Provider-led community antiretroviral therapy distribution in Malawi: Retrospective cohort study of retention, viral load suppression and costs.

BACKGROUND: Outcomes of community antiretroviral therapy (ART) distribution (CAD), in which provider-led ART teams deliver integrated HIV services at health posts in communities, have been mixed in sub-Saharan African countries. CAD outcomes and costs relative to facility-based care have not been reported from Malawi. METHODS: We performed a retrospective cohort study in two Malawian districts (Lilongwe and Chikwawa districts), comparing CAD with facility-based ART care. We selected an equal number of clients in CAD and facility-based care who were aged >13 years, had an undetectable viral load (VL) result in the last year and were stable on first-line ART for ≥1 year. We compared retention in care (alive and no period of ≥60 days without ART) using Kaplan-Meier survival analysis and Cox regression and maintenance of VL suppression (<1,000 copies/mL) during follow-up using logistic regression. We also compared costs (in US$) from the health system and client perspectives for the two models of care. Data were collected in October and November 2020. RESULTS: 700 ART clients (350 CAD, 350 facility-based) were included. The median age was 43 years (IQR 36-51), median duration on ART was 7 years (IQR 4-9), and 75% were female. Retention in care did not differ significantly between clients in CAD (89.4% retained) and facility-based care (89.3%), p = 0.95. No significant difference in maintenance of VL suppression were observed between CAD and facility-based care (aOR: 1.24, 95% CI: 0.47-3.20, p = 0.70). CAD resulted in slightly higher health system costs than facility-based care: $118/year vs. $108/year per person accessing care; and $133/year vs. $122/year per person retained in care. CAD decreased individual client costs compared to facility-based care: $3.20/year vs. $11.40/year per person accessing care; and $3.60/year vs. $12.90/year per person retained in care. CONCLUSION: Clients in provider-led CAD care in Malawi had very good retention in care and VL suppression outcomes, similar to clients receiving facility-based care. While health system costs were somewhat higher with CAD, costs for clients were reduced substantially. More research is needed to understand the impact of other differentiated service delivery models on costs for the health system and clients.

Burnout and depression: A cross sectional study among health care workers providing HIV care during the COVID-19 pandemic in Malawi.

Health care workers (HCWs) in eastern Africa experience high levels of burnout and depression, and this may be exacerbated during the COVID-19 pandemic due to anxiety and increased work pressure. We assessed the prevalence of burnout, depression and associated factors among Malawian HCWs who provided HIV care during the COVID-19 pandemic. From April-May 2021, between the second and third COVID-19 waves in Malawi, we randomly selected HCWs from 32 purposively selected PEPFAR/USAID-supported health facilities for a cross-sectional survey. We screened for depression using the World Health Organization Self Report Questionnaire (positive screen: score≥8) and for burnout using the Maslach Burnout Inventory tool, (positive screen: moderate-high Emotional Exhaustion and/or moderate-high Depersonalization, and/or low-moderate Personal Accomplishment scores). Logistic regression models were used to evaluate factors associated with depression and burnout. We enrolled 435 HCWs, median age 32 years (IQR 28-38), 54% male, 34% were clinical cadres and 66% lay cadres. Of those surveyed, 28% screened positive for depression, 29% for burnout and 13% for both. In analyses that controlled for age, district, and residence (rural/urban), we found that screening positive for depression was associated with expecting to be infected with COVID-19 in the next 12 months (aOR 2.7, 95%CI 1.3-5.5), and previously having a COVID-19 infection (aOR 2.58, 95CI 1.4-5.0). Screening positive for burnout was associated with being in the clinical cadre (aOR 1.86; 95% CI: 1.2-3.0) and having a positive depression screen (aOR 3.2; 95% CI: 1.9-5.4). Reports of symptoms consistent with burnout and depression were common among Malawian HCWs providing HIV care but prevalence was not higher than in surveys before the COVID-19 pandemic. Regular screening for burnout and depression should be encouraged, given the potential for adverse HCW health outcomes and reduced work performance. Feasible interventions for burnout and depression among HCWs in our setting need to be introduced urgently.

Correlates of uptake of COVID-19 vaccines and motivation to vaccinate among Malawian adults.

