In HIV-infected persons, good adherence to antiretroviral therapy (ART) is essential for successful treatment outcomes. Patients’ worries before starting ART may affect their ART adherence and treatment outcomes.
Between 2004 and 2009, HIV-infected individuals in a prospective cohort study in rural Uganda were assessed for ART eligibility. A counsellor explained the ART eligibility criteria, adherence and side effects, and recorded the patients’ worries related to ART. Every quarter, patients who initiated ART had clinical, immunological (CD4 cell counts) and virological (viral loads) assessments, and data were collected on ART adherence using patients’ self-reports and pill counts. We describe the patients’ worries and examine their association with ART adherence, and immunological and virological outcomes.
We assessed 421 patients, 271 (64%) were females, 318 (76%) were aged 30 years and above and 315 (75%) were eligible for ART. 277 (66%) reported any worry, and the proportions were similar by sex, age group and ART eligibility status. The baseline median CD4 counts and viral loads were similar among patients with any worry and those with no worry. The commonest worries were: fear of HIV serostatus disclosure; among 69 (16%) participants, lack of food when appetite improved after starting ART; 50 (12%), concurrent use of other medications; 33 (8%), adherence to ART; 28 (7%) and problems concerning condom use; 27 (6%). After 24 months or more on ART, patients who reported any worry had made more scheduled ART refill visits than patients who reported no worry (p<0.01), but the annual CD4 cell increases were similar (p=0.12). After one year on ART, patients who reported any worry had greater virological suppression than patients who reported no worry (p<0.05).
Despite the lack of significant associations of worries with unfavourable ART outcomes, physicians and counsellors should assist patients in overcoming their worries that can cause stress and discomfort. Food supplements may be desirable for some patients initiating ART.
Antiretroviral therapy; Patients’ worries; Adherence; Treatment outcomes
Cryptococcal meningitis is a leading cause of death in AIDS patients and contributes substantially to the high early mortality in antiretroviral treatment (ART) programs in low-resource settings. Screening for cryptococcal antigen (CRAG) in patients enrolling in ART programs may identify those at risk of cryptococcal meningitis and permit targeted use of pre-emptive therapy.
In this retrospective study, CRAG was measured in stored plasma samples obtained from patients as they enrolled in a well characterised ART cohort in South Africa. The predictive value of screening for CRAG prior to ART for development of microbiologically confirmed cryptococcal meningitis or death during the first year of follow-up was determined.
Of 707 participants with a baseline median CD4 count of 97 (IQR 46-157) cells/μL, 46 (7%) had a positive CRAG. Antigenaemia was 100% sensitive for predicting development of cryptococcal meningitis during the first year of ART and in multivariate analysis was an independent predictor of mortality (AHR 3.2, 95%CI 1.5-6.6). Most (92%) cases of cryptococcal meningitis developed in patients with a CD4 count ≤100 cells/μL. In this sub-set of patients, a CRAG titre ≥1 in 8 was 100% sensitive and 96% specific for predicting incident cryptococcal meningitis during the first year of ART in those with no previous history of the disease.
CRAG screening prior to commencing ART in patients with a CD4 count ≤100 cells/μL is highly effective at identifying those at risk of cryptococcal meningitis and death and might permit implementation of a targeted pre-emptive treatment strategy.
Cryptococcus neoformans; cryptococcosis; Africa; antiretroviral therapy; HIV; cryptococcal antigenemia; screening
Despite the efficacy and tolerability of modern antiretroviral therapy (ART), many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized.
We examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDS-defining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease. We focused on participants who, despite ART had failed to achieve virologic suppression and substantive immune reconstitution.
233 ART-receiving participants entered with a median baseline CD4+ T cell count of 30/mm3 and plasma HIV RNA of 5 log10 copies/mL. During a median 96 weeks of follow-up, 24.0% died (a mortality rate of 10.7/100 patient-years); 27.5% reported a new AIDS-defining condition, and 22.3% a new serious non-AIDS event. Of the deaths, 42.8% were due to an AIDS-defining condition, 44.6% were due to a non-AIDS-defining condition, and 12.5% were of unknown etiology. Decreased risk of mortality was associated with baseline CD4+ T cell count ≥25/mm3 and lower baseline HIV RNA.
Among patients with advanced AIDS prescribed modern ART who achieve neither virologic suppression nor immune reconstitution, crude mortality percentages appear to be lower than reported in cohorts of patients studied a decade earlier. Also, in contrast to the era before modern ART became available, nearly half of the deaths in our modern-era study were caused by serious non-AIDS-defining events. Even among the most advanced AIDS patients who were not obtaining apparent immunologic and virologic benefit from ART, continued prescription of these medications appears to alter the natural history of AIDS—improving survival and shifting the causes of death from AIDS- to non-AIDS-defining conditions.
In South Africa, many HIV-infected patients experience delays in accessing antiretroviral therapy (ART). We examined pre-treatment mortality and access to treatment in patients waiting for ART.
Cohort of HIV-infected patients assessed for ART eligibility at 36 facilities participating in the Comprehensive HIV and AIDS Management (CHAM) program in the Free State Province.
Proportion of patients initiating ART, pre-ART mortality and risk factors associated with these outcomes were estimated using competing risks survival analysis.
