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Viral suppression (VS) in children has remained suboptimal compared to that in adults. We evaluated the impact of transitioning children weighing < 20 kg to a pediatric formulation of dolutegravir (pDTG) on VS in Malawi. We analyzed routine retrospective program data from electronic medical record systems pooled across 169 healthcare facilities in Malawi supported by the Elizabeth Glaser Pediatric AIDS Foundation (EGPAF). We included children who weighed < 20 kg and received antiretroviral therapy (ART) between July 2021-June 2022. Using descriptive statistics, we summarized demographic and clinical characteristics, ART regimens, ART adherence, and VS. We used logistic regression to identify factors associated with post-transition VS. A total of 2468 Children Living with HIV (CLHIV) were included, 55.3% of whom were < 60 months old. Most (83.8%) had initiated on non-DTG-based ART; 71.0% of these had a viral load (VL) test result before transitioning to pDTG, and 62.5% had VS. Nearly all (99.9%) CLHIV transitioned to pDTG-based regimens. Six months after the transition, 52.7% had good ART adherence, and 38.6% had routine VL testing results; 81.7% achieved VS. Post-transition VS was associated with good adherence and pre-transition VS: adjusted odds ratios of 2.79 (95% CI 1.65-4.71), p < 0.001 and 5.32 (95% CI 3.23-9.48), p < 0.001, respectively. After transitioning to pDTG, VS was achieved in most children tested within the first 6 months. However, adherence remained suboptimal post-transition and VL testing at 6 months was limited. Interventions to improve VL testing and enhance ART adherence are still needed in CLHIV on pDTG-based regimens., (© 2024. The Author(s).)

As antiretroviral treatment (ART) coverage for people living with HIV (PLHIV) increases, HIV programmes require up-to-date information about evolving HIV risk behaviour and transmission risk, including those with low-level viremia (LLV; >50 to ≤1000 copies/mL), to guide prevention priorities. We aimed to assess differences in sexual risk behaviours, distribution of viral load (VL) and proportion of transmission across PLHIV subgroups. We analysed data from Population-based HIV Impact Assessment surveys in 14 sub-Saharan African countries during 2015-2019. We estimated adjusted prevalence ratios (aPR) of self-reported HIV high-risk behaviour (multiple partners and condomless sex) across cascade stages via generalised estimation equations. We modelled the proportions of transmission from each subgroup using relative self-reported sexual risk, a Hill function for transmission rate by VL, and proportions within cascade stages from surveys and UNAIDS country estimates for 2010-2020. Compared to PLHIV with undetectable VL (≤50 copies/mL), undiagnosed PLHIV (aPR women: 1.28 [95% CI: 1.08-1.52]; men: 1.61 [1.33-1.95]) and men diagnosed but untreated (2.06 [1.52-2.78]) were more likely to self-report high-risk sex. High-risk behaviour was not significantly associated with LLV. Mean VL was similar among undiagnosed, diagnosed but untreated, and on ART but non-suppressed sub-groups. Across surveys, undiagnosed and diagnosed but untreated contributed most to transmission (40-91% and 1-41%, respectively), with less than 1% from those with LLV. Between 2010 and 2020, the proportion of transmission from individuals on ART but non-suppressed increased. In settings with high ART coverage, effective HIV testing, ART linkage, and retention remain priorities to reduce HIV transmission. Persons with LLV are an increasing share of PLHIV but their contribution to HIV transmission was small. Improving suppression among PLHIV on ART with VL ≥1000 copies/mL will become increasingly important., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Jeffrey W. Imai-Eaton has received grants/contracts from NIH and WHO, consulting fees from BAO Systems, support for attending meetings from UNAIDS, SACEMA and the International AIDS Society and is a member of the editorial board for PLOS Global Public Health. Olanrewaju Edun has received consulting fees from University of Cape Town and WHO and support for attending meetings from UNAIDS. All other authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

