Tuberculosis in Healthcare Workers and Infection Control Measures at Primary Healthcare Facilities in South Africa

Background

Challenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers.

Methods

One hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained.

Results

The standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02) as was the number of staff (OR=3.78, 95%CI 1.77-8.08). In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08).

Conclusion

The high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB.     

Outcomes of Antiretroviral Therapy in Vietnam: Results from a National Evaluation

Objectives

Vietnam has significantly scaled up its national antiretroviral therapy (ART) program since 2005. With the aim of improving Vietnam’s national ART program, we conducted an outcome evaluation of the first five years of the program in this concentrated HIV epidemic where the majority of persons enrolled in HIV care and treatment services are people who inject drugs (PWID). The results of this evaluation may have relevance for other national ART programs with significant PWID populations.

Design

Retrospective cohort analysis of patients at 30 clinics randomly selected with probability proportional to size among 120 clinics with at least 50 patients on ART.

Methods

Charts of patients whose ART initiation was at least 6 months prior to the study date were abstracted. Depending on clinic size, either all charts or a random sample of 300 charts were selected. Analyses were limited to treatment-naïve patients. Multiple imputations were used for missing data.

Results

Of 7,587 patient charts sampled, 6,875 were those of treatment-naïve patients (74.4% male, 95% confidence interval [CI]: 72.4–76.5, median age 30, interquartile range [IQR]: 26–34, 62.0% reported a history of intravenous drug use, CI: 58.6–65.3). Median baseline CD4 cell count was 78 cells/mm³ (IQR: 30–162) and 30.4% (CI: 25.8–35.1) of patients were at WHO stage IV. The majority of patients started d4T/3TC/NVP (74.3%) or d4T/3TC/EFV (18.6%). Retention rates after 6, 12, 24, and 36 months were 88.4% (CI: 86.8–89.9), 84.0% (CI: 81.8–86.0), 78.8% (CI: 75.7–81.6), and 74.6% (CI: 69.6–79.0). Median CD4 cell count gains after 6, 12, 24, and 36 months were 94 (IQR: 45–153), 142 (IQR: 78–217), 213 (IQR: 120–329), and 254 (IQR: 135–391) cells/mm³. Patients who were PWID showed significantly poorer retention.

Conclusions

The study showed good retention and immunological response to ART among a predominantly PWID group of patients despite advanced HIV infections at baseline.     

Strengthening Health Systems at Facility-Level: Feasibility of Integrating Antiretroviral Therapy into Primary Health Care Services in Lusaka,Zambia

Introduction

HIV care and treatment services are primarily delivered in vertical antiretroviral (ART) clinics in sub-Saharan Africa but there have been concerns over the impact on existing primary health care services. This paper presents results from a feasibility study of a fully integrated model of HIV and non-HIV outpatient services in two urban Lusaka clinics.

Methods

Integration involved three key modifications: i) amalgamation of space and patient flow; ii) standardization of medical records and iii) introduction of routine provider initiated testing and counseling (PITC). Assessment of feasibility included monitoring rates of HIV case-finding and referral to care, measuring median waiting and consultation times and assessing adherence to clinical care protocols for HIV and non-HIV outpatients. Qualitative data on patient/provider perceptions was also collected.

Findings

Provider and patient interviews at both sites indicated broad acceptability of the model and highlighted a perceived reduction in stigma associated with integrated HIV services. Over six months in Clinic 1, PITC was provided to 2760 patients; 1485 (53%) accepted testing, 192 (13%) were HIV positive and 80 (42%) enrolled. Median OPD patient-provider contact time increased 55% (6.9 vs. 10.7 minutes; p<0.001) and decreased 1% for ART patients (27.9 vs. 27.7 minutes; p = 0.94). Median waiting times increased by 36 (p<0.001) and 23 minutes (p<0.001) for ART and OPD patients respectively. In Clinic 2, PITC was offered to 1510 patients, with 882 (58%) accepting testing, 208 (24%) HIV positive and 121 (58%) enrolled. Median OPD patient-provider contact time increased 110% (6.1 vs. 12.8 minutes; p<0.001) and decreased for ART patients by 23% (23 vs. 17.7 minutes; p<0.001). Median waiting times increased by 47 (p<0.001) and 34 minutes (p<0.001) for ART and OPD patients, respectively.

