Pretreatment resistance mutations and treatment outcomes in adults living with HIV-1: a cohort study in urban Malawi.

BACKGROUND: Pre-treatment drug resistance (PDR) among antiretroviral drug-naïve people living with HIV (PLHIV) represents an important indicator for the risk of treatment failure and the spread of drug resistant HIV variants. We assessed the prevalence of PDR and treatment outcomes among adults living with HIV-1 in Lilongwe, Malawi. METHODS: We selected 200 participants at random from the Lighthouse Tenofovir Cohort Study (LighTen). Serum samples were drawn prior to treatment initiation in 2014 and 2015, frozen, and later analyzed for the presence of HIV-1 drug resistance mutations. Amplicons were sequenced and interpreted by Stanford HIVdb interpretation algorithm 8.4. We assessed treatment outcomes by evaluating clinical outcome and viral suppression at the end of the follow-up period in October 2019. RESULTS: PDR testing was successful in 197 of 200 samples. The overall NNRTI- PDR prevalence was 13.7% (27/197). The prevalence of intermediate or high level NNRTI- PDR was 11.2% (22/197). The most common mutation was K103N (5.6%, 11/197), followed by Y181C (3.6%, 7/197). In one case, we detected an NRTI resistance mutation (M184V), in combination with multiple NNRTI resistance mutations. All HIV-1 isolates analyzed were of subtype C. Of the 27 patients with NNRTI- PDR, 9 were still alive, on ART, and virally suppressed at the end of follow-up. CONCLUSION: The prevalence of NNRTI- PDR was above the critical level of 10% suggested by the Global Action Plan on HIV Drug Resistance. The distribution of drug resistance mutations was similar to that seen in previous studies from the region, and further supports the introduction of integrase inhibitors in first-line treatment in Malawi. Furthermore, our findings underline the need for continued PDR surveillance and pharmacovigilance in Sub-Saharan Africa.

Collaborative HIV care in primary health care: nurses' views.

BACKGROUND: Collaborative HIV care between the nurses and traditional health practitioners is an important strategy to improve health care of people living with HIV. AIM: To explore and describe the views of nurses regarding collaborative HIV care in primary healthcare services in the City of Tshwane, South Africa. METHOD: A qualitative, descriptive design was used to explore and describe the views of nurses who met the study's inclusion criteria. In-depth individual interviews were conducted to collect data from purposively selected nurses. Content analysis was used to analyse data. RESULTS: Two main categories were developed during the data analysis stage. The views of nurses and health system challenges regarding collaborative HIV care. DISCUSSION: The study findings revealed that there was inadequate collaborative HIV care between the nurses and the traditional health practitioners. CONCLUSION: It is evident that there is inadequate policy implementation, monitoring and evaluation regarding collaboration in HIV care. The study findings might influence policymakers to consider the importance of collaborative HIV care, and improve the quality of care by strengthening the referral system and follow-up of people living with HIV and AIDS, as a result the health outcomes as implied in the Sustainable Development Goals 2030 might be improved. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Training and involvement of traditional health practitioners in the nursing and health policy should be considered to enhance and build a trustworthy working relationship between the nurses and the traditional health practitioners in HIV care.

Providing HIV Treatment during community-wide flooding: experiences of clients and Health Care Workers in Malawi.

Background: In Malawi, community wide flooding, especially in high HIV burdened districts, continues to affect continuity of care and access to facilities. We explored the lived experiences of clients and healthcare workers (HCWs) to gain understanding of challenges and to propose interventions for improved ART care delivery. Methods: Participants came six health facilities and surrounding communities impacted by flooding between Dec 2021-Apr 2022 in Chikwawa, Nsanje and Mulanje districts in Malawi. Facilities are supported by Partners in Hope, a local NGO and PEPFAR/USAID partner.We conducted In-depth interviews with (IDIs) ART clients identified through medical chart reviews and focus group discussions (FGDs) with HCWs. IDIs and FGDs were coded using inductive and deductive methods in Atlas.ti. Results: We conducted IDIs with 23 respondents, of which, ten were women, ten experienced treatment interruption (>28 days without medication) and 17 relocated from their homes. The Six FGDs involved 37 HCWs. (21 ART providers; 16 lay cadre).In IDIs, most clients who relocated and lost livestock, possessions and ART medications. They travelling for income generation. Barriers to care included dangerous travel conditions, competing needs for time and fear of ill treatment at facilities. Some outreach clinics did not provide ART. Respondents were motivated to remain on care and motivators included fear of developing illnesses and HIV-status acceptance.All providers said that lack of standardized guidelines affected preparedness and response and they advocated for guidelines, stakeholder coordination and adequate resources. Most also reported personal physical exhaustion, damage to their own houses and property, and drug stock-outs. Documentation due to loss of registers was also mostly mentioned. Discussion: Clients motivated to remain in care but face barriers and challenges. National flooding protocols, adequate resource planning and seasonal 6-month ART dispensing may improve ART outcomes.

