Results from Two HPV-Based Cervical Cancer Screening-Family Planning Integration Models in Malawi: A Cluster Randomized Trial.

We conducted a cluster randomized trial of two models for integrating HPV self-collection into family-planning (FP) services at 16 health facilities in Malawi between March 2020-December 2021. Model 1 involved providing only clinic-based HPV self-collection, whereas Model 2 included both clinic-based and community-based HPV self-collection. An endline household survey was performed in sampled villages and households between October-December 2021 in the catchment areas of the health facilities. We analyzed 7664 surveys from 400 villages. Participants from Model 2 areas were more likely to have ever undergone cervical cancer screening (CCS) than participants from Model 1 areas, after adjusting for district, facility location (urban versus rural), and facility size (hospital versus health center) (adjusted odds ratio = 1.73; 95% CI: 1.29, 2.33). Among participants who had ever undergone CCS, participants from Model 2 were more likely to report having undergone HPV self-collection than participants from Model 1 (50.5% versus 22.8%, p = 0.023). Participants from Model 2 were more likely to be using modern FP (adjusted odds ratio = 1.01; 95% CI: 1.41, 1.98) than Model 1 participants. The integration of FP and HPV self-collection in both the clinic and community increases CCS and modern FP uptake more than integration at the clinic-level alone.

Assessing community health workers' time allocation for a cervical cancer screening and treatment intervention in Malawi: a time and motion study.

BACKGROUND: Community health workers (CHWs) are essential field-based personnel and increasingly used to deliver priority interventions to achieve universal health coverage. Existing literature allude to the potential for detrimental effects of multi-tasking CHWs. This study objective was to assess the impact of integrating cervical cancer screening and prevention therapy (CCSPT) with family planning (FP) on time utilization among CHWs. METHODS: A time and motion study was conducted in 7 health facilities in Malawi. Data was collected at baseline between October-July 2019, and 12 months after CCSPT implementation between July and August 2021. CHWs trained to deliver CCSPT were continuously observed in real time while their activities were timed by independent observers. We used paired sample t-test to assess pre-post differences in average hours CHWs spent on the following key activities, before and after CCSPT implementation: clinical and preventive care; administration; FP; and non-work-related tasks. Regression models were used to ascertain impact of CCSPT on average durations CHWs spent on key activities. RESULTS: Thirty-seven (n = 37) CHWs were observed. Their mean age and years of experience were 42 and 17, respectively. Overall, CHWs were observed for 323 hours (inter quartile range: 2.8-5.5). Compared with the period before CCSPT, the proportion of hours CHWs spent on clinical and preventive care, administration and non-work-related activities were reduced by 13.7, 8.7 and 34.6%, respectively. CHWs spent 75% more time on FP services after CCSPT integration relative to the period before CCSPT. The provision of CCSPT resulted in less time that CHWs devoted towards clinical and preventive care but this reduction was not significant. Following CCPST, CHWs spent significantly few hours on non-work-related activities. CONCLUSION: Introduction of CCSPT was not very detrimental to pre-existing community services. CHWs managed their time ensuring additional efforts required for CCSPT were not at the expense of essential activities. The programming and policy implications are that multi-tasking CHWs with CCSPT will not have substantial opportunity costs.

Uncovering Regulators of Heterochromatin Mediated Silencing Using a Zebrafish Transgenic Reporter.

Heterochromatin formation and maintenance is critical for the repression of transcription from repetitive sequences. However, in vivo tools for monitoring heterochromatin mediated repression of repeats in the context of vertebrate development have been lacking. Here we demonstrate that a large concatemeric transgene integration containing the dsRed fluorescent reporter under the control of a ubiquitous promoter recapitulates molecular hallmarks of heterochromatic silencing, and that expression from the transgene array can be reactivated by depletion of known regulators of heterochromatin. We then use this reporter to identify a previously unappreciated role for the zebrafish NSD1 orthologs, Nsd1a and Nsd1b, in promoting heterochromatin mediated repression. Our results provide proof-principle that this transgenic reporter line can be used to rapidly identify genes with potential roles in heterochromatic silencing in the context of a live, vertebrate organism.

