The epidemic of HIV-associated tuberculosis in sub-Saharan Africa: does this also impact non-HIV-infected individuals?
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AIDS-Related Opportunistic Infections↗
Biomedical subjects
Robin Wood
Publications and source records attributed to Robin Wood.
Determinants of mortality and nondeath losses from an antiretroviral treatment service in South Africa: implications for program evaluation.
BACKGROUND: The scale-up of antiretroviral treatment (ART) services in resource-limited settings requires a programmatic model to deliver care to large numbers of people. Understanding the determinants of key outcome measures--including death and nondeath losses--would assist in program evaluation and development. METHODS: Between September 2002 and August 2005, all in-program (pretreatment and on-treatment) deaths and nondeath losses were prospectively ascertained among treatment-naive adults (n=1235) who were enrolled in a community-based ART program in South Africa. RESULTS: At study censorship, 927 patients had initiated ART after a median of 34 days after enrollment in the program. One hundred twenty-one (9.8%) patients died. Mortality rates were 33.3 (95% CI, 25.5-43.0), 19.1 (95% CI, 14.4-25.2), and 2.9 (95% CI, 1.8-4.8) deaths/100 person-years in the pretreatment interval, during the first 4 months of ART (early deaths), and after 4 months of ART (late deaths), respectively. Pretreatment and early treatment deaths together accounted for 87% of deaths, and were independently associated with advanced immunodeficiency at enrollment. Late deaths were comparatively few and were only associated with the response to ART at 4 months. Nondeath program losses (loss to follow-up, 2.3%; transfer-out, 1.9%; relocation, 0.7%) were not associated with immune status and were evenly distributed during the study period. CONCLUSIONS: Loss to follow-up and late mortality rates were low, reflecting good cohort retention and treatment response. However, the extremely high pretreatment and early mortality rates indicate that patients are enrolling in ART programs with far too advanced immunodeficiency. Causes of late access to the ART program, such as delays in health care access, health system delays, or inappropriate treatment criteria, need to be addressed.
Adult↗
Burden of tuberculosis in an antiretroviral treatment programme in sub-Saharan Africa: impact on treatment outcomes and implications for tuberculosis control.
OBJECTIVES: To determine burden and risk factors for tuberculosis (TB) in an antiretroviral treatment (ART) programme and its impact on ART outcomes. DESIGN: Prospective cohort study. METHODS: Prevalent TB was assessed at baseline and incident TB was ascertained prospectively over 3 years among 944 patients accessing a community-based ART programme in South Africa. RESULTS: At enrollment, median CD4 cell count was 96 cells/microl and 52% of patients had a previous history of TB. Prevalent TB (current antituberculosis treatment or active TB) was present in 25% and was strongly associated with advanced immunodeficiency. During 782 person-years of ART, 81 cases of TB were diagnosed. The incidence was 22.1/100 person-years during the first 3 months of ART and decreased to an average of 4.5/100 person-years during the second and third years. In multivariate analysis, risk of incident TB during follow-up was only associated with the current absolute CD4 cell count at that time point; an increase of 100 cells/mul was associated with a 25% lower risk (P = 0.007). Although prevalent and incident TB were associated with greater than two-fold increased mortality risk, they did not compromise immunological and virological outcomes among survivors at 48 weeks. CONCLUSIONS: Late initiation of ART was associated with a major burden of TB in this ART programme. TB reduced survival but did not impair immunovirological outcomes. Reductions in TB incidence during ART were dependent on CD4 cell count; however, after 3 years of treatment, rates were still 5- to 10-fold higher than among non-HIV-infected people. Earlier initiation of ART may reduce this burden of TB.
Adult↗
CD4 decline and incidence of opportunistic infections in Cape Town, South Africa: implications for prophylaxis and treatment.