COVID-19 vaccine coverage in most countries in Africa remains low. Determinants of uptake need to be better understood to improve vaccination campaigns. Few studies from Africa have identified correlates of COVID-19 vaccination in the general population. We surveyed adults at 32 healthcare facilities across Malawi, purposively sampled to ensure balanced representation of adults with and without HIV. The survey, informed by the World Health Organization's Behavioural and Social Drivers of Vaccination Framework, asked about people's thoughts and feelings about the vaccine, social processes, motivation to vaccinate, and access issues. We classified respondents' COVID-19 vaccination status and willingness to vaccinate, and used multivariable logistic regression to assess correlates of these. Among 837 surveyed individuals (median age was 39 years (IQR 30-49) and 56% were female), 33% were up-to-date on COVID-19 vaccination, 61% were unvaccinated, and 6% were overdue for a second dose. Those up-to-date were more likely to know someone who had died from COVID-19, feel the vaccine is important and safe, and perceive pro-vaccination social norms. Despite prevalent concerns about vaccine side effects, 54% of unvaccinated respondents were willing to vaccinate. Access issues were reported by 28% of unvaccinated but willing respondents. Up-to-date COVID-19 vaccination status was associated with positive attitudes about the vaccine and with perceiving pro-vaccination social norms. Over half of unvaccinated respondents were willing to get vaccinated. Disseminating vaccine safety messages from trusted sources and ensuring local vaccine availability may ultimately increase vaccine uptake.

Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study.

BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa. METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year. FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs $150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114. INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing. FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Artemether-lumefantrine efficacy among adults on antiretroviral therapy in Malawi.

BACKGROUND: When people with human immunodeficiency virus (HIV) infection (PWH) develop malaria, they are at risk of poor anti-malarial treatment efficacy resulting from impairment in the immune response and/or drug-drug interactions that alter anti-malarial metabolism. The therapeutic efficacy of artemether-lumefantrine was evaluated in a cohort of PWH on antiretroviral therapy (ART) and included measurement of day 7 lumefantrine levels in a subset to evaluate for associations between lumefantrine exposure and treatment response. METHODS: Adults living with HIV (≥ 18 years), on ART for ≥ 6 months with undetectable HIV RNA viral load and CD4 count ≥ 250/mm3 were randomized to daily trimethoprim-sulfamethoxazole (TS), weekly chloroquine (CQ) or no prophylaxis. After diagnosis of uncomplicated Plasmodium falciparum malaria, a therapeutic efficacy monitoring was conducted with PCR-correction according to WHO guidelines. The plasma lumefantrine levels on day 7 in 100 episodes of uncomplicated malaria was measured. A frailty proportional hazards model with random effects models to account for clustering examined the relationship between participant characteristics and malaria treatment failure within 28 days. Pearson's Chi-squared test was used to compare lumefantrine concentrations among patients with treatment failure and adequate clinical and parasitological response (ACPR). RESULTS: 411 malaria episodes were observed among 186 participants over 5 years. The unadjusted ACPR rate was 81% (95% CI 77-86). However, after PCR correction to exclude new infections, ACPR rate was 94% (95% CI 92-97). Increasing age and living in Ndirande were associated with decreased hazard of treatment failure. In this population of adults with HIV on ART, 54% (51/94) had levels below a previously defined optimal day 7 lumefantrine level of 200 ng/ml. This occurred more commonly among participants who were receiving an efavirenz-based ART compared to other ART regimens (OR 5.09 [95% CI 1.52-7.9]). Participants who experienced treatment failure had lower day 7 median lumefantrine levels (91 ng/ml [95% CI 48-231]) than participants who experienced ACPR (190 ng/ml [95% CI 101-378], p-value < 0.008). CONCLUSION: Recurrent malaria infections are frequent in this population of PWH on ART. The PCR-adjusted efficacy of AL meets the WHO criteria for acceptable treatment efficacy. Nevertheless, lumefantrine levels tend to be low in this population, particularly in those on efavirenz-based regimens, with lower concentrations associated with more frequent malaria infections following treatment. These results highlight the importance of understanding drug-drug interactions when diseases commonly co-occur.

Uptake of the COVID-19 vaccine among healthcare workers in Malawi.

