Cotrimoxazole Preventive Therapy Research Articles

Integrating HIV testing and care into tuberculosis services in Benin: programmatic aspects [Short communication

Between 2005 and 2008, the diagnosis and care of human immunodeficiency virus (HIV) infection and tuberculosis (TB) services were integrated in Benin. The appointment of a TB-HIV Coordinator by the National Tuberculosis Control Programme and quarterly supervisory visits to TB clinics have bolstered the implementation of integrated HIV-TB activities. HIV testing and cotrimoxazole preventive therapy were integrated smoothly into the TB services. The strategy chosen to facilitate access of HIV-positive TB patients to antiretroviral treatment contributed to greater integration over time, but perpetuated, for some, the burden of attending two facilities. The integration and decentralisation of TB and HIV care services at national level in Benin resulted in a high uptake of HIV services among TB patients.

Results of rapid and successful integration of HIV diagnosis and care into tuberculosis services in Benin

Benin, where 20 of 54 tuberculosis (TB) clinics caring for 80% of all TB patients began providing integrated human immunodeficiency virus (HIV) care in 2005. To describe the characteristics and TB treatment outcomes of the first cohorts of TB-HIV patients, and to assess programmatic outcomes. Retrospective cohort study using data from the TB register and the register of co-infected patients. During the study period, 8368 TB patients were registered, 7787 (93%) were tested for HIV and 1255 (16%) were HIV-positive, including 385 (32%) who already knew their positive status. Most patients (88%) were tested within 15 days of TB diagnosis. Female and young patients were overrepresented among the co-infected. Cotrimoxazole preventive therapy was administered to 1152 patients (95%) during anti-tuberculosis treatment, and antiretroviral treatment (ART) to 469 (42%). The likelihood of receiving ART increased as initial CD4 lymphocyte counts decreased. Fifteen per cent of TB-HIV patients died during anti-tuberculosis treatment. Patients already on ART prior to anti-tuberculosis treatment experienced the worst outcomes. Patients who initiated ART early during anti-tuberculosis treatment or in the timeframe recommended by the guidelines fared the best. HIV care has been successfully and sustainably integrated into TB services in Benin. However, ensuring the access of co-infected patients to more favourable treatment outcomes still represents significant challenges.

Public-private mix for TB and TB-HIV care in Lagos, Nigeria

Private and public tuberculosis (TB) treatment centres in Lagos State, Nigeria. To assess the contribution of private health care providers to TB and TB-HIV (human immunodeficiency virus) case finding in Lagos State. A retrospective review of programme data submitted to the Lagos State TB and Leprosy Control Programme in 2011 by public, private for-profit (PFP) and private not-for-profit (PNFP) health care providers. A total of 8425 TB cases were notified by 31 private (11 PFP and 20 PNFP) and 99 public health facilities in Lagos State. Overall, the private facilities were responsible for 10.3% (866/8425) of the total TB cases notified. The proportion of TB patients tested for HIV was respectively 86.2%, 53.1% and 96.5% among public, PFP and PNFP facilities. Overall, 22.4% of the TB patients were HIV-positive. The HIV positivity rate among public, PFP and PNFP facilities was respectively 23.8%, 7.8% and 9.9%. Uptake of cotrimoxazole preventive therapy was respectively 69.6%, 25% and 38.2% among public, PFP and PNFP facilities, while that of antiretroviral therapy was respectively 23.8%, 8.3% and 9.1% in public, PFP and PNFP facilities. There is a need to scale up collaboration with the private sector, and particularly PNFP health providers.

