Differentiated service delivery for people using second-line antiretroviral therapy: clinical outcomes from a retrospective cohort study in KwaZulu-Natal, South Africa.

INTRODUCTION: Evidence is needed to guide the inclusion of broader groups of people living with HIV (PLHIV) in differentiated service delivery (DSD) programmes. We assessed treatment outcomes among PLHIV on second-line regimens in a community antiretroviral therapy (ART) delivery programme, compared to those who remained at clinics. METHODS: Using data from 61 public clinics, we did a retrospective cohort study among PLHIV receiving second-line ART following rollout of the Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme in KwaZulu-Natal, South Africa. We included PLHIV from the timepoint when they were first eligible, though not necessarily referred, for community ART within CCMDD and followed them for 18 months. We used multivariable logistic regression to compare 12-month attrition and viraemia between clients referred for community ART and those remaining in clinic care. RESULTS: Among 209,744 PLHIV aged ≥ 18 years who collected ART between October 2016 and December 2018, 7511 (3.6%) received second-line ART. Of these, 2575 (34.3%) were eligible for community ART. The median age was 39.0 years (interquartile range 34.0-45.0) and 1670 (64.9%) were women. Five hundred and eighty-four (22.7%) were referred for community ART within 6 months of meeting eligibility criteria. Overall, 4.5% [95% confidence interval (CI) 3.0-6.6%] in community ART and 4.4% (95% CI 3.5-5.4%) in clinic care experienced attrition at 12 months post eligibility for community ART. Two thousand one hundred and thirty-eight (83.0%) had a viral load recorded 6-18 months after becoming eligible, and of these, 10.3% (95% CI 7.7-13.3%) in community ART and 11.3% (95% CI 9.8-12.9%) in clinic care had viraemia > 200 copies/ml. In separate regressions adjusted for age, gender, district, time on second-line ART, nucleoside reverse transcriptase inhibitor backbone and year of eligibility, no differences in the odds of attrition [adjusted odds ratio (aOR) 1.02, 95% CI 0.71-1.47] or viraemia (aOR 0.91, 95% CI 0.64-1.29) were observed between those in community ART and those remaining in clinic care. CONCLUSIONS: We found good outcomes among PLHIV who were stable on second-line regimens and referred for community ART. Efforts to expand DSD access among this group should be prioritized.

The impact of the COVID-19 lockdown on HIV care in 65 South African primary care clinics: an interrupted time series analysis.

BACKGROUND: The effect of the COVID-19 pandemic on HIV outcomes in low-income and middle-income countries is poorly described. We aimed to measure the impact of the 2020 national COVID-19 lockdown on HIV testing and treatment in KwaZulu-Natal, South Africa, where 1·7 million people are living with HIV. METHODS: In this interrupted time series analysis, we analysed anonymised programmatic data from 65 primary care clinics in KwaZulu-Natal province, South Africa. We included data from people testing for HIV, initiating antiretroviral therapy (ART), and collecting ART at participating clinics during the study period, with no age restrictions. We used descriptive statistics to summarise demographic and clinical data, and present crude summaries of the main outcomes of numbers of HIV tests per month, ART initiations per week, and ART collection visits per week, before and after the national lockdown that began on March 27, 2020. We used Poisson segmented regression models to estimate the immediate impact of the lockdown on these outcomes, as well as post-lockdown trends. FINDINGS: Between Jan 1, 2018, and July 31, 2020, we recorded 1 315 439 HIV tests. Between Jan 1, 2018, and June 15, 2020, we recorded 71 142 ART initiations and 2 319 992 ART collection visits. We recorded a median of 41 926 HIV tests per month before lockdown (January, 2018, to March, 2020; IQR 37 838-51 069) and a median of 38 911 HIV tests per month after lockdown (April, 2020, to July, 2020; IQR 32 699-42 756). In the Poisson regression model, taking into account long-term trends, lockdown was associated with an estimated 47·6% decrease in HIV testing in April, 2020 (incidence rate ratio [IRR] 0·524, 95% CI 0·446-0·615). ART initiations decreased from a median of 571 per week before lockdown (IQR 498-678), to 375 per week after lockdown (331-399), with an estimated 46·2% decrease in the Poisson regression model in the first week of lockdown (March 30, 2020, to April 5, 2020; IRR 0·538, 0·459-0·630). There was no marked change in the number of ART collection visits (median 18 519 visits per week before lockdown [IQR 17 074-19 922] vs 17 863 visits per week after lockdown [17 509-18 995]; estimated effect in the first week of lockdown IRR 0·932, 95% CI 0·794-1·093). As restrictions eased, HIV testing and ART initiations gradually improved towards pre-lockdown levels (slope change 1·183/month, 95% CI 1·113-1·256 for HIV testing; 1·156/month, 1·085-1·230 for ART initiations). INTERPRETATION: ART provision was generally maintained during the 2020 COVID-19 lockdown, but HIV testing and ART initiations were heavily impacted. Strategies to increase testing and treatment initiation should be implemented. FUNDING: Wellcome Trust, Africa Oxford Initiative.

An assessment of nutritional status in children of rural, northern KwaZulu-Natal province.

