The association between HIV pretreatment drug resistance and virological outcomes in children and adults in sub-Saharan Africa: A systematic review and meta-analysis.

INTRODUCTION: Pretreatment drug resistance (PDR) could occur in antiretroviral treatment (ART) naïve individuals, those previously exposed to ART, or individuals re-initiating ARV after a long period of interruption. Few studies have shown its association with virological outcomes, although inconsistent. The objective of this review was to provide a synthesis of the association between PDR and virological outcomes (virological failure or suppression). METHODS: This report is presented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The method was subdivided into three main phases: record identification, screening, and report inclusion. Record identification consisted of an initial search with search term "HIV pretreatment drug resistance". Another search was done using terms "Pretreatment drug resistance OR pre-treatment drug resistance OR Pretreatment drug resist* OR pre-treatment drug resist* OR pretreatment antiretroviral resistance OR pretreatment medic* OR pretreatment medic* resist*" and a list of all the countries in sub-Saharan Africa. After the electronic search, studies were screened from full list based on their title and abstract and then full articles retrieved and studies were assessed based on set criteria. Inclusion criteria involved observational studies that report the association between PDR and virological failure. Data from trials that reported the association were also included. Published articles like modelling studies and reviews, and studies with data that had been previously included in the review were excluded. The Mantel Haenszel method with odds ratios was used for synthesis (meta-analyses) with the weights of each study which depends on the number of events and totals. RESULTS: A total of 733 records(studies) were obtained from all database search of which 74 reported on PDR, virological outcomes in sub-Saharan Africa (SSA). Out of the 74 articles, 11 were excluded and 26 did not explicitly report data needed, and 5 did not meet the inclusion criteria. Of the remaining 32 studies, 19 studies that had complete data on the number of participants with PDR and no PDR according to virological failure (VF) were included in the metanalyses. The pooled results from eleven (13) of these studies showed those with PDR had higher odds of virological failure compared to those without PDR OR 3.64[95% CI 2.93, 4.52]. The result was similar when stratified in adults and in children. In six (6) studies that had Virological suppression (VS) as outcome, there was a reduction in the odds of VS in those with PDR compared to those without PDR, OR 0.42 (95% CI 0.30, 0.58). CONCLUSION: In conclusion, this systematic review indicates that PDR increases the risk of virological failure in sub-Saharan Africa. The risk could be reduced by PDR monitoring for NNRTIs and INSTIs.

Seroprevalence of SARS-CoV-2 in 10 Regional Capitals of Cameroon, October-December 2020.

BACKGROUND: Cameroon was among the most affected African countries during the first wave of the COVID-19 pandemic; however, the true prevalence of SARS-CoV-2 remains unknown. METHODS: From October to December 2020, we conducted a cross-sectional, age-stratified SARS-CoV-2 seroepidemiological survey at 30 purposively selected community-based sites across Cameroon's 10 regional capitals, sampling 10,000 individuals aged 5 years or older. We employed a parallel SARS-CoV-2 antibody testing algorithm (WANTAI ELISA and Abbott Architect) to improve both the positive predictive value and negative predictive value of seroprevalence. RESULTS: The overall weighted and adjusted seroprevalence of SARS-CoV-2 antibodies across the 10 urban capitals of Cameroon was 10.5% (95% CI: 9.1%-12.0%) among participants aged ≥5 years. Of the 9332 participants, 730 males (13.1%, 95% CI: 11.5%-14.9%) had SARS-CoV-2 antibodies compared to 293 females (8.0%, 95% CI: 6.8%-9.3%). Among those who reported a comorbidity at the time of testing, 15.8% (95% CI: 12.8%-19.4%) were seropositive. We estimated that over 2 million SARS-CoV-2 infections occurred in the 10 regional capitals of Cameroon between October and December 2020, compared to 21,160 cases officially reported at that time translating to one laboratory-confirmed case being reported for every 110 SARS-CoV-2 infections across the 10 urban capitals. CONCLUSION: This study's findings point to extensive and under-reported circulation of SARS-CoV-2 in Cameroon-an almost 100-fold more cases compared to the number of cases reported to the World Health Organization. This finding highlights the importance of conducting serosurveys, especially in settings where access to testing may be limited and to repeat such surveys as part of pandemic tracking.