The power of data: using routinely collected data to improve public health programmes and patient outcomes in low‐ and middle‐income countries

‘We are data rich, but information poor!’ So said one of the senior Ministry of Health officials in Fiji when a team from the International Union Against Tuberculosis and Lung Disease and the University of Fiji was discussing the start of an operational research capacity building initiative in that country two years ago. This statement probably sums up the situation for many Ministries of Health and NonGovernmental Organizations (NGOs) in lowand middleincome countries (LMIC), where large amounts of data are regularly collected and collated from health facilities, filed away or shelved and never used, analysed or interpreted to drive improved performance of health services, the scale up of interventions or better outcomes for patients. This paradigm needs to change. Furthermore, such data could be used in the context of operational research to ask more farreaching questions about quality, coverage, safety and effectiveness of programmes or health systems. National tuberculosis control programmes (NTPs) throughout the world serve as a model for data collection. One of the essential components of the WHO Stop TB Strategy is a standardised monitoring, evaluation and reporting system to account for all TB cases diagnosed along with their treatment outcomes through cohort monitoring (WHO 2006). Within well-functioning NTPs, TB officers review patient data every three months in terms of who and how many are accessing treatment, whether treatment outcomes are satisfactory, and whether adverse outcomes such as death or loss to follow-up are being kept to a minimum. These data are used to assess programme performance, and they also serve as the foundation for district and national drug forecasting and procurement. The routine data can also form the basis of operational research, which we define as research into strategies, interventions, tools or knowledge that can enhance the quality, coverage, effectiveness or performance of the health system or disease programme in which the research is being conducted (Zachariah et al. 2009). Between 1996 and 2005, the Malawi NTP formally incorporated operational research into its routine activities, and a large number of research projects were undertaken to improve policy and practice and reduce morbidity and mortality of patients (WHO 1999). One particular example concerned high case-fatality rates in HIV-infected TB patients before the advent of antiretroviral therapy (ART). The country undertook a series of district-based operational research studies to determine whether it was feasible to offer a package of HIV testing and cotrimoxazole preventive therapy (CPT) to TB patients registered under routine programme conditions (Harries et al. 2011). Using routinely collected data, and paying particular attention during this time to ensuring that mortality data were reliable and complete, the studies showed a significant reduction in death rates of between 20–25%. This evidence persuaded the Malawi Ministry of Health to support the scale up of HIV testing and CPT countrywide for TB patients, and activities started soon after completion of the research in 2003. Between 2002 and 2008, routinely collected data showed a significant increase in HIV testing amongst TB patients with the majority of HIVpositive patients being started on CPT. Treatment outcomes in new smear-positive pulmonary TB patients

Determinant Factors Associated with Occurrence of Tuberculosis among Adult People Living with HIV after Antiretroviral Treatment Initiation in Addis Ababa, Ethiopia: A Case Control Study

IntroductionTuberculosis (TB) is a leading morbidity and mortality, and the first presenting sign in majority of people living with Human Immune deficiency Virus (PLWH). Determinants of active TB among HIV patients on anti retroviral treatment (ART) are not well described in resource limited settings. The aim of this study was to assess determinant factors for the occurrence of TB among people living with HIV after ART initiation in public hospitals and health centers in Addis Ababa, Ethiopia.Methods and FindingsA case control study was conducted from December 2011 to February 2012 in 2 public hospitals and 13 health centers in Addis Ababa. The study population consisted of 204 cases and 409 controls. Cases were adult people living with HIV who developed TB after ART initiation and controls were adult people living with HIV who did not develop TB after ART initiation. An interviewer administered structured questionnaire was used to collect information.After adjustment for potential confounders, presence of isoniazid prophylaxis (adjusted odd ratio [AOR] 0.35, 95% confidence interval [CI] 0.125, 0.69) and cotrimoxazole prophylaxis (AOR = 0.19; 95% CI: 0.06, 0.62) had protective benefit against risk of TB. In contrary, bedridden (AOR = 9.36; 95% CI: 3.39, 25.85), having World Health Organization (WHO) clinical stage III/IV (AOR = 3.40; 95% CI: 1.69, 6.87) and hemoglobin level <10 mg/dl (AOR = 7.43; 95% CI; 3.04, 18.31) at enrollment to ART care were predictors for increased risk of tuberculosis in PLWH after ART initiation.ConclusionIncreasing coverage of isoniazid preventive therapy and cotrimoxazole preventive therapy reduced risk of TB among HIV patients who started treatment. All PLWH should be screened for TB, but for patients who have advanced disease condition (WHO clinical stage III/IV, being bedridden and having hemoglobin level <10 mg/dl) intensified screening is highly recommended during treatment follow up.

