Article

HIV and tuberculosis - Science and implementation to turn the tide and reduce deaths

International Union Against Tuberculosis and Lung Disease, Paris, France.
Journal of the International AIDS Society (Impact Factor: 5.09). 07/2012; 15(2):17396. DOI: 10.7448/IAS.15.2.17396
Source: PubMed

ABSTRACT

Every year, HIV-associated tuberculosis (TB) deprives 350,000 mainly young people of productive and healthy lives.People die because TB is not diagnosed and treated in those with known HIV infection and HIV infection is not diagnosed in those with TB. Even in those in whom both HIV and TB are diagnosed and treated, this often happens far too late. These deficiencies can be addressed through the application of new scientific evidence and diagnostic tools.
A strategy of starting antiretroviral therapy (ART) early in the course of HIV infection has the potential to considerably reduce both individual and community burden of TB and needs urgent evaluation for efficacy, feasibility and broader social and economic impact. Isoniazid preventive therapy can reduce the risk of TB and, if given strategically in addition to ART, provides synergistic benefit. Intensified TB screening as part of the "Three I's" strategy should be conducted at every clinic, home or community-based attendance using a symptoms-based algorithm, and new diagnostic tools should increasingly be used to confirm or refute TB diagnoses. Until such time when more sensitive and specific TB diagnostic assays are widely available, bolder approaches such as empirical anti-TB treatment need to be considered and evaluated. Patients with suspected or diagnosed TB must be screened for HIV and given cotrimoxazole preventive therapy and ART if HIV-positive. Three large randomized trials provide conclusive evidence that ART initiated within two to four weeks of start of anti-TB treatment saves lives, particularly in those with severe immunosuppression. The key to ensuring that these collaborative activities are delivered is the co-location and integration of TB and HIV services within the health system and the community.
Progress towards reducing HIV-associated TB deaths can be achieved through attention to simple and deliverable actions on the ground.

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    • "Antiretroviral therapy has been shown to substantially decrease tuberculosis incidence in persons living with HIV, particularly when it is initiated while CD4 counts are still comparatively high [5], [6], [19]. Consistent with this effect, we observed that the scale-up in antiretroviral therapy programs in Kenya coincided with a more pronounced decline in tuberculosis incidence during 2007–2012 among adults with HIV than among adults without HIV, although we cannot conclude causality based on our analysis. "
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    ABSTRACT: Background In Kenya, the comparative incidences of tuberculosis among persons with and without HIV have not been described, and the differential impact of public health interventions on tuberculosis incidence in the two groups is unknown. Methods We estimated annual tuberculosis incidence stratified by HIV status during 2006–2012 based on the numbers of reported tuberculosis patients with and without HIV infection, the prevalence of HIV infection in the general population, and the total population. We also made crude estimates of annual tuberculosis incidence stratified by HIV status during 1998–2012 by assuming a constant ratio of HIV prevalence among tuberculosis patients compared to the general population. Results Tuberculosis incidence among both adults with HIV and adults without HIV increased during 1998–2004 then remained relatively stable until 2007. During 2007–2012, tuberculosis incidence declined by 28–44% among adults with HIV and by 11–26% among adults without HIV, concurrent with an increase in antiretroviral therapy uptake. In 2012, tuberculosis incidence among adults with HIV (1,839–1,936 cases/100,000 population) was still eight times as high as among adults without HIV (231–238 cases/100,000 population), and approximately one third of tuberculosis cases were attributable to HIV. Conclusions Although tuberculosis incidence has declined among adults with and without HIV, the persistent high incidence of tuberculosis among those with HIV and the disparity between the two groups are concerning. Early diagnosis of HIV, early initiation of antiretroviral therapy, regular screening for tuberculosis, and isoniazid preventive therapy among persons with HIV, as well as tuberculosis control in the general population, are required to address these issues.
