Direct measurement of antiretroviral treatment (ART) program indicators essential for evidence-based planning and evaluation – especially HIV incidence, population viral load, and ART eligibility – is rare in sub-Saharan Africa.
To measure key indicators in rural western Kenya, an area with high HIV burden, we conducted a population survey in September to November 2012 via multistage cluster sampling, recruiting everyone aged 15–59 years living in 3330 randomly selected households. Consenting individuals were interviewed and tested for HIV at home. Participants testing positive were assessed for CD4+ cell count and viral load, and their infections classified as either recent or long term based on Limiting Antigen Avidity assays. HIV-negative participants were tested by nucleic acid amplification to detect acute infections.
Of 6833 household members eligible for the study, 6076 (94.7% of all women and 81.0% of men) agreed to participate. HIV prevalence and incidence were 24.1% [95% confidence interval [CI] 23.0–25.2] and 1.9 new cases/100 person-years (95% CI 1.1–2.7), respectively. Among HIV-positive participants, 59.4% (95% CI 56.8–61.9) were previously diagnosed, 53.1% (95% CI 50.5–55.7) were receiving care, and 39.7% (95% CI 37.1–42.4) had viral load less than 1000 copies/ml. Applying 2013 WHO recommendations for ART initiation increased the proportion of ART-eligible people from 60.0% (based on national guidelines in place during the survey; 95% CI 57.3–62.7) to 82.0% (95% CI 79.5–84.5). Among HIV-positive people not receiving ART, viral load increased with decreasing CD4+ cell count (500–749 vs. ≥750 cells/μl, adjusted mean difference, 0.40 log10 copies/ml, 95% CI 0.20–0.60,
This study demonstrates how population-level data can help optimize HIV programs. Based on these results, new regional programs are prioritizing diagnosis and expanding ART eligibility, key steps to reach undetectable viral load.
In 2012, more than 10 million people living with HIV in sub-Saharan Africa were receiving antiretroviral therapy (ART) [
To help plug the data gap, WHO recently published a framework of metrics for evaluating ‘treatment as prevention’ programs [
Despite their complexity, such population surveys are increasingly feasible because HIV incidence can be estimated directly using serologic assays that distinguish recent from established HIV infections [
Equally important, population surveys can directly measure ART eligibility in a population. To monitor the quality of ART coverage and to prepare for implementing new ART guidelines, it is essential to assess the numbers of people needing ART. While many studies have quantified patient losses at key steps along the cascade [
Ndhiwa is a subcounty within the County of Homa-Bay in Kenya and has a population of 172 000 inhabitants. It is located in the Nyanza region, the area of Kenya most affected by HIV, with an estimated prevalence of 15.1% in 2011 [
The Ndhiwa HIV Impact in Population Study was a representative population-based survey conducted from September to November 2012 in Ndhiwa, Kenya. It used a two-stage sampling design to randomly select 3300 households. In the first stage, 165 clusters were selected from a list of Ndhiwa's 402 enumeration areas (administrative units defined by the Kenyan National Bureau of Statistics for the purpose of census-taking) obtained from the 2002 national census. Each cluster was one enumeration area. At the second stage, 20 households were randomly selected from each cluster. All residents aged 15–59 years were considered eligible and, after being informed about the study as described below, invited to participate.
Ethical approval was obtained in Kenya from the Kenya Medical Research Institute Ethical Review Committee (KEMRI, ref 347) and in France, from the ‘Comité de Protection des Personnes d’Ile de France’ (CPP, ref 12056). Written consent for participating in the study and undergoing HIV testing was obtained from each participant prior to the survey interview.
Community mobilization was done prior to the survey in two steps. First, the study team met with all local leaders; then they visited each selected enumeration unit to directly mobilize the community, which involved distributing information leaflets about the survey and each person's right to refuse to participate. Community members were told that the survey was about HIV and that they would be tested for HIV if they agreed to participate.
The questionnaire was based on the MACRO questionnaire framework used for the Demographic and Health Survey, a design meant to ensure maximal comparability of results with Demographic and Health Survey findings [
Questionnaires collected socioeconomic, behavioral, and medical information about each participant. Men self-reported their circumcision status using graphics tools, whereas women reported their history of births, antenatal care and, if HIV-positive, PMTCT care. Participants were also asked about previous HIV testing and the result of their most recent test.