The National Evaluation of Malawi's PMTCT Program (NEMAPP) study: 24-month HIV-exposed infant outcomes from a prospective cohort study.

OBJECTIVES: Data on long-term HIV-free survival in breastfeeding, HIV-exposed infants (HEIs) are limited. The National Evaluation of Malawi's Prevention of Mother-to-Child Transmission (PMTCT) Program (NEMAPP), conducted between 2014 and 2018, evaluated mother-to-child transmission (MTCT) and infant outcomes up to 24 months postpartum. METHODS: We enrolled a nationally representative cohort of HEIs at 54 health facilities across four regional strata in Malawi and used multivariable Cox regression analysis to investigate the risk of adverse outcomes (HIV transmission, infant death and loss to follow-up) to 24 months postpartum. Models, controlling for survey design, were fitted for the total cohort (n = 3462) and for a subcohort that received maternal viral load (VL) monitoring (n = 1282). RESULTS: By 24 months, in 3462 HEIs, weighted cumulative MTCT was 4.9% [95% confidence interval (CI) 3.7-6.4%], 1.3% (95% CI 0.8-2.2%) of HEIs had died, 26.2% (95% CI 24.0-28.6%) had been lost to follow-up and 67.5% (95% CI 65.0-70.0%) were alive and HIV-free. Primiparity [weighted adjusted hazard ratio (aHR) 1.6; 95% CI 1.1-2.2; parity 2-3: weighted aHR 1.5; 95% CI 1.2-1.9], the mother not disclosing her HIV status to her partner (no disclosure: weighted aHR 1.3; 95% CI 1.1-1.6; no partner: weighted aHR 0.7; 95% CI 0.5-0.9), unknown maternal ART start (weighted aHR 2.0; 95% CI 1.0-3.9) and poor adherence (missed ≥ 2 days of ART in the last month: weighted aHR 1.7; 95% CI 1.2-2.2; not on ART: weighted aHR 1.7; 95% CI 1.0-2.7) were associated with adverse outcomes by 24 months. In the subcohort analysis, risk of HIV transmission or infant death was higher among HEIs whose mothers started ART post-conception (during pregnancy: weighted aHR 3.2; 95% CI 1.3-7.7; postpartum: weighted aHR 12.4; 95% CI 1.5-99.6) or when maternal viral load at enrolment was > 1000 HIV-1 RNA copies/mL (weighted aHR 15.7; 95% CI 7.8-31.3). CONCLUSIONS: Infant positivity and infant mortality at 24 months were low for a breastfeeding population. Starting ART pre-conception had the greatest impact on HIV-free survival in HEIs. Further population-level reduction in MTCT may require additional intervention during breastfeeding for women new to PMTCT programmes. Pre-partum diagnosis and linkage to ART, followed by continuous engagement in care during breastfeeding can further reduce MTCT but are challenging to implement.

Prevention of cervical cancer through two HPV-based screen-and-treat implementation models in Malawi: protocol for a cluster randomized feasibility trial.

BACKGROUND: Cervical cancer is the leading cause of cancer incidence and mortality among Malawian women, despite being a largely preventable disease. Implementing a cervical cancer screening and preventive treatment (CCSPT) program that utilizes rapid human papillomavirus (HPV) testing on self-collected cervicovaginal samples for screening and thermal ablation for treatment may achieve greater coverage than current programs that use visual inspection with acetic acid (VIA) for screening and cryotherapy for treatment. Furthermore, self-sampling creates the opportunity for community-based screening to increase uptake in populations with low screening rates. Malawi's public health system utilizes regularly scheduled outreach and village-based clinics to provide routine health services like family planning. Cancer screening is not yet included in these community services. Incorporating self-sampled HPV testing into national policy could address cervical cancer screening barriers in Malawi, though at present the effectiveness, acceptability, appropriateness, feasibility, and cost-effectiveness still need to be demonstrated. METHODS: We designed a cluster randomized feasibility trial to determine the effectiveness, acceptability, appropriateness, feasibility, and budget impact of two models for integrating a HPV-based CCSPT program into family planning (FP) services in Malawi: model 1 involves only clinic-based self-sampled HPV testing, whereas model 2 includes both clinic-based and community-based self-sampled HPV testing. Our algorithm involves self-collection of samples for HPV GeneXpert® testing, visual inspection with acetic acid for HPV-positive women to determine ablative treatment eligibility, and same-day thermal ablation for treatment-eligible women. Interventions will be implemented at 14 selected facilities. Our primary outcome will be the uptake of cervical cancer screening and family planning services during the 18 months of implementation, which will be measured through an Endline Household Survey. We will also conduct mixed methods assessments to understand the acceptability, appropriateness, and feasibility of the interventions, and a cost analysis to assess budget impact. DISCUSSION: Our trial will provide in-depth information on the implementation of clinic-only and clinic-and-community models for integrating self-sampled HPV testing CCSPT with FP services in Malawi. Findings will provide valuable insight for policymakers and implementers in Malawi and other resource-limited settings with high cervical cancer burden. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04286243 . Registered on February 26, 2020.