44,844 patients enrolled in CHAM between May 2004 and December 2007, of whom 22,083 (49.2%) were eligible for ART; pre-ART mortality was 53.2 per 100 person-years (95% CI 51.8-54.7). Median CD4 count at eligibility increased from 87 cells/mm3 in 2004 to 101 cells/mm3 in 2007. Two years after eligibility an estimated 67.7% (67.1% – 68.4%) of patients had started ART, and 26.2% (25.6% - 26.9%) died before starting ART. Among patients with CD4 counts <25 cells/mm3 at eligibility, 48% died before ART and 51% initiated ART. Men were less likely to start treatment and more likely to die than women. Patients in rural clinics or clinics with low staffing levels had lower rates of starting treatment and higher mortality compared with patients in urban/ peri-urban clinics, or better staffed clinics.
Mortality is high in eligible patients waiting for ART in the Free State Province. The most immunocompromised patients had the lowest probability of starting ART and the highest risk of pre-ART death. Prioritization of these patients should reduce waiting times and pre-ART mortality.
HIV; ART; South Africa; waiting times; mortality; treatment access
Many resource-limited countries are scaling up antiretroviral treatment (ART) towards universal access. However, there are few studies which evaluated outcomes of ART programs in these countries. In addition, these studies generally include a limited number of facilities and patients creating a clear need for studies with a wide range of facilities and large numbers of patients. In this study, we intended to evaluate the outcomes of the ART services in 55 health facilities in Ethiopia.
A retrospective longitudinal study was conducted to determine levels of patient retention in care, CD4 count and shift to second-line ART regimen in 30 hospitals and 25 health centers selected as sentinel sites for monitoring the outcomes of ART program in the country. The outcomes were determined at baseline, after 6, 12 and 24 months on ART. Data was collected from routine patient registers and charts, and entered and analyzed using EPI-Info statistical software.
Health facilities were able to retain 29,893 (80%), 20,079 (74%) and 5,069 (68%) of their patients after 6, 12 and 24 months on ART, respectively. Retention rates vary across health facilities, ranging from 51% to 85% after 24 months on ART. Mortality was 5%, 6% and 8% after 6, 12 and 24 months on ART. More than 79% of patients with available CD4-cell counts had a baseline CD4-cell counts less than 200 cells per micro-liter of blood. The median CD4-cell counts (based on patients who were retained after 24 months on ART) increased from 125 (inter-quartile (IQ), 68-189) at baseline to 242 (IQ, 161-343), 269 (IQ, 185-380) and 316 (IQ, 226-445) cells per micro-liter after 6, 12, and 24 months on ART, respectively. The transition to second-line ART remained very low, 0.33%, 0.58% and 2.13% after 6, 12 and 24 months on ART.
The outcomes of the ART services in the 55 health facilities in Ethiopia are similar to those in other countries. Retention of patients in care is a major challenge and varies across health facilities with high, medium and low retention rates. We therefore recommend further studies to understand the organization of care in health facilities with high, medium and low retention rates. It is also imperative that early initiation of patients on ART is taken seriously as more than 79% of the patients had baseline CD4-cell counts less than 200 cells per micro-liter of blood. Finally, we recommend that the shift to second-line ART might be too low and warrants close monitoring.
In sub-Saharan Africa, many patients initiate antiretroviral therapy (ART) at CD4+ cell counts much lower than those recommended in national guidelines. We examined program-level and contextual-level factors associated with low median CD4+ cell count at ART initiation in populations initiating ART.
Multilevel analysis of aggregate and program-level service delivery data.
We examined data on 1690 cohorts of patients initiating ART during 2004–2008 in eight sub-Saharan African countries. Cohorts with median CD4+ less than 111 cells/μl (the lowest quartile) were classified as having low median CD4+ cell count at ART initiation. Cohort information was combined with time-updated program-level data and subnational contextual-level data, and analyzed using multilevel models.
The 1690 cohorts had median CD4+ cell count of 136 cells/μl and included 121 504 patients initiating ART at 267 clinics. Program-level factors associated with low cohort median CD4+ cell count included urban setting [adjusted odds ratio (AOR) 2.1; 95% confidence interval (CI) 1.3–3.3], lower provider-to-patient ratio (AOR 2.2; 95% CI 1.3–4.0), no PMTCT program (AOR 3.6; 95% CI 1.0–12.8), outreach services for ART patients only vs. both pre-ART and ART patients (AOR 2.4; 95% CI 1.5–3.9), fewer vs. more adherence support services (AOR 1.6; 95% CI 1.0–2.5), and smaller cohort size (AOR 2.5; 95% CI 1.4–4.5). Contextual-level factors associated with low cohort median CD4+ cell count included initiating ART in areas where a lower proportion of the population heard of AIDS, tested for HIV recently, and a higher proportion believed ‘limiting themselves to one HIV-uninfected sexual partner reduces HIV risk’.
Determinants of CD4+cell count at ART initiation in populations initiating ART operate at multiple levels. Structural interventions targeting points upstream from ART initiation along the continuum from infection to diagnosis to care engagement are needed.
CD4; HIV/AIDS; HIV scale-up; implementation science; late antiretroviral therapy initiation; multilevel; operations research; PEPFAR
Background and Methods
Little is known about antiretroviral therapy (ART) outcomes in prisoners in Africa. We conducted a retrospective review of outcomes of a large cohort of prisoners referred to a public sector, urban HIV clinic. The review included baseline characteristics, sequential CD4 cell counts and viral load results, complications and co-morbidities, mortality and loss to follow-up up to 96 weeks on ART.