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., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Countries in Southern and Eastern Africa have the highest prevalence of human immunodeficiency virus (HIV) infection in the world; in 2015, 52% (approximately 19 million) of all persons living with HIV infection resided in these two regions.* Voluntary medical male circumcision (VMMC) reduces the risk for heterosexually acquired HIV infection among males by approximately 60% (1). As such, it is an essential component of the Joint United Nations Programme on HIV/AIDS (UNAIDS) strategy for ending acquired immunodeficiency syndrome (AIDS) by 2030 (2). Substantial progress toward achieving VMMC targets has been made in the 10 years since the World Health Organization (WHO) and UNAIDS recommended scale-up of VMMC for HIV prevention in 14 Southern and Eastern African countries with generalized HIV epidemics and low male circumcision prevalence (3). † This has been enabled in part by nearly $2 billion in cumulative funding through the President's Emergency Plan for AIDS Relief (PEPFAR), administered through multiple U.S. governmental agencies, including CDC, which has supported nearly half of all PEPFAR-supported VMMCs to date. Approximately 14.5 million VMMCs were performed globally during 2008-2016, which represented 70% of the original target of 20.8 million VMMCs in males aged 15-49 years through 2016 (4). Despite falling short of the target, these VMMCs are projected to avert 500,000 HIV infections by the end of 2030 (4). However, UNAIDS has estimated an additional 27 million VMMCs need to be performed by 2021 to meet the Fast Track targets (2). This report updates a previous report covering the period 2010-2012, when VMMC implementing partners supported by CDC performed approximately 1 million VMMCs in nine countries (5). During 2013-2016, these implementing partners performed nearly 5 million VMMCs in 12 countries. Meeting the global target will require redoubling current efforts and introducing novel strategies that increase demand among subgroups of males who have historically been reluctant to undergo VMMC.

Background: After increasing coverage of malaria interventions, malaria prevalence remains high in Malawi. Previous studies focus on the impact of malaria interventions among children under 5 years old. However, in Malawi, the prevalence of infection is highest in school-aged children (SAC), ages 5 to 15 years. This study examined the interaction between age group and insecticide-treated net (ITN) use for preventing individual and community-level infection in Malawi., Methods: Six cross-sectional surveys were conducted in the rainy and dry seasons in southern Malawi from 2012 to 2014. Data were collected on household ITN usage and demographics. Blood samples for detection of Plasmodium falciparum infection were obtained from all household members present and over 6 months of age. Generalized linear mixed models were used to account for clustering at the household and community level., Results: There were 17,538 observations from six surveys. The association between ITN use and infection varied by season in SAC, but not in other age groups. The adjusted odds ratio (OR) for infection comparing ITN users to non-users among SAC in the rainy season and dry season was 0.78 (95% CI 0.56, 1.10) and 0.51 (0.35, 0.74), respectively. The effect of ITN use did not differ between children under five and adults. Among all non-SACs the OR for infection was 0.78 (0.64, 0.95) in those who used ITNs compared to those that did not. Community net use did not protect against infection., Conclusions: Protection against infection with ITN use varies by age group and season. Individual estimates of protection are moderate and a community-level effect was not detected. Additional interventions to decrease malaria prevalence are needed in Malawi.

Background: Recent data from Malawi suggest that school-aged children (SAC), aged 5-15 years, have the highest prevalence of Plasmodium falciparum infection among all age groups. They are the least likely group to utilize insecticide-treated nets (ITNs), the most commonly available intervention to prevent malaria in Africa. This study examined the effects of a universal ITN distribution campaign, and their durability over time in SAC in Malawi. This study identified factors that influence net usage among SAC and how these factors changed over time., Methods: Cross-sectional surveys using cluster random sampling were conducted at the end of each rainy and dry season in southern Malawi from 2012 to 2014; six surveys were done in total. Mass net distribution occurred between the first and second surveys. Data were collected on household and individual net usage as well as demographic information. Statistical analyses used generalized linear mixed models to account for clustering at the household and neighbourhood level., Results: There were 7347 observations from SAC and 14,785 from young children and adults. SAC used nets significantly less frequently than the rest of the population (odds ratio (OR) from 0.14 to 0.38). The most important predictors of net usage among SAC were a lower ratio of people to nets in a household and higher proportion of nets that were hanging at the time of survey. Older SAC (11-15 years) were significantly less likely to use nets than younger SAC (5-10 years) [OR = 0.24 (95 % CI: 0.21, 0.28)]. The universal bed net campaign led to a statistically significant population-wide increase in net use, however net use returned to near baseline within 3 years., Conclusions: This study suggests that a single universal net distribution campaign, in combination with routine distribution through health clinics is not sufficient to cause a sustained increase in net usage among SAC. Novel approaches to ITN distribution, such as school-based distribution, may be needed to address the high prevalence of infection in SAC.

