The effect of a Mentor Mothers program on prevention of vertical transmission of HIV outcomes in Zambézia Province, Mozambique: a retrospective interrupted time series analysis.

INTRODUCTION: Mentor Mothers (MM) provide peer support to pregnant and postpartum women living with HIV (PPWH) and their infants with perinatal HIV exposure (IPE) throughout the cascade of prevention of vertical transmission (PVT) services. MM were implemented in Zambézia Province, Mozambique starting in August 2017. This evaluation aimed to determine the effect of MM on PVT outcomes. METHODS: A retrospective interrupted time series analysis was done using routinely collected aggregate data from 85 public health facilities providing HIV services in nine districts of Zambézia. All PPWH (and their IPE) who initiated antiretroviral therapy (ART) from August 2016 through April 2019 were included. Outcomes included the proportion per month per district of: PPWH retained in care 12 months after ART initiation, PPWH with viral suppression and IPE with HIV DNA PCR test positivity by 9 months of age. The effect of MM on outcomes was assessed using logistic regression. RESULTS: The odds of 12-month retention increased 1.5% per month in the pre-MM period, compared to a monthly increase of 7.6% with-MM (35-61% pre-MM, 56-72% with-MM; p < 0.001). The odds of being virally suppressed decreased by 0.9% per month in the pre-MM period, compared to a monthly increase of 3.9% with-MM (49-85% pre-MM, 59-80% with-MM; p < 0.001). The odds of DNA PCR positivity by 9 months of age decreased 8.9% per month in the pre-MM period, compared to a monthly decrease of 0.4% with-MM (0-14% pre-MM, 4-10% with-MM; p < 0.001). The odds of DNA PCR uptake (the proportion of IPE who received DNA PCR testing) by 9 months of age were significantly higher in the with-MM period compared to the pre-MM period (48-100% pre-MM, 87-100% with-MM; p < 0.001). CONCLUSIONS: MM services were associated with improved retention in PVT services and higher viral suppression rates among PPWH. While there was ongoing but diminishing improvement in DNA PCR positivity rates among IPE following MM implementation, this might be explained by increased uptake of HIV testing among high-risk IPE who were previously not getting tested. Additional efforts are needed to further optimize PVT outcomes, and MM should be one part of a comprehensive strategy to address this critical need.

The effect of a Mentor Mothers program on prevention of vertical transmission of HIV outcomes in Zambézia Province, Mozambique: a retrospective interrupted time series analysis

Introduction: Mentor Mothers (MM) provide peer support to pregnant and postpartum women living with HIV (PPWH) and their infants with perinatal HIV exposure (IPE) throughout the cascade of prevention of vertical transmission (PVT) services. MM were implemented in Zambézia Province, Mozambique starting in August 2017. This evaluation aimed to determine the effect of MM on PVT outcomes. Methods: A retrospective interrupted time series analysis was done using routinely collected aggregate data from 85 public health facilities providing HIV services in nine districts of Zambézia. All PPWH (and their IPE) who initiated antiretroviral therapy (ART) from August 2016 through April 2019 were included. Outcomes included the proportion per month per district of: PPWH retained in care 12 months after ART initiation, PPWH with viral suppression and IPE with HIV DNA PCR test positivity by 9 months of age. The effect of MM on outcomes was assessed using logistic regression. Results: The odds of 12-month retention increased 1.5% per month in the pre-MM period, compared to a monthly increase of 7.6% with-MM (35-61% pre-MM, 56-72% with-MM; p < 0.001). The odds of being virally suppressed decreased by 0.9% per month in the pre-MM period, compared to a monthly increase of 3.9% with-MM (49-85% pre-MM, 59-80% with-MM; p < 0.001). The odds of DNA PCR positivity by 9 months of age decreased 8.9% per month in the pre-MM period, compared to a monthly decrease of 0.4% with-MM (0-14% pre-MM, 4-10% with-MM; p < 0.001). The odds of DNA PCR uptake (the proportion of IPE who received DNA PCR testing) by 9 months of age were significantly higher in the with-MM period compared to the pre-MM period (48-100% pre-MM, 87-100% with-MM; p < 0.001). Conclusions: MM services were associated with improved retention in PVT services and higher viral suppression rates among PPWH. While there was ongoing but diminishing improvement in DNA PCR positivity rates among IPE following MM implementation, this might be explained by increased uptake of HIV testing among high-risk IPE who were previously not getting tested. Additional efforts are needed to further optimize PVT outcomes, and MM should be one part of a comprehensive strategy to address this critical need.