    Full-text · Article · Jun 2014 · PLoS ONE
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    • "Significant child mortality can be averted if antiretroviral therapy (ART) is started early [11] [12] [13] [14]. However, despite overwhelming evidence demonstrating the benefits of ART, in practice high mortality and poor retention persist among HIV-infected children and adolescents in care in the resource-limited settings of SSA. "
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    ABSTRACT: We describe factors determining retention and survival among HIV-infected children and adolescents engaged in two health care delivery models in Kampala, Uganda: one is a community home-based care (CHBC) and the other is a facility-based family-centred approach (FBFCA). This retrospective cohort study reviewed records from children aged from 0 to 18 years engaged in the two models from 2003 to 2010 focussing on retention/loss to follow-up, mortality, use of antiretroviral therapy (ART), and clinical characteristics. Kaplan Meier survival curves with log rank tests were used to describe and compare retention and survival. Overall, 1,623 children were included, 90.0% (1460/1623) from the CHBC. Children completed an average of 4.2 years of follow-up (maximum 7.7 years). Median age was 53 (IQR: 11–109) months at enrolment. In the CHBC, retention differed significantly between patients on ART and those not (log-rank test, adjusted, ). Comparing ART patients in both models, there was no significant difference in long-term survival (log-rank test, , adjusted, ), while retention was higher in the CHBC: 94.8% versus 84.7% in the FBFCA (log-rank test, , adjusted ). Irrespective of model of care, children receiving ART had better retention in care and survival.1. Background Sub-Saharan Africa (SSA) is home to the vast majority of infants, children, and adolescents living with HIV and morbidity and mortality remain high [1–3]. For example, mortality among HIV-infected children has been measured at 4.3% per year in East Africa and 8.3% in West Africa [4, 5]. A recent meta-analysis conducted in SSA reported a higher risk of early death among perinatally infected children [6]. Studies have also shown that substantial proportions of children and adolescents initiate treatment in SSA with advanced disease (46.3%–72.0%) and comorbidities such as tuberculosis (TB) (5.7%–34.0%) and malnutrition (33%–54%) that tend to be associated with early mortality and poor clinical outcomes [7–10].Significant child mortality can be averted if antiretroviral therapy (ART) is started early [11–14]. However, despite overwhelming evidence demonstrating the benefits of ART, in practice high mortality and poor retention persist among HIV-infected children and adolescents in care in the resource-limited settings of SSA. In addition to scarce resources for programmes for children, the situation is compounded by a combination of factors including late HIV diagnosis, missed opportunities to initiate ART, health care programmes not tailored to the needs of the infected child and their family, and logistic bottlenecks in implementation of care and treatment programmes [15, 16]. Initiation of ART even among children known to be eligible may be missed. For instance, in a study of ART-eligible children in The Gambia, only 32.7% started ART, 47.1% were lost to follow-up, and 13.5% died before initiating ART [17].Retention in care while awaiting ART eligibility can also be a challenge. As an illustration, retention varied from 71% to 95% and 62% to 93% at 12 and 24 months, respectively, among children and adolescents in ART programmes in several countries of SSA [18]. A prior study in Uganda showed that even with frequent CD4 monitoring, HIV-infected children experienced significant clinical events while ineligible for ART according to the 2006 WHO guidelines [19]. Another study in Uganda showed that mortality was highest among HIV-infected children under two years [20]. Given this situation, it is important to assess factors that determine survival and retention in care among HIV-infected children and adolescents in care in resource-limited settings.The present study focuses on retention and survival in two different ART delivery models for HIV-infected children and adolescents in Kampala, Uganda. One is a facility-based, family-centred approach (FBFCA) adopted by the mother to child transmission (MTCT)-Plus programme of the Makerere University-Johns Hopkins University (MU-JHU) Research Collaboration. The other is a community home-based care (CHBC) implemented by the children’s HIV programme of the Home Care Department of Nsambya Hospital. The American Academy of Paediatrics defined family-centred care as based on the understanding that the family is the child’s primary source of strength and support [21]. Beyond that, the family provides an enabling environment for using index HIV patients to reach other infected and affected family members, build family support for therapy and chronic care, integrate other medical needs for the family, and thus enhance uptake of services for HIV and other medical conditions for the family as a unit [22]. In general, CHBC includes any form of care (physical, psychosocial, palliative, and spiritual) given to the sick and the affected in their own homes and care extended from the hospital or health facility to their homes through family participation and community involvement [23, 24].Factors that determine retention and survival of HIV-infected children and adolescents in these health care models are not well understood. The present study therefore aims at identifying factors that determine these outcomes for the CHBC of Nsambya Hospital and the FBFCA of MU-JHU. We also examine pre-ART deaths among children and adolescents in the CHBC to compare mortality