Unlabelled: Malaria surveillance and interventions in endemic countries often target young children at highest risk of malaria morbidity and mortality. We aimed to determine whether school-age children and adults not captured in surveillance serve as a reservoir for malaria infection and may contribute to malaria transmission. Cross-sectional surveys were conducted in one rainy and one dry season in southern Malawi. Demographic and health information was collected for all household members. Blood samples were obtained for microscopic and PCR identification of Plasmodium falciparum. Among 5796 individuals aged greater than six months, PCR prevalence of malaria infection was 5%, 10%, and 20% in dry, and 9%, 15%, and 32% in rainy seasons in Blantyre, Thyolo, and Chikhwawa, respectively. Over 88% of those infected were asymptomatic. Participants aged 6-15 years were at higher risk of infection (OR=4.8; 95%CI, 4.0-5.8) and asymptomatic infection (OR=4.2; 95%CI, 2.7-6.6) than younger children in all settings. School-age children used bednets less frequently than other age groups. Compared to young children, school-age children were brought less often for treatment and more often to unreliable treatment sources., Conclusion: School-age children represent an underappreciated reservoir of malaria infection and have less exposure to antimalarial interventions. Malaria control and elimination strategies may need to expand to include this age group.

Objectives: Tenofovir disoproxil fumarate (TDF) has been associated with renal insufficiency. Co-administration with boosted protease inhibitors, which increases its exposure, may further increase the risk of renal insufficiency., Methods: We compared the incidence of renal events among women taking TDF co-administered with lopinavir/ritonavir (LPV/r) versus those co-administering TDF with nevirapine (NVP). Renal events were defined as a confirmed drop in creatinine clearance associated with a serum creatinine grade 2 or higher, or that leading to treatment modification., Results: Overall, 741 HIV-infected women were enrolled into the study. Of these, 24 (3.2%) had reportable renal events (18 in LPV/r arm, six in NVP arm). In multivariate analysis, renal events were significantly associated with the LPV/r arm [odds ratio (OR) 3.12, 95% confidence interval (CI) 1.21, 8.05; P = 0.019], baseline HIV-1 RNA (OR 2.65, 95% CI 1.23, 5.69 per 1 log10 copies/ml higher; P = 0.013) and baseline creatinine clearance (OR 0.83, 95% CI 0.70-0.98 per 10 ml/min higher; P = 0.030). In multivariate analysis evaluating renal events requiring treatment modification, only baseline HIV-1 RNA and creatinine clearance were significantly associated (OR 4.41, 95% CI 1.65, 11.78 per 1 log10 copies/ml higher; P = 0.003 and OR 0.80, 95% CI 0.64, 0.99 per 10 ml/min higher; P = 0.040, respectively)., Conclusion: The rates of renal events were relatively low in the two treatment arms. However, patients taking TDF co-administered with LPV/r had significantly more renal events compared to those co-administered with NVP. Furthermore, higher baseline HIV RNA and lower creatinine clearance were associated with the development of renal insufficiency requiring treatment modification.

Background: Data on paediatric reference laboratory values are limited for sub-Saharan Africa., Objective: To describe the distribution of haematological and chemical pathology values among healthy infants from Malawi and Uganda., Methods: A cross-sectional study was conducted among healthy infants, 0-6 months old, born to HIV-uninfected mothers recruited from two settings in Blantyre, Malawi and Kampala, Uganda. Chemical pathology and haematology parameters were determined using standard methods on blood samples. Descriptive analyses by age-group were performed based on 2004 Division of AIDS Toxicity Table age categories. Mean values and interquartile ranges were compared by site and age-group., Results: A total of 541 infants were included altogether, 294 from Malawi and 247 from Uganda. Overall, the mean laboratory values were comparable between the two sites. Mean alkaline phosphatase levels were lower among infants aged ≤21 days while aspartate aminotransferase, creatinine, total bilirubin and gamma-glutamyl transferase were higher in those aged 0-7 days than in older infants. Mean haematocrit, haemoglobin and neutrophil counts were higher in the younger age-groups (<35 days) and overall were lower than US norms. Red and white blood cell counts tended to decrease after birth but increased after ∼2 months of age. Mean basophil counts were higher in Malawi than in Uganda in infants aged 0-1 and 2-7 days; mean counts for eosinophils (for age groups 8-21 or older) and platelets (for all age groups) were higher in Ugandan than in Malawian infants. Absolute lymphocyte counts increased with infant age., Conclusion: The chemical pathology and haematological values in healthy infants born to HIV-uninfected mothers were comparable in Malawi and Uganda and can serve as useful reference values in these settings.