CD4 Trends with evolving treatment initiation policies among children living with HIV in zambézia province, mozambique, 2012-2018

Background: Historically, antiretroviral therapy (ART) initiation was based on CD4 criteria, but this has been replaced with "Test and Start" wherein all people living with HIV are offered ART. We describe the baseline immunologic status among children relative to evolving ART policies in Mozambique. Methods: This retrospective evaluation was performed using routinely collected data. Children living with HIV (CL aged 5-14 years) with CD4 data in the period of 2012-2018 were included. ART initiation "policy periods" corresponded to implementation of evolving guidelines: in period 1 (2012-2016), ART was recommended for CD4 <350 cells/mm3; during period 2 (2016-2017), the CD4 threshold increased to <500 cells/mm3; Test and Start was implemented in period 3 (2017-2018). We described temporal trends in the proportion of children with severe immunodeficiency (CD4 <200 cells/mm3) at enrollment and at ART initiation. Multivariable regression models were used to estimate associations with severe immunodeficiency. Results: The cohort included 1815 children with CD4 data at enrollment and 1922 at ART initiation. The proportion of children with severe immunodeficiency decreased over time: 20% at enrollment into care in period 1 vs. 16% in period 3 (P = 0.113) and 21% at ART initiation in period 1 vs. 15% in period 3 (P = 0.004). Children initiating ART in period 3 had lower odds of severe immunodeficiency at ART initiation compared with those in period 1 [adjusted odds ratio (aOR) = 0.67; 95% CI: 0.51 to 0.88]. Older age was associated with severe immunodeficiency at enrollment (aOR = 1.13; 95% CI: 1.06 to 1.20) and at ART initiation (aOR = 1.14; 95% CI: 1.08 to 1.21). Conclusions: The proportion of children with severe immunodeficiency at ART initiation decreased alongside more inclusive ART initiation guidelines. Earlier treatment of children living with HIV is imperative.

CD4 Trends With Evolving Treatment Initiation Policies Among Children Living With HIV in Zambézia Province, Mozambique, 2012-2018.

BACKGROUND: Historically, antiretroviral therapy (ART) initiation was based on CD4 criteria, but this has been replaced with "Test and Start" wherein all people living with HIV are offered ART. We describe the baseline immunologic status among children relative to evolving ART policies in Mozambique. METHODS: This retrospective evaluation was performed using routinely collected data. Children living with HIV (CL aged 5-14 years) with CD4 data in the period of 2012-2018 were included. ART initiation "policy periods" corresponded to implementation of evolving guidelines: in period 1 (2012-2016), ART was recommended for CD4 <350 cells/mm3; during period 2 (2016-2017), the CD4 threshold increased to <500 cells/mm3; Test and Start was implemented in period 3 (2017-2018). We described temporal trends in the proportion of children with severe immunodeficiency (CD4 <200 cells/mm3) at enrollment and at ART initiation. Multivariable regression models were used to estimate associations with severe immunodeficiency. RESULTS: The cohort included 1815 children with CD4 data at enrollment and 1922 at ART initiation. The proportion of children with severe immunodeficiency decreased over time: 20% at enrollment into care in period 1 vs. 16% in period 3 (P = 0.113) and 21% at ART initiation in period 1 vs. 15% in period 3 (P = 0.004). Children initiating ART in period 3 had lower odds of severe immunodeficiency at ART initiation compared with those in period 1 [adjusted odds ratio (aOR) = 0.67; 95% CI: 0.51 to 0.88]. Older age was associated with severe immunodeficiency at enrollment (aOR = 1.13; 95% CI: 1.06 to 1.20) and at ART initiation (aOR = 1.14; 95% CI: 1.08 to 1.21). CONCLUSIONS: The proportion of children with severe immunodeficiency at ART initiation decreased alongside more inclusive ART initiation guidelines. Earlier treatment of children living with HIV is imperative.

