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Antiretroviral therapy (ART) uptake continues to increase across sub-Saharan Africa and emergence of drug-resistant HIV mutations poses significant challenges to management of treatment-experienced patients with virologic failure. In Zambia, new third-line ART (TLART) guidelines including use of dolutegravir (DTG) were introduced in 2018. We assessed virologic suppression, immunologic response, and HIV drug-resistant mutations (DRMs) among patients on TLART at the University Teaching Hospital (UTH) in Lusaka, Zambia. We conducted a retrospective review of patients enrolled at UTH on TLART for6 months between January 2010 and June 30, 2021. CD4 and HIV viral load (VL) at TLART initiation and post-initiation were assessed to determine virologic and immunologic outcomes. Regression analysis using bivariate and multivariate methods to describe baseline characteristics, virologic, and immunologic response to TLART was performed. A total of 345 patients met inclusion criteria; women comprised 57.6% (199/345) of the cohort. Median age at HIV diagnosis was 30 (interquartile range: 17.3-36.8). In 255 (73.8%) patients with at least two VLs, VL decreased from mean of 3.45 log

Introduction:COVID-19 is often characterized by an acute upper respiratory tract infection. However, information on longer-term clinical sequelae following acute COVID-19 is emerging. We followed a group of persons with COVID-19 in Zambia at two months to assess persistent symptoms. Methods:in September 2020, we re-contacted participants from SARS-CoV-2 prevalence studies conducted in Zambia in July 2020 whose polymerase chain reaction (PCR) tests were positive. Participants with valid contact information were interviewed using a structured questionnaire that captured demographics, pre-existing conditions, and types and duration of symptoms. We describe the frequency and duration of reported symptoms and used chi-square tests to explore variability of symptoms by age group, gender, and underlying conditions. Results:of 302 participants, 155 (51%) reported one or more acute COVID-19-related symptoms in July 2020. Cough (50%), rhinorrhoea (36%) and headache (34%) were the most frequently reported symptoms proximal to diagnosis. The median symptom duration was 7 days (IQR: 3-9 days). At a median follow up of 54 days (IQR: 46-59 day), 27 (17%) symptomatic participants had not yet returned to their pre-COVID-19 health status. These participants most commonly reported cough (37%), headache (26%) and chest pain (22%). Age, sex, and pre-existing health conditions were not associated with persistent symptoms. Conclusion:a notable percentage of persons with SARS-CoV-2 infection in July still had symptoms nearly two months after their diagnosis. Zambia is implementing ´post-acute COVID-19 clinics´ to care for patients with prolonged symptoms of COVID-19, to address their needs and better understand how the disease will impact the population over time.

Background: Tenofovir regimens remain the preferred formulations in the HIV guidelines for adolescents and young adults in Zambia and globally. However, some adolescents and young adults are maintained on abacavir by clinicians because of anxiety about possible proximal tubular dysfunction from tenofovir. We assessed the effect of two regimens on proximal tubular function in adolescents and young adults living with HIV. Methods: This was a cross-sectional study involving 180 participants with HIV receiving either tenofovir or abacavir for ≥12 months at the largest tertiary teaching hospital. Two first-morning urine and blood specimens were collected and analyzed for proximal tubular markers, glomerular function, electrolytes, and routine monitoring tests. Proximal tubular function was determined by measuring the fractional excretion of phosphate (FePO4). Proximal tubular dysfunction was defined by FePO4 ≥20% regardless of serum phosphate and FePO4 ≥10-20% when serum phosphate was below 0.81mmol/L. Results: The prevalence of proximal tubular dysfunction was 6% and was higher in the tenofovir group than the abacavir (10% vs. 2%, p2-microglobulin: creatinine ratio, C-reactive protein, and urine protein: creatinine ratio was all associated with worsening proximal tubular dysfunction. Reduced estimated glomelurar filtration rate (eGFR) was found in four (2.2%) participants; three of which were on tenofovir. Conclusions: Proximal tubular dysfunction defined by FePO4 was more prevalent in the tenofovir group than the abacavir group, but not after adjusting for age. Our findings should be interpreted with caution as age differences between the two groups confounded the results.