Conclusions

Integrating vertical ART and OPD services is feasible in the low-resource and high HIV-prevalence setting of Lusaka, Zambia. Integration enabled shared use of space and staffing that resulted in increased HIV case finding, a reduction in stigma associated with vertical ART services but resulted in an overall increase in patient waiting times. Further research is urgently required to assess long-term clinical outcomes and cost effectiveness in order to evaluate scalability and generalizability.     

Economic Outcomes of Patients Receiving Antiretroviral Therapy for HIV/AIDS in South Africa Are Sustained through Three Years on Treatment

Background

Although the medical outcomes of antiretroviral therapy (ART) for HIV/AIDS are well described, less is known about how ART affects patients'' economic activities and quality of life, especially after the first year on ART. We assessed symptom prevalence, general health, ability to perform normal activities, and employment status among adult antiretroviral therapy patients in South Africa over three full years following ART initiation.

Methodology/Principal Findings

A cohort of 855 adult pre-ART patients and patients on ART for <6 months was enrolled and interviewed an average of 4.4 times each during routine clinic visits for up to three years after treatment initiation using an instrument designed for the study. The probability of pain in the previous week fell from 74% before ART initiation to 32% after three years on ART, fatigue from 66% to 12%, nausea from 28% to 4%, and skin problems from 55% to 10%. The probability of not feeling well physically yesterday fell from 46% to 23%. Before starting ART, 39% of subjects reported not being able to perform their normal activities sometime during the previous week; after three years, this proportion fell to 10%. Employment rose from 27% to 42% of the cohort. Improvement in all outcomes was sustained over 3 years and for some outcomes increased in the second and third year.

Conclusions/Significance

Improvements in adult ART patients'' symptom prevalence, general health, ability to perform normal activities, and employment status were large and were sustained through the first three years on treatment. These results suggest that some of the positive economic and social externalities anticipated as a result of large-scale treatment provision, such as increases in workforce participation and productivity and the ability of patients to carry on normal lives, may indeed be accruing.     

Measuring the Impact of Antiretroviral Therapy Roll-Out on Population Level Fertility in Three African Countries

Background

UNAIDS official estimates of national HIV prevalence are based on trends observed in antenatal clinic surveillance, after adjustment for the reduced fertility of HIV positive women. Uptake of ART may impact on the fertility of HIV positive women, implying a need to re-estimate the adjustment factors used in these calculations. We analyse the effect of antiretroviral therapy (ART) provision on population-level fertility in Southern and East Africa, comparing trends in HIV infected women against the secular trends observed in uninfected women.

Methods

We used fertility data from four community-based demographic and HIV surveillance sites: Kisesa (Tanzania), Masaka and Rakai (Uganda) and uMkhanyakude (South Africa). All births to women aged 15–44 years old were included in the analysis, classified by mother’s age and HIV status at time of birth, and ART availability in the community. Calendar time period of data availability relative to ART Introduction varied across the sites, from 5 years prior to ART roll-out, to 9 years after. Calendar time was classified according to ART availability, grouped into pre ART, ART introduction (available in at least one health facility serving study site) and ART available (available in all designated health facilities serving study site). We used Poisson regression to calculate age adjusted fertility rate ratios over time by HIV status, and investigated the interaction between ART period and HIV status to ascertain whether trends over time were different for HIV positive and negative women.