Perceptions of nurses working in mental health services regarding the recovery-oriented care approach: Findings from Africa.

BACKGROUND: The recovery-oriented care approach in mental health is recognised as the vision for mental health. People with a diagnosis of mental illness value the support and the individualistic approach emphasised in the recovery-oriented mental health care approach as they believe it facilitates their recovery. However, as a developing country, Botswana has a long way to go in availing mental health care resources to people with mental illness, let alone adopting new mental health approaches such as recovery. AIM: The study aimed to explore the perceptions of nurses working in mental health care facilities of recovery-oriented mental health care. METHODS: Four mental health facilities from Botswana consented to participate in the study. A descriptive qualitative approach was utilised to explore nurses' views on how they perceive recovery from mental illness. Thirty nurses participated in the focus group discussions across the four study sites. All participants consented to participate and to be recorded. Tesch's (in Qualitative enquiry and research design: Choosing among five approaches. 3th ed. SAGE, 2013:198) thematic analysis was used for this study. RESULTS: Three main themes were identified in participants' perceptions of recovery-oriented care mental health: Recovery from mental illness is possible, the Meaning of recovery from mental illness and Factors facilitating recovery from mental illness. PUBLIC CONTRIBUTION: The study offers a perspective into how nurses perceive recovery-oriented approaches from a developing country and add to the gap existing in recovery-oriented mental health care approach from the African context.

Characteristics of adults and children diagnosed with tuberculosis in Lilongwe, Malawi: findings from an integrated HIV/TB clinic.

OBJECTIVES: To describe initial registration characteristics of adult and paediatric TB patients at a large, public, integrated TB and HIV clinic in Lilongwe, Malawi, between January 2008 and December 2010. METHODS: Routine data on patient with TB category and TB type, stratified by HIV and ART status, were used to explore differences in proportions among TB only, TB/HIV co-infected patients not on ART and TB/HIV co-infected patients on ART using chi-square tests. Trends over time illustrate strengths and weaknesses of integrated service provision. RESULTS: Among 10 143 adults, HIV ascertainment and ART uptake were high and increased over time. The proportion of relapse was highest among those on ART (5%). The proportion of smear-positive pulmonary TB (PTB) was highest among HIV-negative patients with TB (34.9%); extra-pulmonary TB (EPTB) was lowest among TB only (16.2%). Among 338 children <15 years, EPTB and smear-positive PTB were more common among TB-only patients. Time trends showed significant increases in the proportion of adults with smear-positive PTB and the proportion of adults already on ART before starting TB treatment. However, some co-infected patients still delay ART initiation. CONCLUSIONS: HIV ascertainment and ART uptake among co-infected patients are successful and improving over time. However, delays in ART initiation indicate some weakness linking TB/HIV patients into ART during TB follow-up care. Improved TB diagnostics and screening efforts, especially for paediatric patients, may help improve quality care for co-infected patients. These results may aid efforts to prioritise TB and HIV prevention, education and treatment campaigns for specific populations.

Integrated tuberculosis and HIV care in a resource-limited setting: experience from the Martin Preuss centre, Malawi.