148 inmates (133 male) initiated on ART were included in the study. By week 96 on ART, 73% of all inmates enrolled in the study and 92% of those still accessing care had an undetectable viral load (<400copies/ml). The median CD4 cell count increased from 122 cells/mm3 at baseline to 356 cells/mm3 by 96 weeks. By study end, 96 (65%) inmates had ever received tuberculosis (TB) therapy with 63 (43%) receiving therapy during the study: 28% had a history of TB prior to ART initiation, 33% were on TB therapy at ART initiation and 22% developed TB whilst on ART. Nine (6%) inmates died, 7 in the second year on ART. Loss to follow-up (LTF) was common: 14 (9%) patients were LTF whilst still incarcerated, 11 (7%) were LTF post-release and 9 (6%) whose movements could not be traced. 16 (11%) inmates had inter-correctional facility transfers and 34 (23%) were released of whom only 23 (68%) returned to the ART clinic for ongoing follow-up.
Inmates responded well to ART, despite a high frequency of TB/HIV co-infection. Attention should be directed towards ensuring eligible prisoners access ART programs promptly and that inter-facility transfers and release procedures facilitate continuity of care. Institutional TB control measures should remain a priority.
To assess the effect of aging on the immunological response to antiretroviral therapy (ART) in the West African context.
The change in CD4 T-cell count was analysed according to age at the time of ART initiation among HIV-infected patients enrolled in the International epidemiological Database to Evaluate AIDS (IeDEA) Collaboration in the West African region. CD4 gain over 12 months of ART was estimated using linear mixed models. Models were adjusted for baseline CD4 cell count, sex, baseline clinical stage, calendar period and ART regimen.
The total number of patients included was 24 107, contributing for 50 893 measures of CD4 cell count in the first year of ART. The baseline median CD4 cell count was 144 cells/μl [interquartile range (IQR) 61–235]; median CD4 cell count reached 310 cells/μl (IQR 204–443) after 1 year of ART. The median age at treatment initiation was 36.3 years (10th–90th percentiles=26.5–50.1). In adjusted analysis, the mean CD4 gain was significantly higher in younger patients (P < 0.0001). At 12 months, patients below 30 years recovered an additional 22 cells/μl on average [95% confidence interval (CI) 2–43] compared to patients at least 50 years.
Among HIV-infected adults in West Africa, the immunological response after 12 months of ART was significantly poorer in elderly patients. As the population of treated patients is likely to get older, the impact of this age effect on immunological response to ART may increase over time.
age; antiretroviral treatment; HIV/AIDS; immunological response; linear mixed models; West Africa
Although the survival benefits of antiretroviral therapy (ART) for the treatment of HIV infection are well established, the clinical management of HIV disease continues to present major challenges. There are particular concerns regarding access to appropriate HIV treatment among HIV-infected injection drug users (IDU).
In a prospective cohort study of HIV-infected IDU in Vancouver, Canada, we examined initial ART regimens vis-à-vis the provincial government's therapeutic guidelines at the time ART was initiated. Briefly, there have been four sets of guidelines: Era 1 (1992 to November 1995; double-drug (dual NRTIs) ART for patients with a CD4 cell count of 350 or less); Era 2 (December 1995 to May 1996; double-drug therapy for patients with a CD4+ cell count of 500 or less); Era 3 (June 1996 to June 1997; triple-drug therapy (dual NRTIs with a PI or NNRTI) for patients who had a plasma viral load of > 100,000 HIV-1 RNA copies/mL; dual therapy with two NRTIs for those with a plasma viral load of 5,000 to 100,000 HIV-1 RNA copies/mL); Era 4 (since July 1997; universal use of triple drug therapy as first-line treatment).
Between May 1996 and May 2003, 431 HIV-infected individuals were enrolled into the cohort. By May 31, 2003, 291 (67.5%) individuals had initiated ART. We noted instances of inappropriate antiretroviral prescription in each guideline era, with 9 (53%) in Era 1, 3 (12%) in Era 2, 22 (28%) in Era 3, and 23 (15%) in Era 4. Of the 57 subjects who received an inappropriate ART regimen initially, 14 never received the appropriate therapy; among the remaining 43, the median time to the initiation of a guideline-appropriate ART regimen was 12 months (inter-quartile range 5 – 20).
The present study identified measurable rates of guideline-inappropriate ART prescription for patients who were injection drug users. Rates were highest in the era of dual therapy, although high rates persisted into the triple-therapy era. As therapeutic guidelines continue to evolve, it is critical that mechanisms be put in place to ensure prescription of ART combinations for IDU that are consistent with current expert recommendations.
Barriers to HIV treatment among injection drug users (IDU) are a major public health concern. However, there remain few long-term studies investigating key demographic and behavioral factors - and gender differences in particular - that may pose barriers to antiretroviral therapy (ART), especially in settings with universal healthcare. We evaluated access and adherence to ART in a long-term cohort of HIV-positive IDU in a setting where medical care and antiretroviral therapy are provided free of charge through a universal healthcare system.