OBJECTIVES: To determine the rate of CD4 decline and the incidence of opportunistic infections (OIs) among antiretroviral therapy-naive South African HIV-infected patients and inform timing of OI prophylaxis. METHODS: We used mixed-effect models to estimate CD4 cell decline by CD4 cell count strata in HIV-infected patients in the Cape Town AIDS Cohort between 1984 and 2000. Stratum-specific OI incidence per 100 person-years of observation was determined using incidence density analysis. RESULTS: Nine hundred seventy-four patients with 2 or more CD4 cell counts were included. CD4 counts declined by 47.1 cells/microL per year in the stratum with more than 500 cells/microL stratum, 30.6 cells/microL per year in the stratum with 351 to 500 cells/microL, and 20.5 cells/microL per year in the stratum with 201 to 350 cells/microL. Tuberculosis and oral candidiasis were the only OIs that occurred frequently in the stratum with more than 200 CD4 cells/microL. Rates of chronic diarrhea, wasting syndrome, tuberculosis, and oral and esophageal candidiasis increased in the stratum with less than 200 cells/microL, and rates of all OIs were highest in the stratum with 50 cells/microL or less. CONCLUSIONS: : CD4 cell count declines were dependent on CD4 strata and can inform timing of clinic visits and treatment initiation in South Africa. Incidence rates of OIs suggest that targeted OI prophylaxis could prevent substantial HIV-related morbidity in South Africa.
AIDS-Related Opportunistic Infections↗
Efficacy and tolerability of 10-day monotherapy with apricitabine in antiretroviral-naive, HIV-infected patients.
OBJECTIVE: Apricitabine (formerly AVX754 and SPD754) is a deoxycytidine analogue nucleoside reverse transcriptase inhibitor in clinical development for patients with HIV disease. This study evaluated the antiretroviral efficacy, tolerability and safety of apricitabine monotherapy, administered for 10 days in antiretroviral-naive, HIV-1 infected adults. METHODS: Adult patients (> or = 18 years) with HIV infection (CD4 count > or = 250 cells/microl; plasma HIV-1 RNA level 5000-100 000 copies/ml) were randomized to 10 days' double-blind oral therapy with placebo or apricitabine 400 mg/day, 800 mg/day, 1200 mg/day, or 1600 mg/day. RESULTS: At 7 days, all apricitabine doses produced statistically significant log10 reductions in plasma HIV RNA levels from baseline relative to placebo (n = 13; P < 0.0001), as follows: -1.16 (400 mg; n = 11), -1.28 (800 mg; n = 12), -1.44 (1200 mg; n = 14), -1.30 (1600 mg; n = 13). After 10 days, the log10 viral load reductions with apricitabine 1200 mg (-1.65; P = 0.01) and 1600 mg/day (-1.58; P = 0.04) were significantly greater than that with the 400-mg dose (-1.18). No clinically relevant changes were observed in CD4 or CD8 cell indices. Apricitabine was well tolerated and showed no tendency to select any particular resistance mutation. CONCLUSION: Apricitabine monotherapy showed promising antiretroviral efficacy, good tolerability and a low propensity for resistance selection in antiretroviral-naive HIV-infected patients treated for 10 days. These results warrant further evaluation of the long-term clinical efficacy and tolerability of apricitabine.
Administration, Oral↗
CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa.
BACKGROUND: Patients accessing antiretroviral treatment (ART) programmes in sub-Saharan Africa frequently have very advanced immunodeficiency. Previous data suggest that such patients may have diminished capacity for CD4 cell count recovery. METHODS: Rates of CD4 cell increase were determined over 48 weeks among ART-naïve individuals (n = 596) commencing ART in a South African community-based ART programme. RESULTS: The CD4 cell count increased from a median of 97 cells/microl at baseline to 261 cells/microl at 48 weeks and the proportion of patients with a CD4 cell count < 100 cells/microl decreased from 51% at baseline to just 4% at 48 weeks. A rapid first phase of recovery (0-16 weeks, median rate = 25.5 cells/microl/month) was followed by a slower second phase (16-48 weeks, median rate = 7.7 cells/microl/month). Compared to patients with higher baseline counts, multivariate analysis showed that those with baseline CD4 counts < 50 cells/microl had similar rates of phase 1 CD4 cell recovery (P = 0.42), greater rates of phase 2 recovery (P = 0.007) and a lower risk of immunological non-response (P = 0.016). Among those that achieved a CD4 cell count > 500 cells/microl at 48 weeks, 19% had baseline CD4 cell counts < 50 cells/microl. However, the proportion of these patients that attained a CD4 count 200 cells/microl at 48 weeks was lower than those with higher baseline CD4 cell counts. CONCLUSION: Patients in this cohort with baseline CD4 cell counts < 50 cells/microl have equivalent or greater capacity for immunological recovery during 48 weeks of ART compared to those with higher baseline CD4 cell counts. However, their CD4 counts remain < 200 cells/microl for a longer period, potentially increasing their risk of morbidity and mortality in the first year of ART.
