Initial Accuracy of HIV Rapid Test Kits Stored in Suboptimal Conditions and Validity of Delayed Reading of Oral Fluid Tests.

OBJECTIVES: To evaluate the effect of storing commonly used rapid diagnostic tests above manufacturer-recommended temperature (at 37°C), and the accuracy of delayed reading of oral fluid kits with relevance to HIV self-testing programmes. DESIGN: A quality assurance study of OraQuick (OraSure), Determine HIV 1/2™ (Alere) and Uni-Gold™ (Recombigen®). METHODS: Consecutive adults (≥18y) attending Ndirande Health Centre in urban Blantyre, Malawi in January to April 2012 underwent HIV testing with two of each of the three rapid diagnostic test kits stored for 28 days at either 18°C (optimally-stored) or at 37°C (pre-incubated). Used OraQuick test kits were stored in a laboratory for delayed day 1 and subsequent monthly re-reading was undertaken for one year. RESULTS: Of 378 individuals who underwent parallel testing, 5 (1.3%) were dropped from the final analysis due to discordant or missing reference standard results (optimally-stored Determine and Uni-Gold). Compared to the diagnostic reference standard, OraQuick had a sensitivity of 97.2% (95% CI: 93.6-99.6). There were 7 false negative results among all test kits stored at 37°C and three false negatives among optimally stored kits. Excellent agreement between pre-incubated tests and optimally-stored tests with Kappa values of 1.00 for Determine and Uni-Gold; and 0.97 (95% CI: 0.95; 1.00) for OraQuick were observed. There was high visual stability on re-reading of OraQuick, with only 1/375 pre-incubated and 1/371 optimally-stored OraQuick kits changing from the initial result over 12 months. CONCLUSION: Erroneous results observed during HIV testing in low income settings are likely to be due to factors other than suboptimal storage conditions. Re-reading returned OraQuick kits may offer a convenient and accurate quality assurance approach, including in HIV self-testing programmes.

HIV policy and implementation: a national policy review and an implementation case study of a rural area of northern Malawi.

Malawi is a global leader in the design and implementation of progressive HIV policies. However, there continues to be substantial attrition of people living with HIV across the "cascade" of HIV services from diagnosis to treatment, and program outcomes could improve further. Ability to successfully implement national HIV policy, especially in rural areas, may have an impact on consistency of service uptake. We reviewed Malawian policies and guidelines published between 2003 and 2013 relating to accessibility of adult HIV testing, prevention of mother-to-child transmission and HIV care and treatment services using a policy extraction tool, with gaps completed through key informant interviews. A health facility survey was conducted in six facilities serving the population of a demographic surveillance site in rural northern Malawi to investigate service-level policy implementation. Survey data were analyzed using descriptive statistics. Policy implementation was assessed by comparing policy content and facility practice using pre-defined indicators covering service access: quality of care, service coordination and patient tracking, patient support, and medical management. ART was rolled out in Malawi in 2004 and became available in the study area in 2005. In most areas, practices in the surveyed health facilities complied with or exceeded national policy, including those designed to promote rapid initiation onto treatment, such as free services and task-shifting for treatment initiation. However, policy and/or practice were/was lacking in certain areas, in particular those strategies to promote retention in HIV care (e.g., adherence monitoring and home-based care). In some instances, though, facilities implemented alternative progressive practices aimed at improving quality of care and encouraging adherence. While Malawi has formulated a range of progressive policies aiming to promote rapid initiation onto ART, increased investment in policy implementation strategies and quality service delivery, in particular to promote long-term retention on treatment may improve outcomes further.

Uptake, Accuracy, Safety, and Linkage into Care over Two Years of Promoting Annual Self-Testing for HIV in Blantyre, Malawi: A Community-Based Prospective Study.

