Low-Abundance Resistant Mutations in HIV-1 Subtype C Antiretroviral Therapy-Naïve Individuals as Revealed by Pyrosequencing

Given the recent scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, we sought to determine how often and at what levels do drug-resistant mutant variants exist in ART-naïve HIV subtype C infected individuals. Samples from 10 ART-naïve Zambian individuals were subjected to ultra-deep pyrosequencing (UDPS) to characterize the frequency of low-abundance drug resistance mutations in the pol gene. Low-abundance clinically relevant variants were detected for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in eight of the ten subjects. Intermediate to high-level resistance was predicted for the majority of NRTIs. Mutations conferring resistance to most firstline and some second-line therapy drugs were also observed. UDPS detected a number of additional major resistant mutations suggesting that these individuals may have an increased risk of virological failure after initiating ART. Moreover, the effectiveness of first-line and even some second-line ART may be compromised in this setting

Early Childhood Infection of Kaposi’s Sarcoma-associated Herpesvirus in Zambian Households: a Molecular Analysis

Sub-Saharan Africa is endemic for Kaposi’s sarcoma-associated herpesvirus (KSHV) and there is a high rate of early childhood infection; however, the transmission sources are not well characterized. We examined household members as potential KSHV transmission sources to young children in the KSHV-endemic country of Zambia. To this end, we enrolled and followed Zambian households with at least one KSHV-seropositive child and collected longitudinal buccal swab samples. KSHV burden was evaluated and K1 sequences from the children were determined and analyzed for differences to K1 sequences from household members. The K1 sequences were also analyzed for evolution over time. We generated K1 sequences from 31 individuals across 16 households. Nine households contained multiple KSHV-positive members, including at least one child. In 6 of 9 households, the child had 100% sequence identity to all household members. However, in two households the child and mother had distinct K1 sequences. In the remaining household, the children were the only KSHV-infected individuals. Furthermore, we report that 1 of 18 individuals had K1 sequence variation within the timespan analyzed. In the present study, we provide evidence that (1) early childhood KSHV transmission occurs from both within and outside the household, (2) intra-household transmission can occur via non-maternal sources, (3) viral shedding in the buccal cavity is highly variable, and (4) the dominant K1 sequence within an individual did not rapidly evolve over time. These results are important for developing KSHV intervention strategies

A qualitative assessment of gender roles in child nutrition in Central Malawi

This study was part of a baseline study conducted in 2017 as part of the CARE Southern Africa Nutrition Initiative (SANI), a project undertaken with the financial support of the Government of Canada through Global Affairs Canada.BACKGROUND : Child malnutrition persists globally with men and women playing distinct roles to support children’s nutrition. Women frequently carry the bulk of the workload related to food, care, and health, all of which are critical factors in child nutrition. For this reason, development efforts have emphasised women ignoring the potential role of men in supporting children’s nutrition. This study sought to understand the different roles that Malawian men and women play in children’s nutrition. METHODS : This qualitative was conducted in rural Central Malawi as part of a baseline study in 2017 for the CARE Southern Africa Nutrition Initiative. Seventy-six participants were interviewed, including 19 men and 57 women, using focus group discussions and in-depth interviews. We sought to understand the gender distribution of men’s and women’s roles and how these roles influence child nutrition. RESULTS : We found that both men and women were involved in productive, reproductive, and community work. However, consistent with the literature, women carried a disproportionate workload in supporting child nutrition compared to men. Women’s heavier workloads often prevented them from being able to meet children’s food needs. Nevertheless, shifts in gender roles were observed in some of the sampled communities, with men taking up responsibilities that have been typically associated with women. These changes in gender roles, however, did not necessarily increase women’s power within the household. CONCLUSIONS : Traditional gender roles remain prevalent in the sampled communities. Women continue to be primarily responsible for the food, care, and health of the household. Women’s heavy workloads prevent them from providing optimal care and nutrition for children. While efforts to advance gender equality by encouraging men to participate in child care and other household responsibilities appear to have had marginal success, the extent to which these efforts have successfully encouraged men to share power remains unclear. Improving gender equality and child nutrition will require efforts to redistribute gendered work and encourage men to move towards shared power with women over household decision-making and control over income.CARE Malawi.http://www.biomedcentral.com/bmcpublichealtham2023Agricultural Economics, Extension and Rural Developmen

Low-Abundance Resistant Mutations in HIV-1 Subtype C Antiretroviral Therapy-Naïve Individuals as Revealed by Pyrosequencing

Given the recent scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, we sought to determine how often and at what levels do drug-resistant mutant variants exist in ART-naïve HIV subtype C infected individuals. Samples from 10 ART-naïve Zambian individuals were subjected to ultra-deep pyrosequencing (UDPS) to characterize the frequency of low-abundance drug resistance mutations in the pol gene. Low-abundance clinically relevant variants were detected for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in eight of the ten subjects. Intermediate to high-level resistance was predicted for the majority of NRTIs. Mutations conferring resistance to most firstline and some second-line therapy drugs were also observed. UDPS detected a number of additional major resistant mutations suggesting that these individuals may have an increased risk of virological failure after initiating ART. Moreover, the effectiveness of first-line and even some second-line ART may be compromised in this setting