Adult↗
Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries.
BACKGROUND: Highly active antiretroviral therapy (HAART) is being scaled up in developing countries. We compared baseline characteristics and outcomes during the first year of HAART between HIV-1-infected patients in low-income and high-income settings. METHODS: 18 HAART programmes in Africa, Asia, and South America (low-income settings) and 12 HIV cohort studies from Europe and North America (high-income settings) provided data for 4810 and 22,217, respectively, treatment-naïve adult patients starting HAART. All patients from high-income settings and 2725 (57%) patients from low-income settings were actively followed-up and included in survival analyses. FINDINGS: Compared with high-income countries, patients starting HAART in low-income settings had lower CD4 cell counts (median 108 cells per muL vs 234 cells per muL), were more likely to be female (51%vs 25%), and more likely to start treatment with a non-nucleoside reverse transcriptase inhibitor (NNRTI) (70%vs 23%). At 6 months, the median number of CD4 cells gained (106 cells per muL vs 103 cells per muL) and the percentage of patients reaching HIV-1 RNA levels lower than 500 copies/mL (76%vs 77%) were similar. Mortality was higher in low-income settings (124 deaths during 2236 person-years of follow-up) than in high-income settings (414 deaths during 20,532 person-years). The adjusted hazard ratio (HR) of mortality comparing low-income with high-income settings fell from 4.3 (95% CI 1.6-11.8) during the first month to 1.5 (0.7-3.0) during months 7-12. The provision of treatment free of charge in low-income settings was associated with lower mortality (adjusted HR 0.23; 95% CI 0.08-0.61). INTERPRETATION: Patients starting HAART in resource-poor settings have increased mortality rates in the first months on therapy, compared with those in developed countries. Timely diagnosis and assessment of treatment eligibility, coupled with free provision of HAART, might reduce this excess mortality.
Adolescent↗
Impact of HIV infection on the epidemiology of tuberculosis in a peri-urban community in South Africa: the need for age-specific interventions.
BACKGROUND: In August 2005, the World Health Organization declared the tuberculosis (TB) epidemic in Africa to be a regional emergency. Current TB-control measures are failing, largely as a result of the human immunodeficiency virus (HIV) epidemic. Evaluation of additional control interventions requires detailed understanding of the epidemiological relationship between these diseases at the community level. METHODS: We examined age- and sex-specific trends in TB notifications and their association with the prevalence of HIV infection in a peri-urban township in South Africa during 1996-2004. Denominators for TB notifications were derived from population census data. The local TB-control program used the World Health Organization directly observed treatment, short-course (DOTS) strategy. RESULTS: TB notification rates increased 2.5-fold during the period, reaching a rate of 1468 cases per 100,000 persons in 2004 (P=.007, by test for trend); the estimated population prevalence of HIV infection increased from 6% to 22% during the same period. After stabilization of prevalence of HIV infection, the TB notification rate continued to increase steeply, indicating ongoing amplification of the TB epidemic. In 2004, at least 50% of children aged 0-9 years who developed TB were HIV infected. Annual TB notification rates among adolescents increased from 0 cases in 1996-1997 to 436 cases per 100,000 persons in 2003-2004, and these increases were predominantly among female. However, 20-39-year-old persons were affected most, with TB notification rates increasing from 706 to 2600 cases per 100,000 persons among subjects in their 30s. In contrast, TB rates among persons aged >50 years did not change. CONCLUSIONS: HIV infection is driving the TB epidemic in this population, and use of the DOTS strategy alone is insufficient. TB notifications have reached unprecedented levels, and additional targeted, age-specific interventions for control of TB and HIV infection in such populations are needed.
Adolescent↗
Blood safety--at what cost?
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Blood Banks↗
How can earlier entry of patients into antiretroviral programs in low-income countries be promoted?
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Africa↗
Long-term (120-Week) antiviral efficacy and tolerability of fosamprenavir/ritonavir once daily in therapy-naive patients with HIV-1 infection: an uncontrolled, open-label, single-arm follow-on study.