We evaluated baseline antiretroviral use and subsequent adherence to ART among a Canadian cohort of HIV-positive IDU. We used generalized estimating equation logistic regression to evaluate factors associated with 95% adherence to antiretroviral therapy estimated based on prescription refill compliance.
Between May 1996 and April 2008, 545 IDU participants were followed for a median of 23.8 months (Inter-quartile range: 8.5 - 91.6), among whom 341 (63%) were male and 204 (37%) were female. Within the six-month period prior to the baseline interview, 133 (39%) men and 62 (30%) women were on ART (p = 0.042). After adjusting for clinical characteristics as well as drug use patterns measured longitudinally throughout follow-up, female gender was independently associated with a lower likelihood of being 95% adherent to ART (Odds Ratio [OR] = 0.70; 95% Confidence Interval: 0.53-0.93).
Despite universal access to free HIV treatment and medical care, female IDU were less likely to access and adhere to antiretroviral therapy, a finding that was independent of drug use and clinical characteristics. These data suggest that interventions to improve access to HIV treatment among IDU must be tailored to address unique barriers to antiretroviral therapy faced by female IDU.
Reasons for the variation in reported treatment outcomes from antiretroviral therapy (ART) programmes in developing countries are not clearly defined.
Among ART-naïve individuals in a workplace ART programme in South Africa we determined virological outcomes at 12 months, and risk factors for suboptimal virological outcome, defined as plasma HIV-1 viral load >= 400 copies/ml.
Among 1760 individuals starting ART before July 2004, 1172 were in follow-up at 12 months of whom 953 (81%) had a viral load measurement (median age 41 yrs, 96% male, median baseline CD4 count 156 × 106/l). 71% (681/953) had viral load < 400 copies/ml at 12 months. In a multivariable analysis, independent predictors of suboptimal virological outcome at 12 months were <1 log decrease in viral load at six weeks (odds ratio [OR] 4.71, 95% confidence interval [CI] 2.56–8.68), viral load at baseline (OR 3.63 [95% CI 1.88–7.00] and OR 3.54 [95% CI 1.79–7.00] for 10,001–100,000 and >100,000 compared to <= 10,000 copies/ml, respectively), adherence at six weeks (OR 3.50 [95% CI 1.92–6.35]), WHO stage (OR 2.08 [95% CI 1.28–3.34] and OR 2.03 [95% CI 1.14–3.62] for stage 3 and 4 compared to stage 1–2, respectively) and site of ART delivery. Site of delivery remained an independent risk factor even after adjustment for individual level factors. At 6 weeks, of 719 patients with self-reported adherence and viral load, 72 (10%) reported 100% adherence but had <1 log decrease in viral load; conversely, 60 (8%) reported <100% adherence but had >= 1 log decrease in viral load.
Virological response at six weeks after ART start was the strongest predictor of suboptimal virological outcome at 12 months, and may identify individuals who need interventions such as additional adherence support. Self reported adherence was less strongly associated but identified different patients compared with viral load at 6 weeks. Site of delivery had an important influence on virological outcomes; factors at the health system level which influence outcome need further investigation to guide development of effective ART programmes.
The use of combination antiretroviral therapy (cART) has become a standard of care for the treatment of HIV infection. However, cost and resistance to cART are major obstacles for access to treatment especially in resource-limited settings. In this study, we aimed to determine the incidence and risk factors of treatment failure in a cohort of treatment-naïve Thai HIV-infected patients.
A retrospective cohort study was conducted among HIV-infected patients initiating their first cART at Chiang Mai University Hospital, Thailand.
From January 2002 to December 2008, 788 patients were enrolled; 365 were male (46.3%), and the mean age was 37.9 ± 8.6 years. The median baseline CD4 count was 57.7 cells/mm3 (IQR 22, 127). GPO-VIR® (a fixed-dose combination of lamivudine, stavudine, and nevirapine) was the most common prescribed cART (657 patients, 83.4%). Seventy-six patients developed virological failure given the cumulative incidence of 9.6%. The incidence of virological failure was 2.79 (95% CI 2.47, 3.14) cases per 100 person years. Poor adherence was the strongest predictor for virological failure. Of 535 immunologically evaluable patients, 179 (33.5%) patients developed immunological failure. A low CD4 cell count at baseline (< 100 cells/mm3) and the increment of CD4 cell count of < 50 cell/mm3 after 6 months of cART were the predictors for immunological failure (p < 0.001).
This study demonstrated that even in resource-limited settings, the high rate of success could be expected in the cohort with good and sustainable drug adherence. Poor adherence, older age, and low baseline CD4 cell count are the predictors for unfavorable outcome of cART.
Incidence; Risk factors; Antiretroviral Treatment Failure; Treatment-naïve
National programs are facing challenges of loss to follow-up of people living with HIV/AIDS (PLWHA) on antiretroviral therapy (ART). We sought to identify risk factors associated with early loss to follow-up among HIV-infected patients on ART in Togo and the outcome of such patients.
This was a retrospective cross-sectional study using medical records of all patients older than age 15 years enrolled at 28 treatment centers who were on ART programs and who were lost to follow-up from 2008 to 2011.