Are routine tuberculosis programme data suitable to report on antiretroviral therapy use of HIV-infected tuberculosis patients?

BackgroundAntiretroviral therapy (ART) is lifesaving for HIV-infected tuberculosis (TB) patients. ART-use by these patients lag behind compared to HIV-testing and co-trimoxazole preventive therapy. TB programmes provide the data on ART-use by HIV-infected TB patients, however often the HIV services provide the ART. We evaluated whether the data on ART-use in the TB register were complete and correct. The timing of ART initiation was evaluated to assess whether reporting on ART-use could have happened with the TB case finding reporting. We collected data on TB treatment, HIV testing and ART for adult TB cases in 2007 from three TB clinics in Manica Province, Mozambique. These data on use of ART from TB registers were compared with those from the HIV services.FindingsOf 628 patients included, 504 (81%) were tested and of these 356 (71%) were HIV-infected. Of the co-infected patients, 81% registered with the HIV services in the same facility. The TB register was correct on ART-use in 73% of co-infected cases and complete in 74%. Information on ART-use could have been reported with the TB case finding reports in 56% of co-infected patients.ConclusionThe TB register is reasonably correct and complete on ART-use. However, the HIV patient record seems a much better source to provide this information. Reporting on ART-use at the end of the quarter in which TB treatment starts provides the programme with timely but incomplete information. A more complete but less timely picture is available after a year.

Predictors of mortality among children on Antiretroviral Therapy at a referral hospital, Northwest Ethiopia: A retrospective follow up study

BackgroundAn estimated 2.5 million children were living with HIV/AIDS at the end of 2009, 2.3 million (92%) in sub-Saharan Africa. Without treatment, a third of children with HIV will die of AIDS before their first birthday, half dying before two years of age. Hence, this study aimed to assess magnitude and predictors of mortality among children on Antiretroviral Therapy (ART) at a referral hospital in North-West Ethiopia.MethodsInstitution based retrospective follow up study was carried out among HIV-positive children from January 1st, 2006 - March 31st, 2011. Information on relevant variables was collected from patients’ charts and registries. Life table was used to estimate the cumulative survival of children. Log rank tests were employed to compare survival between the different categories of the explanatory variables. Multivariate Cox proportional hazards model was fitted to identify predictors of mortality.ResultsA total of 549 records were included in the analysis. The mean age at initiation of treatment was 6.35 ±3.78 SD years. The median follow up period was 22 months. At the end of the follow up, 41(7.5%) were dead and 384(69.9%) were alive. Mortality was 4.0 deaths per 100 child-years of follow-up period. The cumulative probabilities of survival at 3, 6, 12, 24, and 60 months of ART were 0.96, 0.94, 0.93, 0.92 and 0.83 respectively. Majority (90.2%) of the deaths occurred within the first year of treatment. Absence of cotrimoxazole preventive therapy (adjusted hazard ratio [AHR] = 4.74, 95% CI: 2.17, 10.34), anaemia (haemoglobin level < 10gm/dl) (AHR=2.44, 95% CI: 1.26, 4.73), absolute CD4 cell count below the threshold for severe immunodeficiency (AHR=2.24, 95% CI: 1.07, 4.69) and delayed or regressing developmental milestones at baseline (AHR=6.31, 95% CI: 2.52, 15.83) were predictors of mortality.ConclusionsThere was a high rate of early mortality. Hence, starting ART very early reduces disease progression and early mortality; close follow up of all children of HIV-positive mothers is recommended to make the diagnosis and start treatment at an earlier time before they develop severe immunodeficiency.