OBJECTIVES: To describe the development and operation of integrated tuberculosis (TB) and HIV care at the Martin Preuss Centre, a multipartner organization bringing together governmental and non-governmental providers of HIV and TB services in Lilongwe, Malawi. METHODS: We used a case study approach to describe the integrated TB/HIV service and to illustrate successes and challenges faced by service providers. We quantified effective TB and HIV integration using indicators defined by the World Health Organization. RESULTS: The custom-designed building facilitates patient flow and infection control, and other important elements include coordinated leadership; joint staff training and meetings; and data systems prompting coordinated care. Some integrated services have worked well from the outset, such as promoting HIV testing among patients with TB (96% of patients with TB had documented HIV status in 2009). Other aspects of integrated care have been more challenging, for example achieving high uptake of antiretroviral therapy among HIV-positive TB patients and combining data from paper and electronic systems. Good TB treatment outcomes (>85% cure or completion) have been achieved among both HIV-positive and HIV-negative individuals. CONCLUSIONS: High-quality integrated services for TB and HIV care can be provided in a resource-limited setting. Lessons learned may be valuable for service providers in other settings of high HIV and TB prevalence.

Second-line treatment in the Malawi antiretroviral programme: high early mortality, but good outcomes in survivors, despite extensive drug resistance at baseline.

OBJECTIVES: The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second-line ART. We report outcomes for patients evaluated and initiated on second-line treatment in Malawi. METHODS: Patients meeting Malawi immunological or clinical criteria for ART failure in two large urban ART clinics were evaluated for virological failure (viral load >400 HIV-1 RNA copies/mL) and, if failure was confirmed, initiated on second-line ART (zidovudine/lamivudine/tenofovir/lopinavir/ritonavir). Patients were seen monthly and laboratory evaluations were performed quarterly and as needed. We performed logistic regression modelling to identify factors associated with mortality, mortality or new HIV illnesses, and virological suppression at 12 months. RESULTS: Of the 109 patients with confirmed virological failure, five patients died prior to initiation, three declined switching and 101 patients initiated second-line treatment. Over 12 months, 10 additional patients died, 34 patients experienced 45 HIV-related events, and 19 patients experienced grade 3 or 4 toxicities. Among survivors, 85.2% had HIV-1 RNA<400 copies/mL at 12 months. While power to distinguish differences was limited, response rates were similar regardless of baseline resistance level. The median CD4 count increase was 142 cells/microL. World Health Organization clinical failure at baseline [odds ratio (OR) 3.47; 95% confidence interval (CI) 1.14-10.59] and body mass index <18.5 (OR 4.43; 95% CI 1.15-17.12) were risk factors for death. Baseline CD4 count <50 cells/microL was associated with increased risk for death or morbidity at 12 months (OR 2.57; 95% CI 1.01-6.52). CONCLUSIONS: Second-line treatment in Malawi was associated with substantial mortality, morbidity and toxicity but, among survivors, virological outcomes were favourable.

Successful establishment of third-line antiretroviral therapy in Malawi: lessons learned.

SETTING: Malawi has an extensive national antiretroviral treatment (ART) program, and although less than 2% of all patients receive second-line ART, there are increasingly more patients failing on these regimens. OBJECTIVE: To establish a virtual ART committee using limited available local facilities and expertise to recommend third-line regimens based on genotype resistance of samples sent abroad. DESIGN: A secretariat and a laboratory sample hub were established. The committee started work after locally organizing training courses. Decisions about ART regimens were mainly based on a relatively simple, previously described algorithm, which allowed decisions to be taken without extensive expert knowledge. RESULTS: Of the 25 applications assessed, 23 samples were sent for resistance testing from June 2017 to April 2018. Major protease inhibitor (PI) resistance was detected in 65% of the samples. PI resistance was found even in patients exposed to PIs for short periods. In particular, patients who received co-administration of PIs and rifampicin frequently showed resistance mutations. CONCLUSION: Third-line ART using genotypic resistance testing and algorithm-based treatment regimens are feasible in low-resource settings. Our model can serve as a base for similar programs initiating programmatic third-line ART in other African countries.

Characteristics and management of presumptive tuberculosis in public health facilities in Malawi, 2014-2016.