Building on Capacity Established through US Centers for Disease Control and Prevention Global Health Programs to Respond to COVID-19, Cameroon.

The COVID-19 pandemic has highlighted the need for resilient health systems with the capacity to effectively detect and respond to disease outbreaks and ensure continuity of health service delivery. The pandemic has disproportionately affected resource-limited settings with inadequate health capacity, resulting in disruptions in health service delivery and worsened outcomes for key health indicators. As part of the US government's goal of ensuring health security, the US Centers for Disease Control and Prevention has used its scientific and technical expertise to build health capacity and address health threats globally. We describe how capacity developed through global health programs of the US Centers for Disease Control and Prevention in Cameroon was leveraged to respond to coronavirus disease and maintain health service delivery. The health system strengthening efforts in Cameroon can be applied in similar settings to ensure preparedness for future global public health threats and improve health outcomes.

Protecting the gains: analysis of HIV treatment and service delivery programme data and interventions implemented in 19 African countries during COVID-19.

INTRODUCTION: The potential disruption in antiretroviral therapy (ART) services in Africa at the start of the COVID-19 pandemic raised concern for increased morbidity and mortality among people living with HIV (PLHIV). We describe HIV treatment trends before and during the pandemic and interventions implemented to mitigate COVID-19 impact among countries supported by the US Centers for Disease Control and Prevention (CDC) through the President's Emergency Plan for AIDS Relief (PEPFAR). METHODS: We analysed quantitative and qualitative data reported by 10,387 PEPFAR-CDC-supported ART sites in 19 African countries between October 2019 and March 2021. Trends in PLHIV on ART, new ART initiations and treatment interruptions were assessed. Viral load coverage (testing of eligible PLHIV) and viral suppression were calculated at select time points. Qualitative data were analysed to summarize facility- and community-based interventions implemented to mitigate COVID-19. RESULTS: The total number of PLHIV on ART increased quarterly from October 2019 (n = 7,540,592) to March 2021 (n = 8,513,572). The adult population (≥15 years) on ART increased by 14.0% (7,005,959-7,983,793), while the paediatric population (<15 years) on ART declined by 2.6% (333,178-324,441). However, the number of new ART initiations dropped between March 2020 and June 2020 by 23.4% for adults and 26.1% for children, with more rapid recovery in adults than children from September 2020 onwards. Viral load coverage increased slightly from April 2020 to March 2021 (75-78%) and viral load suppression increased from October 2019 to March 2021 (91-94%) among adults and children combined. The most reported interventions included multi-month dispensing (MMD) of ART, community service delivery expansion, and technology and virtual platforms use for client engagement and site-level monitoring. MMD of ≥3 months increased from 52% in October 2019 to 78% of PLHIV ≥ age 15 on ART in March 2021. CONCLUSIONS: With an overall increase in the number of people on ART, HIV programmes proved to be resilient, mitigating the impact of COVID-19. However, the decline in the number of children on ART warrants urgent investigation and interventions to prevent further losses experienced during the COVID-19 pandemic and future public health emergencies.

Lessons Learned from Programmatic Gains in HIV Service Delivery During the COVID-19 Pandemic - 41 PEPFAR-Supported Countries, 2020.

The U.S. President's Emergency Plan for AIDS Relief (PEPFAR) supports country programs in identifying persons living with HIV infection (PLHIV), providing life-saving treatment, and reducing the spread of HIV in countries around the world (1,2). CDC used Monitoring, Evaluation, and Reporting (MER) data* to assess the extent to which COVID-19 mitigation strategies affected HIV service delivery across the HIV care continuum† globally during the first year of the COVID-19 pandemic. Indicators included the number of reported HIV-positive test results, the number of PLHIV who were receiving antiretroviral therapy (ART), and the rates of HIV viral load suppression. Percent change in performance was assessed between countries during the first 3 months of 2020, before COVID-19 mitigation efforts began (January-March 2020), and the last 3 months of the calendar year (October-December 2020). Data were reviewed for all 41 countries to assess total and country-level percent change for each indicator. Then, qualitative data were reviewed among countries in the upper quartile to assess specific strategies that contributed to programmatic gains. Overall, positive percent change was observed in PEPFAR-supported countries in HIV treatment (5%) and viral load suppression (2%) during 2020. Countries reporting the highest gains across the HIV care continuum during 2020 attributed successes to reducing or streamlining facility attendance through strategies such as enhancing index testing (offering of testing to the biologic children and partners of PLHIV)§ and community- and home-based testing; treatment delivery approaches; and improvements in data use through monitoring activities, systems, and data quality checks. Countries that reported program improvements during the first year of the COVID-19 pandemic offer important information about how lifesaving HIV treatment might be provided during a global public health crisis.