The first four stages were all self-reported by participants. Stage 1, HIV awareness, was defined as a history of at least one positive HIV test prior to the survey. Linkage to care (stage 2) was defined as at least one medical contact for HIV care after a positive test, whereas retention in care (stage 3) was defined as an HIV-related medical consultation within the prior 6 months. ART use (stage 4) was also self-reported. The last stage, viral load suppression, was defined as a viral load below 1000 copies/ml as measured from the sample collected during the survey visit and tested as described below. ART eligibility was assessed according to the Kenyan 2010 ART guidelines [
Participants were tested for HIV at home using a serial rapid testing algorithm according to Kenyan national guidelines, using Determine Rapid HIV1/2 Antibody (Abbott Laboratories, Abbott Park, Illinois, USA) followed by Unigold Rapid HIV Test (Trinity Biotech, PLC, Bray, Co Wicklow, Ireland). Participants with discordant or equivocal results were tested by ELISA to confirm their status.
For all participants who tested positive, a venous blood sample was collected at home for CD4+ cell count, performed using the PIMA CD4+ cell counter (Alere, PIMA, Jena, Germany), and for both viral load (COBAS Amplirep/Cobas Taqman platform; Roche Diagnostic System, Branchburg, New Jersey, USA) and recent infection using the Limiting Antigen Avidity (LAg) EIA test (Sedia Biosciences Corp., Portland, Oregon, USA). LAg is a serological assay that detects increasing avidity antibody maturation following seroconversion and can detect recent HIV-1 infections (those for which seroconversion occurred during the past 130 days; 95% CI 118–142) [
To identify infections prior to seroconversion (i.e., acute infection), samples from all individuals testing negative for HIV by serological tests underwent NAAT on a COBAS Amplirep/Cobas Taqman platform (Roche Diagnostic System) from a finger prick of whole blood preserved on a dried blood spot. The number of newly acquired infections was obtained by adding the number of NAAT-detected acute infections to LAg-identified recent infections.
Data were entered and checked using Epidata version 3.1 and analyzed using Stata 13 (Stata Corp., College Station, Texas, USA). All data were anonymized. Descriptive analyses were weighted to account for sampling design and are presented here with 95% CIs. We estimated HIV incidence rate per 100 person-years with 95% CIs using the McWalter and Welte formula [
The study was conducted between September and November 2012 and collected information on 3300 households (Fig.
Study flow-chart.
HIV prevalence and incidence results are presented in Table
Of the HIV-positive participants, 11 were NAAT-positive (and rapid diagnostic test negative), that is, had acute infections, while 31 patients were classified as recently infected using the LAg test algorithm. Overall HIV incidence was estimated at 1.90 new cases/100 person-years (95% CI 1.11–2.70). Incidence in women was more than twice that in men (2.47 new cases/100 person-years, 95% CI 1.36–3.58 vs. 1.06 new cases/100 person-years, 95% CI 0.18–1.94) and nearly doubled in people aged 15–29 compared with 45–59 year olds (1.98 new cases/100 person-years [95% CI 1.12–2.85] vs. 1.03 new cases/100 person-years [95% CI 0–2.39]). Among men, HIV incidence among uncircumcised men was over four-fold more in uncircumcised compared with medically circumcised men (1.20 [95% CI 0.08–2.33] vs. 0.24 new cases/100 person-years [95% CI 0.00–1.28]).
The proportions of HIV-positive people retained at each key step in the cascade of care are shown in Fig.
HIV Cascade of care, Ndhiwa, Kenya, 2012.
The proportion of HIV-positive individuals in need of ART based on the guidelines in effect in Kenya at the time of the study (2010 national guidelines: CD4+ cell count less than 350 cells/μl and PMTCT option A), and those eligible under the 2013 WHO guidelines (CD4+ cell count < 500 cells/μl and PMTCT option B+), are shown in Table
Distribution of the population viral load stratified by ART use and awareness of HIV status is shown in electronic supplementary Fig.