BACKGROUND: Little is known about coronavirus disease 2019 (COVID-19) vaccination in Africa. We sought to understand Malawian healthcare workers' (HCWs') COVID-19 vaccination and its hypothesized determinants. METHODS: In March 2021, as the COVID-19 vaccine roll-out commenced in Malawi, we surveyed clinical and lay cadre HCWs (n=400) about their uptake of the vaccine and potential correlates (informed by the WHO Behavioral and Social Drivers of COVID-19 Vaccination framework). We analyzed uptake and used adjusted multivariable logistic regression models to explore how 'what people think and feel' constructs were associated with HCWs' motivation to be vaccinated. RESULTS: Of the surveyed HCWs, 82.5% had received the first COVID-19 vaccine dose. Motivation (eagerness to be vaccinated) was strongly associated with confidence in vaccine benefits (adjusted OR [aOR] 9.85, 95% CI 5.50 to 17.61) and with vaccine safety (aOR 4.60, 95% CI 2.92 to 7.23), but not with perceived COVID-19 infection risk (aOR 1.38, 95% CI 0.88 to 2.16). Of all the information sources about COVID-19 vaccination, 37.5% were reportedly negative in tone. CONCLUSIONS: HCWs in Malawi have a high motivation to be vaccinated and a high COVID-19 vaccine uptake. Disseminating vaccine benefits and safety messages via social media and social networks may be persuasive for individuals who are unmotivated to be vaccinated and less likely to accept the COVID-19 vaccine.

Virological Findings and Treatment Outcomes of Cases That Developed Dolutegravir Resistance in Malawi's National HIV Treatment Program.

Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were <1000 copies/mL. Twenty-four cases with dolutegravir resistance among 89 individuals with confirmed virological failure suggests a considerable prevalence in the Malawi HIV program. Successful management of dolutegravir resistance was possible, but early mortality was high. More research on the management of treatment-experienced individuals with dolutegravir resistance is needed.

Isoniazid preventive therapy-related adverse events among Malawian adults on antiretroviral therapy: A cohort study.

Adverse events may be a cause of observed poor completion of isoniazid preventive therapy (IPT) among people living with HIV in high tuberculosis burden areas. Data on IPT-related adverse events (AE) from sub-Saharan Africa are scarce. We report IPT-related AEs, associated clinical characteristics, and IPT discontinuations in adults who were stable on antiretroviral therapy (ART) when they initiated IPT. Cohort study nested within a randomized, controlled, clinical trial of cotrimoxazole and chloroquine prophylaxis in Malawians aged ≥ 18 years and virologically suppressed on ART. Eight hundred sixty-nine patients were followed for a median of 6 months after IPT initiation. IPT relatedness of AEs was determined retrospectively with the World Health Organization case-causality tool. Frailty survival regression modeling identified factors associated with time to first probably IPT-related AE. The overall IPT-related AE incidence rate was 1.1/person year of observation. IPT relatedness was mostly uncertain and few AEs were severe. Most common were liver and hematological toxicities. Higher age increased risk of a probably IPT-related AE (aHR = 1.02; 95% CI 1.00-1.06; P = .06) and higher weight reduced this risk (aHR = 0.98; 95% CI 0.96-1.00; P = .03). Of 869 patients, 114 (13%) discontinued IPT and 94/114 (82%) discontinuations occurred at the time of a possibly or probably IPT-related AE. We observed a high incidence of mostly mild IPT-related AEs among individuals who were stable on ART. More than 1 in 8 persons discontinued IPT. These findings inform strategies to improve implementation of IPT in adults on ART, including close monitoring of groups at higher risk of IPT-related AEs.

High burden of malaria among Malawian adults on antiretroviral therapy after discontinuing prophylaxis.