Early post-partum viremia predicts long-term non-suppression of viral load in HIV-positive women on ART in Malawi: Implications for the elimination of infant transmission.

BACKGROUND: Long-term viral load (VL) suppression among HIV-positive, reproductive-aged women on ART is key to eliminating mother-to-child transmission (MTCT) but few data exist from sub-Saharan Africa. We report trends in post-partum VL in Malawian women on ART and factors associated with detectable VL up to 24 months post-partum. METHODS: 1-6 months post-partum mothers, screened HIV-positive at outpatient clinics in Malawi, were enrolled (2014-2016) with their infants. At enrollment, 12- and 24-months post-partum socio-demographic and PMTCT indicators were collected. Venous samples were collected for determination of maternal VL (limit of detection 40 copies/ml). Results were returned to clinics for routine management. RESULTS: 596/1281 (46.5%) women were retained in the study to 24 months. Those retained were older (p<0.01), had higher parity (p = 0.03) and more likely to have undetectable VL at enrollment than those lost to follow-up (80.0% vs 70.2%, p<0.01). Of 590 women on ART (median 30.1 months; inter-quartile range 26.8-61.3), 442 (74.9%) with complete VL data at 3 visits were included in further analysis. Prevalence of detectable VL at 12 and 24 months was higher among women with detectable VL at enrollment than among those with undetectable VL (74 detectable VL results/66 women vs. 19/359; p<0.001). In multivariable analysis (adjusted for age, parity, education, partner disclosure, timing of ART start and self-reported adherence), detectable VL at 24 months was 9 times more likely among women with 1 prior detectable VL (aOR 9.0; 95%CI 3.5-23.0, p<0.001) and 226 times more likely for women with 2 prior detectable VLs (aOR 226.4; 95%CI 73.0-701.8, p<0.001). CONCLUSIONS: Detectable virus early post-partum strongly increases risk of ongoing post-partum viremia. Due to high loss to follow-up, the true incidence of detectable VL over time is probably underestimated. These findings have implications for MTCT, as well as for the mothers, and call for intensified VL monitoring and targeted adherence support for women during pregnancy and post-partum.

Implications of HIV treatment policies on the health workforce in rural Malawi and Tanzania between 2013 and 2017: Evidence from the SHAPE-UTT study.

Effective implementation of policies for expanding antiretroviral therapy (ART) requires a well-trained and adequately staffed workforce. Changes in national HIV workforce policies, health facility practices, and provider experiences were examined in rural Malawi and Tanzania between 2013 and 2017. In both countries, task-shifting and task-sharing policies were explicit by 2013. In facilities, the cadre mix of providers varied by site and changed over time, with a higher and growing proportion of lower cadre staff in the Malawi site. In Malawi, the introduction of lay counsellors was perceived to have eased the workload of other providers, but lay counsellors reported inadequate support. Both countries had guidance on the minimum numbers of personnel required to deliver HIV services. However, patient loads per provider increased in both settings for HIV tests and visits by ART patients and were not met with corresponding increases in provider capacity in either setting. Providers reported this as a challenge. Although increasing patient numbers bodes well for achieving universal antiretroviral therapy coverage, the quality of care may be undermined by increased workloads and insufficient provider training. Task-shifting strategies may help address workload concerns, but require careful monitoring, supervision and mentoring to ensure effective implementation.