Results

Age-adjusted fertility rates declined significantly over time for HIV negative women in all four studies. However HIV positives either had no change in fertility (Masaka, Rakai) or experienced a significant increase over the same period (Kisesa, uMkhanyakude). HIV positive fertility was significantly lower than negative in both the pre ART period (age adjusted fertility rate ratio (FRR) range 0.51 95%CI 0.42–0.61 to 0.73 95%CI 0.64–0.83) and when ART was widely available (FRR range 0.57 95%CI 0.52–0.62 to 0.83 95%CI 0.78–0.87), but the difference has narrowed. The interaction terms describing the difference in trends between HIV positives and negatives are generally significant.

Conclusions

Differences in fertility between HIV positive and HIV negative women are narrowing over time as ART becomes more widely available in these communities. Routine adjustment of ANC data for estimating national HIV prevalence will need to allow for the impact of treatment.     

Taking ART to Scale: Determinants of the Cost and Cost-Effectiveness of Antiretroviral Therapy in 45 Clinical Sites in Zambia

Background

We estimated the unit costs and cost-effectiveness of a government ART program in 45 sites in Zambia supported by the Centre for Infectious Disease Research Zambia (CIDRZ).

Methods

We estimated per person-year costs at the facility level, and support costs incurred above the facility level and used multiple regression to estimate variation in these costs. To estimate ART effectiveness, we compared mortality in this Zambian population to that of a cohort of rural Ugandan HIV patients receiving co-trimoxazole (CTX) prophylaxis. We used micro-costing techniques to estimate incremental unit costs, and calculated cost-effectiveness ratios with a computer model which projected results to 10 years.

Results

The program cost $69.7 million for 125,436 person-years of ART, or $556 per ART-year. Compared to CTX prophylaxis alone, the program averted 33.3 deaths or 244.5 disability adjusted life-years (DALYs) per 100 person-years of ART. In the base-case analysis, the net cost per DALY averted was $833 compared to CTX alone. More than two-thirds of the variation in average incremental total and on-site cost per patient-year of treatment is explained by eight determinants, including the complexity of the patient-case load, the degree of adherence among the patients, and institutional characteristics including, experience, scale, scope, setting and sector.

Conclusions and Significance

The 45 sites exhibited substantial variation in unit costs and cost-effectiveness and are in the mid-range of cost-effectiveness when compared to other ART programs studied in southern Africa. Early treatment initiation, large scale, and hospital setting, are associated with statistically significantly lower costs, while others (rural location, private sector) are associated with shifting cost from on- to off-site. This study shows that ART programs can be significantly less costly or more cost-effective when they exploit economies of scale and scope, and initiate patients at higher CD4 counts.     

Outcomes in Cochrane Systematic Reviews Addressing Four Common Eye Conditions: An Evaluation of Completeness and Comparability

Introduction

Choice of outcomes is critical for clinical trialists and systematic reviewers. It is currently unclear how systematic reviewers choose and pre-specify outcomes for systematic reviews. Our objective was to assess the completeness of pre-specification and comparability of outcomes in all Cochrane reviews addressing four common eye conditions.

Methods

We examined protocols for all Cochrane reviews as of June 2013 that addressed glaucoma, cataract, age-related macular degeneration (AMD), and diabetic retinopathy (DR). We assessed completeness and comparability for each outcome that was named in ≥25% of protocols on those topics. We defined a completely-specified outcome as including information about five elements: domain, specific measurement, specific metric, method of aggregation, and time-points. For each domain, we assessed comparability in how individual elements were specified across protocols.

Results

We identified 57 protocols addressing glaucoma (22), cataract (16), AMD (15), and DR (4). We assessed completeness and comparability for five outcome domains: quality-of-life, visual acuity, intraocular pressure, disease progression, and contrast sensitivity. Overall, these five outcome domains appeared 145 times (instances). Only 15/145 instances (10.3%) were completely specified (all five elements) (median = three elements per outcome). Primary outcomes were more completely specified than non-primary (median = four versus two elements). Quality-of-life was least completely specified (median = one element). Due to largely incomplete outcome pre-specification, conclusive assessment of comparability in outcome usage across the various protocols per condition was not possible.