BACKGROUND: In the SOLO study (APV30002), once-daily antiretroviral treatment with the protease inhibitor fosamprenavir (FPV) 1,400 mg boosted by ritonavir (r) 200 mg plus abacavir/lamivudine (ABC/3TC) was found to be noninferior to nelfinavir plus ABC/3TC over 48 weeks in treatment-naive patients with HIV -1 infection. OBJECTIVE: This interim report presents antiviral efficacy and tolerability data from 211 patients who received FPV/r QD for at least 48 weeks in SOLO and continued this treatment in the follow-on study (APV30005) for up to 120 weeks. METHODS: APV30005 is an international, multicenter, uncontrolled, open-label, follow-on study conducted to provide continued access to FPV in patients with HIV-1 infection who had participated in previous FPV studies, including SOLO, and to obtain longer-term data on the antiviral response and tolerability of an FPV-containing regimen. Patients who had completed at least 48 weeks of FPV/r therapy in the SOLO study were eligible to enter the follow-on study and continue receiving FPV/r 1,400/200 QD, with study visits every 12 weeks. Their background regimens were chosen at the investigators' discretion and could be changed at any time. Antiviral response end points included plasma HIV-1 RNA levels <400 and <50 copies/mL, median plasma HIV-1 RNA levels, median and absolute changes from baseline in the CD4 cell count, and the frequency of HIV disease progression. Genotype and phenotype analyses were performed for patients meeting the criterion for virologic failure (defined as plasma HIV -1 RNA >1,000 copies/mL on 2 consecutive occasions on or after week 12). Tolerability was assessed in terms of adverse-event reports evaluated by the primary investigator and changes in laboratory values. Assessments were conducted at 12-week intervals during the follow-on study. Data from the baseline visit (day 1 of SOLO) were compared with data from the follow-on study through March 31, 2004, when all patients had completed at least 120 weeks of therapy with FPV/r QD. Because this was a rollover study, no significance testing was performed and all reported results are descriptive. RESULTS: The demographic and baseline characteristics of the patients who received FPV/r QD in this follow on study (N = 211) were similar to those of the 322 patients randomized to receive FPV/r QD in the SOLO study. Their median age was 36 years, 72% were male, 49% were white, and 39% were black. The median baseline plasma HIV 1 RNA level was 4.82 log(10) copies/ mL, and the median baseline CD4+ cell count was 168 cells/mm(3). The median duration of exposure to FPV/r QD from SOLO baseline through the cutoff date was 996 days (142 weeks), ranging from 372 to 1,226 days (53-175 weeks). At week 120, plasma HIV-1 RNA levels <400 and <50 copies/mL were achieved and maintained in 75% (159) and 66% (139) of patients, respectively, when missing data and discontinuations were counted as failures. The median CD4+ cell count at week 120 was 451 cells/mm(3), a median change from baseline of 292 cells/mm(3). In 14 patients with no baseline resistance who met the criterion for virologic failure, no viral protease resistance mutations were detected. Extended treatment was generally well tolerated. The most frequently reported drug-related grade 2-4 adverse events were diarrhea (22 [10%]), nausea (17 [8%]), drug hypersensitivity (14 [7%], all cases attributed to ABC, which was a study drug in SOLO), and increased triglycerides (14 [7%]). The nature of adverse events reported after 48 weeks of therapy was comparable to that reported before week 48. Adverse events occurred at a similar or lower frequency between weeks 48 and 120 compared with before week 48. Similarly, laboratory abnormalities seen by week 120 were comparable to those seen by week 48, although they were less frequent. CONCLUSIONS: Extended treatment (120 weeks) with FPV/r QD in these antiretroviral therapy-naive, HIV-1-infected patients was associated with sustained antiviral response and immunologic improvement. Adverse events had generally developed by 48 weeks of therapy and did not occur at a higher frequency through 120 weeks of treatment.
Adult↗
Evaluating a model for monitoring the virological efficacy of antiretroviral treatment in resource-limited settings.
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Acquired Immunodeficiency Syndrome↗
Design and evaluation of a drama-based intervention to promote voluntary counseling and HIV testing in a South African community.
