Blood pressure changes during tenofovir-based antiretroviral therapy among people living with HIV in Lilongwe, Malawi: results from the prospective LighTen Cohort Study.

BACKGROUND: Sub-Saharan Africa is one of the regions in the world with the highest numbers of uncontrolled hypertension as well as people living with HIV/AIDS (PLHIV). However, the association between hypertension and antiretroviral therapy is controversial. METHODS: Participant demographics, medical history, laboratory values, WHO clinical stage, current medication, and anthropometric data were recorded at study entry and during study visits at 1, 3, 6 months, and every 6 months thereafter until month 36. Patients who stopped or changed their antiretroviral therapy (tenofovir, lamivudine, efavirenz) were censored on that day. Office blood pressure (BP) was categorized using ≥ 2 measurements on ≥ 2 occasions during the first three visits. Factors associated with systolic and mean BP were analyzed using bivariable and multivariable multilevel linear regression. RESULTS: 1,288 PLHIV (751 females, 58.3%) could be included and 832 completed the 36 months of observation. Weight gain and a higher BP level at study entry were associated with an increase in BP (p < 0.001), while female sex (p < 0.001), lower body weight at study entry (p < 0.001), and high glomerular filtration rate (p = 0.009) protected against a rise in BP. The rate of uncontrolled BP remained high (73.9% vs. 72.1%) and despite indication treatment, adjustments were realized in a minority of cases (13%). CONCLUSION: Adherence to antihypertensive treatment and weight control should be addressed in patient education programs at centers caring for PLHIV in low-resources settings like Malawi. Together with intensified training of medical staff to overcome provider inertia, improved control rates of hypertension might eventually be achieved. TRIAL REGISTRATION: NCT02381275.

24-h-Ambulatory Blood Pressure Monitoring in Sub-Saharan Africa: Hypertension Phenotypes and Dipping Patterns in Malawian HIV+ Patients on Antiretroviral Therapy.

Background: Cardiovascular disease and especially hypertension are a growing problem among people living with HIV (PLHIV) on antiretroviral therapy (ART) in sub-Saharan Africa. Objectives: As robust data on hypertension phenotypes associated with distinct cardiovascular risks among PLHIV are limited, we aimed to assess the frequency of white-coat (WCH), masked (MH) hypertension, and blood pressure dipping-patterns in a group of Malawian PLHIV. Methods: As part of the prospective Lighthouse-Tenofovir-Cohort-Study, we analyzed clinical, laboratory and 24-h-ambulatory blood pressure monitoring (ABPM) data of PLHIV from urban Lilongwe with treated or untreated hypertension or raised office blood pressure (OBP) during routine study-visits. Results: 118 PLHIV were included and data of 117 participants could be analyzed. Twenty-four-hour ABPM normotension was found in a total of 73 PLHIV including 14/37 on antihypertensive treatment (37.8%). Using strict definitions, i.e. normal OBP plus normal mean BP for all periods of ABPM, controlled hypertension was found in only 4/37 (10.8%) PLHIV on antihypertensive treatment while true normotension was observed in 10/24 untreated patients (41.7%) with previously diagnosed hypertension and 22/56 patients (39.3%) without a medical history of hypertension. WCH with normal BP during all periods of 24-h-ABPM was identified in 12/64 OBP-hypertensive PLHIV (18.8%), primarily in patients with grade 1 hypertension (11/41 patients; 26.8%). MH was found in 17/53 PLHIV with OBP-normotension (32.1%), predominantly in patients with high normal BP (11/20 patients; 55%). The estimated glomerular filtration rate tended to be lower in MH compared to strictly defined normotensive PLHIV (92.0±20.4 vs. 104.8±15.7 ml/min/m²). 64.1 percent of PLHIV (59.5% with 24-h hypertension and 66.7% with 24-h normotension) had abnormal systolic dipping. Conclusion: The high prevalence of WCH and MH with signs of early renal end-organ damage and an abnormal dipping in approximately 2/3 of PLHIV warrants further investigation as these factors may contribute to the increased cardiovascular risk in PLHIV in resource-limited settings like Malawi. Clinical Trial Registration: https://clinicaltrials.gov (NCT02381275), registered March 6th, 2015.

Prevalence and correlates of probable depression diagnosis and suicidal ideation among patients receiving HIV care in Lilongwe, Malawi.

BACKGROUND: Depression and suicide ideation among people living with HIV (PLHIV) can threaten the success of HIV care and treatment programs, particularly within high HIV prevalence settings. We describe the prevalence and correlates associated with depression and suicidal ideation among PLHIV receiving HIV care in Lilongwe, Malawi. METHODS: From July to September 2013, 206 HIV clinic patients, who were ≥18 years of age and either pre-antiretroviral therapy (ART) or established on ART for ≥6 months prior to study, participated in a survey to assess the prevalence of a likely depressive disorder and suicidal ideation using the Patient Health Questionnaire-9. We explored factors associated with depression using bivariable linear regression and suicidal ideation using bivariable log-binomial regression. RESULTS: The prevalence of a likely depressive disorder and suicidal ideation was 12% (95% CI: 8%, 17%) and 16% (95% CI: 11%, 21%), respectively. Pre-ART patients (ß=1.17, 95% CI: 0.03, 2.30, p-value=0.04) and those with problematic alcohol use (ß=0.49, 95% CI: 0.07, 0.92, p-value=0.02) were associated with a higher depression severity. Suicidal ideation was relatively common (8%, 95% CI: 5%, 13%) among those without a likely depressive disorder and significantly correlated with having no primary, secondary, or tertiary education (ß=-1.52, 95% CI: -2.46, -0.59, p-value<0.01). CONCLUSIONS: Interventions that enhance identification and management of depressive disorders and suicidal ideation should be integrated within HIV care clinics in Malawi.