BACKGROUND: Home-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population. METHODS AND FINDINGS: Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test) to adult (≥16 y old) residents (n = 16,660) and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA) sample. Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover) residents self-tested during months 1-12, with adolescents (16-19 y) most likely to test. 10,614/14,004 (75.8%) participants shared results with volunteer-counsellors. Of 1,257 (11.8%) HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3%) newly accessed care with a median CD4 count of 250 cells/µl (interquartile range 159-426). HIVST uptake in months 13-24 was more rapid (70.9% uptake by 6 mo), with fewer (7.3%, 95% CI 6.8%-7.8%) positive participants. Being "forced to test", usually by a main partner, was reported by 2.9% (95% CI 2.6%-3.2%) of 10,017 questionnaire respondents in months 1-12, but satisfaction with HIVST (94.4%) remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1,649 systematically selected (1 in 20) QA participants (99.4%), giving a sensitivity of 93.6% (95% CI 88.2%-97.0%) and a specificity of 99.9% (95% CI 99.6%-100%). Key limitations included use of aggregate data to report uptake of HIVST and being unable to adjust for population turnover. CONCLUSIONS: Community-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings.

A comparative analysis of national HIV policies in six African countries with generalized epidemics.

OBJECTIVE: To compare national human immunodeficiency virus (HIV) policies influencing access to HIV testing and treatment services in six sub-Saharan African countries. METHODS: We reviewed HIV policies as part of a multi-country study on adult mortality in sub-Saharan Africa. A policy extraction tool was developed and used to review national HIV policy documents and guidelines published in Kenya, Malawi, South Africa, Uganda, the United Republic of Tanzania and Zimbabwe between 2003 and 2013. Key informant interviews helped to fill gaps in findings. National policies were categorized according to whether they explicitly or implicitly adhered to 54 policy indicators, identified through literature and expert reviews. We also compared the national policies with World Health Organization (WHO) guidance. FINDINGS: There was wide variation in policies between countries; each country was progressive in some areas and not in others. Malawi was particularly advanced in promoting rapid initiation of antiretroviral therapy. However, no country had a consistently enabling policy context expected to increase access to care and prevent attrition. Countries went beyond WHO guidance in certain areas and key informants reported that practice often surpassed policy. CONCLUSION: Evaluating the impact of policy differences on access to care and health outcomes among people living with HIV is challenging. Certain policies will exert more influence than others and official policies are not always implemented. Future research should assess the extent of policy implementation and link these findings with HIV outcomes.

Strategies for monitoring and evaluation of resource-limited national antiretroviral therapy programs: the two-phase design.

BACKGROUND: In resource-limited settings, monitoring and evaluation (M&E) of antiretroviral treatment (ART) programs often relies on aggregated facility-level data. Such data are limited, however, because of the potential for ecological bias, although collecting detailed patient-level data is often prohibitively expensive. To resolve this dilemma, we propose the use of the two-phase design. Specifically, when the outcome of interest is binary, the two-phase design provides a framework within which researchers can resolve ecological bias through the collection of patient-level data on a sub-sample of individuals while making use of the routinely collected aggregated data to obtain potentially substantial efficiency gains. METHODS: Between 2005-2007, the Malawian Ministry of Health conducted a one-time cross-sectional survey of 82,887 patients registered at 189 ART clinics. Using these patient data, an aggregated dataset is constructed to mimic the type of data that it routinely available. A hypothetical study of risk factors for patient outcomes at 6 months post-registration is considered. Analyses are conducted based on: (i) complete patient-level data; (ii) aggregated data; (iii) a hypothetical case-control study; (iv) a hypothetical two-phase study stratified on clinic type; and, (v) a hypothetical two-phase study stratified on clinic type and registration year. A simulation study is conducted to compare statistical power to detect an interaction between clinic type and year of registration across the designs. RESULTS: Analyses and conclusions based solely on aggregated data may suffer from ecological bias. Collecting and analyzing patient data using either a case-control or two-phase design resolves ecological bias to provide valid conclusions. To detect the interaction between clinic type and year of registration, the case-control design would require a prohibitively large sample size. In contrast, a two-phase design that stratifies on clinic and year of registration achieves greater than 85% power with as few as 1,000 patient samples. CONCLUSIONS: Two-phase designs have the potential to augment current M&E efforts in resource-limited settings by providing a framework for the collection and analysis of patient data. The design is cost-efficient in the sense that it often requires far fewer patients to be sampled when compared to standard designs.