Early Childhood Infection of Kaposi’s Sarcoma-associated Herpesvirus in Zambian Households: a Molecular Analysis

Sub-Saharan Africa is endemic for Kaposi’s sarcoma-associated herpesvirus (KSHV) and there is a high rate of early childhood infection; however, the transmission sources are not well characterized. We examined household members as potential KSHV transmission sources to young children in the KSHV-endemic country of Zambia. To this end, we enrolled and followed Zambian households with at least one KSHV-seropositive child and collected longitudinal buccal swab samples. KSHV burden was evaluated and K1 sequences from the children were determined and analyzed for differences to K1 sequences from household members. The K1 sequences were also analyzed for evolution over time. We generated K1 sequences from 31 individuals across 16 households. Nine households contained multiple KSHV-positive members, including at least one child. In 6 of 9 households, the child had 100% sequence identity to all household members. However, in two households the child and mother had distinct K1 sequences. In the remaining household, the children were the only KSHV-infected individuals. Furthermore, we report that 1 of 18 individuals had K1 sequence variation within the timespan analyzed. In the present study, we provide evidence that (1) early childhood KSHV transmission occurs from both within and outside the household, (2) intra-household transmission can occur via non-maternal sources, (3) viral shedding in the buccal cavity is highly variable, and (4) the dominant K1 sequence within an individual did not rapidly evolve over time. These results are important for developing KSHV intervention strategies

Effects of Antiretroviral Therapy on Kaposi’s Sarcoma–Associated Herpesvirus (KSHV) Transmission Among HIV-Infected Zambian Children

Background: The risk of Kaposi’s sarcoma–associated herpesvirus (KSHV) acquisition among children is increased by HIV infection. Antiretroviral therapy (ART) was recently made widely available to HIV-infected children in Zambia. However, the impact of early ART on KSHV transmission to HIV-infected children is unknown. Methods: We enrolled and followed a cohort of 287 HIV-exposed, KSHV-negative children under 12 months of age from Lusaka, Zambia, to identify KSHV seroconversion events. Potential factors associated with KSHV infection—with an emphasis on HIV, ART, and immunological measures—were assessed through structured questionnaires and blood analyses. Incidence rate, Kaplan- Meier, and multivariable Cox regression models were used to assess differences in time to event (KSHV seroconversion) between groups. All statistical tests were two-sided. Results: During follow-up, 151 (52.6%) children underwent KSHV seroconversion. Based on 3552 months of follow-up, we observed similar KSHV incidence rates between HIV-infected and uninfected children. Among HIV-infected children, ARTnaive children had statistically significantly increased risk of KSHV acquisition (adjusted hazard ratio [AHR] = 5.04, 95% confidence interval [CI] = 2.36 to 10.80, P \u3c .001). Time-updated CD4+ T-cell percentage was also statistically significantly associated with risk of KSHV acquisition (AHR = 0.82, 95% CI = 0.74 to 0.92, P \u3c .001), such that each 5% increase of CD4+ T-cells represented an 18% decrease in risk of acquiring KSHV. Conclusions: Our data suggest that early ART and prevention of immune suppression reduce the risk of KSHV acquisition among HIV-infected children in an area where both viruses are highly endemic. This study highlights the importance of programs in Africa to provide children with ART immediately after HIV infection is diagnosed. Includes supplementary materials

Short Communication: Antiretroviral Therapy Resistance Mutations Present in the HIV Type 1 Subtype C \u3ci\u3epol\u3c/i\u3e and \u3ci\u3eenv\u3c/i\u3e Regions from Therapy-Naive Patients in Zambia

The prevalence of antiretroviral therapy (ART) resistance mutations present in HIV-1 subtype C pol and env regions of the proviral DNA was analyzed and compared from therapy-naive individuals before (Cohort A) and after (Cohort B) the availability of free ART in Zambia. Mutations present in sequences published in a previous study from Zambian ART-naive individuals infected with subtype C were analyzed using current parameters for the classification of ART drug resistance and compared with Cohorts A and B. No statistically significant differences were observed when comparing mutations present in the pol and env of these cohorts. However, an increase in the number of minor, borderline, or partial resistance mutations as well as the presence of major resistance mutations were observed in Cohort B. These results suggest there is an increasing trend of drug resistance-associated mutations that could be a result of the availability of free ART in Zambia. Moreover, the high prevalence of resistance mutations observed for maraviroc and vicriviroc in both cohorts may suggest a limited efficacy of entry inhibitors on HIV-1 subtype C