BACKGROUND: Childhood malnutrition in South Africa is largely perceived as one of undernutrition, with the opposite end of the spectrum (overnutrition) being evidenced in the increasing prevalence of childhood obesity, demonstrated to be associated with chronic metabolic diseases in adulthood. Targeting childhood malnutrition is a potential interventional strategy to prevent non-communicable diseases amongst adults. As the prevalence of malnutrition (undernutrition and overnutrition) in rural, northern KwaZulu-Natal province, South Africa, is largely unknown, this study aimed to determine the baseline nutritional status of children attending primary healthcare facilities within the Bethesda Hospital catchment area. METHODS: This quantitative, cross-sectional study included children aged 6 weeks to 19 years, attending any primary healthcare clinics for over a 3 months period. Anthropometric measurements were obtained to categorise the children according to the World Health Organisation's (WHO) nutritional classifications. RESULTS: Stunting in children aged less than 5 years was found to be lower (14%) than nationally representative studies (27%); however, 14.4% of the infants aged 6 weeks to 5 months were overweight, increasing to 32.3% in those aged 14-19 years. Males in the 6-weeks to 5-month age group were more likely to be overweight/obese and stunted than females in the same age group. CONCLUSION: Undernutrition is showing a downward trend, which is a testament to initiatives to reduce food insecurity amongst the poor. However, the emerging upward trend of overweight/obesity in children of all ages, indicates the need to have a national discussion on over- and undernutrition, its causes and implications.

HIV treatment outcomes among people with initiation CD4 counts >500 cells/µL after implementation of Treat All in South African public clinics: a retrospective cohort study.

INTRODUCTION: The World Health Organisation recommends to Treat All people with HIV, irrespective of CD4 count. However, people with CD4 counts >500 cells/µL may be asymptomatic and therefore less motivated to adhere to antiretroviral therapy (ART). We aimed to assess whether people initiated with CD4 counts >500 cells/µL had worse treatment outcomes compared to those initiated at lower CD4 counts. METHODS: We performed a retrospective cohort study among non-pregnant adults initiating ART at eight public clinics in South Africa between September 2016, when Treat All was implemented, and August 2017. We assessed whether initiation CD4 count >500 cells/µL was associated with the outcomes of attrition (death, lost to follow-up or treatment interruption >180 days), and viraemia >1000 copies/mL, by twelve months using Cox proportional hazards and Poisson regression models. RESULTS AND DISCUSSION: Among 4952 patients initiating ART, the median age was 32.4 years (interquartile range (IQR) 27.2 to 39.7), 58.9% were women and 30.3% had an initiation CD4 count >500 cells/µL. After twelve months, 3382 (68.3%) were retained in care, 303 (6.1%) had transferred to another clinic, 1010 (20.4%) were lost to follow-up, 232 (4.7%) had a treatment interruption >180 days and 25 (0.5%) were known to have died. Overall, 1267 experienced attrition at a median time of 91 days (IQR 23 to 213), with 302 of these (23.8%) experiencing attrition immediately after their ART initiation visit. Among those in care at twelve months with viral load results, 4.6% had viraemia. In multivariable analysis, the hazard of attrition was similar between patients newly eligible for ART with CD4 counts >500 cells/µL compared to those with CD4 ≤500 cells/µL (adjusted hazard ratio 1.03, 95% confidence interval (CI) 0.90 to 1.17). The risk of viraemia was lower among patients with CD4 counts >500 cells/µL compared to those with CD4 ≤500 cells/µL (adjusted risk ratio 0.58, 95% CI 0.37 to 0.92). CONCLUSIONS: After implementation of Treat All in South African public clinics, we found that patients newly eligible for ART with initiation CD4 counts >500 cells/µL had comparable or better outcomes compared to those with lower CD4 counts. These finding support ongoing implementation of Treat All in our setting.

Reasons for failure of prevention of mother-to-child HIV transmission in a rural South African district hospital.

Further reduction of mother-to-child transmission (MTCT) of HIV requires improved understanding of the reasons for MTCT. We reviewed maternal and infant case notes for HIV-positive infants diagnosed by polymerase chain reaction at Bethesda Hospital. Nineteen cases were analysed. Median gestation at first antenatal consultation (ANC) was 22.5 (interquartile range [IQR] 19.25-24). Eleven (57.9%) mothers were HIV positive at first ANC, whilst eight tested negative and later positive (2 antepartum, 6 postpartum). Median maternal CD4 was 408 cells/µL (IQR 318-531). Six (31.6%) received no antenatal antiretroviral therapy (ART) because they were diagnosed as HIV positive postpartum; 9 (47.3%) received antenatal ART and 3 (15.8%) were never initiated on ART. At 6 weeks postpartum, 5 infants (26.3%) were not on prophylactic nevirapine (NVP) because their mothers had not yet been diagnosed. Maternal seroconversion in pregnancy and breastfeeding, and possibly false-negative HIV tests, were important reasons for prevention of mother-to-child transmission (PMTCT) failure.

Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study.

BACKGROUND: Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance. METHODS: An observational cohort of 49 symptomatic patients, diagnosed with uncomplicated P. falciparum malaria by rapid diagnostic test, had blood taken for malaria blood films and P. falciparum DNA polymerase chain reaction (PCR). Following diagnosis, patients were treated with artemether-lumefantrine (Coartem®) and invited to return to the health facility after 28 days for repeat blood film and PCR. All PCR P. falciparum positive samples were analysed for molecular markers of lumefantrine and chloroquine resistance. RESULTS: Of 49 patients recruited on the basis of a positive rapid diagnostic test, only 16 were confirmed to have P. falciparum by PCR. At follow-up, 14 were PCR-negative for malaria, one was lost to follow-up and one blood specimen had insufficient blood for a PCR analysis. All 16 with PCR-confirmed malaria carried a single copy of the multi-drug resistant (mdr1) gene, and the wild type asparagine allele mdr1 codon 86 (mdr1 86N). Ten of the 16 samples carried the wild type haplotype (CVMNK) at codons 72-76 of the chloroquine resistance transporter gene (pfcrt); three samples carried the resistant CVIET allele; one carried both the resistant and wild type, and in two samples the allele could not be analysed. CONCLUSIONS: The absence of mdr1 gene copy number variation detected in this study suggests lumefantrine resistance has yet to emerge in KwaZulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation.