.15-0.38); ART and co-trimoxazole with 3.5 episodes per 100 person-years (0.08, 0.04-0.17); and co-trimoxazole, ART, and bednets with 2.1 episodes per 100 person-years (0.05, 0.03-0.08). Malaria incidence was significantly lower during ART and co-trimoxazole than during co-trimoxazole alone (IRR 0.36 [95% CI 0.18-0.74], p=0.0056). INTERPRETATION: A combination of co-trimoxazole, antiretroviral therapy, and insecticide-treated bednets substantially reduced the frequency of malaria in adults with HIV.

Determining eligibility for antiretroviral therapy in resource-limited settings using total lymphocyte counts, hemoglobin and body mass index.

BACKGROUND: CD4+ T lymphocyte (CD4) cell count testing is the standard method for determining eligibility for antiretroviral therapy (ART), but is not widely available in sub-Saharan Africa. Total lymphocyte counts (TLCs) have not proven sufficiently accurate in identifying subjects with low CD4 counts. We developed clinical algorithms using TLCs, hemoglobin (Hb), and body mass index (BMI) to identify patients who require ART. METHODS: We conducted a cross-sectional study of HIV-infected adults in Uganda, who presented for assessment for ART-eligibility with WHO clinical stages I, II or III. Two by two tables were constructed to examine TLC thresholds, which maximized sensitivity for CD4 cell counts 350 cells microL. Hb and BMI values were then examined to try to improve model performance. RESULTS: 1787 subjects were available for analysis. Median CD4 cell counts and TLCs, were 239 cells/microL and 1830 cells/microL, respectively. Offering ART to all subjects with a TLCs 3000 cells/microL, and used Hb and/or BMI values to determine eligibility for those with TLC values between 2000 and 3000 cells/microL, marginally improved accuracy. CONCLUSION: TLCs appear useful in predicting who would be eligible for ART based on CD4 cell count criteria. Hb and BMI values may be useful in prioritizing patients for ART, but did not improve model accuracy.

Changes in sexual behavior and risk of HIV transmission after antiretroviral therapy and prevention interventions in rural Uganda.

BACKGROUND: The impact of antiretroviral therapy (ART) on sexual risk behavior and HIV transmission among HIV-infected persons in Africa is unknown. OBJECTIVE: To assess changes in risky sexual behavior and estimated HIV transmission from HIV-infected adults after 6 months of ART. DESIGN AND METHODS: A prospective cohort study was performed in rural Uganda. Between May 2003 and December 2004 a total of 926 HIV-infected adults were enrolled and followed in a home-based ART program that included prevention counselling, voluntary counseling and testing (VCT) for cohabitating partners and condom provision. At baseline and follow-up, participants' HIV plasma viral load and partner-specific sexual behaviors were assessed. Risky sex was defined as inconsistent or no condom use with partners of HIV-negative or unknown serostatus in the previous 3 months. The rates of risky sex were compared using a Poisson regression model and transmission risk per partner was estimated, based on established viral load-specific transmission rates. RESULTS: Six months after initiating ART, risky sexual behavior reduced by 70% [adjusted risk ratio, 0.3; 95% confidence interval (CI), 0.2-0.7; P = 0.0017]. Over 85% of risky sexual acts occurred within married couples. At baseline, median viral load among those reporting risky sex was 122 500 copies/ml, and at follow-up, < 50 copies/ml. Estimated risk of HIV transmission from cohort members declined by 98%, from 45.7 to 0.9 per 1000 person years. CONCLUSIONS: Providing ART, prevention counseling, and partner VCT was associated with reduced sexual risk behavior and estimated risk of HIV transmission among HIV-infected Ugandan adults during the first 6 months of therapy. Integrated ART and prevention programs may reduce HIV transmission in Africa.

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.

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.

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.

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.

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.

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.