Discussion

Outcome pre-specification was largely incomplete; we encourage systematic reviewers to consider all five elements. This will indicate the importance of complete specification to clinical trialists, on whose work systematic reviewers depend, and will indirectly encourage comparable outcome choice to reviewers undertaking related research questions. Complete pre-specification could improve efficiency and reduce bias in data abstraction and analysis during a systematic review. Ultimately, more completely specified and comparable outcomes could make systematic reviews more useful to decision-makers.     

An Evaluation of Systematic Tuberculosis Screening at Private Facilities in Karachi,Pakistan

Background

In Pakistan, like many Asian countries, a large proportion of healthcare is provided through the private sector. We evaluated a systematic screening strategy to identify people with tuberculosis in private facilities in Karachi and assessed the approaches'' ability to diagnose patients earlier in their disease progression.

Methods and Findings

Lay workers at 89 private clinics and a large hospital outpatient department screened all attendees for tuberculosis using a mobile phone-based questionnaire during one year. The number needed to screen to detect a case of tuberculosis was calculated. To evaluate early diagnosis, we tested for differences in cough duration and smear grading by screening facility. 529,447 people were screened, 1,010 smear-positive tuberculosis cases were detected and 942 (93.3%) started treatment, representing 58.7% of all smear-positive cases notified in the intervention area. The number needed to screen to detect a smear-positive case was 124 (prevalence 806/100,000) at the hospital and 763 (prevalence 131/100,000) at the clinics; however, ten times the number of individuals were screened in clinics. People with smear-positive TB detected at the hospital were less likely to report cough lasting 2–3 weeks (RR 0.66 95%CI [0.49–0.90]) and more likely to report cough duration >3 weeks (RR 1.10 95%CI [1.03–1.18]). Smear-positive cases at the clinics were less likely to have a +3 grade (RR 0.76 95%CI [0.63–0.92]) and more likely to have +1 smear grade (RR 1.24 95%CI [1.02–1.51]).

Conclusions

Tuberculosis screening at private facilities is acceptable and can yield large numbers of previously undiagnosed cases. Screening at general practitioner clinics may find cases earlier than at hospitals although more people must be screened to identify a case of tuberculosis. Limitations include lack of culture testing, therefore underestimating true TB prevalence. Using more sensitive and specific screening and diagnostic tests such as chest x-ray and Xpert MTB/RIF may improve results.     

Elimination of HIV in South Africa through Expanded Access to Antiretroviral Therapy: A Model Comparison Study

Background

Expanded access to antiretroviral therapy (ART) using universal test and treat (UTT) has been suggested as a strategy to eliminate HIV in South Africa within 7 y based on an influential mathematical modeling study. However, the underlying deterministic model was criticized widely, and other modeling studies did not always confirm the study''s finding. The objective of our study is to better understand the implications of different model structures and assumptions, so as to arrive at the best possible predictions of the long-term impact of UTT and the possibility of elimination of HIV.

Methods and Findings

We developed nine structurally different mathematical models of the South African HIV epidemic in a stepwise approach of increasing complexity and realism. The simplest model resembles the initial deterministic model, while the most comprehensive model is the stochastic microsimulation model STDSIM, which includes sexual networks and HIV stages with different degrees of infectiousness. We defined UTT as annual screening and immediate ART for all HIV-infected adults, starting at 13% in January 2012 and scaled up to 90% coverage by January 2019. All models predict elimination, yet those that capture more processes underlying the HIV transmission dynamics predict elimination at a later point in time, after 20 to 25 y. Importantly, the most comprehensive model predicts that the current strategy of ART at CD4 count ≤350 cells/µl will also lead to elimination, albeit 10 y later compared to UTT. Still, UTT remains cost-effective, as many additional life-years would be saved. The study''s major limitations are that elimination was defined as incidence below 1/1,000 person-years rather than 0% prevalence, and drug resistance was not modeled.