The path from a volunteer initiative to an established institution: evaluating 15 years of the development and contribution of the Lighthouse trust to the Malawian HIV response.

BACKGROUND: The HIV epidemic has triggered the development of new health institutions with a special focus on HIV care. The role of these relatively new institutions within the health systems of low-income countries like Malawi is not clearly determined. We evaluate and describe the development of one example, the Lighthouse Trust (Lighthouse), over a period of 15 years (2000-2015). METHODS: Data from multiple sources, including a document review, participatory observation and interviews were analysed, triangulated and synthesized. The institution's development, function, cooperation, financing, research and training were analysed using institutional administrative documents, annual reviews, project reports. For the assessment of the research activities, all publications that the Lighthouse contributed to were retrieved and categorized. Participatory observation and interviews with key Lighthouse staff members and external stakeholders were conducted. RESULTS: Established in 1997 as a volunteer initiative for home-based care, the Lighthouse has developed considerably. Major steps include being registered as a trust, moving into their own buildings, expanding clinical services, becoming a centre for clinical service, training and research working with close to 300 employees. As an independent legal entity, Lighthouse Trust works in close cooperation with Malawian public health services and plays an important role in the government's HIV programme. Funding comes from various sources with a lion's share from the US Centers for Disease Control and Prevention. Throughout 2015, the Lighthouse performed 58,210 HIV testing and counselling encounters and by year's end, 28,302 patients were alive and on ART. From 2000 to 2015 Lighthouse staff contributed to 94 peer-reviewed publications. CONCLUSION: Novel institutions like the Lighthouse have been developed in the response to HIV. The Lighthouse has demonstrated its capacity to deliver health services and contributed significantly to the current level of success in addressing the disease. However, this kind of institution's position in local health care systems is still developing. The Lighthouse will need to continue to work on well-planned strategies that consider the changing landscape of health needs, health care provision and financing. Independent institutions like the Lighthouse can contribute to the development of health systems in countries like Malawi that improve health care responsiveness and quality for the entire population.

Factors Associated with Hormonal and Intrauterine Contraceptive Use among HIV-Infected Men and Women in Lilongwe, Malawi: A Cross-Sectional Study.

Background. Understanding the factors associated with the use of hormonal and intrauterine contraception among HIV-infected men and women may lead to interventions that can help reduce high unintended pregnancy rates. Materials and Methods. This study is a subanalysis of a cross-sectional survey of 289 women and 241 men who were sexually active and HIV-infected and were attending HIV care visits in Lilongwe, Malawi. We estimated adjusted prevalence ratios (PRs) to evaluate factors associated with hormonal and intrauterine contraceptive use for men and women in separate models. Results and Discussion. 39.8% of women and 33.2% of men (p = 0.117) reported that they were using hormonal or intrauterine contraception at last intercourse. Having greater than 3 children was the only factor associated with hormonal and intrauterine contraceptive use among men. Among women, younger age, not wanting a pregnancy in 2 years, being with their partner for more than 4 years, and being able to make family planning decisions by themselves were associated with hormonal and intrauterine contraceptive use. Conclusions. The men and women in our study population differed in the factors associated with hormonal and intrauterine contraceptive use. Understanding these differences may help decrease unmet FP needs among HIV-infected men and women.

Implementation and Operational Research: Early Tracing of Children Lost to Follow-Up From Antiretroviral Treatment: True Outcomes and Future Risks.

BACKGROUND: Loss to follow-up (LTFU) challenges the success of antiretroviral therapy (ART) scale-up among pediatric patients. Little is known about children who drop out of care. We aim to analyze risk factors for LTFU among children on ART, find their true outcomes through tracing, and investigate their final outcomes after resuming ART. METHODS: This is a descriptive, retrospective, cohort study of children on ART between April 2006 and December 2010 in 2 clinics in urban Malawi. Routine data from an electronic data system were used and matched with information obtained through routine tracing procedures. RESULTS: Of 985 children (1999 child-years) on ART, 251 were LTFU: 12.6/100 child-years. At ART initiation, wasting [adjusted hazard ratio (AHR) 1.58 and 95% confidence interval (CI): 1.02 to 2.44] was independently associated with higher risk of LTFU. Of 201 LTFU children traced, 79% were found: 11% died, 25% stopped, 26% transferred-out, and 37% were still on ART. Median time between last visit and first tracing was 84 days (interquartile range: 64-101 days). Tracing reduced risk of LTFU by 38% (AHR 0.62 and 95% CI: 0.42 to 0.91) and decreased LTFU from 23.2% to 8.5%. Additional outcomes of stop, death, and transfer-out increased 4.4-fold, 1.8-fold, and 1.3-fold, respectively. Traced children with gaps in ART intake who resumed ART had higher risk of stopping (AHR 4.92 and 95% CI: 1.67 to 14.5) and transfer out (AHR 2.70 and 95% CI: 1.75 to 4.17) as final outcome. CONCLUSIONS: Early tracing substantially reduces LTFU; approximately one-third presumed LTFU was found to be still on ART. Children with wasting at initiation and those traced and found to have irregular ART intake require targeted interventions.