TB/HIV integration at primary care level: A quantitative assessment at 3 clinics in Johannesburg, South Africa

In 2004 the World Health Organization WHO) released the Interim Policy on Collaborative TB/ HIV activities. According to the policy, for people living with HIV (PLWH), activities include intensified case finding, isoniazid preventive therapy (IPT) and infection control. For TB patients, activities included HIV counselling and testing HCT), prevention messages, and cotrimoxazole preventive therapy (CPT), care and support, and antiretroviral therapy ART) for those with HIV-associated TB. While important progress has been made in implementation, targets of the WHO Global Plan to Stop TB have not been reached. To quantify TB/HIV integration at 3 primary healthcare clinics in Johannesburg, South Africa. Routinely collected TB and HIV data from the HCT register, TB 'suspect' register, TB treatment register, clinic files and HIV electronic database, collected over a 3-month period, were reviewed. Of 1 104 people receiving HCT: 306 (28%) were HIV-positive; a CD4 count was documented for 57%; and few received TB screening or IPT. In clinic encounters among PLWH, 921 (15%) had documented TB symptoms; only 10% were assessed by smear microscopy, and few asymptomatic PLWH were offered IPT. Infection control was poorly documented and implemented. HIV status was documented for 155 (75%) of the 208 TB patients; 90% were HIV-positive and 88% had a documented CD4 count. Provision of CPT and ART was poorly documented. The coverage of most TB/HIV collaborative activities was below Global Plan targets. The lack of standardised recording tools and incomplete documentation impeded assessment at facility level and limited the accuracy of compiled data.

TB/HIV integration at primary care level: A quantitative assessment at 3 clinics in Johannesburg, South Africa

Background. In 2004 the World Health Organization (WHO) released the Interim Policy on Collaborative TB/HIV activities. According to the policy, for people living with HIV (PLWH), activities include intensified case finding, isoniazid preventive therapy (IPT) and infection control. For TB patients, activities included HIV counselling and testing (HCT), prevention messages, and cotrimoxazole preventive therapy (CPT), care and support, and antiretroviral therapy (ART) for those with HIV-associated TB. While important progress has been made in implementation, targets of the WHO Global Plan to Stop TB have not been reached. &#x0D; &#x0D; Objective. To quantify TB/HIV integration at 3 primary healthcare clinics in Johannesburg, South Africa.&#x0D; &#x0D; Methods. Routinely collected TB and HIV data from the HCT register, TB ‘suspect’ register, TB treatment register, clinic files and HIV electronic database, collected over a 3-month period, were reviewed. &#x0D; &#x0D; Results. Of 1 104 people receiving HCT: 306 (28%) were HIV-positive; a CD4 count was documented for 57%; and few received TB screening or IPT. In clinic encounters among PLWH, 921 (15%) had documented TB symptoms; only 10% were assessed by smear microscopy, and few asymptomatic PLWH were offered IPT. Infection control was poorly documented and implemented. HIV status was documented for 155 (75%) of the 208 TB patients; 90% were HIV-positive and 88% had a documented CD4 count. Provision of CPT and ART was poorly documented.&#x0D; &#x0D; Conclusion. The coverage of most TB/HIV collaborative activities was below Global Plan targets. The lack of standardised recording tools and incomplete documentation impeded assessment at facility level and limited the accuracy of compiled data.

Scale‐up of TB and HIV programme collaborative activities in Zambia – a 10‐year review

To review the activities, progress, achievements and challenges of the Zambia Ministry of Health tuberculosis (TB)/HIV collaborative activities over the past decade. Analysis of Zambia Ministry of Health National TB and HIV programme documents and external independent programme review reports pertaining to 2000-2010. The number of people testing for HIV increased from 37 557 persons in 2003 to 1 327 995 persons in 2010 nationally. Those receiving anti-retroviral therapy (ART) increased from 143 in 2003 to 344 304 in 2010. The national HIV prevalence estimates declined from 14.3% in 2001 to 13.5% in 2009. The proportion of TB patients being tested for HIV increased from 22.6% in 2006 to 84% in 2010 and approximately 70% were HIV positive. The proportion of the HIV-infected TB patients who: (i) started on ART increased from 38% in 2006 to 50% in 2010; (ii) commenced co-trimoxazole preventive therapy (CPT) increased from 31% in 2006 to 70% in 2010; and (iii) were successfully treated increased to an average of 80% resulting in decline of deaths from 13% in 2006 to 9% in 2010. The scale-up of TB/HIV collaborative programme activities in Zambia has steadily increased over the past decade resulting in increased testing for TB and HIV, and anti-retroviral (ARV) rollout with improved treatment outcomes among TB patients co-infected with HIV. Getting service delivery points to adhere to WHO guidelines for collaborative TB/HIV activities remains problematic, especially those meant to reduce the burden of TB in people living with HIV/AIDS (PLWHA).