Immunodeficiency at antiretroviral therapy start: five-Year adult data (2012-2017) based on evolving national policies in rural mozambique

Before the 2015 implementation of "Test and Start," the initiation of combination antiretroviral therapy (ART) was guided by specific CD4 cell count thresholds. As scale-up efforts progress, the prevalence of advanced HIV disease at ART initiation is expected to decline. We analyzed the temporal trends in the median CD4 cell counts among adults initiating ART and described factors associated with initiating ART with severe immunodeficiency in Zambézia Province, Mozambique. We included all HIV-positive, treatment-naive adults (age ≥ 15 years) who initiated ART at a Friends in Global Health (FGH)-supported health facility between September 2012 and September 2017. Quantile regression and multivariable logistic regression models were applied to ascertain the median change in CD4 cell count and odds of initiating ART with severe immunodeficiency, respectively. A total of 68,332 patients were included in the analyses. The median change in CD4 cell count under "Test and Start" was higher at +68 cells/mm3 (95% CI: 57.5-78.4) compared with older policies. Younger age and female sex (particularly those pregnant/lactating) were associated with higher median CD4 cell counts at ART initiation. Male sex, advanced age, WHO Stage 4 disease, and referrals to the health facility through inpatient provider-initiated testing and counseling (PITC) were associated with higher odds of initiating ART with severe immunodeficiency. Although there were reassuring trends in increasing median CD4 cell counts with ART initiation, ongoing efforts are needed that target universal HIV testing to ensure the early initiation of ART in men and older patients.

Immunodeficiency at Antiretroviral Therapy Start: Five-Year Adult Data (2012-2017) Based on Evolving National Policies in Rural Mozambique.

Before the 2015 implementation of "Test and Start," the initiation of combination antiretroviral therapy (ART) was guided by specific CD4 cell count thresholds. As scale-up efforts progress, the prevalence of advanced HIV disease at ART initiation is expected to decline. We analyzed the temporal trends in the median CD4 cell counts among adults initiating ART and described factors associated with initiating ART with severe immunodeficiency in Zambézia Province, Mozambique. We included all HIV-positive, treatment-naive adults (age ≥ 15 years) who initiated ART at a Friends in Global Health (FGH)-supported health facility between September 2012 and September 2017. Quantile regression and multivariable logistic regression models were applied to ascertain the median change in CD4 cell count and odds of initiating ART with severe immunodeficiency, respectively. A total of 68,332 patients were included in the analyses. The median change in CD4 cell count under "Test and Start" was higher at +68 cells/mm3 (95% CI: 57.5-78.4) compared with older policies. Younger age and female sex (particularly those pregnant/lactating) were associated with higher median CD4 cell counts at ART initiation. Male sex, advanced age, WHO Stage 4 disease, and referrals to the health facility through inpatient provider-initiated testing and counseling (PITC) were associated with higher odds of initiating ART with severe immunodeficiency. Although there were reassuring trends in increasing median CD4 cell counts with ART initiation, ongoing efforts are needed that target universal HIV testing to ensure the early initiation of ART in men and older patients.

Measuring Health Literacy Among Adults with HIV Infection in Mozambique: Development and Validation of the HIV Literacy Test.

The role of health literacy on HIV outcomes has not been evaluated widely in Africa, in part because few appropriate literacy measures exist. We developed a 16-item scale, the HIV Literacy Test (HIV-LT) to assess literacy-related tasks needed to participate in HIV care. Items were scored as correct or incorrect; higher scores indicated higher literacy skill (range 0-100 %). We tested internal reliability (Kuder-Richardson coefficient) of the HIV-LT in a convenience sample of 319 Portuguese-speaking, HIV infected adults on antiretroviral treatment in Maputo, Mozambique. Construct validity was assessed by a hypothetical model developed a priori. The HIV-LT was reliable and valid to measure participants' literacy skills. The mean HIV-LT score was 42 %; literacy skills applicable to HIV care were challenging for many participants. The HIV-LT could be used to assess the relationship of literacy and HIV-related outcomes in diverse settings, and evaluate interventions to improve health communication for those in HIV care.