During the July 2020 first wave of severe acute respiratory syndrome coronavirus 2 in Zambia, PCR-measured prevalence was 13.4% among outpatients at health facilities, an absolute difference of 5.7% compared with prevalence among community members. This finding suggests that facility testing might be an effective strategy during high community transmission.

BackgroundCOVID-19 is often characterized by an acute upper respiratory tract infection. However, information on longer-term clinical sequelae following acute COVID-19 is emerging. We followed a group of persons with COVID-19 in Zambia at two months to assess persistent symptoms.MethodsIn September 2020, we re-contacted participants from SARS-CoV-2 prevalence studies conducted in Zambia in July 2020 whose PCR tests were positive. Participants with valid contact information were interviewed using a structured questionnaire that captured demographics, pre-existing conditions, and types and duration of symptoms. We describe the frequency and duration of reported symptoms and used chi-square tests to explore variability of symptoms by age group, gender, and underlying conditions.ResultsOf 302 participants, 155 (51%) reported one or more acute COVID-19-related symptoms in July 2020. Cough (50%), rhinorrhoea (36%) and headache (34%) were the most frequently reported symptoms proximal to diagnosis. The median symptom duration was 7 days (IQR: 3-9 days). At a median follow up of 54 days (IQR: 46-59 day), 27 (17%) symptomatic participants had not yet returned to their pre-COVID-19 health status. These participants most commonly reported cough (37%), headache (26%) and chest pain (22%). Age, sex, and pre-existing health conditions were not associated with persistent symptoms.ConclusionA notable percentage of persons with SARS-CoV-2 infection in July still had symptoms nearly two months after their diagnosis. Zambia is implementing ‘post-acute COVID-19 clinics’ to care for patients with prolonged symptoms of COVID-19, to address their needs and better understand how the disease will impact the population over time.

The effect of HIV infection on COVID-19 outcomes is unclear. Studies in South Africa (1) and the United Kingdom (2) found an independent association between HIV infection and COVID-19 mortality; however, other studies have not found an association between poor COVID-19 outcomes and either HIV status among hospitalized patients (3-5) or HIV-associated factors such as CD4 count, viral load, or type of antiretroviral therapy (ART) (6). The effect of HIV infection on COVID-19 outcomes remains an urgent question in sub-Saharan Africa, where many countries are experiencing dual HIV and COVID-19 epidemics, and capacity to treat severe COVID-19 is limited. Using data from patients with probable or confirmed COVID-19 admitted to specialized treatment centers during March-December 2020 in Zambia, the Zambian Ministry of Health and CDC assessed the relationship between HIV infection and severe COVID-19 and COVID-19-associated death. Among 443 patients included in the study, 122 (28%) were HIV-positive, and of these, 91 (89%) were receiving ART at the time of hospitalization. HIV status alone was not significantly associated with severe COVID-19 at admission or during hospitalization or with COVID-19-associated death. However, among HIV-positive persons, those with severe HIV disease were more likely to develop severe COVID-19 and were at increased risk for COVID-19-associated death. Ensuring that persons maintain HIV disease control, including maintaining ART continuity and adherence, achieving viral suppression, and addressing and managing underlying medical conditions, could help reduce COVID-19-associated morbidity and mortality in sub-Saharan Africa.

Established antiretroviral therapy (ART) programs in sub-Saharan Africa have well-defined first-and second-line therapies but no standard third-line ART regimen. The impact of third-line ART on patients with multiclass-resistant HIV in resource-limited settings has not been well characterized. We conducted a retrospective review of patients on third-line ART at the University Teaching Hospital in Lusaka, Zambia. We assessed virologic and immunologic outcomes following 6 months of third-line therapy and found among those with a documented viral load, viral suppression (≤1000 copies/ml) at 24 weeks was 95% (63/66) with a mean increase in CD4 count of 116 cells/mm3 and viral suppression of 63% (63/100) by imputation of missing data. This study suggests that third-line therapy is clinically and virologically effective among patients with multiclass-resistance in a resource-limited setting in sub-Saharan Africa.

Background Healthcare workers (HCWs) in Zambia have become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19). However, SARS-CoV-2 prevalence among HCWs is not known in Zambia. Methods We conducted a cross-sectional SARS-CoV-2 prevalence survey among Zambian HCWs in 20 health facilities in 6 districts in July 2020. Participants were tested for SARS-CoV-2 infection using polymerase chain reaction (PCR) and for SARS-CoV-2 antibodies using enzyme-linked immunosorbent assay (ELISA). Prevalence estimates and 95% confidence intervals (CIs), adjusted for health facility clustering, were calculated for each test separately, and a combined measure for those who had PCR and ELISA was performed. Results In total, 660 HCWs participated in the study, with 450 (68.2%) providing a nasopharyngeal swab for PCR and 575 (87.1%) providing a blood specimen for ELISA. Sixty-six percent of participants were females, and median age was 31.5 years (interquartile range, 26.2–39.8). The overall prevalence of the combined measure was 9.3% (95% CI, 3.8%–14.7%). PCR-positive prevalence of SARS-CoV-2 was 6.6% (95% CI, 2.0%–11.1%), and ELISA-positive prevalence was 2.2% (95% CI, .5%–3.9%). Conclusions SARS-CoV-2 prevalence among HCWs was similar to a population-based estimate (10.6%) during a period of community transmission in Zambia. Public health measures such as establishing COVID-19 treatment centers before the first cases, screening for COVID-19 symptoms among patients who access health facilities, infection prevention and control trainings, and targeted distribution of personal protective equipment based on exposure risk might have prevented increased SARS-CoV-2 transmission among Zambian HCWs.

Summary Background Between March and December, 2020, more than 20 000 laboratory-confirmed cases of SARS-CoV-2 infection were reported in Zambia. However, the number of SARS-CoV-2 infections is likely to be higher than the confirmed case counts because many infected people have mild or no symptoms, and limitations exist with regard to testing capacity and surveillance systems in Zambia. We aimed to estimate SARS-CoV-2 prevalence in six districts of Zambia in July, 2020, using a population-based household survey. Methods Between July 4 and July 27, 2020, we did a cross-sectional cluster-sample survey of households in six districts of Zambia. Within each district, 16 standardised enumeration areas were randomly selected as primary sampling units using probability proportional to size. 20 households from each standardised enumeration area were selected using simple random sampling. All members of selected households were eligible to participate. Consenting participants completed a questionnaire and were tested for SARS-CoV-2 infection using real-time PCR (rtPCR) and anti-SARS-CoV-2 antibodies using ELISA. Prevalence estimates, adjusted for the survey design, were calculated for each diagnostic test separately, and combined. We applied the prevalence estimates to census population projections for each district to derive the estimated number of SARS-CoV-2 infections. Findings Overall, 4258 people from 1866 households participated in the study. The median age of participants was 18·2 years (IQR 7·7–31·4) and 50·6% of participants were female. SARS-CoV-2 prevalence for the combined measure was 10·6% (95% CI 7·3–13·9). The rtPCR-positive prevalence was 7·6% (4·7–10·6) and ELISA-positive prevalence was 2·1% (1·1–3·1). An estimated 454 708 SARS-CoV-2 infections (95% CI 312 705–596 713) occurred in the six districts between March and July, 2020, compared with 4917 laboratory-confirmed cases reported in official statistics from the Zambia National Public Health Institute. Interpretation The estimated number of SARS-CoV-2 infections was much higher than the number of reported cases in six districts in Zambia. The high rtPCR-positive SARS-CoV-2 prevalence was consistent with observed community transmission during the study period. The low ELISA-positive SARS-CoV-2 prevalence might be associated with mitigation measures instituted after initial cases were reported in March, 2020. Zambia should monitor patterns of SARS-CoV-2 prevalence and promote measures that can reduce transmission. Funding US Centers for Disease Control and Prevention.