Setting: Public health facilities providing tuberculosis (TB) and human immunodeficiency virus (HIV) services in Malawi. Objectives: Using routinely collected health service delivery data to describe trends in HIV ascertainment and use of the Xpert® MTB/RIF assay to diagnose TB among HIV-positive presumptive TB cases. Design: This was an implementation study of presumptive TB cases who sought care from 21 facilities between April 2014 and June 2016. Descriptive statistics were used to summarise patient, facility and service level characteristics. Results: Of 28 567 presumptive TB cases analysed, 23 198 (81%) had known HIV status. The proportion of ascertained HIV status in presumptive TB cases increased over the study period. HIV prevalence was 49%, with 73% of HIV-positive presumptive TB cases on antiretroviral therapy. Access to Xpert ranged between 37% and 63% per quarter among HIV-positive presumptive TB patients with smear-negative sputum results. Of 7829 patients with documented Xpert results, 68% were HIV-positive. Conclusion: After the introduction of registers with HIV-related variables, HIV ascertainment among presumptive TB cases increased over time. Access to Xpert was suboptimal among HIV-positive presumptive TB cases. Further collaboration between national TB and HIV programmes may facilitate increased use of Xpert for HIV-positive patients with presumptive TB who seek care in public health facilities.

Contexte : Structures de santé publiques offrant des services de la tuberculose (TB) et du virus de l'immunodéficience humaine (VIH) au Malawi.Objectifs : Utilisant des données recueillies en routine de prestation des services de santé, décrire les tendances de la vérification du VIH et de l'utilisation du test Xpert® MTB/RIF afin de diagnostiquer la TB parmi les cas présumés de TB qui sont VIH positifs.Schéma : Etude de mise en œuvre des cas présumés de TB qui ont sollicité des soins dans 21 structures entre avril 2014 et juin 2016. Nous avons utilisé des statistiques descriptives pour résumer les caractéristiques des patients, des structures et des services.Résultats : Sur les 28 567 cas présumés de TB qui ont été analysés, 23 198 (81%) connaissaient leur statut VIH. La proportion de statuts VIH vérifiés parmi les cas de TB présumés a augmenté tout au long de la période d'étude. La prévalence du VIH a été de 49%, avec 73% des patients VIH positifs présumés TB sous traitement antirétroviral. L'accès à Xpert était entre 37% et 63% par trimestre parmi les patients VIH positifs présumés TB avec des résultats de frottis de crachats négatifs. Sur les 7829 patients ayant des résultats documentés d'Xpert, 68% ont été VIH positifs.Conclusion : Après l'introduction des registres comportant des variables liées au statut VIH, la constatation du VIH parmi les cas présumés de TB a augmenté dans le temps. L'accès à Xpert a été sous-optimal parmi les cas de TB présumés VIH-positifs. Davantage de collaboration entre les programmes nationaux TB et VIH pourrait faciliter une utilisation accrue d'Xpert pour les patients VIH positifs avec une présomption de TB qui sollicitent des soins dans des structures de santé publiques.

Marco de referencia: Los establecimientos públicos de atención de salud que prestan servicios relacionados con la tuberculosis (TB) y la infección por el virus de la inmunodeficiencia humana (VIH) en Malawi.Objetivos: A partir de los datos recogidos de manera sistemática sobre la prestación de los servicios de salud, describir la evolución de la determinación de la situación frente al VIH y de la utilización de la prueba Xpert® MTB/RIF para el diagnóstico de TB, en los casos positivos frente al VIH con presunción clínica de esta enfermedad.Método: Se llevó a cabo un estudio de implementación de los casos con presunción de TB que buscaron atención en 21 centros, de abril 2014 a junio 2016. Se utilizaron estadísticas descriptivas a fin de resumir las características de los pacientes, los establecimientos y los servicios.Resultados: De los 28 567 casos con presunción de TB analizados, 23 198 conocían su situación frente al VIH (81%). La proporción de determinación de la situación frente al VIH en los casos analizados aumentó durante el período del estudio. La prevalencia de infección por el VIH fue 49% y el 73% de estos casos recibía tratamiento antirretrovírico. El acceso a la prueba Xpert osciló entre 37% y 63% por trimestre en los pacientes positivos frente al VIH con presunción de TB y resultados negativos de la baciloscopia de esputo. De los 7829 pacientes con resultado de la prueba Xpert, en el 68% la prueba fue positiva.Conclusión: Tras la introducción de los registros que comportan variables relacionadas con el VIH, la determinación de la situación frente al VIH en los casos con presunción de TB ha aumentado en el transcurso del tiempo. El acceso a la prueba Xpert fue deficiente en los pacientes positivos frente al VIH, con presunción clínica de TB. Una mayor colaboración entre los programas nacionales contra la TB y el VIH facilitaría la utilización de la prueba Xpert en los pacientes seropositivos con presunción de TB que buscan atención en los centros públicos de atención de salud.