Conclusions

Our results confirm previous predictions that the HIV epidemic in South Africa can be eliminated through universal testing and immediate treatment at 90% coverage. However, more realistic models show that elimination is likely to occur at a much later point in time than the initial model suggested. Also, UTT is a cost-effective intervention, but less cost-effective than previously predicted because the current South African ART treatment policy alone could already drive HIV into elimination. Please see later in the article for the Editors'' Summary     

Determinants and Consequences of Failure of Linkage to Antiretroviral Therapy at Primary Care Level in Blantyre, Malawi: A Prospective Cohort Study

Background

Poor rates of linkage from HIV diagnosis to ART initiation are a major barrier to universal coverage of ART in sub-Saharan Africa, with reasons for failure poorly understood. In the first study of this kind at primary care level, we investigated the pathway to care in the Malawian National Programme, one of the strongest in Africa.

Methods and Findings

A prospective cohort study was undertaken at two primary care clinics in Blantyre, Malawi. Newly diagnosed HIV-positive adults (>15 years) were followed for 6-months to assess completion of eligibility assessments, initiation of ART and death. Two hundred and eighty participants were followed for 82.6 patient-years. ART eligibility assessments were problematic: only 134 (47.9%) received same day WHO staging and 121 (53.2%) completed assessments by 6-months. Completion of CD4 measurement (stage 1/2 only) was 81/153 (52.9%). By 6-months, 87/280 (31.1%) had initiated ART with higher uptake in participants who were ART eligible (68/91, 74.7%), and among participants who received same-day staging (52/134 [38.8%] vs. 35/146 [24.0%] p = 0.007). Non-completion of ART eligibility assessments (adjusted hazard ratio: 0.11, 95% CI: 0.06–0.21) was associated with failure to initiate ART. Retention in pre-ART care for non-ART initiators was low (55/193 [28.5%]). Of the 15 (5.4%) deaths, 11 (73.3%) occurred after ART initiation.

Conclusions

Although uptake of ART was high and prompt for patients with known eligibility, there was frequent failure to complete eligibility assessment and poor retention in pre-ART care. HIV care programmes should urgently evaluate the way patients are linked to ART. In particular, there is a critical need for simplified, same-day ART eligibility assessments, reduced requirements for hospital visits, and active defaulter follow-up.     

Point-of-Care CD4 Testing to Inform Selection of Antiretroviral Medications in South African Antenatal Clinics: A Cost-Effectiveness Analysis

Background

Many prevention of mother-to-child HIV transmission (PMTCT) programs currently prioritize antiretroviral therapy (ART) for women with advanced HIV. Point-of-care (POC) CD4 assays may expedite the selection of three-drug ART instead of zidovudine, but are costlier than traditional laboratory assays.

Methods

We used validated models of HIV infection to simulate pregnant, HIV-infected women (mean age 26 years, gestational age 26 weeks) in a general antenatal clinic in South Africa, and their infants. We examined two strategies for CD4 testing after HIV diagnosis: laboratory (test rate: 96%, result-return rate: 87%, cost: $14) and POC (test rate: 99%, result-return rate: 95%, cost: $26). We modeled South African PMTCT guidelines during the study period (WHO “Option A”): antenatal zidovudine (CD4 ≤350/μL) or ART (CD4>350/μL). Outcomes included MTCT risk at weaning (age 6 months), maternal and pediatric life expectancy (LE), maternal and pediatric lifetime healthcare costs (2013 USD), and cost-effectiveness ($/life-year saved).

Results

In the base case, laboratory led to projected MTCT risks of 5.7%, undiscounted pediatric LE of 53.2 years, and undiscounted PMTCT plus pediatric lifetime costs of $1,070/infant. POC led to lower modeled MTCT risk (5.3%), greater pediatric LE (53.4 years) and lower PMTCT plus pediatric lifetime costs ($1,040/infant). Maternal outcomes following laboratory were similar to POC (LE: 21.2 years; lifetime costs: $23,860/person). Compared to laboratory, POC improved clinical outcomes and reduced healthcare costs.