Assessing the implementation of facility-based HIV testing policies in Malawi, South Africa and Tanzania from 2013-2018: Findings from SHAPE-UTT study.

National HIV testing policies aim to increase the proportion of people living with HIV who know their status. National HIV testing policies were reviewed for each country from 2013 to 2018, and compared with WHO guidance. Three rounds of health facility surveys were conducted to assess facility level policy implementation in Karonga (Malawi), uMkhanyakude (South Africa), and Ifakara (Tanzania). A policy 'implementation' score was developed and applied to each facility by site for each round. Most HIV testing policies were explicit and aligned with WHO recommendations. Policies about service coverage, access, and quality of care were implemented in >80% of facilities per site and per round. However, linkage to care and the provision of outreach HIV testing for key populations were poorly implemented. The proportion of facilities reporting HIV test kit stock-outs in the past year reduced over the study period in all sites, but still occurred in ≥17% of facilities per site by 2017. The implementation score improved over time in Karonga and Ifakara and declined slightly in uMkhanyakude. Efforts are needed to address HIV test kit stock-outs and to improve linkage to care among people testing positive in order to reach the 90-90-90 targets.

Breast and cervical cancer screening services in Malawi: a systematic review.

BACKGROUND: To identify and to assess factors enhancing or hindering the delivery of breast and cervical cancer screening services in Malawi with regard to accessibility, uptake, acceptability and effectiveness. METHODS: Systematic review of published scientific evidence. A search of six bibliographic databases and grey literature was executed to identify relevant studies conducted in Malawi in the English language, with no time or study design restrictions. Data extraction was conducted in Excel and evidence synthesis followed a thematic analysis approach to identify and compare emerging themes. RESULTS: One hundred and one unique records were retrieved and 6 studies were selected for final inclusion in the review. Multiple factors affect breast and cervical cancer service delivery in Malawi, operating at three interlinked levels. At the patient level, lack of knowledge and awareness of the disease, location, poor screening environment and perceived quality of care may act as deterrent to participation in screening; at the health facility level, services are affected by the availability of resources and delivery modalities; and at the healthcare system level, inadequate funding and staffing (distribution, supervision, retention), and lack of appropriate monitoring and guidelines may have a negative impact on services. Convenience of screening, in terms of accessibility (location, opening times) and integration with other health services (e.g. reproductive or HIV services), was found to have a positive effect on service uptake. Building awareness of cancer and related services, and offering quality screening (dedicated room, privacy, staff professionalism etc.) are significant determinants of patient satisfaction. CONCLUSIONS: Capitalising on these lessons is essential to strengthen breast and cervical cancer service delivery in Malawi, to increase early detection and to improve survival of women affected by the disease.

Impact of inter-partner HIV disclosure patterns in Malawi's PMTCT program: A mixed-method study.