Effect of optional home initiation of HIV care following HIV self-testing on antiretroviral therapy initiation among adults in Malawi: a randomized clinical trial.

IMPORTANCE: Self-testing for HIV infection may contribute to early diagnosis of HIV, but without necessarily increasing antiretroviral therapy (ART) initiation. OBJECTIVE: To investigate whether offering optional home initiation of HIV care after HIV self-testing might increase demand for ART initiation, compared with HIV self-testing accompanied by facility-based services only. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized trial conducted in Blantyre, Malawi, between January 30 and November 5, 2012, using restricted 1:1 randomization of 14 community health worker catchment areas. Participants were all adult (≥16 years) residents (n = 16,660) who received access to home HIV self-testing through resident volunteers. This was a second-stage randomization of clusters allocated to the HIV self-testing group of a parent trial. INTERVENTIONS: Clusters were randomly allocated to facility-based care or optional home initiation of HIV care (including 2 weeks of ART if eligible) for participants reporting positive HIV self-test results. MAIN OUTCOMES AND MEASURES: The preplanned primary outcome compared between groups the proportion of all adult residents who initiated ART within the first 6 months of HIV self-testing availability. Secondary outcomes were uptake of HIV self-testing, reporting of positive HIV self-test results, and rates of loss from ART at 6 months. RESULTS: A significantly greater proportion of adults in the home group initiated ART (181/8194, 2.2%) compared with the facility group (63/8466, 0.7%; risk ratio [RR], 2.94, 95% CI, 2.10-4.12; P < .001). Uptake of HIV self-testing was high in both the home (5287/8194, 64.9%) and facility groups (4433/8466, 52.7%; RR, 1.23; 95% CI, 0.96-1.58; P = .10). Significantly more adults reported positive HIV self-test results in the home group (490/8194 [6.0%] vs the facility group, 278/8466 [3.3%]; RR, 1.86; 95% CI, 1.16-2.97; P = .006). After 6 months, 52 of 181 ART initiators (28.7%) and 15 of 63 ART initiators (23.8%) in the home and facility groups, respectively, were lost from ART (adjusted incidence rate ratio, 1.18; 95% CI, 0.62-2.25, P = .57). CONCLUSIONS AND RELEVANCE: Among Malawian adults offered HIV self-testing, optional home initiation of care compared with standard HIV care resulted in a significant increase in the proportion of adults initiating ART. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01414413.

A novel community health worker tool outperforms WHO clinical staging for assessment of antiretroviral therapy eligibility in a resource-limited setting.

The accuracy of a novel community health worker antiretroviral therapy eligibility assessment tool was examined in community members in Blantyre, Malawi. Nurses independently performed World Health Organization (WHO) staging and CD4 counts. One hundred ten (55.6%) of 198 HIV-positive participants had a CD4 count of <350 cells per cubic millimeter. The community health worker tool significantly outperformed WHO clinical staging in identifying CD4 count of <350 cells per cubic millimeter in terms of sensitivity (41% vs. 19%), positive predictive value (75% vs. 68%), negative predictive values (53% vs. 47%), and area under the receiver-operator curve (0.62 vs. 0.54; P = 0.017). Reliance on WHO staging is likely to result in missed and delayed antiretroviral therapy initiation.

Task-sharing of HIV care and ART initiation: evaluation of a mixed-care non-physician provider model for ART delivery in rural Malawi.

BACKGROUND: Expanding access to antiretroviral therapy (ART) in sub-Saharan Africa requires implementation of alternative care delivery models to traditional physician-centered approaches. This longitudinal analysis compares outcomes of patients initiated on antiretroviral therapy (ART) by non-physician and physician providers. METHODS: Adults (≥15 years) initiating ART between September 2007 and March 2010, and with >1 follow-up visit were included and classified according to the proportion of clinical visits performed by nurses or by clinical officers (≥ 80% of visits). Multivariable Poisson models were used to compare 2-year program attrition (mortality and lost to follow-up) and mortality by type of provider. In sensitivity analyses only patients with less severe disease were included. RESULTS: A total of 10,112 patients contributed 14,012 person-years to the analysis: 3386 (33.5%) in the clinical officer group, 1901 (18.8%) in the nurse care group and 4825 (47.7%) in the mixed care group. Overall 2-year program retention was 81.8%. Attrition was lower in the mixed care and higher in the clinical officer group, compared to the nurse group (adjusted incidence rate ratio [aIRR]=0.54, 95%CI 0.45-0.65; and aIRR=3.03, 95%CI 2.56-3.59, respectively). While patients initiated on ART by clinical officers in the mixed care group had lower attrition (aIRR=0.36, 95%CI 0.29-0.44) than those in the overall nurse care group; no differences in attrition were found between patients initiated on ART by nurses in the mixed care group and those included in the nurse group (aIRR=1.18, 95%CI 0.95-1.47). Two-year mortality estimates were aIRR=0.72, 95%CI 0.49-1.09 and aIRR=5.04, 95%CI 3.56-7.15, respectively. Slightly higher estimates were observed when analyses were restricted to patients with less severe disease. CONCLUSION: The findings of this study support the use of a mixed care model with well trained and regularly supervised nurses and medical assistants to provide HIV care in countries with high HIV prevalence.

Development and validation of a global positioning system-based "map book" system for categorizing cluster residency status of community members living in high-density urban slums in Blantyre, Malawi.

A significant methodological challenge in implementing community-based cluster-randomized trials is how to accurately categorize cluster residency when data are collected at a site distant from households. This study set out to validate a map book system for use in urban slums with no municipal address systems, where classification has been shown to be inaccurate when address descriptions were used. Between April and July 2011, 28 noncontiguous clusters were demarcated in Blantyre, Malawi. In December 2011, antiretroviral therapy initiators were asked to identify themselves as cluster residents (yes/no and which cluster) by using map books. A random sample of antiretroviral therapy initiators was used to validate map book categorization against Global Positioning System coordinates taken from participants' households. Of the 202 antiretroviral therapy initiators, 48 (23.8%) were categorized with the map book system as in-cluster residents and 147 (72.8%) as out-of-cluster residents, and 7 (3.4%) were unsure. Agreement between map books and the Global Positioning System was 100% in the 20 adults selected for validation and was 95.0% (κ = 0.96, 95% confidence interval: 0.84, 1.00) in an additional 20 in-cluster residents (overall κ = 0.97, 95% confidence interval: 0.90, 1.00). With map books, cluster residents were classified rapidly and accurately. If validated elsewhere, this approach could be of widespread value in that it would enable accurate categorization without home visits.

Treatment initiation, program attrition and patient treatment outcomes associated with scale-up and decentralization of HIV care in rural Malawi.