OBJECTIVE: Many individuals living with the human immunodeficiency virus (HIV) infection and receiving antiretroviral therapy (ART) reside in areas at high risk for malaria but how malaria affects clinical outcomes is not well described in this population. We evaluated the burden of malaria infection and clinical malaria, and impact on HIV viral load and CD4 + cell count among adults on ART. DESIGN: We recruited Malawian adults on ART who had an undetectable viral load and ≥250 CD4 +  cells/µl to participate in this randomized trial to continue daily trimethoprim-sulfamethoxazole (TS), discontinue daily co-trimoxazole, or switch to weekly chloroquine (CQ). METHODS: We defined clinical malaria as symptoms consistent with malaria and positive blood smear, and malaria infection as Plasmodium falciparum DNA detected from dried blood spots (collected every 4-12 weeks). CD4 + cell count and viral load were measured every 24 weeks. We used Poisson regression and survival analysis to compare the incidence of malaria infection and clinical malaria. Clinicaltrials.gov NCT01650558. RESULTS: Among 1499 participants enrolled, clinical malaria incidence was 21.4/100 person-years of observation (PYO), 2.4/100 PYO and 1.9/100 PYO in the no prophylaxis, TS, and CQ arms, respectively. We identified twelve cases of malaria that led to hospitalization and all individuals recovered. The preventive effect of staying on prophylaxis was approximately 90% compared to no prophylaxis (TS: incidence rate ratio [IRR] 0.11, 95% confidence interval [CI] 0.08, 0.15 and CQ: IRR 0.09, 95% CI 0.06, 0.13). P. falciparum infection prevalence among all visits was 187/1475 (12.7%), 48/1563 (3.1%), and 29/1561 (1.9%) in the no prophylaxis, TS, and CQ arms, respectively. Malaria infection and clinical malaria were not associated with changes in CD4 + cell count or viral load. CONCLUSION: In clinically stable adults living with HIV on ART, clinical malaria was common after chemoprophylaxis stopped. However, neither malaria infection nor clinical illness appeared to affect HIV disease progression.

Dolutegravir Resistance in Malawi's National HIV Treatment Program.

Dolutegravir HIV drug resistance (HIVDR) data from Africa remain sparse. We reviewed HIVDR results of Malawians on dolutegravir-based antiretroviral therapy (November 2020-September 2021). Of 6462 eligible clients, 33 samples were submitted to South Africa, 27 were sequenced successfully, and 8 (30%) had dolutegravir HIVDR. Malawi urgently requires adequate HIVDR testing capacity.

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.

High Rates of Uncontrolled Blood Pressure in Malawian Adults Living with HIV and Hypertension.

Background: Hypertension is among the most commonly diagnosed non-communicable diseases in Africa, and studies have demonstrated a high prevalence of hypertension among individuals with HIV. Despite high prevalence, there has been limited attention on the clinical outcomes of hypertension treatment in this population. Objective: We sought to characterize rates of and factors associated with blood pressure control over one year among individuals on antiretroviral therapy (ART) and antihypertensive medications. Methods: We performed a prospective observational cohort study at an HIV clinic in Malawi. We defined uncontrolled hypertension as a systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg at two or more follow-up visits during the year, while controlled hypertension was defined as <140 mm Hg systolic and <90 mm Hg diastolic at all visits, or at all but one visit. We calculated an antihypertensive non-adherence score based on self-report of missed doses at each visit (higher score = worse adherence) and used rank sum and chi-square tests to compare sociodemographic and clinical factors (including adherence) associated with blood pressure control over the year. Results: At study entry, 158 participants (23.5%) were on antihypertensive medication; participants had a median age of 51.0 years, were 66.5% female, and had a median of 6.9 years on ART. 19.0% (n = 30) achieved blood pressure control over the year of follow-up. Self-reported non-adherence to hypertension medications was the only factor significantly associated with uncontrolled blood pressure. The average non-adherence score for those with controlled blood pressure was 0.22, and for those with uncontrolled blood pressure was 0.61 (p = 0.009). Conclusions: Adults living with HIV and hypertension in our cohort had low rates of blood pressure control over one year associated with self-reported non-adherence to antihypertensive medications. Given the high prevalence and incidence of hypertension, interventions to improve blood pressure control are needed to prevent associated long-term cardio- and cerebrovascular morbidity and mortality.

Short-term Mortality Outcomes of HIV-Associated Cryptococcal Meningitis in Antiretroviral Therapy-Naïve and -Experienced Patients in Sub-Saharan Africa.