Incidence of pregnancy among women accessing antiretroviral therapy in urban Malawi: a retrospective cohort study.

Although previous studies investigated pregnancy rates among women on antiretroviral therapy (ART), incidence of, and factors associated with pregnancy among these women remain poorly understood. We, therefore, conducted a retrospective cohort study at a large public HIV clinic in Lilongwe, Malawi, between July 2007 and December 2010. At each clinic visit, pregnancy status was assessed. Time to event analysis was conducted using Poisson regression. Among 4,738 women, 589 pregnancies were observed. Pregnancy incidence was 9.3/100 person-years. After 6 months on ART, women on ART had similar total fertility rates to women in the urban population. In multivariable analysis, increasing age and advanced WHO clinical stage were associated with decreased probability of becoming pregnant while higher body mass index and longer time on ART were associated with increased probability of becoming pregnant. We recommend that ART clinics integrate comprehensive family planning services to address reproductive health needs among women on ART.

Tenofovir in second-line ART in Zambia and South Africa: collaborative analysis of cohort studies.

OBJECTIVES: Tenofovir (TDF) is increasingly used in second-line antiretroviral treatment (ART) in sub-Saharan Africa. We compared outcomes of second-line ART containing and not containing TDF in cohort studies from Zambia and the Republic of South Africa (RSA). METHODS: Patients aged 16 years and older starting protease-inhibitor-based second-line ART in Zambia (1 cohort) and RSA (5 cohorts) were included. We compared mortality, immunological failure (all cohorts), and virological failure (RSA only) between patients receiving and not receiving TDF. Competing risk models and Cox models adjusted for age, sex, CD4 count, time on first-line ART, and calendar year were used to analyze mortality and treatment failure, respectively. Hazard ratios (HRs) were combined in fixed-effects meta-analysis. FINDINGS: 1687 patients from Zambia and 1556 patients from RSA, including 1350 (80.0%) and 206 (13.2%) patients starting TDF, were followed over 4471 person-years. Patients on TDF were more likely to have started second-line ART in recent years and had slightly higher baseline CD4 counts than patients not on TDF. Overall, 127 patients died, 532 were lost to follow-up, and 240 patients developed immunological failure. In RSA, 94 patients had virologic failure. Combined HRs comparing TDF with other regimens were 0.60 (95% confidence interval [CI]: 0.41 to 0.87) for immunologic failure and 0.63 (0.38-1.05) for mortality. The HR for virologic failure in RSA was 0.28 (0.09-0.90). CONCLUSIONS: In this observational study, patients on TDF-containing second-line ART were less likely to develop treatment failure than patients on other regimens. TDF seems to be an effective component of second-line ART in southern Africa.

Virological failure and drug resistance in patients on antiretroviral therapy after treatment interruption in Lilongwe, Malawi.

BACKGROUND: Since 2004, Malawi has rapidly scaled up access to antiretroviral therapy (ART) in the national program following a public health approach with limited laboratory monitoring. We examined virological outcomes in patients with treatment interruption at 2 clinics of the Lighthouse Trust, Lilongwe, Malawi. METHODS: We evaluated patients who resumed first-line ART after having at least 1 treatment interruption documented in the electronic data system in 2008-2009. Viral load (VL) was analyzed at least 2 months after resumption of ART. For VL ≥1000 copies/mL, drug-resistance genotype was characterized using the Stanford database. RESULTS: Between June and November 2009, we enrolled 133 patients (58.7% female) with a mean age of 38.4 years. Mean duration of ART prior to treatment interruption was 14.3 months. After a minimum of 2 months following ART resumption, VL was undetectable in 81 (60.9%) patients, was 400-1000 copies/mL in 12 (9.0%) patients, and was ≥1000 copies/mL in 40 (30.1%) patients. Genotyping and drug-resistance testing were successfully performed for 36 of 40 patients, all carrying human immunodeficiency virus type 1 subtype C. Relevant mutations affecting nonnucleoside reverse transcriptase inhibitors were found in 32 of 133 (24.1%) patients and combined with relevant nucleoside reverse transcriptase mutations in 27 of 133 (20.3%) patients. CONCLUSIONS: Virological failure combined with drug resistance after resumption of first-line ART occurred in 24.1% of the patients with treatment interruption, requiring a switch to protease inhibitor-based second-line therapy. Patients with treatment interruption should receive VL assessment after resumption of ART to detect treatment failure and to reduce development and spread of drug resistance.