BACKGROUND: Evidence suggests that disclosure of HIV status between partners may influence prevention of maternal-to-child transmission of HIV (PMTCT) outcomes. We report partner disclosure in relation to maternal antiretroviral therapy (ART) uptake and adherence, and MTCT among postpartum HIV-infected Malawian women. METHODS: A cross-sectional mixed-method study was conducted as part of a nationally representative longitudinal cohort study. Between 2014-2016, all (34,637) mothers attending 54 under-5 clinics with their 4-26 week-old infants were approached, of which 98% (33,980) were screened for HIV; infants received HIV-1 DNA testing. HIV-exposure was confirmed in 3,566/33,980 (10.5%). Baseline data from mothers who were known to be HIV-infected at time of screening were included in the current analysis. Guardians (n = 17), newly diagnosed HIV-infected mothers (n = 256) and mothers or infants with undetermined HIV status (n = 30) were excluded. Data collected included socio-demographics, partner disclosure, maternal ART uptake, and adherence. Between 2016-2017, in-depth interviews and focus group discussions were conducted with adult mothers (n = 53) and their spouse/cohabiting partners (n = 19), adolescent mothers (n = 13), lost-to-follow up (LTFU) mothers (n = 22), community leaders (n = 23) and healthcare workers (n = 154). RESULTS: Of 3153 known HIV-infected mothers, 2882 (91.4%) reported having a spouse/cohabiting partner. Among 2882 couples, both partners, one partner, and neither partner disclosed to each other in 2090 (72.5%), 622 (21.6%), and 169 (5.9%), respectively. In multivariable models, neither partner disclosing was associated with no maternal ART (aOR 4.7; 95%CI 2.5-8.8), suboptimal treatment adherence (aOR 1.8; 95%CI 1.1-2.8) and MTCT (aOR 2.1; 95%CI 1.1-4.1). Women's fear of blame by partners was central to decisions not to disclose within couples and when starting new relationships. LTFU mothers struggled to accept and disclose their status, hindering treatment initiation; some were unable to hide ART and feared involuntary disclosure. CONCLUSION: Partner disclosure seems to play an important role in women's decisions regarding ART initiation and adherence. Inter-partner non-disclosure was associated with no ART uptake, suboptimal treatment adherence and MTCT.

National estimates and risk factors associated with early mother-to-child transmission of HIV after implementation of option B+: a cross-sectional analysis.

BACKGROUND: Routine data from Malawi's prevention of mother-to-child transmission (MTCT) option B+ programme suggest high uptake of antiretroviral therapy (ART) among pregnant women. Malawi's Ministry of Health led the National Evaluation of Malawi's PMTCT Program to obtain nationally representative data on maternal ART coverage and prevention of MTCT effectiveness. Here, we present the early transmission data for infants aged 4-12 weeks. METHODS: We used a multistage cluster design to recruit a nationally representative sample of HIV-exposed infants and their mothers in Malawi. Between October 16, 2014, and May 17, 2016, we screened for HIV in all mothers attending an under-5 vaccination or outpatient sick-child clinic with infants aged 4-26 weeks at 54 health facilities selected across ten districts and four regional sampling zones. Infants with mothers identified as HIV-infected were enrolled in the cohort. We calculated weighted MTCT rates for only the subset of infants aged 4-12 weeks at screening, thereby capturing MTCT from early pregnancy, to delivery, and early breastfeeding. We collected data on maternal and infant demographics and self-reported use of HIV services, ART, and antenatal clinics. We tested HIV-exposed infants for the virus and assessed associations of certain variables with infant HIV status. FINDINGS: We confirmed HIV exposure in 3542 (10·4%) of 33 980 mother (guardian)-infant pairs with infants aged 4-26 weeks. Of those, 2530 (2514 mothers and 16 guardians) had infants aged 4-12 weeks at the time of screening (2498 singlets and 32 twins). We excluded 25 infants from the analysis because no information was available about their HIV status. 91·3% (95% CI 85·6-96·9) of mothers were on ART during pregnancy. The MTCT rate was 3·7% (2·3-6·0) overall and ranged from 1·4% (0·4-4·4) in women who initiated ART before pregnancy to 19·9% (13·4-28·6) in women not on ART. In multivariable logistic regression analysis, the odds of early MTCT were higher in mothers starting ART post partum (adjusted odds ratio 16·7, 95% CI 1·6-171·5; p=0·022) and in those not on ART with an unknown HIV status during pregnancy (19·1, 8·5-43·0; p<0·0001) than in mothers on ART before pregnancy. Among HIV-exposed infants, 98·0% (95% CI 96·9-99·1) were reported by the mother to have received infant nevirapine prophylaxis, and only 45·6% (34·8-56·4) were already enrolled in an exposed infant HIV care clinic at the time of study screening. INTERPRETATION: These data suggest that Malawi's decentralisation of ART services has resulted in higher ART coverage and lower early MTCT. However, the uptake of services for HIV-exposed infants remains suboptimal. FUNDING: President's Emergency Plan for AIDS Relief.

Impact of Facility- and Community-Based Peer Support Models on Maternal Uptake and Retention in Malawi's Option B+ HIV Prevention of Mother-to-Child Transmission Program: A 3-Arm Cluster Randomized Controlled Trial (PURE Malawi).