Of the 16,617 patients on ART, 1,216 (7.3%) were lost to follow-up. Most (94.1%) were infected with HIV-1 and 32.6% were in WHO stage III or IV. The median CD4 count was 118/mm3 (IQR: 58-178 cells/mm3). No telephone number was mentioned in the medical records of 212 patients. Of the 1004 patients whose phone number was listed, 802 patients (79.9%) were not reachable on the recorded number, 114 patients (11.4%) were alive and 88 patients (8.8%) had died. In multivariate analysis, factors associated with loss to follow-up during the first 6 months of ART were: age below 35 years (OR = 1.6; 95%CI: 1.2-2.2), female sex (OR = 1.8; 95%CI: 1.3-2.5), WHO stage III or IV (OR = 1.7; 95%CI: 1.3-2.2), existence of an opportunistic infection (OR = 2.3; 95%CI: 1.5-3.1), and follow-up in a public centre (OR = 1.9; 95%CI: 1.2-3.3).
This study identified several factors associated with lost to follow-up during the first 6 months of ART, and confirmed high mortality among these patients. The National AIDS Program should strengthen medical support of PLWHA in Togo including active case follow-up.
Africa; HIV; human immunodeficiency virus; lost to follow-up; people living with HIV; Togo
Retention in long-term antiretroviral therapy (ART) program remains a major challenge for effective management of HIV infected people in sub-Saharan Africa. Highly Active Antiretroviral Therapy (ART) discontinuation raises concerns about drug resistance and could negate much of the benefit sought by ART programs.
Based on existing patient records, we assessed determinants of retention in HIV care among HIV patients enrolled in an urban ART at two urban hospitals in Cameroon. Extended Cox regression procedures were used to identify significant predictors of retention in HIV care.
Of 455 patients, 314 (69%) were women, median (IQR) age and baseline CD4 cell count were respectively 36 years (30 – 43) and 110 cells/μL (39 – 177). Forty patients (9%) had active tuberculosis (TB) at enrollment. After a median (IQR) follow-up of 18 months (10–18), 346 (75%) were still in care, 8 (2%) were known dead, and 101 (22%) were lost to follow-up (LFU). Severe immunosuppression (CD4 cell count ≤ 50 cells/μL) at baseline (aHR 2.3; 95% CI 1.4 – 3.7) and active tuberculosis upon enrollment (aHR 1.8; 95% CI 1.0 – 3.6) were independent predictors of cohort losses to follow-up within the first 6 months after HAART initiation.
These data suggest that three-quarter of HIV patients initiated on HAART remained in care and on HAART by 18 months; however, those with compromised immunologic status at treatment initiation, and those co-infected with TB were at increased risk for being lost to follow-up within the first 6 months on treatment.
low income country
retention in care
loss to follow-up
In Mozambique during 2004–2007 numbers of adult patients (≥15 years
old) enrolled on antiretroviral therapy (ART) increased about 16-fold, from
<5,000 to 79,500. All ART patients were eligible for co-trimoxazole. ART
program outcomes, and determinants of outcomes, have not yet been
In a retrospective cohort study, we investigated rates of mortality,
attrition (death, loss to follow-up, or treatment cessation), immunologic
treatment failure, and regimen-switch, as well as determinants of selected
outcomes, among a nationally representative sample of 2,596 adults
initiating ART during 2004–2007. At ART initiation, median age of
patients was 34 and 62% were female. Malnutrition and advanced
disease were common; 18% of patients weighed <45 kilograms, and
15% were WHO stage IV. Median baseline CD4+ T-cell
count was 153/µL and was lower for males than females (139/µL
vs. 159/µL, p<0.01). Stavudine, lamivudine, and nevirapine or
efavirenz were prescribed to 88% of patients; only 31% were
prescribed co-trimoxazole. Mortality and attrition rates were 3.4 deaths and
19.8 attritions per 100 patient-years overall, and 12.9 deaths and 57.2
attritions per 100 patient-years in the first 90 days. Predictors of
attrition included male sex [adjusted hazard ratio (AHR) 1.5;
95% confidence interval (CI), 1.3–1.8], weight <45 kg
(AHR 2.1; 95% CI, 1.6–2.9, reference group >60 kg), WHO
stage IV (AHR 1.7; 95% CI, 1.3–2.4, reference group WHO stage
I/II), lack of co-trimoxazole prescription (AHR 1.4; 95% CI,
1.0–1.8), and later calendar year of ART initiation (AHR 1.5;
95% CI, 1.2–1.8). Rates of immunologic treatment failure and
regimen-switch were 14.0 and 0.6 events per 100-patient years,
ART initiation at earlier disease stages and scale-up of co-trimoxazole among
ART patients could improve outcomes. Research to determine reasons for low
regimen-switch rates and increasing rates of attrition during program
expansion is needed.
To determine the baseline prevalence of tuberculosis (TB) in a cohort using a strategy of intensive pretreatment screening for TB and the subsequent incidence rate and temporal distribution of cases during the first year of antiretroviral therapy (ART).
Prospective observational community-based ART cohort in South Africa.
Adults enrolling for ART and who did not have a current TB diagnosis were intensively screened for TB at baseline using culture of two sputum samples, chest radiography and investigations for extrapulmonary disease as required. Patients who developed symptoms consistent with incident TB during ART were similarly investigated.