rates prior to and after ART initiation and to ascertain whether children experiencing mortality prior to initiating ART had met the 2010 WHO [25] or the 2011 updated United States (US) [26] treatment guidelines for initiating ART or not.2. Methods2.1. Study Design, Setting, and PopulationThis retrospective cohort study covered eight years of records review (2003 to 2010) from two facilities implementing HIV paediatric programmes in Kampala, Uganda. They included the children’s HIV programme of the Home Care Department of Nsambya Hospital, which uses community home-based care (CHBC) and the MTCT-plus programme of MU-JHU Research Collaboration, which adopts a facility-based family-centred approach (FBFCA). Prior to the study, all children in the FBFCA had been initiated on ART; thus, the record review at the FBFCA involved only children on ART. The facilities are both private-not-for-profit but differ in service delivery approaches, including catchment areas and enrolment practices. The study population included all HIV positive infants, children, and adolescents aged 0–18 years, enrolled in both programmes over the study period. Services are generally free of charge under both models.2.2. Description of Health Care ModelsThe FBFCA of MU-JHU Collaboration was established in 2003 with funding from Columbia University. Its catchment area includes Kampala and Wakiso districts and covers approximately 20 km radius from Mulago hospital in Kampala. Enrolment into the FBFCA occurred between 2003 and 2005 and targeted all HIV-infected family members as a unit. However, HIV-infected pregnant women in PMTCT served as the starting point for identifying other infected family members such as infants, children, and spouses or partners to be enrolled into care. Eligibility of the women included being pregnant, testing HIV positive, attendance of PMTCT clinic, disclosure of HIV status to spouse or partner, willingness to be home visited, and living within 20 km radius from Mulago Hospital. The FBFCA offered comprehensive HIV care, including early infant diagnosis (EID), treatment and psychosocial support services, other medical services, and routine follow-up to eligible women and their families. All children enrolled in the study had been initiated on ART prior to the study start date, in contrast to the CHBC. The programme has a uniform design that has been implemented in many countries. Although funding ended in December 2011, the families continue to be followed in a family care approach with funding from the US President’s Emergency Plan for AIDS Relief (PEPFAR).The CHBC also started in 2003 and it integrates facility-based care with home-based care using community involvements as important linkages to decentralize HIV services. It has a catchment area covering four districts: Kampala, Wakiso, Mukono, and Mpigi within 21 km radius from Nsambya hospital. In contrast to the FBFCA, children and adolescents in the CHBC were identified directly for participation. The components of the CHBC, details of enrolment practice, pre-ART care, and ART care packages, as well as patient tracking system, have been described in an earlier work [27]. The CHBC was funded by international donors and partners and indirectly supported by PEPFAR.Both health care models share some common elements such as providing additional support including nutritional supplements, patient education, and counselling of patients and their caregivers. Additionally, peer support groups for both adults and children have been developed to promote emotional support. Other components of psychosocial support include financial assistance for income generating activities, a music, dance, and drama group, and home visiting to track defaulting patients. Furthermore, the FBFCA trains peer-educators to provide support and help in the clinics.2.3. Clinical and Laboratory Follow-UpPatients were followed up routinely using similar appointment systems, standard guidelines, and procedures. Generally, children on ART had monthly clinic visits under both models, while visits for pre-ART patients depended on their clinical conditions and varied between one month under the CHBC and 3–6 months under the FBFCA. Initiation of ART was based on the Ugandan National ART guidelines that are adopted from the WHO guidelines [25, 28–30], which have changed over time, especially with the more recent move in 2013 to initiate treatment in all children under 5 years of age, irrespective of clinical or immune status [11]. During visits, patients were evaluated clinically using WHO clinical staging, age, weight, height, ART status, and laboratory investigations like haemoglobin levels and 6-monthly CD4 cell counts to monitor response to therapy. Adherence to clinical appointments was assessed using appointment schedules, while adherence to medication was assessed by caregivers and self-reports in addition to pill counts. Apart from ART, patients in care received universal Cotrimoxazole prophylaxis for opportunistic infections and secondary prophylaxis for cryptococcal meningitis.2.4. Study OutcomesThe main study outcomes were (a) retention in care, (b) deaths among patients on ART, and (c) pre-ART deaths (deaths before ART initiation) among patients in the CHBC programme. Death was ascertained through medical records and verbal autopsies carried out by trained community volunteers and counsellors. Retention was defined as the proportion of patients known to be alive (either by patient record review or by telephone calls or home visits) and in care at the end of the follow-up period. We defined loss to follow-up (LTFU) as 90 days or more (if on ART) and 180 days or more (if not on ART) without contact since the last clinic appointment. Attrition included deaths and LTFU. Known transfers to continue ART or care at other facilities