Overall mean and median population viral load measurements were 2.87 log10 copies/ml (95% CI 2.75–3.00) and 7272 copies/ml [IQR 0–75200], respectively (Table
This study reports the direct measurement of HIV incidence and key steps along the cascade of care in a rural district in Nyanza province, Kenya. To our knowledge, it is among the first reports from sub-Saharan Africa to directly evaluate incidence and cascade of care, from diagnosis to ART eligibility and viral suppression, in a single population-based study.
Most HIV programs in sub-Saharan Africa are based on relatively limited data, often extrapolated from selected populations and/or sites, or from modeling studies. WHO and other stakeholders have been urgently calling for better evidence to support program planning and assessment of populations and how many people need which services, and how many are receiving them. These data are essential for evaluating the impact of treatment-as-prevention strategies on reducing the rate of new infections, and ultimately curbing the epidemic. Several countries in the region, including Kenya, Uganda, and Swaziland, have begun implementing population studies to measure these indicators [
Our findings clarified some prevailing notions about the HIV epidemic in the region and brought a far more detailed picture of the cascade, while also offering several surprises.
HIV incidence in the adult population of the Ndhiwa subcounty, which we estimated at 1.9 new cases per 100 person-years, was four times higher than the national estimate derived from the 2012 Kenya AIDS Indicator survey, highlighting (among other factors) the heterogeneous distribution of the HIV epidemic in Kenya [
One key finding was that 60.3% of the HIV-positive population, representing 13.8% of the overall adult Ndhiwa population, had a viral load above 1000 copies/ml. Only the Swaziland HIV measurement survey used similar methodology, and it found similar results [
By studying risk factors associated with viral load among people not receiving ART, this study also provides new information to help identify individuals most at risk of transmitting HIV. One such group is people with CD4+ cell count levels in the 500–749 CD4+ cells/μl range, who are not eligible for ART under either Kenyan (2010) or WHO (2013) guidelines but who we found to have higher viral load levels proportional to their decreased CD4+ cell count. Although this relationship between CD4+ cell count levels and viral load is well characterized in Western settings [
Our data on the cascade of care found that patients were lost mostly at two points: HIV testing and ART initiation. First, 40% of all HIV-positive individuals were unaware of their status, a similar figure to those from the most recent Kenya AIDS Indicator survey and from Swaziland [
Our estimate that 60% of the total HIV-positive population was in need of ART is higher than that derived from the mathematical model (42%) used in program planning by Kenya's Ministry of Health, in Homa-Bay, the county where Ndhiwa is situated [
This study presents some limitations. Because of the cross-sectional observational design, no causal inference can be made between HIV incidence and population viral load. Furthermore, other than the laboratory data, the information we collected was self-reported by participants, which can lead to recall bias and misclassifications. This was seen, for example, during the clinical trial HPTN 052, where approximately 3% of the participants who did not self-report using ART nevertheless had detectable blood levels of ART [
Based on the unexpectedly high incidence and prevalence rates found in this survey, Kenya's MoH, together with Médecins Sans Frontières, launched several new initiatives in Ndhiwa in early 2014 to strengthen the two weakest points in the cascade of care – that is, improving HIV diagnosis and expanding ART eligibility by implementing the 2013 WHO guidelines. The survey will be repeated four years after the initial one presented here, to assess whether these initiatives have led to improved programmatic outcomes and to decreasing HIV incidence. Similarly, population-based studies that measure these same indicators in other high prevalence settings should provide useful information for identifying the weakest points in the cascade of care and prioritizing programs to address them, thereby increasing impact on patient outcomes and on realizing the promise of treatment as prevention strategies.
The authors would like to thank the participants and their family for their participation and collaboration. We are also grateful to the Ndhiwa community for their support and to the field team of Epicentre for their commitment to conduct this study in difficult conditions, with a special mention for Isaac Nabaasa; and to the Epicentre headquarter team (Jihane BenFarhat, Serge Balandine, Stephane Crisan) for their continuous support. We are grateful to the team of the biostatistics department of the University of Lyon (René Ecochard and Stephanie Blaizot) for the statistical support and to KEMRI/CDC team who performed the laboratory analysis. We also thank Patricia Kahn, Medical Editor of Doctors Without Borders/Médecins Sans Frontière, New York, for her editorial work.