Community-based referral for tuberculosis preventive therapy is effective for treatment completion.

Expansion of tuberculous preventive therapy (TPT) is essential to curb TB incidence and mortality among people with HIV (PWH), yet implementation has been slow. Innovative strategies to operationalize TPT are urgently needed. Here we present an evaluation of community-based identification and referral of PWH on completion of a six-month course of isoniazid in a highly prevalent region in rural South Africa. Using a community-based TB/HIV intensive case finding strategy, a team of nurses and lay workers identified community members with HIV who were without fever, night sweats, weight loss, or cough and referred them to the government primary care clinics for daily oral isoniazid, the only available TPT regimen. We measured monthly adherence and six-month treatment completion in the community-based identification and referral (CBR) group compared to those already engaged in HIV care. Adherence was measured by self-report and urine isoniazid metabolite testing. A multivariable analysis was performed to identify independent predictors of TPT completion. Among 240 participants, 81.7% were female, median age 35 years (IQR 30-44), and 24.6% had previously been treated for TB. The median CD4 count in the CBR group was 457 (IQR 301-648), significantly higher than the clinic-based comparison group median CD4 of 344 (IQR 186-495, p<0.001). Independent predictors of treatment completion included being a woman (aOR 2.41, 95% 1.02-5.72) and community-based identification and referral for TPT (aOR 2.495, 95% 1.13-5.53). Among the CBR group, treatment completion was 90.0%, an absolute 10.8% higher than the clinic-based comparison group (79.2%, p = 0.02). Adherence was significantly greater in the CBR group than the clinic-based comparison group, as measured by self-report (p = 0.02) and urine isoniazid testing (p = 0.01). Among those not on ART at baseline, 10% of eligible PWH subsequently initiated ART. Community members living with HIV in TB endemic regions identified and referred for TPT demonstrated higher treatment completion and adherence compared to PWH engaged for TPT while receiving clinic-based care. Community-based identification and referral is an innovative adjunctive strategy to facilitate implementation of TB preventive therapy in people living with HIV.

Systematic identification of facility-based stillbirths and neonatal deaths through the piloted use of an adapted RAPID tool in Liberia and Nepal.

Maternal, fetal, and neonatal health outcomes are interdependent. Designing public health strategies that link fetal and neonatal outcomes with maternal outcomes is necessary in order to successfully reduce perinatal and neonatal mortality, particularly in low- and middle- income countries. However, to date, there has been no standardized method for documenting, reporting, and reviewing facility-based stillbirths and neonatal deaths that links to maternal health outcomes would enable a more comprehensive understanding of the burden and determinants of poor fetal and neonatal outcomes. We developed and pilot-tested an adapted RAPID tool, Perinatal-Neonatal Rapid Ascertainment Process for Institutional Deaths (PN RAPID), to systematically identify and quantify facility-based stillbirths and neonatal deaths and link them to maternal health factors in two countries: Liberia and Nepal. This study found an absence of stillbirth timing documented in records, a high proportion of neonatal deaths occurring within the first 24 hours, and an absence of documentation of pregnancy-related and maternal factors that might be associated with fetal and neonatal outcomes. The use of an adapted RAPID methodology and tools was limited by these data gaps, highlighting the need for concurrent strengthening of death documentation through training and standardized record templates.

Persistence of Ebola virus after the end of widespread transmission in Liberia: an outbreak report.