OBJECTIVE: To describe patient antiretroviral therapy (cART) outcomes associated with intensive decentralization of services in a rural HIV program in Malawi. METHODS: Longitudinal analysis of data from HIV-infected patients starting cART between August 2001 and December 2008 and of a cross-sectional immunovirological assessment conducted 12 (±2) months after therapy start. One-year mortality, lost to follow-up, and attrition (deaths and lost to follow-up) rates were estimated with exact Poisson 95% confidence intervals (CI) by type of care delivery and year of initiation. Association of virological suppression (<50 copies/mL) and immunological success (CD4 gain ≥100 cells/µL), with type of care was investigated using multiple logistic regression. RESULTS: During the study period, 4322 cART patients received centralized care and 11,090 decentralized care. At therapy start, patients treated in decentralized health facilities had higher median CD4 count levels (167 vs. 130 cell/µL, P<0.0001) than other patients. Two years after cART start, program attrition was lower in decentralized than centralized facilities (9.9 per 100 person-years, 95% CI: 9.5-10.4 vs. 20.8 per 100 person-years, 95% CI: 19.7-22.0). One year after treatment start, differences in immunological success (adjusted OR=1.23, 95% CI: 0.83-1.83), and viral suppression (adjusted OR=0.80, 95% CI: 0.56-1.14) between patients followed at centralized and decentralized facilities were not statistically significant. CONCLUSIONS: In rural Malawi, 1- and 2-year program attrition was lower in decentralized than in centralized health facilities and no statistically significant differences in one-year immunovirological outcomes were observed between the two health care levels. Longer follow-up is needed to confirm these results.

Determinants and consequences of failure of linkage to antiretroviral therapy at primary care level in Blantyre, Malawi: a prospective cohort study.

BACKGROUND: Poor rates of linkage from HIV diagnosis to ART initiation are a major barrier to universal coverage of ART in sub-Saharan Africa, with reasons for failure poorly understood. In the first study of this kind at primary care level, we investigated the pathway to care in the Malawian National Programme, one of the strongest in Africa. METHODS AND FINDINGS: A prospective cohort study was undertaken at two primary care clinics in Blantyre, Malawi. Newly diagnosed HIV-positive adults (>15 years) were followed for 6-months to assess completion of eligibility assessments, initiation of ART and death. Two hundred and eighty participants were followed for 82.6 patient-years. ART eligibility assessments were problematic: only 134 (47.9%) received same day WHO staging and 121 (53.2%) completed assessments by 6-months. Completion of CD4 measurement (stage 1/2 only) was 81/153 (52.9%). By 6-months, 87/280 (31.1%) had initiated ART with higher uptake in participants who were ART eligible (68/91, 74.7%), and among participants who received same-day staging (52/134 [38.8%] vs. 35/146 [24.0%] p = 0.007). Non-completion of ART eligibility assessments (adjusted hazard ratio: 0.11, 95% CI: 0.06-0.21) was associated with failure to initiate ART. Retention in pre-ART care for non-ART initiators was low (55/193 [28.5%]). Of the 15 (5.4%) deaths, 11 (73.3%) occurred after ART initiation. CONCLUSIONS: Although uptake of ART was high and prompt for patients with known eligibility, there was frequent failure to complete eligibility assessment and poor retention in pre-ART care. HIV care programmes should urgently evaluate the way patients are linked to ART. In particular, there is a critical need for simplified, same-day ART eligibility assessments, reduced requirements for hospital visits, and active defaulter follow-up.

Improving data quality and supervision of antiretroviral therapy sites in Malawi: an application of Lot Quality Assurance Sampling.

BACKGROUND: High quality program data is critical for managing, monitoring, and evaluating national HIV treatment programs. By 2009, the Malawi Ministry of Health had initiated more than 270,000 patients on HIV treatment at 377 sites. Quarterly supervision of these antiretroviral therapy (ART) sites ensures high quality care, but the time currently dedicated to exhaustive record review and data cleaning detracts from other critical components. The exhaustive record review is unlikely to be sustainable long term because of the resources required and increasing number of patients on ART. This study quantifies the current levels of data quality and evaluates Lot Quality Assurance Sampling (LQAS) as a tool to prioritize sites with low data quality, thus lowering costs while maintaining sufficient quality for program monitoring and patient care. METHODS: In January 2010, a study team joined supervision teams at 19 sites purposely selected to reflect the variety of ART sites. During the exhaustive data review, the time allocated to data cleaning and data discrepancies were documented. The team then randomly sampled 76 records from each site, recording secondary outcomes and the time required for sampling. RESULTS: At the 19 sites, only 1.2% of records had discrepancies in patient outcomes and 0.4% in treatment regimen. However, data cleaning took 28.5 hours in total, suggesting that data cleaning for all 377 ART sites would require over 350 supervision-hours quarterly. The LQAS tool accurately identified the sites with the low data quality, reduced the time for data cleaning by 70%, and allowed for reporting on secondary outcomes. CONCLUSIONS: Most sites maintained high quality records. In spite of this, data cleaning required significant amounts of time with little effect on program estimates of patient outcomes. LQAS conserves resources while maintaining sufficient data quality for program assessment and management to allow for quality patient care.