Providing HIV care for tuberculosis patients in sub-Saharan Africa.

Human immunodeficiency virus (HIV)/acquired immunedeficiency syndrome (AIDS) and tuberculosis (TB) cause an immense burden of disease in sub-Saharan Africa. A large amount of knowledge has been gathered in the last 15 years about the negative impact that HIV has on TB control, both at a programme level and at the level of the individual patient. Equally, interventions that are known to benefit patients have been tested and piloted, and these form important components of international TB-HIV guidelines, a TB-HIV strategic framework and an interim policy on TB-HIV coordination. Unfortunately, in sub-Saharan Africa there is little evidence that these interventions are being implemented on the ground, and one of the reasons for this paralysis is that the operational details are not well developed. This paper takes the three important HIV interventions of HIV testing and counselling, cotrimoxazole preventive treatment and antiretroviral treatment, and discusses some of the practical details of on-the-ground implementation. We hope that this will generate discussion, but above all, the impetus to start delivering services to patients.

Assessment of non-standard HIV antiretroviral therapy regimens at Lighthouse Trust in Lilongwe, Malawi.

AIM: Lighthouse Trust in Lilongwe, Malawi serves approximately 25,000 patients with HIV antiretroviral therapy (ART) regimens standardized according to national treatment guidelines. However, as a referral centre for complex cases, Lighthouse Trust occasionally treats patients with non-standard ART regimens (NS-ART) that deviate from the treatment guidelines. We evaluated factors contributing to the use of NS-ART and whether patients could transition to standard regimens. METHODS: This was a cross-sectional study of all adult patients at Lighthouse Trust being treated with NS-ART as of February 2012. Patients were identified using the electronic data system. Medical charts were reviewed and descriptive statistics were obtained. RESULTS: One hundred six patients were initially found being treated with NS-ART, and 92 adult patients were confirmed to be on NS-ART after review. Mean patient age was 42.4 ± 10.3 years, and 52 (57%) were female. Mean duration of treatment with the NS-ART being used at the time of data collection was 2.1 ± 1.5 years. Eight patients (9%) were on modified first-line NS-ART and 84 (91%) were on modified second-line NS-ART, with 90 patients (98%) having multiple factors contributing to NS-ART use. Severe toxicity from one medication contributed in 28 cases (30%) and toxicity from multiple medications contributed in 46 cases (50%), while 22 patients (24%) were transitioned to NS-ART following a stockout of their original medication. Following clinical review, 84 patients (91%) were transitioned to standard regimens, and eight (9%) were maintained on NS-ART because of incompatibility of their clinical features with the latest national guidelines. CONCLUSIONS: Primary factors contributing to NS-ART use were medication toxicities and medication stockouts. Most patients were transitioned to standard regimens, although the need for NS-ART remains.

Preserved antigenicity of HIV-1 p24 produced and purified in high yields from plants inoculated with a tobacco mosaic virus (TMV)-derived vector.