Poor clinical outcomes for HIV infected children on antiretroviral therapy in rural Mozambique: need for program quality improvement and community engagement.

INTRODUCTION: Residents of Zambézia Province, Mozambique live from rural subsistence farming and fishing. The 2009 provincial HIV prevalence for adults 15-49 years was 12.6%, higher among women (15.3%) than men (8.9%). We reviewed clinical data to assess outcomes for HIV-infected children on combination antiretroviral therapy (cART) in a highly resource-limited setting. METHODS: We studied rates of 2-year mortality and loss to follow-up (LTFU) for children <15 years of age initiating cART between June 2006-July 2011 in 10 rural districts. National guidelines define LTFU as >60 days following last-scheduled medication pickup. Kaplan-Meier estimates to compute mortality assumed non-informative censoring. Cumulative LTFU incidence calculations treated death as a competing risk. RESULTS: Of 753 children, 29.0% (95% CI: 24.5, 33.2) were confirmed dead by 2 years and 39.0% (95% CI: 34.8, 42.9) were LTFU with unknown clinical outcomes. The cohort mortality rate was 8.4% (95% CI: 6.3, 10.4) after 90 days on cART and 19.2% (95% CI: 16.0, 22.3) after 365 days. Higher hemoglobin at cART initiation was associated with being alive and on cART at 2 years (alive: 9.3 g/dL vs. dead or LTFU: 8.3-8.4 g/dL, p<0.01). Cotrimoxazole use within 90 days of ART initiation was associated with improved 2-year outcomes Treatment was initiated late (WHO stage III/IV) among 48% of the children with WHO stage recorded in their records. Marked heterogeneity in outcomes by district was noted (p<0.001). CONCLUSIONS: We found poor clinical and programmatic outcomes among children taking cART in rural Mozambique. Expanded testing, early infant diagnosis, counseling/support services, case finding, and outreach are insufficiently implemented. Our quality improvement efforts seek to better link pregnancy and HIV services, expand coverage and timeliness of infant diagnosis and treatment, and increase follow-up and adherence.

Health literacy predicts pediatric dosing accuracy for liquid zidovudine.

OBJECTIVES: Little is known about adult caregivers' ability to accurately dose pediatric antiretroviral medications. We aimed to characterize the frequency of dosing errors for liquid zidovudine using two dosing devices and to evaluate the association between HIV literacy and dosing errors in adults living with HIV infection. DESIGN: Cross-sectional study enrolling 316 adults receiving combination antiretroviral therapy (cART) for HIV infection in Maputo Province, Mozambique. METHODS: Participants were administered the HIV Literacy Test (HIV-LT) and asked to measure 2.5 ml of liquid zidovudine using both a cup and syringe. Dosing measurement errors for liquid zidovudine were defined as 'any error' (≥ 20% deviation from reference dose) and 'major error' (≥ 40% deviation from reference dose). RESULTS: Dosing errors were common using the cup (any error: 50%, major error: 28%) and syringe (any error: 48% of participants, major error: 28%). There were no significant differences in proportions of any dosing error (P=0.61) or major dosing errors (P=0.82) between dosing instruments. In multivariable models, associations (P ≤ 0.03) were found between higher HIV-LT score and dosing errors for both the cup [any error adjusted odds ratio, AOR: 0.91 (0.84-0.99), major error AOR: 0.84 (0.75-0.92)] and syringe [any error AOR: 0.82 (0.75-0.90), major error AOR: 0.88 (0.80-0.97)]. CONCLUSION: Liquid antiretroviral medications are critical for prevention and treatment of pediatric HIV infections, yet dosing errors were exceedingly common in this population and were significantly associated with lower HIV literacy levels. Targeted interventions are needed to improve HIV knowledge and skills for pediatric medication dosing, particularly for caregivers with limited literacy.

Translation of biomedical prevention strategies for HIV: prospects and pitfalls.