HIV and tuberculosis – science and implementation to turn the tide and reduce deaths

IntroductionEvery 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.DiscussionA 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.ConclusionsProgress towards reducing HIV-associated TB deaths can be achieved through attention to simple and deliverable actions on the ground. John Donne, Meditation XVII, Devotions upon Emergent Occasions: … any mans death diminishes me because I am involved in Mankinde; And therefore never send to know for whom the bell tolls; it tolls for thee ….

Linking women who test HIV‐positive in pregnancy‐related services to long‐term HIV care and treatment services: a systematic review

To quantify attrition between women testing HIV-positive in pregnancy-related services and accessing long-term HIV care and treatment services in low- or middle-income countries and to explore the reasons underlying client drop-out by synthesising current literature on this topic. A systematic search in Medline, EMBASE, Global Health and the International Bibliography of the Social Sciences of literature published 2000-2010. Only studies meeting pre-defined quality criteria were included. Of 2543 articles retrieved, 20 met the inclusion criteria. Sixteen (80%) drew on data from sub-Saharan Africa. The pathway between testing HIV-positive in pregnancy-related services and accessing long-term HIV-related services is complex, and attrition was usually high. There was a failure to initiate highly active antiretroviral therapy (HAART) among 38-88% of known-eligible women. Providing 'family-focused care', and integrating CD4 testing and HAART provision into prevention of mother-to-child HIV transmission services appear promising for increasing women's uptake of HIV-related services. Individual-level factors that need to be addressed include financial constraints and fear of stigma. Too few women negotiate the many steps between testing HIV-positive in pregnancy-related services and accessing HIV-related services for themselves. Recent efforts to stem patient drop-out, such as the MTCT-Plus Initiative, hold promise. Addressing barriers and enabling factors both within health facilities and at the levels of the individual woman, her family and society will be essential to improve the uptake of services.

Operational research in Malawi: making a difference with cotrimoxazole preventive therapy in patients with tuberculosis and HIV

BackgroundIn Malawi, high case fatality rates in patients with tuberculosis, who were also co-infected with HIV, and high early death rates in people living with HIV during the initiation of antiretroviral treatment (ART) adversely impacted on treatment outcomes for the national tuberculosis and ART programmes respectively. This article i) discusses the operational research that was conducted in the country on cotrimoxazole preventive therapy, ii) outlines the steps that were taken to translate these findings into national policy and practice, iii) shows how the implementation of cotrimoxazole preventive therapy for both TB patients and HIV-infected patients starting ART was associated with reduced death rates, and iv) highlights lessons that can be learnt for other settings and interventions.DiscussionDistrict and facility-based operational research was undertaken between 1999 and 2005 to assess the effectiveness of cotrimoxazole preventive therapy in reducing death rates in TB patients and subsequently in patients starting ART under routine programme conditions. Studies demonstrated significant reductions in case fatality in HIV-infected TB patients receiving cotrimoxazole and in HIV-infected patients about to start ART. Following the completion of research, the findings were rapidly disseminated nationally at stakeholder meetings convened by the Ministry of Health and internationally through conferences and peer-reviewed scientific publications. The Ministry of Health made policy changes based on the available evidence, following which there was countrywide distribution of the updated policy and guidelines. Policy was rapidly moved to practice with the development of monitoring tools, drug procurement and training packages. National programme performance improved which showed a significant decrease in case fatality rates in TB patients as well as a reduction in early death in people with HIV starting ART.SummaryKey lessons for moving this research endeavour through to policy and practice were the importance of placing operational research within the programme, defining relevant questions, obtaining "buy-in" from national programme staff at the beginning of projects and having key actors or "policy entrepreneurs" to push forward the policy-making process. Ultimately, any change in policy and practice has to benefit patients, and the ultimate judge of success is whether treatment outcomes improve or not.

National policy development for cotrimoxazole prophylaxis in Malawi, Uganda and Zambia: the relationship between Context, Evidence and Links

BackgroundSeveral frameworks have been constructed to analyse the factors which influence and shape the uptake of evidence into policy processes in resource poor settings, yet empirical analyses of health policy making in these settings are relatively rare. National policy making for cotrimoxazole (trimethoprim-sulfamethoxazole) preventive therapy in developing countries offers a pertinent case for the application of a policy analysis lens. The provision of cotrimoxazole as a prophylaxis is an inexpensive and highly efficacious preventative intervention in HIV infected individuals, reducing both morbidity and mortality among adults and children with HIV/AIDS, yet evidence suggests that it has not been quickly or evenly scaled-up in resource poor settings.MethodsComparative analysis was conducted in Malawi, Uganda and Zambia, using the case study approach. We applied the ‘RAPID’ framework developed by the Overseas Development Institute (ODI), and conducted a total of 47 in-depth interviews across the three countries to examine the influence of context (including the influence of donor agencies), evidence (both local and international), and the links between researcher, policy makers and those seeking to influence the policy process.ResultsEach area of analysis was found to have an influence on the creation of national policy on cotrimoxazole preventive therapy (CPT) in all three countries. In relation to context, the following were found to be influential: government structures and their focus, donor interest and involvement, healthcare infrastructure and other uses of cotrimoxazole and related drugs in the country. In terms of the nature of the evidence, we found that how policy makers perceived the strength of evidence behind international recommendations was crucial (if evidence was considered weak then the recommendations were rejected). Further, local operational research results seem to have been taken up more quickly, while randomised controlled trials (the gold standard of clinical research) was not necessarily translated into policy so swiftly. Finally the links between different research and policy actors were of critical importance, with overlaps between researcher and policy maker networks crucial to facilitate knowledge transfer. Within these networks, in each country the policy development process relied on a powerful policy entrepreneur who helped get cotrimoxazole preventive therapy onto the policy agenda.ConclusionsThis analysis underscores the importance of considering national level variables in the explanation of the uptake of evidence into national policy settings, and recognising how local policy makers interpret international evidence. Local priorities, the ways in which evidence was interpreted, and the nature of the links between policy makers and researchers could either drive or stall the policy process. Developing the understanding of these processes enables the explanation of the use (or non-use) of evidence in policy making, and potentially may help to shape future strategies to bridge the research-policy gaps and ultimately improve the uptake of evidence in decision making.

Translating evidence into policy in low-income countries: lessons from co-trimoxazole preventive therapy.

In the April 2010 issue of this journal, Date et al. expressed concern over the slow scale-up in low-income settings of two therapies for the prevention of opportunistic infections in people living with the human immunodeficiency virus: co-trimoxazole prophylaxis and isoniazid preventive therapy. This short paper discusses the important ways in which policy analysis can be of use in understanding and explaining how and why certain evidence makes its way into policy and practice and what local factors influence this process. Key lessons about policy development are drawn from the research evidence on co-trimoxazole prophylaxis, as such lessons may prove helpful to those who seek to influence the development of national policy on isoniazid preventive therapy and other treatments. Researchers are encouraged to disseminate their findings in a manner that is clear, but they must also pay attention to how structural, institutional and political factors shape policy development and implementation. Doing so will help them to understand and address the concerns raised by Date et al. and other experts. Mainstreaming policy analysis approaches that explain how local factors shape the uptake of research evidence can provide an additional tool for researchers who feel frustrated because their research findings have not made their way into policy and practice.

A randomized controlled trial of intermittent compared with daily cotrimoxazole preventive therapy in HIV-infected children

Cotrimoxazole preventive therapy (CPT) reduces morbidity and mortality in HIV-infected children. The WHO recommends prolonged daily CPT for HIV-infected infants and children. In adults, intermittent CPT has been associated with less adverse events than daily, with increased tolerability and equal efficacy. We investigated the efficacy and tolerability of intermittent CPT compared with daily CPT in HIV-infected children over a 5-year period. A prospective randomized controlled study. HIV-infected children aged at least 8 weeks were randomized to thrice weekly or daily CPT. Outcome measures were mortality, bacterial infections, hospitalizations and adverse events. Three hundred and twenty-four children (median age 23 months) were followed for 672 child-years; 165 (51%) were randomized to intermittent CPT. Most children (287, 89%) were Centers for Disease Control and Prevention clinical category B or C; 207 (64%) received HAART during the study. Mortality (53 deaths, 16%) was similar in the intermittent CPT compared with the daily CPT group {24 (14%) vs. 29 (18%), hazard ratio 0.75 [95% confidence interval (CI) 0.44-1.29]}. The predominant causes of death in both groups were sepsis (17, 32%), pneumonia (13, 25%) or diarrhoea (8, 15%). Intermittent CPT was associated with more bacteraemias [incidence rate ratio 2.36 (95% CI 1.21-4.86)]. Children receiving intermittent CPT also spent more days in hospital [incidence rate ratio 1.15 (95% CI 1.04-1.28)]. The rate of serious adverse events was similar between groups [incidence rate ratio 1.07 (95% CI 0.58-2.02)]. Intermittent CPT was associated with more invasive bacterial disease than daily CPT, but survival was similar. Both regimens were well tolerated. On balance, daily CPT remains preferable to intermittent therapy for HIV-infected children.

Reducing mortality with cotrimoxazole preventive therapy at initiation of antiretroviral therapy in South Africa

To assess the effectiveness of cotrimoxazole preventive therapy (CPT) among individuals with CD4 cell count above 200 cells/microl and varying WHO clinical stages in reducing mortality during combination antiretroviral therapy (cART). A cohort study. Using proportional hazards modeling, we compared mortality during the first 12 months after cART initiation among patients receiving CPT with patients not receiving CPT. We adjusted for clinic level confounding throughout. We included 14 097 patients starting cART between January 2003 and January 2008, 62% of whom were men, the median CD4 cell count was 132 cells/microl, and 1289 died (11%). The baseline median CD4 cell count was lower (118 vs. 153 cells/microl) among the 7508 patients who received CPT compared with the 6589 patients who did not. In adjusted multivariate modeling, stratifying for baseline CD4 cell count and WHO stage, CPT reduced mortality overall (hazard ratio 0.64, P < 0.001) and for all individuals with CD4 cell count below 200 cells/microl or WHO clinical stage 3 or 4 conditions but did not reduce mortality for patients with both CD4 cell count above 200 cells/microl and WHO clinical stage 1 or 2. We demonstrated a 36% reduction in mortality extending to patients associated with CPT when used with cART that extended to patients with CD4 cell count above 350 cells/microl in a setting with minimal malaria and high rates of cotrimoxazole-resistant bacteria. This provides important additional data toward efforts to increase CPT provision among all cART initiators in resource limited settings.