BACKGROUND: Many sub-Saharan African countries have adopted Option B+, a prevention of mother-to-child transmission approach providing HIV-infected pregnant and lactating women with immediate lifelong antiretroviral therapy. High maternal attrition has been observed in Option B+. Peer-based support may improve retention. METHODS: A 3-arm stratified cluster randomized controlled trial was conducted in Malawi to assess whether facility- and community-based peer support would improve Option B+ uptake and retention compared with standard of care (SOC). In SOC, no enhancements were made (control). In facility-based and community-based models, peers provided patient education, support groups, and patient tracing. Uptake was defined as attending a second scheduled follow-up visit. Retention was defined as being alive and in-care at 2 years without defaulting. Attrition was defined as death, default, or stopping antiretroviral therapy. Generalized estimating equations were used to estimate risk differences (RDs) in uptake. Cox proportional hazards regression with shared frailties was used to estimate hazard of attrition. RESULTS: Twenty-one facilities were randomized and enrolled 1269 women: 447, 428, and 394 in facilities that implemented SOC, facility-based, and community-based peer support models, respectively. Mean age was 27 years. Uptake was higher in facility-based (86%; RD: 6%, confidence interval [CI]: -3% to 15%) and community-based (90%; RD: 9%, CI: 1% to 18%) models compared with SOC (81%). At 24 months, retention was higher in facility-based (80%; RD: 13%, CI: 1% to 26%) and community-based (83%; RD: 16%, CI: 3% to 30%) models compared with SOC (66%). CONCLUSIONS: Facility- and community-based peer support interventions can benefit maternal uptake and retention in Option B+.

Viral Suppression and HIV Drug Resistance at 6 Months Among Women in Malawi's Option B+ Program: Results From the PURE Malawi Study.

BACKGROUND: In 2011, Malawi launched Option B+, a program of universal antiretroviral therapy (ART) treatment for pregnant and lactating women to optimize maternal health and prevent pediatric HIV infection. For optimal outcomes, women need to achieve HIVRNA suppression. We report 6-month HIVRNA suppression and HIV drug resistance in the PURE study. METHODS: PURE study was a cluster-randomized controlled trial evaluating 3 strategies for promoting uptake and retention; arm 1: Standard of Care, arm 2: Facility Peer Support, and arm 3: Community Peer support. Pregnant and breastfeeding mothers were enrolled and followed according to Malawi ART guidelines. Dried blood spots for HIVRNA testing were collected at 6 months. Samples with ART failure (HIVRNA ≥1000 copies/ml) had resistance testing. We calculated odds ratios for ART failure using generalized estimating equations with a logit link and binomial distribution. RESULTS: We enrolled 1269 women across 21 sites in Southern and Central Malawi. Most enrolled while pregnant (86%) and were WHO stage 1 (95%). At 6 months, 950/1269 (75%) were retained; 833/950 (88%) had HIVRNA testing conducted, and 699/833 (84%) were suppressed. Among those with HIVRNA ≥1000 copies/ml with successful amplification (N = 55, 41% of all viral loads > 1000 copies/ml), confirmed HIV resistance was found in 35% (19/55), primarily to the nonnucleoside reverse transcriptase inhibitor class of drugs. ART failure was associated with treatment default but not study arm, age, WHO stage, or breastfeeding status. CONCLUSIONS: Virologic suppression at 6 months was <90% target, but the observed confirmed resistance rates suggest that adherence support should be the primary approach for early failure in option B+.

Lessons Learned From Option B+ in the Evolution Toward "Test and Start" From Malawi, Cameroon, and the United Republic of Tanzania.