Two hundred forty-one patients had a median CD4 cell count of 125 cells/μl (interquartile range 70–186) and 200 (83%) started ART. TB was diagnosed in 87 (36%) patients, with 82% of pulmonary cases being culture-proven. Most TB cases (87%) were prevalent disease detectable at baseline, whereas just 11 (13%) were incident cases that presented during the first year of ART. The incidence rate during 0–4 months of ART was similar to the rate during months 5–12 of ART [10.9 (95% confidence interval [CI] 4.6–23.3) cases per 100 person-years versus 8.1 (95% CI 3.6–18.0) cases per 100 person-years].
Systematic culture-based screening detected a very high burden of prevalent TB present at baseline. This intensified screening strategy was associated with an approximately two-fold lower incidence rate in the first 4 months of ART than previously observed in this cohort. This suggests that many incident cases of symptomatic TB presenting during early ART can be detected as prevalent disease prior to ART initiation using sensitive diagnostic tests.
The clinical data of plasma NVP level, safety and efficacy of antiretroviral therapy (ART) for the concurrent use of nevirapine (NVP)-based ART and fluconazole (FLU) is scanty.
A retrospective study was conducted in patients who were initiated NVP-based ART between October 2004 and November 2005. The objectives were to compare NVP levels, adverse events, and 36-week efficacy of NVP-based ART between patients who did not receive FLU (group A) and those who received FLU 200 mg/day or 400 mg/day (group B).
There were 122 patients with mean ± SD age of 36 ± 9 years; 81 in group A and 41 in group B. Median (IQR) baseline CD4 cell count was 29 (8–79) cell/mm3 in group A and 19 (8–33) cell/mm3 in group B (P = 0.102). Baseline characteristics between the two groups were similar. Mean ± SD NVP levels were 6.5 ± 3.0 mg/L in group A and 11.4 ± 6.1 mg/L in group B(P < 0.001). One (2.4%) patient in group B developed clinical hepatitis (P = 0.336). Six (7.4%) patients in group A developed NVP-related skin rashes (P = 0.096). There were no differences in term of 36-week antiviral efficacy between the two groups (P > 0.05).
Co-administration of NVP and daily dosage of FLU (200 mg/day and 400 mg/day) results in markedly increased trough plasma NVP level when compared to the administration of NVP alone. The concurrent use of NVP and FLU in very advanced HIV-infected patients is well-tolerated. The immunological and virological responses are favorable.
Random effects models were used to explore how the shape of CD4 cell count responses after commencing combination antiretroviral therapy (cART) develop over time, and in particular the role of baseline and follow-up covariates.
Patients in APHOD who first commenced cART after January 1, 1997, and who had a baseline CD4 cell count and viral load measure and at least one follow-up measure between 6 and 24 months, were included. CD4 cell counts were determined at every 6-month period following the commencement of cART for up to 6 years.
1638 patients fulfilled the inclusion criteria with a median follow up time of 58 months. Lower post-cART mean CD4 cell counts were found to be associated with increasing age (p<0.001), pre-cART hepatitis C co-infection (p=0.038), prior AIDS (p=0.019), baseline viral load ≤ 100,000 copies/ml (p<0.001), and the Asia-Pacific region compared with Australia (p=0.005). A highly significant 3-way interaction between the effects of time, baseline CD4 cell count and post-cART viral burden (p<0.0001) was demonstrated. Higher long-term mean CD4 cell counts were associated with lower baseline CD4 cell count and consistently undetectable viral loads. Among patients with consistently detectable viral load CD4 cell counts appeared to converge for all baseline CD4 levels.
Our analyses suggest that the long-term shape of post-cART CD4 cell count changes depends only on a 3-way interaction between baseline CD4 cell count, viral load response and time.
antiretroviral therapy; long-term CD4 response; viral load response
Ekiti State of Nigeria is known to have the lowest prevalence of HIV in Nigeria. University Teaching Hospital (UTH), Ado Ekiti was recently upgraded to serve as one of the three centres for HIV/AIDS referral, diagnosis and treatment in Ekiti State. We evaluated the baseline immunologic and biochemical parameters of patients presenting at the ART clinic of University Teaching Hospital, Ado Ekiti, Ekiti State.
All HIV seropositive patients not yet on antiretroviral therapy, who presented at the ART Clinic within the study period had at the first visit to the clinic, their blood sample taken for CD4 cell counts estimation, HBsAg and anti- HCV screening, ALT, AST as well as hemoglobin estimation as part of the routine workup to assess their disease health status and need for antiretroviral therapy. Statistical significance was taken as p< 0.05.
A total of 273 patients comprising 79 (28.9%) males and 194 (71.1%) females were included in the study (F:M = 2.46: 1). The mean age of the study population was 36.21± 10.20 years with mean age of males (39.52 ± 9.95years) significantly higher than females (34.88 ± 10.02; p=0.001). The overall prevalence of HBsAg in the study population was 6.6% with a sex specific prevalence of 8.1% and 6% for males and females, respectively. No statistically significance difference in the mean serum alanine transaminase, serum aspartate transaminase, hemoglobin and CD4+ T- Lymphocytes cell count of those who had HBsAg negative status compared to those who had HBsAg positive status. Two (0.7%) of the patients had positive serum anti HCV antibodies. The CD4+ T- Lymphocytes cell count ranged between 5 – 1050 cells/µl with a mean of 286.19 ± 233.31 cells/µl. The majority of patients (71.8%) had a CD4+ T- Lymphocytes cell count < 350 cells/µl.