BACKGROUND: Outbreak response efforts for the 2014-15 Ebola virus disease epidemic in west Africa brought widespread transmission to an end. However, subsequent clusters of infection have occurred in the region. An Ebola virus disease cluster in Liberia in November, 2015, that was identified after a 15-year-old boy tested positive for Ebola virus infection in Monrovia, raised the possibility of transmission from a persistently infected individual. METHODS: Case investigations were done to ascertain previous contact with cases of Ebola virus disease or infection with Ebola virus. Molecular investigations on blood samples explored a potential linkage between Ebola virus isolated from cases in this November, 2015, cluster and epidemiologically linked cases from the 2014-15 west African outbreak, according to the national case database. FINDINGS: The cluster investigated was the family of the index case (mother, father, three siblings). Ebola virus genomes assembled from two cases in the November, 2015, cluster, and an epidemiologically linked Ebola virus disease case in July, 2014, were phylogenetically related within the LB5 sublineage that circulated in Liberia starting around August, 2014. Partial genomes from two additional individuals, one from each cluster, were also consistent with placement in the LB5 sublineage. Sequencing data indicate infection with a lineage of the virus from a former transmission chain in the country. Based on serology and epidemiological and genomic data, the most plausible scenario is that a female case in the November, 2015, cluster survived Ebola virus disease in 2014, had viral persistence or recurrent disease, and transmitted the virus to three family members a year later. INTERPRETATION: Investigation of the source of infection for the November, 2015, cluster provides evidence of Ebola virus persistence and highlights the risk for outbreaks after interruption of active transmission. These findings underscore the need for focused prevention efforts among survivors and sustained capacity to rapidly detect and respond to new Ebola virus disease cases to prevent recurrence of a widespread outbreak. FUNDING: US Centers for Disease Control and Prevention, Defense Threat Reduction Agency, and WHO.

Bolstering Community Cooperation in Ebola Resurgence Protocols: Combining Field Blood Draw and Point-of-Care Diagnosis.

Alison Galvani and colleagues describe a community-based protocol to improve cooperation with Ebola testing as well as contact tracing, quarantining, and treatment.

Antiretroviral therapy (ART) for treating HIV infection in ART-eligible pregnant women.