The acceleration of prevention of mother-to-child transmission (PMTCT) activities, coupled with the rollout of 2010 World Health Organization (WHO) guidelines, led to important discussions and innovations at global and country levels. One paradigm-shifting innovation was Option B+ in Malawi. It was later included in WHO guidelines and eventually adopted by all 22 Global Plan priority countries. This article presents Malawi's experience with designing and implementing Option B+ and provides complementary narratives from Cameroon and Tanzania. Malawi's HIV program started in 2002, but by 2009, the PMTCT program was lagging far behind the antiretroviral therapy (ART) program because of numerous health system challenges. When WHO recommended Option A and Option B for PMTCT in 2010, it was clear that Malawi's HIV program would not be able to successfully implement either option without increasing existing barriers to PMTCT services and potentially decreasing women's access to care. Subsequent stakeholder discussions led to the development of Option B+. Operationalizing Option B+ required several critical considerations, including the complete integration of ART and PMTCT programs, systematic reduction of barriers to facilitate doubling the number of ART sites in less than a year, building consensus with stakeholders, and securing additional resources for the new program. During the planning and implementation process, several lessons were learned which are considerations for countries transitioning to "treat-all": Comprehensive change requires effective government leadership and coordination; national clinical guidelines must accommodate health system limitations; ART services and commodities should be decentralized within facilities; the general public should be well informed about major changes in the national HIV program; and patients should be educated on clinic processes to improve program monitoring.

Exploring the Experiences of Women and Health Care Workers in the Context of PMTCT Option B Plus in Malawi.

INTRODUCTION: Malawi has embarked on a "test-and-treat" approach to prevent mother-to-child transmission (PMTCT) of HIV, known as "Option B+," offering all HIV-infected pregnant and breastfeeding women lifelong antiretroviral therapy (ART) regardless of CD4 count or clinical stage. A cross-sectional qualitative study was conducted to explore early experiences surrounding "Option B+" for patients and health care workers (HCWs) in Malawi. METHODS: Study participants were purposively selected across 6 health facilities in 3 regional health zones in Malawi. Semi-structured interviews were conducted with women enrolled in "Option B+" (n = 24), and focus group discussions were conducted with HCWs providing Option B+ services (n = 6 groups of 8 HCWs). Data were analyzed using a qualitative thematic coding framework. RESULTS: Patients and HCWs identified the lack of male involvement as a barrier to retention in care and expressed concerns at the rapidity of the test-and-treat process, which makes it difficult for patients to "digest" a positive diagnosis before starting ART. Fear regarding the breach of privacy and confidentiality were also identified as contributing to loss to follow-up of women initiated under the Option B+. Disclosure remains a difficult process within families and couples. Lifelong ART was also perceived as an opportunity to plan future pregnancies. CONCLUSIONS: As "Option B+" continues to be rolled out, novel interventions to support and retain women into care must be implemented. These include providing space, time, and support to accept a diagnosis before starting ART, engaging partners and families, and addressing the need for peer support and confidentiality.

Scaling-up antiretroviral therapy in Malawi.

PROBLEM: In Malawi, health-system constraints meant that only a fraction of people infected with human immunodeficiency virus (HIV) and in immediate need of antiretroviral treatment (ART) received treatment. APPROACH: In 2004, the Malawian Ministry of Health launched plans to scale-up ART nationwide, adhering to the principle of equity to ensure fair geographical access to therapy. A public health approach was used with standardized training and treatment and regular supervision and monitoring of the programme. LOCAL SETTING: Before the scale-up, an estimated 930 000 people in Malawi were HIV-infected, with 170 000 in immediate need of ART. About 3000 patients were on ART in nine clinics. RELEVANT CHANGES: By December 2015, cumulatively 872 567 patients had been started on ART from 716 clinics, following national treatment protocols and using the standard monitoring system. LESSONS LEARNT: Strong national leadership allowed the ministry of health to implement a uniform system for scaling-up ART and provided benchmarks for implementation on the ground. New systems of training staff and accrediting health facilities enabled task-sharing and decentralization to peripheral health centres and a standardized approach to starting and monitoring ART. A system of quarterly supervision and monitoring, into which operational research was embedded, ensured stocks of drug supplies at facilities and adherence to national treatment guidelines.

Act local, think global: how the Malawi experience of scaling up antiretroviral treatment has informed global policy.