At the time of presentation, majority of our patients had a CD4+ T- Lymphocytes cell count less than 350 cells/µl consistent with significant immune-suppression. More sustained and vigorous awareness campaigns still need to be done in Ekiti State to diagnose this disease early. There is also a need to accelerate the integration of hepatitis B virus screening and treatment programme into HIV/AIDS programme because of the morbidity and mortality implication of HBV and HIV co-infection.
HIV AIDS infection; CD4+ T-lymphocyte cell counts; Hepatitis B virus infection
Despite proven benefits of antiretroviral therapy (ART), many HIV-infected injection drug users (IDU) do not access treatment even in settings with free health care. We examined whether methadone maintenance therapy (MMT) increased initiation and adherence to ART among an IDU population with free health care.
We prospectively examined a cohort of opioid-using antiretroviral-naïve HIV-infected IDU and investigated factors associated with initiation of antiretroviral therapy as well as subsequent adherence. Factors independently associated with time to first initiation of antiretroviral therapy were modelled using Cox proportional hazards regression.
Between May 1996 and April 2008, 231 antiretroviral-naïve HIV-infected opioid using IDU were enrolled, among whom 152 (65.8%) initiated ART, for an incidence density of 30.5 (95% confidence interval [CI]: 25.9–35.6) per 100 person-years. After adjustment for time-updated clinical characteristics and other potential confounders, use of MMT was independently associated with more rapid uptake of antiretroviral therapy (relative hazard = 1.62 [95% CI: 1.15–2.28]; p = 0.006). Those prescribed methadone also had higher rates of ART adherence after first antiretroviral initiation (odds ratio = 1.49 [95% CI: 1.07–2.08]; p = 0.019).
These results demonstrate that MMT contributes to more rapid initiation and subsequent adherence to ART among opioid-using HIV-infected IDU. Addressing international barriers to the use and availability of methadone may dramatically increase uptake of HIV treatment among this population.
HIV; AIDS; methadone; ART; Vancouver; Canada
To estimate loss to follow up (LTFU) between initial enrolment and the first scheduled return medical visit of a pre-antiretroviral therapy (ART) care program for patients not eligible for ART.
The study was conducted at a public-sector HIV clinic in Johannesburg. We reviewed records of all patients newly enrolled in the pre-ART care program and not yet eligible for ART between January 2007 and February 2008. Crude proportions of patients completing their first return medical visit stratified by patient characteristics were calculated. A modified-Poisson approach was used to estimate directly relative risks of returning for their first return medical visit within 1 year adjusting for patient characteristics as potential confounders.
A total of 356 patients were identified. Two-thirds had a CD4 count > 350 cells/μl (median [IQR] CD4 = 458 [394, 585]) and were scheduled to return in 6 months for a first medical visit. Seventy-four percent of these patients did not return within one year for this visit. The remaining 36% of all patients had a baseline CD4 count 251–350 cells/μl and were scheduled to return in 3 months. Only 6% of these patients returned within 4 months; 41% returned within one year. Relative risks were positively associated with a patient being employed and negatively associated with the baseline CD4 count.
Given the high rate of LTFU immediately after enroling in pre-ART care, it is clear that care programs are not expediting the timely initiation of ART. Significantly improved adherence to pre-ART care and monitoring for patients not yet eligible for ART is required for South Africa to achieve its AIDS strategy goals and reduce the problem of late presentation and initiation of ART.
HIV care; pre-antiretroviral therapy loss to follow up; South Africa
Antiretroviral therapy (ART) effectively decreases tuberculosis (TB) incidence long-term, but is associated with high TB incidence rates in the first 6 months. We sought to determine the incidence and the long-term effects of TB during ART on HIV treatment outcome, and the risk factors for incident TB during ART in a large urban HIV clinic in Uganda.
Routinely collected longitudinal clinical data from all patients initiated on first-line ART was retrospectively analysed. 5,982 patients were included with a median baseline CD4+ T cell count (CD4 count) of 117 cells/mm3 (interquartile range [IQR]; 42, 182). In the first 2 years, there were 336 (5.6%) incident TB events in 10,710 person-years (py) of follow-up (3.14 cases/100pyar [95% CI 2.82–3.49]); incidence rates at 0–3, 3–6, 6–12 and 12–24 months were 11.25 (9.58–13.21), 6.27 (4.99–7.87), 2.47 (1.87–3.36) and 1.02 (0.80–1.31), respectively. Incident TB during ART was independently associated with baseline CD4 count of <50 cells/mm3 (hazard ratio [HR] 1.84 [1.25–2.70], P = 0.002) and male gender (HR 1.68 [1.34–2.11], P<0.001). After two years on ART, the patients who had developed TB in the first 12 months had a significantly lower median CD4 count increase (184 cells/mm3 [IQR; 107, 258, n = 118] vs 209 cells/mm3 [124, 309, n = 2166], P = 0.01), a larger proportion of suboptimal immune reconstitution according to two definitions (increase in CD4 count <200 cells/mm3: 57.4% vs 46.9%, P = 0.03, and absolute CD4 count <200 cells/mm3: 30.4 vs 19.9%, P = 0.006), and a higher percentage of immunological failure according to the WHO criteria (13.6% vs 6.5%, P = 0.003). Incident TB during ART was independently associated with poor CD4 count recovery and fulfilling WHO immunogical failure definitions.