Conclusions

In antenatal clinics implementing Option A, the higher initial cost of a one-time POC CD4 assay will be offset by cost-savings from prevention of pediatric HIV infection.     

Monitoring of Antiretroviral Therapy and Mortality in HIV Programmes in Malawi,South Africa and Zambia: Mathematical Modelling Study

Objectives

Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference.

Design:

Mathematical modelling study based on data from ART programmes.

Methods

We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained.

Results

RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74–1.03) in scenario A, 0.94 (0.77–1.02) with delayed switching (scenario B) and 0.80 (0.44–1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality.

Conclusions

VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates.     

Comparison of Perceived and Technical Healthcare Quality in Primary Health Facilities: Implications for a Sustainable National Health Insurance Scheme in Ghana

Background

Quality care in health facilities is critical for a sustainable health insurance system because of its influence on clients’ decisions to participate in health insurance and utilize health services. Exploration of the different dimensions of healthcare quality and their associations will help determine more effective quality improvement interventions and health insurance sustainability strategies, especially in resource constrained countries in Africa where universal access to good quality care remains a challenge.

Purpose

To examine the differences in perceptions of clients and health staff on quality healthcare and determine if these perceptions are associated with technical quality proxies in health facilities. Implications of the findings for a sustainable National Health Insurance Scheme (NHIS) in Ghana are also discussed.

Methods

This is a cross-sectional study in two southern regions in Ghana involving 64 primary health facilities: 1,903 households and 324 health staff. Data collection lasted from March to June, 2012. A Wilcoxon-Mann-Whitney test was performed to determine differences in client and health staff perceptions of quality healthcare. Spearman’s rank correlation test was used to ascertain associations between perceived and technical quality care proxies in health facilities, and ordered logistic regression employed to predict the determinants of client and staff-perceived quality healthcare.

Results

Negative association was found between technical quality and client-perceived quality care (coef. = -0.0991, p<0.0001). Significant staff-client perception differences were found in all healthcare quality proxies, suggesting some level of unbalanced commitment to quality improvement and potential information asymmetry between clients and service providers. Overall, the findings suggest that increased efforts towards technical quality care alone will not necessarily translate into better client-perceived quality care and willingness to utilize health services in NHIS-accredited health facilities.

Conclusion

There is the need to intensify client education and balanced commitment to technical and perceived quality improvement efforts. This will help enhance client confidence in Ghana’s healthcare system, stimulate active participation in the national health insurance, increase healthcare utilization and ultimately improve public health outcomes.     

Temporal Trends in the Characteristics of Children at Antiretroviral Therapy Initiation in Southern Africa: The IeDEA-SA Collaboration

Background

Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration.

Methodology/Principal Findings

Data from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick''s test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<−3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines.

Conclusions/Significance

Between 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children.     

Maternal Antiretroviral Therapy for the Prevention of Mother-To-Child Transmission of HIV in Malawi: Maternal and Infant Outcomes Two Years after Delivery

Background

Optimized preventive strategies are needed to reach the objective of eliminating pediatric AIDS. This study aimed to define the determinants of residual HIV transmission in the context of maternal antiretroviral therapy (ART) administration to pregnant women, to assess infant safety of this strategy, and to evaluate its impact on maternal disease.