Suboptimal patterns of provider initiated HIV testing and counselling, antiretroviral therapy eligibility assessment and referral in primary health clinic attendees in Blantyre, Malawi.

OBJECTIVE: To understand reasons for suboptimal and delayed uptake of antiretroviral therapy (ART) by describing the patterns of HIV testing and counselling (HTC) and outcomes of ART eligibility assessments in primary clinic attendees. METHODS: All clinic attendances and episodes of HTC were recorded at two clinics in Blantyre. A cohort of newly diagnosed HIV-positive adults (>15 years) was recruited and exit interviews undertaken. Logistic regression models were constructed to investigate factors associated with referral to start ART. Qualitative interviews were conducted with providers and patients. RESULTS: There were 2398 episodes of HTC during 18,021 clinic attendances (13.3%) between January and April 2011. The proportion of clinic attendees undergoing HTC was lowest in non-pregnant women (6.3%) and men (8.5%), compared with pregnant women (47.2%). Men had more advanced HIV infection than women (79.7% WHO stage 3 or 4 vs. 56.4%). Problems with WHO staging and access to CD4 counts affected ART eligibility assessments; only 48% completed ART eligibility assessment, and 54% of those reporting WHO stage 3/4 illnesses were not referred to start ART promptly. On multivariate analysis, HIV-positive pregnant women were significantly less likely to be referred directly for ART initiation (adjusted OR: 0.29, 95% CI: 0.13-0.63). CONCLUSIONS: These data show that provider-initiated testing and counselling (PITC) has not yet been fully implemented at primary care clinics. Suboptimal ART eligibility assessments and referral (reflecting the difficulties of WHO staging in primary care) mean that simplified eligibility assessment tools are required to reduce unnecessary delay and attrition in the pre-ART period. Simplified initiation criteria for pregnant women, as being introduced in Malawi, should improve linkage to ART.

Mortality and loss to follow-up in the first year of ART: Malawi national ART programme.

OBJECTIVES: To analyse mortality, loss to follow-up (LTFU) and retention on antiretroviral treatment (ART) in the first year of ART across all age groups in the Malawi national ART programme. DESIGN: Cohort study including all patients who started ART in Malawi's public sector clinics between 2004 and 2007. METHODS: ART registers were photographed, information entered into a database and merged with data from clinics with electronic records. Rates per 100 patient-years and cumulative incidence of retention were calculated. Subhazard ratios (sHRs) of outcomes adjusted for patient and clinic-level characteristics were calculated in multivariable analysis, applying competing risk models. RESULTS: A total of 117,945 patients contributed 85,246 person-years: 1.0% were infants below 2 years, 7.4% children 2-14, 7.5% young people 15-24, and 84.2% adults 25 years and above. Sixty percent of patients were female: women outnumbered men from age 14 to 35 years. Mortality and LTFU were higher in men from age 20 years. Infants and young people had the highest rates per 100 person-years for mortality (23.0 and 19.4) and LTFU (24.7 and 19.3), and the highest adjusted relative risks compared to age group 25-34 years: sHRs were 1.37 [95% confidence interval (CI) 1.17-1.60] and 1.17 (95% CI 1.10-1.25) for death and 1.37 (95% CI 1.18-1.59) and 1.27 (95% CI 1.19-1.35) for LTFU, respectively. CONCLUSION: In this country-wide study patients aged 0-1 and 15-24 years had the highest risk of death and LTFU, and from age 20 men were at higher risk than women. Interventions to improve outcomes in these patient groups are required.