BACKGROUND: An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) before presentation. There is some evidence suggesting an increased 2-week mortality in those receiving ART for <14 days compared with those on ART for >14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or nonadherence, are not well described. METHODS: Six hundred seventy-eight adults with a first episode of cryptococcal meningitis recruited into a randomized, noninferiority, multicenter phase 3 trial in 4 Sub-Saharan countries were analyzed to compare clinical presentation and 2- and 10-week mortality outcomes between ART-naïve and -experienced patients and between patients receiving ART for varying durations before presentation. RESULTS: Over half (56%; 381/678) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2 weeks (17% vs 20%; hazard ratio [HR], 0.85; 95% CI, 0.6-1.2; P = .35) and 10 weeks (38% vs 36%; HR, 1.03; 95% CI, 0.8-1.32; P = .82) for ART-experienced and ART-naïve patients. Among ART-experienced patients, using different cutoff points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART. CONCLUSIONS: In this study, there were no significant differences in mortality at 2 and 10 weeks between ART-naïve and -experienced patients and between ART-experienced patients according to duration on ART.

Frequency of visits to health facilities and HIV services offered to men, Malawi.

OBJECTIVE: To determine how often men in Malawi attend health facilities and if testing for human immunodeficiency virus (HIV) is offered during facility visits. METHODS: We conducted a cross-sectional, community-representative survey of men (15-64 years) from 36 villages in Malawi. We excluded men who ever tested HIV-positive. Primary outcomes were: health facility visits in the past 12 months (for their own health (client visit) or to support the health services of others (guardian visit)); being offered HIV testing during facility visits; and being tested that same day. We disaggregated all results by HIV testing history: tested ≤ 12 months ago, or in need of testing (never tested or tested > 12 months before). FINDINGS: We included 1116 men in the analysis. Mean age was 34 years (standard deviation: 13.2) and 55% (617/1116) of men needed HIV testing. Regarding facility visits, 82% (920/1116) of all men and 70% (429/617) of men in need of testing made at least one facility visit in the past 12 months. Men made a total of 1973 visits (mean two visits): 39% (765/1973) were as guardians and 84% (1657/1973) were to outpatient departments. Among men needing HIV testing, only 7% (30/429) were offered testing during any visit. The most common reason for not testing was not being offered services (37%; 179/487). CONCLUSION: Men in Malawi attend health facilities regularly, but few of those in need of HIV testing are offered testing services. Health screening services should capitalize on men's routine visits to outpatient departments as clients and guardians.

Regression discontinuity analysis demonstrated varied effect of Treat-All on CD4 testing among Southern African countries.

OBJECTIVE: To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. STUDY DESIGN AND SETTING: We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption. RESULTS: We found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (-21.4 percentage points (pp), 95% confidence interval, CI: -26.8, -16.0) and in Mozambique (-8.8pp, 95% CI: -14.9, -2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0). CONCLUSION: Treat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa.

Individual- and Facility-Level Factors Associated with Facility Testing among Men in Malawi: Findings from a Representative Community Survey.

(1) Background: Men frequent outpatient departments (OPD) but are underrepresented in HIV testing services throughout sub-Saharan Africa. (2) Methods: We conducted a secondary analysis on data from a community-based survey with men in rural Malawi to assess factors associated with HIV testing, and being offered testing, during men's OPD visits. We include OPD visits made by men in-need of testing as our unit of observation. Multilevel mixed-effects logistic regression models were conducted. (3) Results: 782 men were eligible for these analyses, with 1575 OPD visits included (median two visits per man; IQR 1-3). 17% of OPD visits resulted in HIV testing. Being offered testing (aOR 42.45; 95% CI 15.13-119.10) and satisfaction with services received (aOR 3.27; 95% CI 1.28-8.33) were significantly associated with HIV testing. 14% of OPD visits resulted in being offered HIV testing. Being married/steady relationship (aOR 2.53; 95% CI 1.08-5.91) and having a sexual partner living with HIV (aOR 8.22; 95% CI 1.67-40.49) were significantly associated with being offered testing. (4) Conclusion: Being offered HIV testing was the strongest factor associated with testing uptake, while HIV status of sexual partner had the strongest association with being offered testing. Implementation of provider-initiated-testing should be prioritized for male OPD visits.

Fungal Burden and Raised Intracranial Pressure Are Independently Associated With Visual Loss in Human Immunodeficiency Virus-Associated Cryptococcal Meningitis.

Among 472 patients with human immunodeficiency virus-associated cryptococcal meningitis, 16% had severe visual loss at presentation, and 46% of these were 4-week survivors and remained severely impaired. Baseline cerebrospinal fluid opening pressure ≥40 cmH2O (adjusted odds ratio [aOR], 2.56; 95% confidence interval [CI], 1.36-4.83; P = .02) and fungal burden >6.0 log10 colonies/mL (aOR, 3.01; 95% CI, 1.58-5.7; P = .003) were independently associated with severe visual loss.