were not considered as attrition.2.5. Statistical AnalysisWe analysed factors that determined retention and mortality among children and adolescents enrolled in the two HIV service delivery models described above. We used frequency distributions, medians, and interquartile range (IQR) to describe baseline characteristics and compared these using Chi-square and Wilcoxon Rank-Sum tests, respectively. The baseline characteristics included age groups (at enrolment), gender, CD4 cell counts, CD4 percent, growth responses (weight-for-age and height-for-age -scores), WHO disease stages, ART status, and age at ART initiation. Because of differences in baseline characteristics in the two study groups, all analyses were adjusted for age at ART initiation, CD4 percent, CD4 cell counts, proportions on ART, nutritional status, and WHO clinical staging using Cox regression. In addition, Cox regression was used to determine factors associated with attrition among patients on ART in both models and among patients in the CHBC separately, in unadjusted and adjusted analyses. Kaplan Meier curves with log rank tests were used to describe and compare retention and survival, stratified by model of care as well as by age groups. Data on CD4 cell count and CD4 percent were log transformed because of skewed distribution. Finally, we used Chi-square test to examine the number and proportions of children dying prior to ART initiation in terms of whether they met or did not meet the 2011 US or 2010 WHO guidelines for initiating ART. All statistical testing was two-sided and conducted at the 5% significance level. Data from both programmes were extracted from databases, merged, and analysed with Intercooled STATA software version 12.Ethical clearance was approved by the MildMay Institutional Review Board and Ethics Committee, and the study was registered by the Uganda National Council for Science and Technology (UNCST, ref. no. HS 1021). The relevant committees waived informed consent. The study was funded by the University of Padua and supported by Casa Accoglienza alla vita padre Angelo and PENTA Foundation.3. Results3.1. Baseline CharacteristicsOverall, 1,623 infants, children, and adolescents were included in the analyses, 90.0% (1460/1623) were in the CHBC (Table 1). There were slightly but not significantly more females compared to males. At enrolment, 47.1% in the CHBC and 38.9% in the FBFCA were over 60 months of age (). Baseline median CD4 cell counts were 393 cells/mm3 in the CHBC versus 727 cells/mm3 in FBFCA () and median CD4 percents were 5.8% in CHBC versus 17.0% in FBFCA (). By WHO clinical staging, 86.4% and 96.9% were in stages I-II in the CHBC and FBFCA, respectively, versus 13.6% and 3.1% in stages III-IV in the CHBC and FBFCA, respectively (). ART was initiated among 30.2% in the CHBC model compared to 100% in the FBFCA (). Median age at ART initiation was 91.0 months for children in the CHBC versus 45.9 months in the FBFCA (). In terms of growth response, 37.4% in the CHBC versus 16.9% in the FBFCA had weight-for-age -scores of ≤−2SD (), while 55.7% in the CHBC versus 69.7% in the FBFCA had height-for-age -scores of >−2SD ().
    Full-text · Article · Apr 2014
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    • "A very encouraging finding from this is that almost all (i.e. all but one) co-infected HIV-TB patient and all HIV-positive pregnant women reached ART centres which is very encouraging as compared to results of studies elsewhere [7,9]. This reflects the fruits of joint operational efforts led by both NACP and the Revised National Tuberculosis Control Programme (RNTCP) to improve joint TB-HIV management in recent years. "
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    ABSTRACT: Introduction One important operational challenge facing antiretroviral treatment (ART) programmes in low- and middle-income countries is the loss to follow-up between diagnosis of human immunodeficiency virus (HIV) and initiation of ART. This is a major obstacle to achieving universal access to ART. This study from Karnataka, India, tried to measure such losses by determining the number of HIV-positive individuals diagnosed, the number of them reaching ART centres, the number initiated on ART and the reasons for non-initiation of ART. Methods A review of records routinely maintained under the National AIDS Control Programme (NACP) was carried out in six districts of Karnataka. HIV-positive persons diagnosed during the months from January to June 2011 in 233 public HIV-testing sites were followed up until December 2011 based on the pre-ART registers. A chi-square test was used to assess statistical significance. Results Of 2291 HIV-positive persons diagnosed (52% male; mean age of 35 years), 1829 (80%) reached ART centres. Of the latter, 1166 (64%) were eligible for ART, and 959 (82%) were initiated on treatment. Overall losses (attrition) on the road between HIV diagnosis and ART initiation were 669 (29%). Deaths, migration and not willing to go to the ART centres were cited as the main known reasons for not reaching ART centres. For ART-eligible individuals who did not initiate ART, the most common known reasons for non-initiation included dying before initiation of ART and not being willing to start ART. Conclusions In a large state of India, eight in ten HIV-positive persons reached ART centres, and of those found ART eligible, 82% start treatment. Although this is an encouraging achievement, the programme needs to take further steps to improve the current performance by further reducing pre-ART attrition. We recommend online registering of diagnosed HIV-positive patients to track the patients more efficiently.
    Full-text · Article · Aug 2013 · Journal of the International AIDS Society
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