Production of structural proteins from foot-and-mouth disease virus (FMDV) and bovine herpes virus (BHV-1) in Nicotiana benthamiana through the use of a tobacco mosaic virus-based vector (TMV-30B) has been reported previously. The development of the TMV-30B-HISc vector, a new version that adds a C-terminal histidine (His) sequence to the foreign protein expressed is described. Coding sequences from the FMDV VPl protein and the core protein, p24, from a clade C HIV-1 isolate from Zambia were cloned into the new vector and infective RNAs were generated for each construct to inoculate N. benthamiana plants. His-tagged proteins were purified from inoculated leaves using immobilized metal affinity chromatography (IMAC) as detected by Coomassie blue staining and proteins were further characterized in Western blot assays using a commercial anti-6xHis mAb and specific polyclonal antisera for each protein. While yields obtained for the VPl-His protein after purification were similar to those in crude extracts obtained with the previous TMV-VPl vector, p24-His yields were 10-15 times higher than those of VPl-His. Twenty-five grams of TMV-p24-HISc inoculated leaves were processed to obtain 2.5 mg of isolated p24-His and the recombinant protein was inoculated in rabbits to test immunogenicity and antigenic integrity of the plant-produced p24-His. Animals developed a strong and specific humoral response to the p24-His after the first booster and immune sera was able to recognize the native p24 from a different clade expressed on the surface of the HIV-1 chronically infected HUT78/ARV T-cell line. Importantly, the recombinant p24-His proved its efficiency by confirming the serology of 117 samples previously tested by two rapid HIV-1 tests, thus representing an excellent alternative for production of highly specific diagnostic reagents for HIV endemic regions in the developing world.

What causes smear-negative pulmonary tuberculosis in Malawi, an area of high HIV seroprevalence?

SETTING: The Central Hospital and the District Tuberculosis (TB) Registry in Lilongwe, the capital of Malawi. In this setting smear-negative pulmonary tuberculosis (PTB) is diagnosed using clinical and radiographic criteria for TB, and mycobacterial cultures are not routinely available. OBJECTIVE: To determine the proportion of patients being registered for smear-negative PTB treatment in Lilongwe who have TB that can be confirmed microbiologically. DESIGN: Prospective cohort study of patients about to start treatment under operational conditions for smear-negative PTB in Lilongwe between October 1997 and June 1998. Patients referred to the study team underwent a detailed clinical re-assessment, testing for human immunodeficiency virus (HIV), repeat sputum smear microscopy for acid-fast bacilli and mycobacterial cultures of sputum and blood. Bronchoscopy and bronchoalveolar lavage (BAL) were performed and BAL fluid was examined for TB, Pneumocystis carinii and other fungi. RESULTS: Of 352 smear-negative PTB suspects assessed, the diagnosis of TB was confirmed in 137 (39%) cases. Eighty-nine per cent of patients assessed were HIV-positive, of whom 81% met the expanded case definition for the acquired immune-deficiency syndrome (AIDS). CONCLUSION: TB was the most commonly confirmed diagnosis amongst patients about to start treatment for smear-negative PTB in an area of high background HIV seroprevalence.

Bloody diarrhoea of adults in Malawi: clinical features, infectious agents, and antimicrobial sensitivities.

In a prospective study, 132 hospital out-patients presenting with bloody diarrhoea ('cases') were evaluated in Malawi, Central Africa; 73 out-patient tuberculosis suspects acted as controls. Most (100/132, 76%) subjects reported an illness lasting < or = 5 d with > 5 bowel actions in the preceding 12 h; 39/132 (30%) reported use of systemic antimicrobial drugs in the preceding week; 57% (74/130) had a body mass index < 20; 4% (5/131) were febrile; and 18/130 (13%) had one or more sign(s) of dehydration. The 73 controls reported no diarrhoea and more systemic antimicrobial drug use (P = 0.0003), but were otherwise comparable to the subjects. All stool samples from controls and 38/124 (31%) from cases were macroscopically normal. Only 32% (40/124) of the cases had blood visible in the stool. Parasitic gut infections were found in 42/124 (34%) cases compared with 1/60 (2%) controls (P < 0.0001). The commonest parasite was Schistosoma mansoni. Bacterial cultures were positive in 32/124 (26%) of the subjects. Shigella dysenteriae (Sd) 1 accounted for 53% (17/32) of these. All bacterial isolates were sensitive in vitro to nalidixic acid and ciprofloxacin, while only 18% were sensitive to cotrimoxazole. Sd 1 with significant antimicrobial resistance continues to cause seasonal epidemics of dysentery in Malawi. During these, approximately two-thirds of patients presenting with bloody diarrhoea have no blood visible in the stool. Nalidixic acid remains the drug of choice but its use should be restricted to patients at greatest risk of complicated shigellosis.

Pneumocystis carinii pneumonia in patients being registered for smear-negative pulmonary tuberculosis in Malawi.