Incident TB during ART occurs most often within 3 months and in patients with CD4 counts less than 50 cells/mm3. Incident TB during ART is associated with long-term impairment in immune recovery.
Background. Substantial morbidity occurs during the first year of antiretroviral therapy (ART) in persons with advanced human immunodeficiency virus (HIV) disease despite HIV suppression. Biomarkers may identify high-risk groups.
Methods. Pre-ART and 1-month samples from an initial ART trial were evaluated for biomarkers associated with AIDS events or death within 1–12 months. Case patients (n = 63) and control patients (n = 126) were 1:2 matched on baseline CD4 cell count, hepatitis status, and randomization date. All had ≥1 log10 HIV RNA level decrease at 1 month.
Results. Case patients had more frequent prior AIDS events, compared with control patients (P = .004), but similar HIV RNA levels at baseline. Pre-ART and 1-month C-reactive protein (CRP), D-dimer, and interleukin 6 (IL-6) levels and pre-ART hyaluronic acid (HA) levels were associated with new AIDS events or death (P ≤ .01). Patients who experienced immune reconstitution inflammatory syndrome (IRIS) events had higher pre-ART tumor necrosis factor α (TNF-α) and HIV RNA levels and significant 1-month increases in CRP, D-dimer, IL-6, interleukin 8, CXCL10, TNF-α, and interferon-γ levels, compared with patients who experienced non-IRIS events (P ≤ .03). Individuals with baseline CRP and HA levels above the cohort median (>2.1 mg/L and >50.0 ng/mL, respectively) had increased risk of AIDS or death (OR, 4.6 [95% CI, 2.0–10.3]; P < .001) and IRIS (OR, 8.7 [95% CI, 2.2–34.8] P = .002).
Conclusions. Biomarkers of Inflammation (CRP, IL-6), coagulation (D-dimer), and tissue fibrosis (HA) measured pre-ART and at 1 month are associated with higher risk of AIDS events, IRIS, or death, warranting additional study as risk stratification strategies.
Clinical outcomes of HIV-infected children on antiretroviral treatment (ART) in a decentralised, nurse/counsellor-led programme.
KwaZulu-Natal, South Africa.
HIV-infected children aged ≤15 years on ART, June 2004–2008.
Main outcome measures
Survival according to baseline characteristics including age, WHO clinical stage, haemoglobin and CD4%, was assessed in Kaplan–Meier analyses. Hazard ratios for mortality were estimated using Cox proportional hazards regression and changes in laboratory parameters and weight-for-age z scores after 6–12 months' treatment were calculated.
477 HIV-infected children began ART at a median age of 74 months (range 4–180), median CD4 count (CD4%) of 433 cells/mm3 (17%) and median HIV viral load of log 4.2 copies/ml; 105 (22%) were on treatment for tuberculosis and 317 (76.6%) were WHO stage 3/4. There were significant increases after ART initiation in CD4% (17% vs 22%; p<0.001), haemoglobin (9.9 vs 11.7 g/l; p≤0.001) and albumin (30 vs 36 g/l; p≤0.001). 32 (6.7%) children died over 732 child-years of follow-up (43.7 deaths/1000 child-years; 95% CI 32.7 to 58.2), 17 (53.1%) within 90 days of treatment initiation; median age of death was 84 (IQR 10–181) months. Children with baseline haemoglobin ≤8 g/l were more likely to die (adjusted HR 4.5; 95% CI 1.6 to 12.3), as were those aged <18 months compared with >60 months (adjusted HR 3.2; 95% CI 1.2 to 9.1).
Good clinical outcomes in HIV-infected children on ART are possible in a rural, decentralised service. Few young children are on ART, highlighting the urgent need to identify HIV-exposed infants.
CD4 cell count and plasma viral load are well known predictors of AIDS and mortality in HIV-1-infected patients treated with combination antiretroviral therapy (cART). This study investigated, in patients treated for at least 3 years, the respective prognostic importance of values measured at cART initiation, and 6 and 36 months later, for AIDS and death.
Patients from 15 HIV cohorts included in the ART Cohort Collaboration, aged at least 16 years, antiretroviral-naive when they started cART and followed for at least 36 months after start of cART were eligible.
Among 14 208 patients, the median CD4 cell counts at 0, 6 and 36 months were 210, 320 and 450 cells/µl, respectively, and 78% of patients achieved viral load less than 500 copies/ml at 6 months. In models adjusted for characteristics at cART initiation and for values at all time points, values at 36 months were the strongest predictors of subsequent rates of AIDS and death. Although CD4 cell count and viral load at cART initiation were no longer prognostic of AIDS or of death after 36 months, viral load at 6 months and change in CD4 cell count from 6 to 36 months were prognostic for rates of AIDS from 36 months.
Although current values of CD4 cell count and HIV-1 RNA are the most important prognostic factors for subsequent AIDS and death rates in HIV-1-infected patients treated with cART, changes in CD4 cell count from 6 to 36 months and the value of 6-month HIV-1 RNA are also prognostic for AIDS.
cART; CD4 cell count; mortality; plasma HIV-1 RNA; prognosis of AIDS