Background
The Joint United Nations Programme on HIV/AIDS (UNAIDS) has developed the ambitious 90–90-90 strategy with the objective to end the AIDS epidemic by 2030 by achieving the following three targets: 90% of all people living with HIV know their status; 90% of all people diagnosed with HIV receive sustained antiretroviral therapy (ART); and 90% of all people on ART are virally suppressed (73% of all with HIV) [
1].
The achievement of these targets and in general the HIV cascade of care may be different in women and men as well as in individuals belonging to different age groups [
2‐
5]. In addition, in the current context where test and treat and follow-up of stable HIV-positive patients on ART through viral load is recommended [
6], some national programs have stopped systematic measurement of CD4 counts in newly diagnosed HIV-positive patients and/or during follow-up. Data from household-based studies on the immunological status and viral load of HIV-positive individuals can be helpful to direct program activities and resources towards underserved population groups [
7].
South Africa is one of the countries with the HIV highest prevalence in the world and KwaZulu-Natal (KZN) is the province most affected by the epidemic, with an HIV prevalence of 27.9% in 2012 [
8]. In 2005, the KZN Department of Health (DOH) initiated an HIV program in the Mbongolwane and Eshowe Health Service Areas, uMlalazi Municipality, KZN province, which included HIV testing, HIV care and ART initiation. In 2011, Médecins Sans Frontières (MSF) started supporting this program with large-scale HIV testing, training, mentoring and clinical support in primary care clinics to improve coverage and viral suppression.
In order to better understand the HIV epidemic at local level and adapt the strategies of intervention we assessed progress towards the UNAIDS 90–90-90 targets in the overall population and by sex and age groups.
Methods
Design and population
We conducted a cross-sectional household-based community survey between July and October 2013.
A two-stage stratified cluster probability sampling strategy was used for the selection of households according to the 2011 Census [
9]. In total, 125 clusters of 25 households each were selected from 14 administrative units called Wards. Google Earth maps from 2011 with exhaustive identification of the households were used to sample the households to be visited by choosing randomly the first household and then sequentially the closest to the first/previous one. Field staff used Global Positioning System (GPS) receivers to find the geographic coordinates of each household.
People aged 15–59 years old living in Mbongolwane and Eshowe Health Service Areas were eligible for enrolment in the study. Those who signed a written informed consent were included.
Study setting
Mbongolwane, a rural area, and Eshowe, the main town of the municipality, account for approximately 120,000 inhabitants [
9]. Decentralization of ART care to the peripheral level was implemented gradually in this area. In 2011, the KZN province embraced the notion of nurse-initiated and managed ART (NIM-ART). MSF support to the KZN Department of Health (DOH) included prevention activities such as condom distribution, voluntary medical male circumcision, community mobilisation, large-scale community-based HIV counselling and testing, implementation of point of care CD4 testing, linkage to care, and training and mentoring of health staff in facilities in support of NIM-ART. In 2013, two district hospitals and their linked 10 primary healthcare facilities were ART-initiating centres. The survey was conducted 8 years after the initiation of the HIV program in the area. At the time of the survey the CD4 threshold for ART initiation was 350 cells/μL.
Procedures
Prior to starting the survey, we conducted community information and mobilization activities through several channels: information on radio spots, meetings with community leaders and health facilities workers, information in schools, leaflets and posters. In order to reach a maximum of eligible individuals in their houses the survey teams visited the houses from Tuesday to Sunday. Time slots from early morning to late evening were covered in different days of the week in order to maximize the possibilities of finding the eligible participants at home. Due to the importance that blood has in the Zulu culture, the survey teams made a particular effort in explaining the purpose of collecting and storing blood and the use of it. The survey teams used face-to-face interviewer-administered questionnaires to collect information at the participant’s home on socio-demographics and history of HIV testing and care (see Additional files
1,
2 and
3). Questionnaires were developed for the Demographic and Health Surveys [
10] and adapted for the study. Certified lay counsellors performed rapid HIV testing on site and provided pre and post-test counselling to the participants willing to test at home. Counsellors used Determine Rapid HIV-1/2 Antibody test kit for screening, and if positive, Unigold Rapid HIV test kit for confirmation according to the South African National guidelines for HIV Counselling and Testing. The tests were standardised and validated for this use. In addition, HIV-positivity was confirmed by ELISA at the laboratory. Survey nurses collected venous blood specimens from HIV-positive participants for antiretroviral (ARV) drug presence test, CD4 count and viral load. Venous blood samples were transported every evening to Global Clinical and Viral Laboratory in Durban. CD4 count was performed using a FACSCalibur™ device from Becton, Dickinson and Company (BD) according to standard manufacturer’s instructions on samples reported as HIV positive. Two dry blood spots (DBS) samples were prepared using the venous blood samples from each participant and transported in batches to the Department of Pharmacology laboratory at Groote Schuur Hospital, University of Cape Town, for ARV drug levels. Qualitative testing for ARV drug levels was performed for the presence of nevirapine, efavirenz and lopinavir which covered all ARV regimens in use in the public sector in the area. A liquid chromatography tandem mass spectrometry assay with a limit of quantification of 0.04 μg/mL was used for all drugs. The assay was developed and validated at the Division of Clinical Pharmacology, University of Cape Town. Viral load was performed for participants on ART for more than 6 months (determined by questionnaire) at Global Clinical and Viral Laboratory in Durban using a NucliSens EasyQ HIV-1v2.0 assay from Biomerieux according to manufacturer’s instructions. The test could quantify HIV-1 RNA over the range of 20 copies to 20 million copies for 0.5 mL sample.