The National TB Control Programme of Malawi registers and treats large numbers of patients with chronic cough for smear-negative pulmonary tuberculosis (PTB). Smear-negative PTB is diagnosed according to clinical and radiographic criteria, as mycobacterial cultures are not routinely available. In an area of high HIV seroprevalence there is a concern that other opportunistic infections apart from TB, such as Pneumocystis carinii, may be missed owing to lack of diagnostic facilities. The aims of this study were to investigate (i) the extent of P. carinii pneumonia (PCP) in patients about to be registered for smear-negative PTB; (ii) whether there were any clinical or radiological features that could help identify PCP in the absence of more detailed investigations; and (iii) the treatment outcome of PCP patients. A cohort of 352 patients who were about to be started on treatment for smear-negative PTB were investigated further in 1997-99 by clinical assessment, HIV testing and bronchoscopy. HIV sero-prevalence was 89% (278/313). A total of 186 patients underwent bronchoscopy and bronchoalveolar lavage, and PCP was diagnosed by indirect immunofluorescence or polymerase chain reaction in 17 (9%) of this subgroup. Dyspnoea was significantly more common in PCP cases compared to non-PCP cases (RR 1.35; 95% CI 1.24-1.48; P = 0.008), but discrimination between the groups was difficult using clinical criteria alone. The outcome of PCP cases was poor despite management with high-dose co-trimoxazole and secondary co-trimoxazole prophylaxis, with a median survival of 4 months (25-75% range: 2-12 months).

Factors associated with timely initiation of antiretroviral therapy in two HIV clinics in Lilongwe, Malawi.

The World Health Organization (WHO) estimates that only 30% of eligible, HIV-infected individuals start antiretroviral therapy (ART). This study seeks to explore the geographic and individual factors associated with starting ART on time. This retrospective study includes 15,734 HIV-positive adults initiating ART at two HIV clinics in Lilongwe, Malawi. The outcome was starting ART within two weeks of meeting ART eligibility as defined by the Malawi ART guidelines. Euclidean distance from patient neighbourhood to their clinic was calculated using Google Earth. Logistic regression models assessed factors influencing starting ART on time. Of 15,734 adults initiating ART, 8178 were from Lighthouse (LH) and 7556 were from Martin Preuss Center (MPC). Combined, 68.7% started treatment on time. Patients who were eligible for ART based on a CD4 cell count <250 cells/mm(3) versus WHO stage were less likely to begin ART on time at both LH (odds ratio [OR] 0.16; 95% CI 0.13-0.19) and MPC (OR 0.24; 95% CI 0.21-0.28). Likelihood of starting on time decreased with each kilometer further from clinic location among LH patients (OR 0.97; 95% CI 0.94-0.99); distance was not significant at MPC. In conclusion, predictors differed by clinic. Distance to clinic and type of eligibility for ART significantly influence starting ART on time.

'Task shifting' in an antiretroviral clinic in Malawi: can health surveillance assistants manage patients safely?

Malawi has a critical shortage of clinicians and nurses. This study evaluated whether health surveillance assistants (HSAs) could provide antiretroviral therapy (ART) efficiently and safely for stable patients. HSAs could identify patients with previously established criteria requiring clinical management, including ART initiates, children and patients on second-line treatment. HSAs were not capable of correctly identifying current complications, including potentially severe side effects and toxicities, and inappropriately referred stable patients to clinicians, reducing efficiency. While task shifting to HSAs appears promising, to be safe and efficient, additional clinical training is needed before potentially task shifting stable ART patient care to less skilled health care cadres.

Le Malawi connait un manque critique de cliniciens et d'infirmières. Cette étude a évalué dans quelle mesure les assistants de surveillance de santé (HSA) pourraient distribuer un traitement antirétroviral (ART) de manière efficiente et sûre à des patients en état stable. Les HSA pourraient identifier les patients répondant à des critères préalablement établis, exigeant une prise en charge clinique, notamment les débuts d'ART, les enfants et les patients sous traitement de deuxième ligne. Les HSA n'ont pas été capables d'identifier correctement les complications courantes, notamment les effets collatéraux potentiellement graves et les toxicités ; ils n'ont pas référé de manière appropriée les patients stables aux cliniciens, ce qui a réduit leur efficience. Alors que le transfert de tâches vers les HSA paraît prometteur, pour qu'il soit sûr et efficient, une formation clinique complémentaire s'impose avant de transférer la tâche des soins aux patients ART stables à des cadres de la santé de moindre compétence.