Characteristics of HIV-infected children seen in Western Kenya

To describe the characteristics and outcomes of children registered for care in a large HIV care programme in Western Kenya. A retrospective descriptive study. USAID-AMPATH HIV clinics in health centres; district and sub-district hospitals; Moi Teaching and Referral Hospital in Western Kenya. HIV-infected children below age of 15 years seen in a network of 18 clinics in Western Kenya. Paediatric HIV diagnosis and care including treatment and prevention of opportunistic infections and provision of combination antiretroviral therapy (CART). Diagnosis, clinical stage and immune status at enrollment and follow-up; hospitalisation and death. Descriptive statistical analyses and chi square tests were performed. Four thousand and seventeen HIV-infected children seen between June 2002 and April 2008. Median age at enrollment was four years (0-14.2 years), 51% girls, 25% paternal orphans, 10% total orphans and 13% maternal orphans. At enrollment, 25% had weight-for-Age Z scores (WAZ) > or = -1 and 21% had WAZ scores < or = 3. Orphaned children had worse WAZ scores (p=0.0001). Twenty five per cent of children were classified as WHO clinical stage 3 and 4, 56% were WHO clinical stages 1 and 2 with 19% missing clinical staging at enrollment. Cough (25%), gastroenteritis (21%), fever (15%), pneumonia (10%) were the commonest presenting features. Twenty six per cent had been diagnosed with tuberculosis and only 25% started on cotrimoxazole preventive therapy (CPT). Median CD4% at enrollment was 16% (0-64%); latest recorded values were 22% (0-64). Sixty four per cent were on cART (cART+), median age at start was 5.4 (014.4 years). The median initial CD4% among cART+ was 13 (0-62) compared to 24 (0-64) for those not on ART (cART-). Median CD4% for cART+ improved to 22% (0-59); whereas cART- was 23% (0-64) at last appointment. During the period of follow-up, one fifth (19%) of children on cART were lost to follow-up compared to slightly over one third (37%) for those not on cART. Thirty four percent were hospitalised; 41% diagnosed with pneumonia. Six per cent of 4017 were confirmed dead. HIV-infected children were enrolled in care early in childhood. Orphanhood was prevalent in these children as were gastroenteritis, fever, pneumonia and advanced immuno-suppression. Orphans were more likely to be severely malnourished. Only a quarter of children were put on cotrimoxazole preventive therapy. Children commenced on cART late but responded well to treatment. Loss to follow-up was less prevalent among those on cART.

Confronting TB/HIV in the era of increasing anti-TB drug resistance.

HIV associated TB is a major public health problem. In 2006, it was estimated that there were over 700,000 people who suffered from HIV associated TB, of whom about 200, 000 have died. The burden of HIV associated TB is greatest in Sub-Saharan Africa where the TB epidemic is primarily driven by HIV. There has been steady progress made in reducing the burden of HIV in TB patients with an increasing number of TB patients tested for HIV and provided with cotrimoxazole preventive therapy (CPT) and anti-retroviral treatment (ART). Less progress is being made to reduce the burden of TB in people living with HIV. The number of HIV infected persons reported to have been screened for TB was less than 1% while Isoniazid preventive therapy was reported to have been provided to less than 0.1% of eligible persons in 2006. A major push is urgently needed to accelerate the implementation of three important interventions. The three are Intensified TB Screening (ICF) among people living with HIV, the provision of Isoniazid Preventive Therapy (IPT) and TB Infection Control(IC). These interventions are best carried out by HIV control programmes which should therefore be encouraged to take greater responsibility in implementing these interventions.

The White and the Three-Letter Plague: Integration of TB and HIV Care in Sub-Saharan Africa

Although sub-Saharan Africa contains approximately 12% of the world’s population, it hosts an estimated 68% of all living HIV-infected people (22.5 million persons) and 30% of annual cases of TB (4.4 million persons). In countries with an extended epidemic of both HIV and TB, both infections commonly affect the same individuals. However, TB care services (WHO’s Directly Observed Therapy Short Course) and HIV care services essentially function as separate vertical programs. In 2004, in an effort to improve the management and control of TB and HIV, WHO produced an Interim Policy on collaborative TB/HIV Activities with a range of measures to improve the integration of TB care into HIV treatment programs (intensified TB case finding, isoniazid preventive therapy and TB infection control in healthcare settings) and the integration of HIV care into TB treatment programs (HIV testing and counseling, HIV prevention, co-trimoxazole preventive therapy, HIV/AIDS care and support, and antiretroviral therapy). In this review, we describe and critically discuss the evidence relating to the implementation of the proposed collaborative activities in sub-Saharan Africa.