BackgroundHIV drug resistance (HIVDR) poses a threat to the HIV epidemic control in Zambia especially in sub-populations such as the 15-24 years where there is poor virological suppression. Understanding the prevalence and patterns of HIVDR in this population (15-24 years) will contribute to defining effective antiretroviral therapy (ART) regimens, improving clinical decision making, and supporting behavioral change interventions needed to achieve HIV epidemic control.MethodsA cross-sectional analysis of study enrollment data from the Project YES! Youth Engaging for Success randomized controlled trial was conducted. Participants were 15 to 24 years old, who knew their HIV status, and had been on ART for at least 6 months. All participants completed a survey and underwent viral load (VL) testing. Participants with viral failure (VL ≥1,000 copies/mL) underwent HIVDR testing which included analysis of mutations in the protease and reverse transcriptase genes.ResultsA total of 99 out of 273 analyzed participants receiving ART had VL failure, of whom 77 had successful HIVDR amplification and analysis. Out of the 77, 75% (58) had at least one drug resistant mutation, among which 83% (48/58) required a drug change. Among the 58 with HIVDR mutations, the prevalence of at least one HIVDR mutation to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) were 81%, 65.5% and 1.7%. The mutation M184V which confers resistance to NRTI drugs of lamivudine (3TC) and emtricitabine (FTC) was the most common (81%) among NRTI associated mutations followed by K65R (34.5%) which is associated with both tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF) resistance. Thymidine analogue mutations (TAMs) which confer resistance primarily to zidovudine (AZT), stavudine (d4T) and other NRTIs were observed at 32.8%. Common TAMs were K70RTQNE (32.8%), K219QE (22.4%), D67N (17.2%) and T215IT (15.5%). The most common NNRTI associated mutation was the K103N (65.5%) which confers resistance to both efavirenz (EFV) and nevirapine (NVP). There was a relatively high occurrence of other NNRTI mutations V106A (36.2%), as well as Y188C (36.2%) and Y181C (36.2%) which confer resistance to etravirine.ConclusionsThere is a high prevalence of HIVDR including TAMs despite majority of these patients (90.48%) being on AZT or d4T sparing first line ART among the youth. Emergence of these mutations including the NNRTI associated mutations (Y181C and Y188C) may compromise future second- and third-line regimens in the absence of routine HIVDR testing. HIVDR monitoring at start of ART or at first-line failure can better inform clinical decision making and ART programing.

Background In Zambia, third-line regimens consist of a switch to darunavir/ritonavir (DRV/r) and/or raltegravir (RAL) and/or etravirine (ETV), and as of 2017, dolutegravir (DTG), from a failing second-line therapy.5 We assessed virologic suppression (HIV viral load (VL) ≤1000 copies/ml per Zambian national guidelines), immunological response, and patterns of HIV drug resistance mutation among patients on third-line ART at the University Teaching Hospital (UTH) in Lusaka, Zambia. Methods A retrospective evaluation of adults ≥18 years old on third-line ART regimens at UTH between January 2012 to June 30, 2020 was conducted. Patients were referred for second-line virologic failure defined as HIV RNA VL > 1000 copies/mL on two consecutive measurements after 6 months on second-line ART.5 We assessed virologic suppression VL ≤1000 copies/ml, CD4, mutations, and third-line regimens of this cohort. Patients were excluded if they were on third-line ART < 6 months or received RAL and/or ETV and/or DTG before starting third-line ART. Results A total of 539 patients were included; 231 males (42.9%) and 308 (57.1%) females. The mean age of third-line initiation was 29.8 years; mean time from ART initiation to third-line initiation was 9.9 years. Out of 25 combination 349 (64.7%) received DTG, 272 (50.5%) DRV/r, 85(15.8%) ETR, and 49 (9.1%) RAL. There were 215 (39.9%) genotypes; common mutations were to zidovudine (80%), non-nucleoside reverse transcriptase inhibitors (NNRTIs) (78%), and protease inhibitors (PIs) (41%). Patients with at least one viral load and CD4 upon third-line initiation was 296 (54.9%) and 350 (64.9%), respectively. Among patients with sufficient data (21%, n=115), VL suppression increased from 44 (38%) patients at baseline to 53 (46%) at next available follow-up; with mean baseline VL and follow-up VL of log10 3.60 and 3.33, respectively. The immunologic response revealed 49 (56.3%) had CD4 increase with mean increase of 61.1 cells/mm3. (See Table 1.) Conclusion We found moderate improvements in VL suppression and immunologic response. Nearly all third-line patients had genotypic resistance to first-line NNRTI and nearly half to second-line PI regimens. Quality improvement measures are needed to improve viral load timing following ART changes to better assess regimen efficacy. Disclosures All Authors: No reported disclosures