Malaui afronta una grave escasez de personal médico y de enfermería. En el presente estudio se investigó si los auxiliares de vigilancia de la salud (HSA) podrían realizar un suministro eficaz y seguro del tratamiento antirretrovírico (ART) a los pacientes estables. Los ayudantes de vigilancia sanitaria podrían detectar a los pacientes que precisan manejo médico con base en criterios establecidos antes, como los pacientes que comenzaron recientemente el ART, los niños y los pacientes que reciben medicamentos de segunda línea. Los HSA no pudieron reconocer las complicaciones frecuentes, ni las reacciones adversas y las toxicidades que podrían ser graves y remitieron a los médicos, sin razón válida, pacientes estables con lo cual se redujo su eficacia. Si bien la delegación de tareas a los HSA podría parecer prometedora, a fin de velar por la seguridad y la eficiencia de la iniciativa, es preciso impartir una mayor capacitación clínica antes de confiar al personal sanitario menos calificado la atención de pacientes estables que reciben el ART.

Timing and uptake of ART during treatment for active tuberculosis in HIV co-infected adults in Malawi.

SETTING: Uptake of antiretroviral therapy (ART) in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) has historically been low in Malawi. In response, the National TB Programme piloted the initiation of ART 2 weeks after initiation of TB treatment in 2008-2009, a change from the prior policy of 2 months. OBJECTIVE: To determine at programme level if earlier initiation of ART in co-infected patients receiving TB treatment will increase the uptake and continuation of ART. DESIGN: A prospective observational pilot programme evaluation using routinely collected monitoring data from the first two sites with integrated TB-HIV services in Malawi. RESULTS: There was wide variability in the ART start time before and after the policy change. Before the policy change, 16% of patients initiated ART by 3 months compared to 24% after the policy change (P < 0.001). The proportion of all co-infected patients on ART increased from 32% before the policy change to 39% after (P < 0.001). Earlier initiation of ART did not increase the occurrence of side effects and did not reduce adherence to TB treatment. CONCLUSION: Earlier initiation of ART in co-infected patients receiving TB treatment improved the uptake and continuation of ART. Malawi ART guidelines in 2011 were changed from initiating ART after 2 months to as soon as possible after starting anti-tuberculosis treatment.

Tuberculosis in HIV programmes in lower-income countries: practices and risk factors.

BACKGROUND: Tuberculosis (TB) is a common diagnosis in human immunodeficiency virus (HIV) infected patients on antiretroviral treatment (ART). OBJECTIVE: To describe TB-related practices in ART programmes in lower-income countries and identify risk factors for TB in the first year of ART. METHODS: Programme characteristics were assessed using standardised electronic questionnaire. Patient data from 2003 to 2008 were analysed and incidence rate ratios (IRRs) calculated using Poisson regression models. RESULTS: Fifteen ART programmes in 12 countries in Africa, South America and Asia were included. Chest X-ray, sputum microscopy and culture were available free of charge in respectively 13 (86.7%), 14 (93.3%) and eight (53.3%) programmes. Eight sites (53.3%) used directly observed treatment and five (33.3%) routinely administered isoniazid preventive treatment (IPT). A total of 19 413 patients aged ≥ 16 years contributed 13,227 person-years of follow-up; 1081 new TB events were diagnosed. Risk factors included CD4 cell count (>350 cells/µl vs. <25 cells/µl, adjusted IRR 0.46, 95%CI 0.33-0.64, P < 0.0001), sex (women vs. men, adjusted IRR 0.77, 95%CI 0.68-0.88, P = 0.0001) and use of IPT (IRR 0.24, 95%CI 0.19-0.31, P < 0.0001). CONCLUSIONS: Diagnostic capacity and practices vary widely across ART programmes. IPT prevented TB, but was used in few programmes. More efforts are needed to reduce the burden of TB in HIV co-infected patients in lower income countries.