BACKGROUND: Voluntary counseling and testing (VCT) services are a major component of HIV prevention and treatment efforts. We developed a drama-based intervention to promote VCT services in a peri-urban community in South Africa. METHODS: Young adults from the community received training in HIV/AIDS and drama, and developed sketches to address perceived barriers to VCT. Over 12 months, 80 performances were held in busy community settings. The intervention was evaluated through changes in VCT uptake at the local clinic compared with comparable communities nearby. RESULTS: After the start of the intervention in August 2003, a 172% increase in the uptake of VCT services was observed in the intervention community. This was significantly greater than demand for VCT in either of the control communities during the same period (P < 0.0001). CONCLUSION: A structured, community-based education program based on drama can lead to substantial increases in the demand for VCT services in resource-limited settings.
Adult↗
When to initiate highly active antiretroviral therapy in sub-Saharan Africa? A South African cost-effectiveness study.
BACKGROUND: Large-scale programmes increasing access to highly active antiretroviral therapy (HAART) are being implemented in sub-Saharan Africa. However, cost-effectiveness of initiating treatment at different CD4 count thresholds has not been explored in resource-poor settings. METHODS: A cost-effectiveness analysis was conducted from a public health perspective using primary treatment outcomes, healthcare utilisation and cost data (Jan 2004 local prices; US dollars 1=7.6 Rands) derived from the Cape Town AIDS Cohort. A Markov state-transition model was developed to estimate life-expectancy, lifetime costs, quality-adjusted life-years (QALYs), cost per life-year and QALY gained for initiating HAART at three CD4 cell count thresholds (<200/microl, 200-350/microl and >350/microl), including the no antiretroviral therapy (No-ART) alternative. Each treatment option was compared with the next most effective undominated option. RESULTS: Mean life-expectancy was 6.2, 18.8, 21.0 and 23.3 years; discounted (8%) QALYs were 3.1, 6.2, 6.7 and 7.4; and discounted lifetime costs were US dollars 5,250, US dollars 5,434, US dollars 5,740, US dollars 6,588 for No-ART, and therapy initiation at <200/microl, 200-350/microl and >350/microl scenarios respectively. Clinical benefits increased significantly with early therapy initiation. Initiating therapy at <200/microl had an incremental cost-effectiveness ratio (ICER) of US dollars 54 per QALY versus No-ART, 200-350/microl had an ICER of US dollars 616 versus therapy initiation at <200/microl, and >350/microl had an ICER of US dollars 1,137 versus therapy initiation at 200-350/microl. ICERs were sensitive to HAART cost. CONCLUSIONS: HAART is reasonably cost-effective for HIV-infected patients in South Africa, and most effective if initiated when CD4 count >200/microl. Deferring treatment to <200/microl would reduce the aggregate cost of treatment, but this should be balanced against the significant clinical benefits associated with early therapy.
Adult↗
Rapid scale-up of a community-based HIV treatment service: programme performance over 3 consecutive years in Guguletu, South Africa.
BACKGROUND: Despite rapid expansion of antiretroviral therapy (ART) in sub-Saharan Africa there are few longitudinal data describing programme performance during rapid scale-up. METHODS: We compared mortality, viral suppression and programme retention in 3 consecutive years of a public sector community-based ART clinic in a South African township. Data were collected prospectively from establishment of services in October 2002 to the censoring date in September 2005. Viral load and CD4 counts were monitored at 4-monthly intervals. Community-based counsellors provided adherence and programme support. RESULTS: During the study period 1139 ART-naïve patients received ART (161, 280 and 698 in the 1st, 2nd and 3rd years respectively). The median CD4 cell counts were 84 cells/microl (interquartile range (IQR) 42-139), 89 cells/microl (IQR 490-149), and 110 cells/microl (IQR 55-172), and the proportions of patients with World Health Organization (WHO) clinical stages 3 and 4 were 90%, 79% and 76% in each sequential year respectively. The number of counsellors increased from 6 to 28 and the median number of clients allocated to each counsellor increased from 13 to 33. The overall loss to follow-up was .9%. At the date of censoring, the Kaplan-Meier estimates of the proportion of patients still on the programme were 82%, 86% and 91%, and the proportion who were virally suppressed (< 400 copies/ml) were 100%, 92% and 98% for the 2002, 2003 and 2004 cohorts respectively. CONCLUSIONS: While further operational research is required into optimal models of care in different populations across sub-Saharan Africa, these results demonstrate that a single community-based public sector ART clinic can extend care to over 1000 patients in an urban setting without compromising programme performance.
Adolescent↗
Tuberculosis control in South Africa--will HAART help?
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AIDS-Related Opportunistic Infections↗
Cost-effectiveness of highly active antiretroviral therapy in South Africa.