Data analyses
We calculated progression towards the 90–90-90 UNAIDS targets by estimating three proportions: HIV positive individuals who knew their status (first 90), those diagnosed who were on ART (second 90), and those on ART who were virally suppressed (third 90). Viral suppression was defined as having less than 1000 copies/mL. In addition, we calculated five steps of the HIV cascade of care using the total number of HIV positive individuals as a common denominator. ‘Diagnosed’ were the individuals who knew their HIV positive status prior to the survey; ‘Linked to care’ were those who declared having sought care for their HIV infection; ‘In care’ were those who were still receiving HIV care at the time of the survey; ‘On ART’ were those who had ARV detected in blood; ‘Virally suppressed’ were those with viral load less below 1000 copies/mL. All statistical analyses were adjusted for clustering at the level of Ward and household. Descriptive analyses are presented here with 95% confidence intervals (CI). Categorical variables were compared using proportional test. Analyses were primarily performed using Stata 13 (™StataCorp, College Station, Texas, USA).
Ethics
The protocol was approved by the University of Cape Town Human Research Ethics Committee (HREC), the Health Research Committee of the Health Research and Knowledge Management Unit of KZN Department of Health, and the Comité de Protection de Personnes de Paris in France. All participants provided written informed consent. Participants under 18 years provided assent and their parents, guardians or caregivers provided written informed consent for them.
Discussion
In this area of KwaZulu-Natal, eight years into the public ART program, of which two with MSF support, we found that significant but insufficient progress towards the 90–90-90 UNAIDS targets was achieved. Progress towards the first and second targets was moderate and was particularly poor in men and individuals aged 15–29 years. The third target was achieved (or very close to achievement) in all sex and age categories. This progress has been made in a context of high HIV prevalence where one quarter of the overall population is HIV positive.
These findings suggest that achieving the UNAIDS 2020 targets of 90–90-90 is feasible in South Africa, but will require additional community-based investments in testing and ART initiation especially among young people and men. Investments to reach men may need to include strategies to improve HIV knowledge [
11]. A household-based survey conducted in the 2 years following ours in Botswana has reported a high coverage: 83.3% of individuals knew their status, 87.4% of those were on ART, and 96.5% of those on ART had a viral load of 400 copies/mL or less (70.2% of all people with HIV) in a context of high HIV prevalence, 29% [
4]. The early initiation and strong political leadership of the ART programme in Botswana might partially explain the relatively high ART coverage achieved at a time when both South African and Botswana guidelines recommended a CD4 threshold for ART initiation of 350 cells/μL. However, a household-based survey conducted the year following ours in another area of KwaZulu-Natal, found lower rates of HIV-positivity awareness (65% of the HIV-positive women and 52% of the men), similar rates of ART among those who knew their status (70% in women and 69% in men) and lower rates of viral suppression (90% in women and 85% in men) compared to our findings [
3]. Other studies in KZN have shown lower proportions of ART coverage among HIV-positive individuals than ours [
12‐
14] and at national level only 33% of the HIV-positive individuals are on ART and 24% are virally suppressed [
15]. Similarly to others in this context [
13,
16‐
19], in the area surveyed the largest losses in the HIV cascade of care occurred on diagnosis and on linkage from diagnosis into ART care. In addition, the cascade in men and people 15–29 years of age showed greater falls at each step [
20,
21].
High incidence in the past associated with increased access to ART [
22‐
25], and other factors [
26] may explain the current picture of a very high prevalence. Prevalence in women increased dramatically from 15 years with a peak at 30–34 years. A rapid increase (though lower) was also observed in men but with a lag of around 5 years of age. Similar prevalence in women and men after 45 years of age could be a reflection of a differential mortality by age groups in the pre-ART era, a higher HIV incidence at older ages in men compared to women, or other competing risks such as maternal mortality [
24,
27‐
29]. The 2012 national survey found similar age/gender trends at national level [
8]. Regarding the immunological status of the people living with HIV, although the proportion in an advanced stage of HIV disease with CD4 below 200 cells/μL was relatively low, the fact that more than half were not on ART highlights that a non-negligible proportion of people with HIV don’t access care or access it very late, with significant risk of morbidity and mortality. These findings support current recommendations that HIV programmes retain the capacity to perform CD4 cell count at baseline and in case of treatment failure, as this remains one of the best predictors of general patient wellness, disease progression and mortality risk [
30]. They also support the need for innovative strategies to reach individuals with high barriers to HIV testing before they develop advanced disease, such as self-testing and home-based testing.
Our study has some limitations. Some information, such as HIV status awareness used in the cascade of care for the identification of individuals already diagnosed and linked to care, was self-reported, which may have led to misclassifications. Otherwise, most of the results, crucially including ART coverage, are based on laboratory data.
Conclusions
Significant progress has been achieved in this area with regards to reaching the UNAIDS 90–90-90 targets. The third 90, viral suppression in people on ART, was achieved among women and men. However, further efforts on diagnosis and ART initiation are needed in order to reach the first and second targets particularly in men and individuals younger than 30 years. Indeed, almost half of the people virally unsuppressed were undiagnosed. Achieving 90–90-90 is feasible but requires significant additional investment.
Acknowledgements
The authors thank the participants and the community of Mbongolwane and Eshowe for their collaboration. We are grateful to the Epicentre study field team for their work and the Médecins Sans Frontières field team for their support. Special mention to Serge Balandine for his work using satellite maps for sampling and creating the database; Madurai S and the rest of Global Clinical and Viral laboratories team for their collaboration and work performing part of the laboratory tests. We thank Ahidjo Ayouba for his advice on the manuscript. The Division of Clinical Pharmacology at the University of Cape Town was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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