How operational research influenced the scale up of antiretroviral therapy in Malawi.

The national scale up of antiretroviral therapy in Malawi is based on a public health approach, with principles and practices borrowed from the successful World Health Organization "DOTS" tuberculosis control framework. The scale up of antiretroviral therapy was under-pinned by a very strong monitoring and evaluation system, which was used to audit the scale up approach and conduct operational research to answer relevant questions. Examples of research included:- i) access to antiretroviral therapy, populations and social groups served, and how the different groups fared with regard to outcomes; ii) determining whether the quality of data at antiretroviral therapy sites was adequate and whether external supervision was needed; iii) finding feasible ways of reducing the high early mortality in patients starting treatment in both Malawi and the sub-Saharan African region; iv) the causes of loss-to-follow-up, what happened to patients who transferred out of sites and whether transfer-out patients had outcomes comparable to those who did not transfer; and v) the important question of whether antiretroviral therapy scale up reduced population mortality. The answers to these questions had an important influence on how treatment was delivered in the country, and show the value of this work within a programme setting. Key generic lessons include the importance of i) research questions being relevant to programme needs, ii) studies being coordinated, designed and undertaken within a programme, iii) study findings being disseminated at national stakeholder meetings and through publications in peer-reviewed journals and iv) research being used to influence policy and practice, improve programme performance and ultimately patient treatment outcomes.

Barriers and facilitators to linkage to ART in primary care: a qualitative study of patients and providers in Blantyre, Malawi.

INTRODUCTION: Linkage from HIV testing and counselling (HTC) to initiation of antiretroviral therapy (ART) is suboptimal in many national programmes in sub-Saharan Africa, leading to delayed initiation of ART and increased risk of death. Reasons for failure of linkage are poorly understood. METHODS: Semi-structured qualitative interviews were undertaken with health providers and HIV-positive primary care patients as part of a prospective cohort study at primary health centres in Blantyre, Malawi. Patients successful and unsuccessful in linking to ART were included. RESULTS: Progression through the HIV care pathway was strongly influenced by socio-cultural norms, particularly around the perceived need to regain respect lost during a period of visibly declining health. Capacity to call upon the support of networks of families, friends and employers was a key determinant of successful progression. Over-busy clinics, non-functioning laboratories and unsuitable tools used for ART eligibility assessment (WHO clinical staging system and centralized CD4 count measurement) were important health systems determinants of drop-out. CONCLUSIONS: Key interventions that could rapidly improve linkage include guarantee of same-day, same-clinic ART eligibility assessments; utilization of the support offered by peer-groups and community health workers; and integration of HTC and ART programmes.

Stigmatising attitudes among people offered home-based HIV testing and counselling in Blantyre, Malawi: construction and analysis of a stigma scale.

BACKGROUND: HIV/AIDS related stigma is a major barrier to uptake of HIV testing and counselling (HTC). We assessed the extent of stigmatising attitudes expressed by participants offered community-based HTC, and their anticipated stigma from others to assess relationship with HIV test uptake. From these data, we constructed a brief stigma scale for use around the time of HIV testing. METHODS AND FINDINGS: Adult members of 60 households in urban Blantyre, Malawi, were selected using population-weighted random cluster sampling and offered HTC with the option to self-test before confirmatory HTC. Prior to HTC a 15-item HIV stigma questionnaire was administered. We used association testing and principal components analysis (PCA) to construct a scale measure of stigma. Of 226 adults invited to participate, 216 (95.6%) completed questionnaires and 198/216 (91.7%) opted to undergo HTC (all self-tested). Stigmatising attitudes were uncommon, but anticipated stigma was common, especially fearing verbal abuse (22%) or being abandoned by their partner (11%). Three questions showed little association or consistency with the remaining 12 stigma questions and were not included in the final scale. For the 12-question final scale, Cronbach's alpha was 0.75. Level of stigma was not associated with previously having tested for HIV (p = 0.318) or agreeing to HTC (p = 0.379), but was associated with expressed worry about being or becoming HIV infected (p = 0.003). CONCLUSIONS: Anticipated stigma prior to HTC was common among both men and women. However, the high uptake of HTC suggests that this did not translate into reluctance to accept community-based testing. We constructed a brief scale to measure stigma at the time of HIV testing that could rapidly identify individuals requiring additional support following diagnosis and monitor the impact of increasing availability of community-based HTC on prevalence of stigma.