The scale-up of antiretroviral therapy (ART) in Malawi was based on a public health approach adapted to its resource-poor setting, with principles and practices borrowed from the successful tuberculosis control framework. From 2004 to 2015, the number of new patients started on ART increased from about 3000 to over 820,000. Despite being a small country, Malawi has made a significant contribution to the 15 million people globally on ART and has also contributed policy and service delivery innovations that have supported international guidelines and scale up in other countries. The first set of global guidelines for scaling up ART released by the World Health Organization (WHO) in 2002 focused on providing clinical guidance. In Malawi, the ART guidelines adopted from the outset a more operational and programmatic approach with recommendations on health systems and services that were needed to deliver HIV treatment to affected populations. Seven years after the start of national scale-up, Malawi launched a new strategy offering all HIV-infected pregnant women lifelong ART regardless of the CD4-cell count, named Option B+. This strategy was subsequently incorporated into a WHO programmatic guide in 2012 and WHO ART guidelines in 2013, and has since then been adopted by the majority of countries worldwide. In conclusion, the Malawi experience of ART scale-up has become a blueprint for a public health response to HIV and has informed international efforts to end the AIDS epidemic by 2030.

Correction: Validation of the Surgical Fear Questionnaire in Adult Patients Waiting for Elective Surgery.

[This corrects the article DOI: 10.1371/journal.pone.0100225.].

HIV and tuberculosis in prisons in sub-Saharan Africa.

Given the dual epidemics of HIV and tuberculosis in sub-Saharan Africa and evidence suggesting a disproportionate burden of these diseases among detainees in the region, we aimed to investigate the epidemiology of HIV and tuberculosis in prison populations, describe services available and challenges to service delivery, and identify priority areas for programmatically relevant research in sub-Saharan African prisons. To this end, we reviewed literature on HIV and tuberculosis in sub-Saharan African prisons published between 2011 and 2015, and identified data from only 24 of the 49 countries in the region. Where data were available, they were frequently of poor quality and rarely nationally representative. Prevalence of HIV infection ranged from 2·3% to 34·9%, and of tuberculosis from 0·4 to 16·3%; detainees nearly always had a higher prevalence of both diseases than did the non-incarcerated population in the same country. We identified barriers to prevention, treatment, and care services in published work and through five case studies of prison health policies and services in Zambia, South Africa, Malawi, Nigeria, and Benin. These barriers included severe financial and human-resource limitations and fragmented referral systems that prevent continuity of care when detainees cycle into and out of prison, or move between prisons. These challenges are set against the backdrop of weak health and criminal-justice systems, high rates of pre-trial detention, and overcrowding. A few examples of promising practices exist, including routine voluntary testing for HIV and screening for tuberculosis upon entry to South African and the largest Zambian prisons, reforms to pre-trial detention in South Africa, integration of mental health services into a health package in selected Malawian prisons, and task sharing to include detainees in care provision through peer-educator programmes in Rwanda, Zimbabwe, Zambia, and South Africa. However, substantial additional investments are required throughout sub-Saharan Africa to develop country-level policy guidance, build human-resource capacity, and strengthen prison health systems to ensure universal access to HIV and tuberculsosis prevention, treatment, and care of a standard that meets international goals and human rights obligations.

Improving PMTCT uptake and retention services through novel approaches in peer-based family-supported care in the clinic and community: a 3-arm cluster randomized trial (PURE Malawi).

In July 2011, Malawi introduced an ambitious public health program known as "Option B+," which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy, regardless of clinical stage or CD4 count. Option B+ is expected to have benefits for HIV-infected women, their HIV-exposed infants, and their HIV-uninfected male sex partners. However, these benefits hinge on early uptake of prevention of mother-to-child transmission, good adherence, and long-term retention in care. The Prevention of mother-to-child transmission Uptake and REtention (PURE) study is a 3-arm cluster randomized controlled trial to evaluate whether clinic- or community-based peer support will improve care-seeking and retention in care by HIV-infected pregnant and breastfeeding women, their HIV-exposed infants, and their male sex partners, and ultimately improve health outcomes in all 3 populations. We describe the PURE Malawi Consortium, the initial work conducted to inform the trial and interventions, the trial design, and the analysis plan. We then discuss concerns and expected contributions to Malawi and the region.