BACKGROUND: This systematic review focuses on antiretroviral therapy (ART) for treating human immunodeficiency virus (HIV) infection in ART-eligible pregnant women. Mother-to-child transmission (MTCT) is the primary means by which children worldwide acquire HIV infection. MTCT occurs during three major timepoints during pregnancy and the postpartum period: in utero, intrapartum, and during breastfeeding. Strategies to reduce MTCT focus on these periods of exposure and include maternal and infant use of ART, caesarean section before onset of labour or rupture of membranes, and complete avoidance of breastfeeding. Where these combined interventions are available, the risk of MTCT is as low as 1-2%. Thus, ART used among mothers who require treatment of HIV for their own health also plays a significant role in decreasing MTCT.This review is one in a series of systematic reviews performed in preparation for the revision of the 2006 World Health Organization (WHO) Guidelines regarding "Antiretroviral Drugs for Treating Pregnant Women and Preventing HIV Infection in Infants" and "Antiretroviral therapy (ART) for HIV Infections in Adults and Adolescents." The findings from these reviews were discussed with experts, key stakeholders, and country representatives at the 2009 WHO guideline review meeting. The resulting WHO 2009 "rapid advice" preliminary guidance on adult and adolescent ART now recommends lifelong treatment for all adults with HIV infection and CD4 counts <350 cells/mm(3). These recommendations also apply to pregnant women who are HIV-infected and they place a high value on early ART to benefit the mother's own health (WHO 2009). The "rapid advice" preliminary guidance also aims to minimize side effects for mothers and their infants (WHO 2009). OBJECTIVES: Our objective was to assess the current literature regarding the treatment of HIV infection in pregnant women who are clinically or immunologically eligible for ART. This review includes an evaluation of the optimal time to start therapy in relation to the woman's laboratory parameters and/or gestational age. It also includes an analysis of which specific antiretroviral medications to start in women who are not yet on ART and which agents to continue in women who are already on ART. SEARCH STRATEGY: In June 2009, electronic searches were undertaken in these databases: Cochrane's "CENTRAL," EMBASE, PubMed, LILACS, and Web of Science/Web of Social Science. Hand searches were performed of the reference lists of all pertinent reviews and studies identified. Abstracts from relevant conferences were searched. Experts in the field were contacted to locate additional studies. The search strategy was iterative. SELECTION CRITERIA: We selected randomized controlled trials and observational studies that evaluated pregnant women with HIV infection who were eligible for ART according to criteria defined by the WHO guideline review committee. Studies were included in the systematic review when a comparison group was clearly defined and where the intervention comprised triple ART. For a study to be considered, each medication in the ART regimen needed to be clearly described. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the selected studies for relevance and inclusion. Relevant data was then extracted from included studies, and the risk of bias assessed. In each included study, the relative risk (RR) for the intervention versus the comparison group was calculated for each outcome, as appropriate, with 95% confidence intervals (CIs). MAIN RESULTS: To our knowledge, there are no randomized controlled trials or observational studies that address the optimal time to start antiretroviral drugs in ART-eligible pregnant women in relation to the woman's laboratory parameters and/or gestational age. The medications to continue in ART-eligible pregnant women who are already receiving ART also have not been evaluated systematically in the current literature. The long-term mortality of HIV-positive pregnant women on ART for their own health, and the long-term virologic or clinical efficacy of ART in treating them, has not been evaluated in randomized clinical trials. In this review, surrogate outcomes for long-term mortality and virologic and clinical efficacy (e.g. MTCT and infant HIV transmission or death) were evaluated to determine the efficacy of specific antiretroviral regimens to start in women who are not yet on ART.Three randomized controlled trials and six observational studies were selected. No studies addressed comparative maternal mortality, which regimens to continue in women already on ART, or the laboratory parameters and gestational age at which to start therapy. The use of zidovudine (AZT), lamivudine (3TC) and lopinavir/ritonavir (LPV-r) starting at 28-36 weeks gestation in a breastfeeding population reduced infant HIV-transmission or death at 12 months compared to a short-course regimen (RR 0.64, 95% CI: 0.44-0.92) (deVincenzi, 2009). Starting AZT, 3TC, and nevirapine (NVP) at 34 weeks in a mixed-feeding population reduced infant HIV-transmission or death at 7 months compared to a short-course regimen (RR 0.39, 95% CI: 0.12-0.85) (Bae, 2008).In the Mma Bana study (a randomized controlled trial in a breastfeeding population) there was no difference in MTCT at six months between the AZT/3TC/LPV-r and AZT, 3TC, and abacavir (ABC) arms (RR 0.17, 95% CI: 0.02-1.44) (Shapiro, 2009). Both regimens also showed 92-95% efficacy in virologic suppression at delivery and during the breastfeeding period. In the Kesho Bora study there was a significant difference in MTCT at 12 months between breastfeeding women who initiated AZT/3TC/LPV-r starting between 28 and 36 weeks and those receiving a short course regimen (RR 0.58, 95% CI: 0.34-0.97) (deVincenzi, 2009). MTCT also decreased significantly when AZT/3TC/NVP was compared with a short-course regimen at seven months in a feeding intervention study (RR 0.15, 95% CI: 0.04-0.62) (Bae, 2008) and 12 months in a population where either exclusive breastfeeding or replacement feeding was encouraged (RR 0.14, CI: 0.04-0.47) (Ekouevi, 2008).In the Mma Bana study, there was increased risk of prematurity among infants born to women receiving AZT/3TC/LPV-r (RR 1.52, CI: 1.07- 2.17) compared with AZT/3TC/ABC (Shapiro, 2009). Ekouevi 2008 showed higher rates of infant low birth weight on AZT/3TC/NVP started at 24 weeks compared to a short course regimen started between 32 and 36 weeks (RR 1.81, 95% CI: 1.09- 3.0). Tonwe-Gold 2007 showed an increase in maternal severe adverse events among the women receiving AZT/3TC/NVP compared with a short-course regimen (RR 25.33, CI 1.49- 340.51). AUTHORS' CONCLUSIONS: In ART-eligible pregnant women with HIV infection, ART is a safe and effective means of providing maternal virologic suppression, decreasing infant mortality, and reducing MTCT. Specifically, AZT/3TC/NVP, AZT/3TC/LPV-r, and AZT/3TC/ABC have been shown to decrease MTCT. More research is needed regarding the use of specific regimens and their maternal and infant side-effect profiles.