Methodology/Principal Findings

A total of 311 HIV-infected pregnant women were enrolled in Malawi in an observational study and received a nevirapine-based regimen from week 25 of gestation until 6 months after delivery (end of breastfeeding period) if their CD4+ count was > 350/mm³ at baseline (n = 147), or indefinitely if they met the criteria for treatment (n. 164). Mother/child pairs were followed until 2 years after delivery. The Kaplan-Meier method was used to estimate HIV transmission, maternal disease progression, and survival at 24 months. The rate of HIV infant infection was 3.2% [95% confidence intervals (CI) 1.0-5.4]. Six of the 8 transmissions occurred among mothers with baseline CD4+ count > 350/mm³. HIV-free survival of children was 85.8% (95% CI 81.4-90.1). Children born to mothers with baseline CD4+ count < 350/mm³ were at increased risk of death (hazard ratio 2.6, 95% CI 1.1-6.1). Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm³ was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation.

Conclusions

HIV transmission in this cohort was rare however, it occurred in a significative proportion among women with high CD4+ counts. Strategies to improve treatment adherence should be implemented to further reduce HIV transmission. Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage. Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered.     

Predictors of CD4:CD8 Ratio Normalization and Its Effect on Health Outcomes in the Era of Combination Antiretroviral Therapy

Background

HIV leads to CD4:CD8 ratio inversion as immune dysregulation progresses. We examined the predictors of CD4:CD8 normalization after combination antiretroviral therapy (cART) and determined whether normalization is associated with reduced progression to AIDS-defining illnesses (ADI) and death.

Methods

A Canadian cohort of HIV-positive adults with CD4:CD8<1.2 prior to starting cART from 2000–2010 were analyzed. Predictors of (1) reaching a CD4:CD8 ≥1.2 on two separate follow-up visits >30 days apart, and (2) ADI and death from all causes were assessed using adjusted proportional hazards models.

Results

4206 patients were studied for a median of 2.77 years and 306 (7.2%) normalized their CD4:CD8 ratio. Factors associated with achieving a normal CD4:CD8 ratio were: baseline CD4+ T-cells >350 cells/mm³, baseline CD8+ T-cells <500 cells/mm³, time-updated HIV RNA suppression, and not reporting sex with other men as a risk factor. There were 213 ADIs and 214 deaths in 13476 person-years of follow-up. Achieving a normal CD4:CD8 ratio was not associated with time to ADI/death.

Conclusions

In our study, few individuals normalized their CD4:CD8 ratios within the first few years of initiating modern cART. This large study showed no additional short-term predictive value of the CD4:CD8 ratio for clinical outcomes after accounting for other risk factors including age and HIV RNA.     

Integrating HIV Care into Primary Care Services: Quantifying Progress of an Intervention in South Africa

Background

Integration of human immunodeficiency virus (HIV) care into primary care services is one strategy proposed to achieve universal access to antiretroviral treatment (ART) for HIV-positive patients in high burden countries. There is a need for controlled studies of programmes to integrate HIV care with details of the services being integrated.

Methods

A semi-quantitative questionnaire was developed in consultation with clinic staff, tested for internal consistency using Cronbach''s alpha coefficients and checked for inter-observer reliability. It was used to conduct four assessments of the integration of HIV care into referring primary care clinics (mainstreaming HIV) and into the work of all nurses within ART clinics (internal integration) and the integration of pre-ART and ART care during the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) trial in South Africa. Mean total integration and four component integration scores at intervention and control clinics were compared using one way analysis of variance (ANOVA). Repeated measures ANOVA was used to analyse changes in scores during the trial.

Results

Cronbach''s alpha coefficients for total integration, pre-ART and ART integration and mainstreaming HIV and internal integration scores showed good internal consistency. Mean total integration, mainstreaming HIV and ART integration scores increased significantly at intervention clinics by the third assessment. Mean pre-ART integration scores were almost maximal at the first assessment and showed no further change. There was no change in mean internal integration score.

Conclusion

The questionnaire developed in this study is a valid tool with potential for monitoring integration of HIV care in other settings. The STRETCH trial interventions resulted in increased integration of HIV care, particularly ART care, by providing HIV care at referring primary care clinics, but had no effect on integrating HIV care into the work of all nurses with the ART clinic.