Early achievements in biomedical approaches for HIV prevention included physical barriers (condoms), clean injection equipment (both for medical use and for injection drug users), blood and blood product safety, and prevention of mother-to-child transmission. In recent years, antiretroviral drugs to reduce the risk of transmission (when the infected person takes the medicines; treatment as prevention) or reduce the risk of acquisition (when the seronegative person takes them; preexposure prophylaxis) have proven to be efficacious. Circumcision of men has also been a major tool relevant for higher prevalence regions such as sub-Saharan Africa. Well-established prevention strategies in the control of sexually transmitted diseases and tuberculosis are highly relevant for HIV (ie, screening, linkage to care, early treatment, and contact tracing). Unfortunately, only slow progress is being made in some available HIV-prevention strategies such as family planning for HIV-infected women who do not want more children and prevention of mother-to-child HIV transmission. Current studies seek to integrate strategies into approaches that combine biomedical, behavioral, and structural methods to achieve prevention synergies. This review identifies the major biomedical approaches demonstrated to be efficacious that are now available. We also highlight the need for behavioral risk reduction and adherence as essential components of any biomedical approach.

Transitioning HIV care and treatment programs in southern Africa to full local management.

Global AIDS programs such as the US President's Emergency Plan for AIDS Relief (PEPFAR) face a challenging health care management transition. HIV care must evolve from vertically-organized, externally-supported efforts to sustainable, locally controlled components that are integrated into the horizontal primary health care systems of host nations. We compared four southern African nations in AIDS care, financial, literacy, and health worker capacity parameters (2005 to 2009) to contrast in their capacities to absorb the huge HIV care and prevention endeavors that are now managed with international technical and fiscal support. Botswana has a relatively high national income, a small population, and an advanced HIV/AIDS care program; it is well poised to take on management of its HIV/AIDS programs. South Africa has had a slower start, given HIV denialism philosophies of the previous government leadership. Nonetheless, South Africa has the national income, health care management, and health worker capacity to succeed in fully local management. The sheer magnitude of the burden is daunting, however, and South Africa will need continuing fiscal assistance. In contrast, Zambia and Mozambique have comparatively lower per capita incomes, many fewer health care workers per capita, and lower national literacy rates. It is improbable that fully independent management of their HIV programs is feasible on the timetable being contemplated by donors, nor is locally sustainable financing conceivable at present. A tailored nation-by-nation approach is needed for the transition to full local capacitation; donor nation policymakers must ensure that global resources and technical support are not removed prematurely.

Addressing poor retention of infants exposed to HIV: a quality improvement study in rural Mozambique.

OBJECTIVE: Early infant diagnosis (EID) is the first step in HIV care, yet 75% of HIV-exposed infants born at 2 hospitals in Mozambique failed to access EID. DESIGN: Before/after study. SETTING: Two district hospitals in rural Mozambique. PARTICIPANTS: HIV-infected mother/HIV-exposed infant pairs (n = 791). INTERVENTION: We planned 2 phases of improvement using quality improvement methods. In phase 1, we enhanced referral by offering direct accompaniment of new mothers to the EID suite, increasing privacy, and opening a medical record for infants before postpartum discharge. In phase 2, we added enhanced referral activity as an item on the maternity register to standardize the process of referral. MAIN OUTCOME MEASURE: The proportion of HIV-infected mothers who accessed EID for their infant <90 days of life. RESULTS: We tracked mother/infant pairs from June 2009 to March 2011 (phase 0: n = 144; phase 1: n = 479; phase 2: n = 168), compared study measures for mother/infant pairs across intervention phases with χ², estimated time-to-EID by Kaplan-Meier, and determined the likelihood of EID by Cox regression after adjusting for likely barriers to follow-up. At baseline (phase 0), 25.7% of infants accessed EID <90 days. EID improved to 32.2% after phase 1, but only 17.3% had received enhanced referral. After phase 2, 61.9% received enhanced referral and 39.9% accessed EID, a significant 3-phase improvement (P = 0.007). In adjusted analysis, the likelihood of EID at any time was higher in the phase 2 group versus phase 0 (adjusted hazard ratio: 1.68, 95% confidence interval: 1.19 to 2.37, P = 0.003). CONCLUSIONS: Retention improved by 55% with a simple referral enhancement. Quality improvement efforts could help improve care in Mozambique and other low-resource countries [added].