Semi Structured questionnaire. Both the FGDs and IDs followed the questions as outlined in the semi structured questionnaire. (DOCX 13 kb)

Phylogenetic analysis of a 280-bp region of the partial RNA dependent-RNA polymerase region in norovirus detections (1A: Genogroup I; 1B: Genogroup II). (PDF 79 kb)

Background As HIV-infected patients are living longer due to ART and decreasing mortality, the burden of noncommunicable diseases (NCDs) is expected to rise. With the implication of Insulin resistance (IR) and inflammation in the pathogenesis of Diabetes Mellitus (DM), DM is likely to be increasing in the HIV-infected patients in the Sub-Saharan Africa (SSA). HIV is characterized with systemic inflammation and markers which quickly decrease with ART initiation regardless of type of ARV regimen though they do not normalize. We thus assessed the relationship between IR and Virologic treatment failure among HIV-1-infected individuals at 12 months of first-line ART in the Zambian ART program. Methods We conducted a cross-sectional survey among HIV-1-infected individuals at 12 months (±3 months) of first-line ART. Systematic sampling was performed and 20 clinics were selected based on the random starting-point, sampling interval and cumulative population size giving a sample size of 460. Eligible patients had their fasting blood specimens collected for VL, insulin, blood glucose, high sensitive c-reactive protein (hsCRP), tumour necrosis factor alfa (TNFa) and Lipogram. Anthropometric indices were also measured including visceral fat. Insulin resistance (IR) was determined using Homeostatic model assessment (HOMA). Proportions for each outcome at linearized standard error 95% confidence interval and summary estimates were determined. Viral Load suppression (VLS) was defined according to the detection threshold which was 1,000 copies/mL. Results Of the 473 patients enrolled, 142 (30%): 95% CI (26%, 34%) had IR. 19% of Individuals with IR had treatment failure compared with 5.7% with treatment failure and without IR (P-value < 0.0001). Treatment success was associated with less likelihood of IR (OR 0.26 (0.14, 0.48), P-value < 0.0001. Among individuals with VLS, 82, out of 142 (58%) 95% CI (0.54%, 0.70%) had IR compared with 232 out of 331, (70%) 95% CI (65%, 75%) who did not have IR (P-value = 0.042) Conclusion Patients with poor virological outcomes at 12 months of first-line ART had increased likelihood of insulin resistance compared with those with treatment success. There was good evidence to suggest that the proportion of those with VLS and IR was less than those with VLS and no IR. Disclosures All authors: No reported disclosures.

In settings of resource constraint, an understanding of HIV drug resistance can guide antiretroviral therapy (ART) at switch to second-line therapy. To determine the prevalence of such HIV drug resistance mutations (HIV DRM), we used an in-house sequencing assay in the pol gene (protease and partial reverse transcriptase) in a cohort of patients suspected of failing a first-line regimen, which in Zambia comprises two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and one non-nucleoside reverse transcriptase inhibitor (NNRTI). Our analysis cohort (n = 68) was referred to the University Teaching Hospital in Lusaka from November 2009 to October 2012. Median duration on first-line ART to suspected treatment failure was 3.2 years (IQR 1.7-4.7 years). The majority of patients (95%) harbored HIV-1 subtype C virus. Analysis of reverse transcriptase revealed M184V (88%), K103N/S (32%), and Y181C/I/V (41%) DRMs, with the latter conferring reduced susceptibility to the salvage therapy candidates etravirine and rilpivirine. Three patients (5%) had major protease inhibitor (PI) resistance mutations: all three had the V82A mutation, and one patient (Clade J virus) had a concurrent M46I, Q58E, and L76V DRM. HIV-1 genotyping revealed major and minor DRMs as well as high levels of polymorphisms in subtype C isolates from patients failing first-line antiretroviral therapy. Closer monitoring of DRM mutations at first-line failure can inform clinicians about future options for salvage therapy.

Background The burden, clinical features, and molecular epidemiology of norovirus infection in young children in southern Africa are not well defined. Methods Using data from a health facility-based surveillance study of children

Phylogenetic analysis of a 280-bp region of the partial RNA dependent-RNA polymerase region in norovirus detections (1A: Genogroup I; 1B: Genogroup II). (PDF 79 kb)