Antiretroviral drug supply challenges in the era of scaling up ART in Malawi.

The number of people receiving antiretroviral treatment (ART) has increased considerably in recent years and is expected to continue to grow in the coming years. A major challenge is to maintain uninterrupted supplies of antiretroviral (ARV) drugs and prevent stock outs. This article discusses issues around the management of ARVs and prevention of stock outs in Malawi, a low-income country with a high HIV/AIDS burden, and a weak procurement and supply chain management system. This system for ARVs, paid for by the Global Fund to Fight AIDS, Tuberculosis and Malaria, and bypassing the government Central Medical Stores, is in place, using the United Nations Children's Fund's (UNICEF's) procurement services. The system, managed by a handful of people who spend limited time on supply management, is characterized by a centrally coordinated quantification based on verified data from all national ART clinics, parallel procurement through UNICEF, and direct distribution to ART clinics. The model worked well in the first years of the ART programme with a single first-line ARV regimen, but with more regimens becoming available (e.g., alternative first-line, second-line and paediatric regimens), it has become more difficult to administer. Managing supplies through a parallel system has the advantage that weaknesses in the national system have limited influence on the ARV procurement and supply chain management system. However, as the current system operates without a central warehouse and national buffer stock capacity, it diminishes the ability to prevent ARV stock outs. The process of ordering ARVs, from the time that estimates are made to the arrival of supplies in health facilities, takes approximately one year. Addressing the challenges involved in maintaining ARVs through an efficient procurement and supply chain management system that prevents ARV stock outs through the establishment of a dedicated procurement team, a central warehouse and/or national buffer stock is a priority.

The uptake and accuracy of oral kits for HIV self-testing in high HIV prevalence setting: a cross-sectional feasibility study in Blantyre, Malawi.

BACKGROUND: Although HIV testing and counseling (HTC) uptake has increased dramatically in Africa, facility-based services are unlikely to ever meet ongoing need to the full. A major constraint in scaling up community and home-based HTC services is the unacceptability of receiving HTC from a provider known personally to prospective clients. We investigated the potential of supervised oral HIV self-testing from this perspective. METHODS AND FINDINGS: Adult members of 60 households and 72 members of community peer groups in urban Blantyre, Malawi, were selected using population-weighted random cluster sampling. Participants were offered self-testing plus confirmatory HTC (parallel testing with two rapid finger-prick blood tests), standard HTC alone, or no testing. 283 (95.6%) of 298 selected adults participated, including 136 (48.0%) men. 175 (61.8%) had previously tested (19 known HIV positive), although only 64 (21.5%) within the last year. HIV prevalence was 18.5%. Among 260 (91.9%) who opted to self-test after brief demonstration and illustrated instructions, accuracy was 99.2% (two false negatives). Although 98.5% rated the test "not hard at all to do," 10.0% made minor procedural errors, and 10.0% required extra help. Most participants indicated willingness to accept self-test kits, but not HTC, from a neighbor (acceptability 94.5% versus 46.8%, p = 0.001). CONCLUSIONS: Oral supervised self-testing was highly acceptable and accurate, although minor errors and need for supervisory support were common. This novel option has potential for high uptake at local community level if it can be supervised and safely linked to counseling and care.