BACKGROUND: Little information exists on the impact of highly active antiretroviral therapy (HAART) on health-care provision in South Africa despite increasing scale-up of access to HAART and gradual reduction in HAART prices. METHODS AND FINDINGS: Use and cost of services for 265 HIV-infected adults without AIDS (World Health Organization [WHO] stage 1, 2, or 3) and 27 with AIDS (WHO stage 4) receiving HAART between 1995 and 2000 in Cape Town were compared with HIV-infected controls matched for baseline WHO stage, CD4 count, age, and socioeconomic status, who did not receive antiretroviral therapy (ART; No-ART group). Costs of service provision (January 2004 prices, USD 1 = 7.6 Rand) included local unit costs, and two scenarios for HAART prices for WHO recommended first-line regimens: scenario 1 used current South African public-sector ART drug prices of $730 per patient-year (PPY), whereas scenario 2 was based on the anticipated public-sector price for locally manufactured drug of $181 PPY. All analyses are presented in terms of patients without AIDS and patients with AIDS. For patients without AIDS, the mean number of inpatient days PPY was 1.08 (95% confidence interval [CI]: 0.97-1.19) for the HAART group versus 3.73 (95% CI: 3.55-3.97) for the No-ART group, and 8.71 (95% CI: 8.40-9.03) versus 4.35 (95% CI: 4.12-5.61), respectively, for mean number of outpatient visits PPY. Average service provision PPY was $950 for the No-ART group versus $1,342 and $793 PPY for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per life-year gained (LYG) was $1,622 for scenario 1 and $675 for scenario 2. For patients with AIDS, mean inpatients days PPY was 2.04 (95% CI: 1.63-2.52) for the HAART versus 15.36 (95% CI: 13.97-16.85) for the No-ART group. Mean outpatient visits PPY was 7.62 (95% CI: 6.81-8.49) compared with 6.60 (95% CI: 5.69-7.62) respectively. Average service provision PPY was $3,520 for the No-ART group versus $1,513 and $964 for the HAART group for scenario 1 and 2, respectively, whereas the incremental cost per LYG was cost saving for both scenarios. In a sensitivity analysis based on the lower (25%) and upper (75%) interquartile range survival percentiles, the incremental cost per LYG ranged from $1,557 to $1,772 for the group without AIDS and from cost saving to $111 for patients with AIDS. CONCLUSION: HAART is a cost-effective intervention in South Africa, and cost saving when HAART prices are further reduced. Our estimates, however, were based on direct costs, and as such the actual cost saving might have been underestimated if indirect costs were also included.
Acquired Immunodeficiency Syndrome↗
Early mortality among adults accessing a community-based antiretroviral service in South Africa: implications for programme design.
OBJECTIVES: To determine rates, risk factors and causes of death among patients accessing a community-based antiretroviral treatment (ART) programme both prior to and following initiation of treatment. METHODS: All in-programme deaths were ascertained between September 2002 and March 2005 among treatment-naive patients enrolled into a prospective community-based ART cohort in Cape Town, South Africa. RESULTS: Of 712 patients (median CD4 cell count, 94 cells/microl), 578 (81%) started triple ART a median of 29 days after enrollment. 68 (9.5%) patients died during 563 person-years of observation. The high pretreatment mortality rate of 35.6 deaths/100 person-years [95% confidence interval (CI), 23.0-55.1) decreased to 2.5/100 person-years (95% CI, 0.9-6.6) at 1 year among those who received ART. However, within the first 90 days from enrollment, 29 of 44 (66%) deaths occurred among patients awaiting ART; these would not be identified by an on-treatment analysis. Multivariate analysis showed that risk of death (both pre-treatment and on-treatment) was independently associated with baseline CD4 cell count and World Health Organization (WHO) clinical stage; stage 4 disease was the strongest risk factor. Major attributed causes of death were wasting syndrome, tuberculosis, acute bacterial infections, malignancy and immune reconstitution disease. CONCLUSIONS: Most early in-programme deaths occurred among patients with advanced immunodeficiency but who had not yet started ART. Programme evaluation using on-treatment analyses greatly underestimated early mortality. This mortality would be reduced by minimizing unnecessary in-programme delays in treatment initiation and by starting ART before development of WHO stage 4 disease.
Adolescent↗