Background: This analysis updates and extends efficacy estimates of the PEPI-Malawi trial through age 24 months at study completion in September 2009., Methods: Infants of breastfeeding HIV-infected women were randomized at birth to the following: (1) single-dose nevirapine (NVP) + 1-week zidovudine (ZDV) (control); (2) control + extended daily NVP (ExtNVP) through 14 weeks; (3) control + extended daily NVP + ZDV (ExtNVP/ZDV) through 14 weeks. We estimated rates of HIV infection, death and HIV infection, or death using Kaplan-Meier analysis., Results: This analysis includes 3126 infants uninfected at birth as follows: 1004 control, 1071 ExtNVP, and 1051 ExtNVP/ZDV. By 9 months, HIV infection rates were 5.0% in ExtNVP, 6.0% in ExtNVP/ZDV, and 11.1% in control (P < 0.001 comparing extended regimens with control). At age 24 months, HIV infection rates had risen to ~11% in the extended arms compared with 15.6% in the controls (P < 0.05). The rates of HIV infection or death were also significantly lower in extended arms. There were no differences in severe adverse events with the exception of higher possibly related events in the ExtNVP/ZDV arm., Conclusions: Daily infant antiretroviral prophylaxis reduces postnatal HIV infection by ~70% during the period of prophylaxis. But continued HIV transmission after prophylaxis stops suggests more prolonged infant prophylaxis is needed.

Background: We assessed gastroenteritis (GE) burden in 2 randomized trials conducted in Malawi to reduce postnatal HIV transmission before and after World Health Organization recommendations regarding exclusive breastfeeding for HIV-exposed infants were adopted. The 2 trials were the nevirapine/AZT (NVAZ, 2000-2003 with prolonged breastfeeding) and the Postexposure Prophylaxis to the Infant (PEPI, 2004-2007 with breastfeeding cessation by 6 months)., Methods: From NVAZ and PEPI trials data, GE frequency through age 12 months among HIV-negative exposed infants was evaluated. Overall and GE-related cumulative mortality rates were estimated using Kaplan-Meier curves., Results: The frequency of at least one GE-related hospitalization was greater in PEPI vs. NVAZ after age 6 months (respectively, 2.9% vs. 0.1%, at 7-9 months and 1.6% vs. 0.2% at 10-12 months, P < 0.001). Cumulative GE-related mortality was significantly higher in PEPI than in NVAZ after age 6 months; at ages 9 and 12 months GE-related mortality was 19 and 24 per 1000 infants in PEPI vs. 7 and 12 per 1000 infants in NVAZ (P = 0.0002)., Conclusions: Early weaning was associated with increased risk of severe GE and GE-related mortality among HIV-exposed infants. Strategies are urgently needed which allow longer breastfeeding while reducing the risk of HIV breast milk transmission in resource-limited settings.

Background: Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) through breast-feeding in resource-limited settings., Methods: Women with HIV-1 infection who were breast-feeding infants were enrolled in a randomized, phase 3 trial in Blantyre, Malawi. At birth, the infants were randomly assigned to one of three regimens: single-dose nevirapine plus 1 week of zidovudine (control regimen) or the control regimen plus daily extended prophylaxis either with nevirapine (extended nevirapine) or with nevirapine plus zidovudine (extended dual prophylaxis) until the age of 14 weeks. Using Kaplan-Meier analyses, we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth., Results: Among 3016 infants in the study, the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months. At 9 months, the estimated rate of HIV-1 infection (the primary end point) was 10.6% in the control group, as compared with 5.2% in the extended-nevirapine group (P<0.001) and 6.4% in the extended-dual-prophylaxis group (P=0.002). There were no significant differences between the two extended-prophylaxis groups. The frequency of breast-feeding did not differ significantly among the study groups. Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events (primarily neutropenia) that were deemed to be possibly related to a study drug., Conclusions: Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants. (ClinicalTrials.gov number, NCT00115648.), (2008 Massachusetts Medical Society)