D.M. designed the study. D.M., C.Z., B.R., and J.F.E. wrote the study protocol. D.M., S.M., and B.R. participated to the data collection and cleaning. C.Z. and V.O. performed the laboratory analysis. D.M. and B.R. performed the statistical analysis. D.M. and J.F.E. drafted the article. All authors reviewed, revised and approved the final paper.
This study was funded by Médecins Sans Frontières, France.
The authors declare they have no conflict of interest with respect to this article.
HIV incidence and prevalence, Ndhiwa, Kenya, 2012.
| Total tested | Number of HIV-infected patients | Weighted HIV prevalence (95% CI) | HIV incidence rate (new cases per 100 PY(95% CI) | |
| Sex | ||||
| Male | 2321 | 457 | 19.8 (18.2–21.6) | 1.06 (0.18–1.94) |
| Female | 3755 | 1000 | 26.7 (25.3–28.3) | 2.47 (1.36–3.58) |
| Age (years) | ||||
| 15–29 | 3154 | 533 | 16.7 (15.4–18.1) | 1.98 (1.12–2.85) |
| 30–44 | 1786 | 614 | 34.7 (32.4–30.8) | 1.51(0.06–2.96) |
| 45–59 | 1136 | 310 | 27.9 (25.3–30.8) | 1.03 (0.00–2.39) |
| Marital status (missing: 36) | ||||
| Never married | 1291 | 49 | 4.0 (3.0–5.3) | 1.62 (0.44–2.80) |
| Married/living together | 4133 | 1095 | 26.4 (25.1–27.8) | 2.30 (1.26–3.33) |
| Divorced/separated | 105 | 28 | 28.6 (20.3–38.6) | NA |
| Widowed | 511 | 279 | 55.6 (51.0–60.0) | NA |
| Education (missing: 4) | ||||
| Primary or less | 5046 | 1283 | 25.6 (24.4–26.9) | 1.91 (1.04–2.79) |
| Secondary or higher | 1026 | 174 | 16.8 (14.6–19.4) | 1.86 (0.28–3.45) |
| History of HIV testing (missing: 19) | ||||
| Never tested | 1224 | 191 | 26.2 (24.9–27.5) | 1.03 (0.00–2.15) |
| Ever tested | 4833 | 1266 | 16.3 (14.2–18.7) | 2.16 (1.22–3.11) |
| Residence Ndhiwa (missing: 3) | ||||
| <10 years | 1422 | 333 | 23.3 (21.1–25.7) | 3.79 (1.80–5.79) |
| ≥10 years | 4651 | 1089 | 24.3 (23.1–25.6) | 1.27 (0.52–2.02) |
| Mobility (nights outside/month) (missing: 19) | ||||
| 0 | 2009 | 367 | 18.5 (16.8–20.3) | 2.15 (0.93–3.38) |
| 1–5 | 3177 | 840 | 26.8 (25.2–28.5) | 1.72 (0.68–2.75) |
| 6+ | 871 | 245 | 24.1 (23.0–25.2) | 1.56 (0.00–3.38) |
| Pregnant or breastfeeding | ||||
| Yes | 1411 | 312 | 21.7 (19.6–24.1) | 2.70 (1.00–4.40) |
| No | 2344 | 688 | 29.8 (27.8–31.7) | 2.34 (0.97–3.71) |
| Medical circumcision | ||||
| Yes | 563 | 84 | 14.9 (12.1–18.3) | 0.24 (0.00–1.28) |
| No | 1743 | 372 | 21.5 (19.5–23.6) | 1.20 (0.08–2.33) |
| Total | 6076 | 1457 | 24.1 (23.0–25. 2) | 1.90 (1.11–2.70) |
CI, confidence interval; PY, person-years.
aOnly women.
bOnly men.
Art eligibility and coverage, Ndhiwa, Kenya, 2012.
| Kenya 2010 guidelines | WHO 2013 guidelines | |
| ART eligibility (% +95% CI) | ||
| Women | 57.8 (54.4–61.0) | 83.0 (80.2–85.4) |
| Men | 65.0 (60.1–69.6) | 79.0 (74.9–82.7) |
| Total | 60.0 (53.3–62.7) | 81.7 (74.5–83.8) |
| ART coverage (% +95% CI) | ||
| Women | 70.3 (66.2–74.2) | 49.0 (45.4–52.6) |
| Men | 66.6 (60.7–72.1) | 54.8 (49.3–60.3) |
| Total | 69.1 (65.8–72.2) | 50.7 (47.8–50.7) |
ART, antiretroviral treatment; CI, confidence interval.