Prisoners' access to HIV services in southern Malawi: a cross-sectional mixed methods study.

BACKGROUND: The prevalence of Human Immunodeficiency Virus (HIV) among prisoners remains high in many countries, especially in Africa, despite a global decrease in HIV incidence. Programs to reach incarcerated populations with HIV services have been implemented in Malawi, but the success of these initiatives is uncertain. We explored which challenges prisoners face in receiving essential HIV services and whether HIV risk behavior is prevalent in prisons. METHODS: We conducted a mixed-methods (qualitative and quantitative), cross-sectional study in 2018 in six prisons in Southern Malawi, two large central prisons with on-site, non-governmental organization (NGO) supported clinics and 4 smaller rural prisons. Four hundred twelve prisoners were randomly selected and completed a structured questionnaire. We conducted in-depth interviews with 39 prisoners living with HIV, which we recorded, transcribed and translated. We used descriptive statistics and logistic regression to analyze quantitative data and content analysis for qualitative data. RESULTS: The majority of prisoners (93.2%) were male, 61.4% were married and 63.1% were incarcerated for 1-5 years. Comprehensive services were reported to be available in the two large, urban prisons. Female prisoners reported having less access to general medical services than males. HIV risk behavior was reported infrequently and was associated with incarceration in urban prisons (adjusted odds ratio [aOR] 18.43; 95% confidence interval [95%-CI] 7.59-44.74; p = < 0.001) and not being married (aOR 17.71; 95%-CI 6.95-45.13; p = < 0.001). In-depth interviews revealed that prisoners living with HIV experienced delays in referrals for more severe illnesses. Prisoners emphasized the detrimental impact of poor living conditions on their personal health and their ability to adhere to antiretroviral therapy (ART). CONCLUSIONS: Malawian prisoners reported adequate knowledge about HIV services albeit with gaps in specific areas. Prisoners from smaller, rural prisons had suboptimal access to comprehensive HIV services and female prisoners reported having less access to health care than males. Prisoners have great concern about their poor living conditions affecting general health and adherence to ART. These findings provide guidance for improvement of HIV services and general health care in Malawian institutionalized populations such as prisoners.

Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial.

BACKGROUND: Daily co-trimoxazole is recommended for African adults living with human immunodeficiency virus (HIV) irrespective of antiretroviral treatment, immune status, or disease stage. Benefits of continued prophylaxis and whether co-trimoxazole can be stopped following immune reconstitution are unknown. METHODS: We conducted a randomized controlled trial at 2 sites in Malawi that enrolled adults with HIV with undetectable viral load and CD4 count of >250/mm3 and randomized them to continue daily co-trimoxazole, discontinue daily co-trimoxazole and begin weekly chloroquine, or discontinue daily co-trimoxazole. The primary endpoint was the preventive effect of co-trimoxazole prophylaxis against death or World Health Organization (WHO) HIV/AIDS stage 3-4 events, using Cox proportional hazards modeling, in an intention-to-treat population. RESULTS: 1499 adults were enrolled. The preventive effect of co-trimoxazole on the primary endpoint was 22% (95% CI: -14%-47%; P = .20) versus no prophylaxis and 25% (-10%-48%; P = .14) versus chloroquine. When WHO HIV/AIDS stage 2 events were added to the primary endpoint, preventive effect increased to 31% (3-51%; P = .032) and 32% (4-51%; P = .026), respectively. Co-trimoxazole and chloroquine prophylaxis effectively prevented clinical malaria episodes (3.8 and 3.0, respectively, vs 28/100 person-years; P < .001). CONCLUSIONS: Malawian adults with HIV who immune reconstituted on ART and continued co-trimoxazole prophylaxis experienced fewer deaths and WHO HIV/AIDS stage 3-4 events compared with prophylaxis discontinuation, although statistical significance was not achieved. Co-trimoxazole prevented a composite of death plus WHO HIV/AIDS stage 2-4 events. Given poor healthcare access and lack of routine viral load monitoring, co-trimoxazole prophylaxis should continue in adults on ART after immune reconstitution in sub-Saharan Africa. Clinical Trials Registration. NCT01650558.