Population viral load and associated risk factors among HIV-positive individuals not on art in Ndhiwa, Kenya, weighted multivariate linear model.
| No HIV-positive | Median VL (copies/ml) [+IQR] | Mean log (VL) (copies/ml) (+95% CI) | Unadjusted difference in mean viral load in log10 (copies/ml) (+95% CI) | Adjusted difference in mean viral load in log10 (copies/ml) (+95% CI) | |||
| Sex | |||||||
| Female | 547 | 36 788 [6446–109 000] | 4.38 (4.30–4.46) | Ref | Ref | ||
| Male | 240 | 86 165 [24 612–202 856] | 4.76 (4.64–4.88) | 0.37 (0.22–0.52) | <0.01 | 0.27 (0.12–0.42) | <0.01 |
| Age (years) | |||||||
| 15–29 | 369 | 39 852 [7220–109 000] | 4.41 (4.31–4.51) | Ref | Ref | ||
| 30–44 | 305 | 49 400 [13 852–167 662] | 4.58 (4.47–4.68) | 0.18 (0.03–0.33) | 0.02 | 0.05 (−0.09–0.20) | 0.46 |
| 45–59 | 113 | 61 152 [9962–173 586] | 4.58 (4.38–4.77) | 0.12 (−0.11–0.37) | 0.29 | −0.03 (−0.27–0.19) | 0.74 |
| CD4+ cell count (cells/μl) | |||||||
| ≥750 | 136 | 11 377 [2029–55 631] | 3.95 (3.79–4.11) | Ref | Ref | ||
| 500–749 | 232 | 33 026 [6589–101 993] | 4.37 (4.26–4.48) | 0.43 (0.23–0.64) | <0.01 | 0.40 (0.20–0.60) | <0.01 |
| 350–499 | 172 | 52 509 [17 001–134 006] | 4.57 (4.45–4.70) | 0.60 (0.38–0.81) | <0.01 | 0.55 (0.34–0.76) | <0.01 |
| 200–349 | 129 | 78 248 [29 978–188 678] | 4.72 (4.56–4.89) | 0.72 (0.49–0.96) | <0.01 | 0.68 (0.44–0.90) | <0.01 |
| 0/199 | 105 | 149 356 [52 138–339 712] | 5.01 (4.86–5.18) | 0.99 (0.73–1.25) | <0.01 | 0.91 (0.65–1.18) | <0.01 |
| HIV status awareness | |||||||
| Not aware | 524 | 51 154 [9508–151 106] | 4.52 (4.44–4.60) | Ref | |||
| Aware | 263 | 40 572 [9 576–114 684] | 4.45 (4.34–4.56) | −0.07 (−0.22–0.07) | 0.32 | ||
| Marital status (missing: 6) | |||||||
| Never married | 31 | 56 220 [16 028–239 374] | 4.70 (4.37–5.04) | Ref | |||
| Married/living together | 617 | 46 838 [10 388–135 942]– | 4.51 (4.43–4.58) | −0.16 (−0.45–0.13) | 0.29 | ||
| Divorced/Separated | 13 | 46 196 [4574–105 816] | 4.26 (3.74–4.77) | −0.46 (−1.04–0.11) | 0.12 | ||
| Widowed | 120 | 52 574 [6625–136 161] | 4.43 (4.25–4.61) | −0.28 (−0.63–0.07) | 0.11 | ||
| Education | |||||||
| Primary or less | 715 | 49 400 [10 580–144 708] | 4.51 (4.45–4.59) | Ref | |||
| Secondary or less | 72 | 31 337 [4171–94 153] | 4.31 (4.06–4.55 | −0.20 (−0.47–0.07) | 0.15 | ||
| Total | 787 | 47 312 [9576–140 066] | 4.50 (4.43–5.56] | ||||
CI, confidence internal; VL, viral load.