Viral load detection and management on first line ART in rural Rwanda

Despite significant efforts made in the prevention and the fight against HIV, the number of annual new HIV infections remains high [1]. The sub-Saharan Africa region carries the highest burden of the disease, with nearly 70% of all people living with HIV (PLHIV), and 76% of all HIV related deaths coming from this region [2]. In 2015, UNAIDS launched the ambitious 90–90-90 targets: by 2020, 90% of all PLHIV should know their serological status, 90% of all diagnosed PLHIV should receive antiretroviral treatment (ART), and 90% of all PLHIV on ART should have a suppressed viral load (VL) [3]. This corresponds with 73% of all PLHIV having a suppressed VL. By achieving these targets, HIV transmission and HIV related mortality should decrease drastically.

To monitor progress towards achieving these targets, routine VL monitoring is indispensable. However, due to logistical and financial constraints, most sub-Saharan ART programs are unable to provide a regular access to VL testing for most of their patients on ART. A review showed important disparities between seven sub-Saharan Africa countries and revealed a number of countries without adequate capacities to perform VL test to all their patients on ART. The percentage of patients on ART with at least one VL test done ranged from 9% in Tanzania to 91% in South Africa [4].

In the last 20 years, Rwanda has made tremendous progress in the fight against HIV, with a massive increase of HIV counseling and testing services and the decentralization of ART provision [5]. Today, in Rwanda, the first and the second UNAIDS targets are close to be reached: in 2016, an estimated 87% of 220,000 PLHIV knew their status and 80% of PLHIV were on ART [6]. However, achieving and monitoring the third UNAIDS target may be more challenging.

Since 2011, the Rwandan national guideline recommends routine annually VL testing in all patients on ART. However, its implementation has been challenged by the insufficient number of VL testing platforms, especially in the rural areas. In the last three years, the number of VL testing platforms has increased progressively. In addition, health care providers were trained on indications and the importance of having a routine VL [7]. Two studies conducted in Rwanda showed a high variability: virological suppression ranged between 82.1% virological suppression in adult patients on ART for the first study, [8] and 52.2% virological suppression in pregnant women on ART for the second study [9]. Furthermore, the management of patients with detectable VL was not studied.

In most resource-poor countries, VL testing is not decentralized. Hence, samples need to be transported to a central laboratory, which reduces accessibility to the VL testing [10]. We therefore studied the use of routine VL testing in patients on ART in the rural area of Rwanda, after installing a VL testing platform in the District of Musanze. We identified predictors of virological failure and described the management of patients with a detectable VL.

A total of 775 patients enrolled on ART between July 2012 and June 2015 were included in the study. Most (67%) were female. The median age of patients enrolled on ART was 34 years (IQR: 27–41) (Table 1). Most (61.2%) patients were farmers. Of all patients, 48.1 and 51.9% started ART in the hospital and in the health center, respectively.

Of 775 patients, about half were asymptomatic when they started ART (51.7%). The median CD4 count at ART initiation was 364 cells /mm³ (IQR: 265–531). At ART initiation, the vast majority of patients (88%) were prescribed TDF + 3TC + EFV combined regimen.

At the end of the study period, 70.6% (n = 547) were active on ART; 21.4% (n = 166) were transferred out to another health facility, 2.7% (n = 21) died and 5.3% (n = 41) were lost to follow up. Retention on ART was 95.8% after one year on ART, 93.4 and 92% respectively after two and three years on ART. The median follow-up time for our cohort was 29 months (IQR: 21–41) on ART.

The uptake of VL among patients on ART has been gradually increasing since 2013. (Fig. 1) The proportion of patients active on ART that had a yearly VL increased from 25.6% (39/152) to 62.5% (195/312) between 2013 and 2014 (p < 0.001), from 62.5% (195/312) to 70.2% (347/494) between 2014 and 2015 (p < 0.001), and from 70.2% (347/494) to 93.2% (510/547) between 2015 and 2016 (p < 0.0001). Yearly VL uptake increased significantly during the four consecutive years, between 2013 and 2016.

Out of 510 patients with a VL result in 2016, 88.5% (n = 451) had a suppressed VL (< 1000 copies/ml) and 11.5% (n = 59) had a detectable VL (≥ 1000 copies/ml) (Fig. 2). Predictors of having a detectable VL included being male (aOR 2.1; 95%CI 1.12–4.02; p = 0.02), being a sex worker (aOR 6.4; 95%CI 1.1–36.0; p = 0.04), having a WHO clinical stage IV when starting ART (aOR 8.8; 95%CI 1.8–43.0; p < 0.001), having had a detectable VL before 2016 (aOR 7.2; 95%CI 3.5–14.5; p < 0.001), and having had no VL before 2016 (aOR 3.1; 95%CI 1.2–8.1; p = 0.02) (Table 2).

Considering all 775 patients enrolled on ART, 90% (n = 698) had an initial VL (first VL between July 2012 and June 2015), of which 146 (20.9%) patients had a high initial VL (≥ 1000 copies/ml). Out of 146 patients with a detectable VL, 29 exited the program without having a follow-up VL: 18 were transferred out, five died, and six were lost to follow-up. Among the 117 that were active 6 months after their high initial VL, 88.0% (n = 103) had a follow-up VL, of whom 60.2% (n = 62) had a VL below 1000 copies/ml (Fig. 3). Overall, the median time between the high initial VL and the follow-up VL was 12.5 months (IQR: 8.7–19.0). Among 41 patients with a follow-up VL higher than 1000 copies/ml, 26 (63.4%) started second-line ART (Fig. 3). The median time between the date of the follow-up VL and the date for second-line ART initiation was 17 days (IQR: 8–42).

This study from a rural district in Rwanda shows a high uptake of routine VL testing: 93.2% of eligible patient had a VL in 2016. Virological suppression was close to the 90% global UNAIDS target. Identified predictors of having a detectable VL were male gender, being a sex worker, having a WHO clinical stage IV when starting ART, having had a detectable VL before 2016, and having had no VL before 2016. The vast majority (88.5%) of patients with a high initial VL had a follow-up VL done. The median time between the initial and follow-up VL was 12.5 months. After a high initial VL, most (60.2%) patients had a suppressed follow-up VL. Most of patients (63.4%) with virologic failure (with a high follow-up VL) were initiated on second line ART.

The uptake of VL in rural area of Rwanda was remarkably high when compared to other sub-Saharan Africa studies [4]. Studies from Mozambique and Swaziland reported respectively 40 and 73% VL uptake [14, 15]. In countries where uptake was low, reported barriers included non-compliance with the WHO guideline regarding routine VL testing, lack of awareness among clinicians and patients on the benefits of VL testing, logistical constraints associated with sample transport, the long turnaround time between sampling and having a result available in the patient file, lack of funding for the implementation of routine VL testing, and the high cost of consumables required for VL testing [4, 10]. The high uptake of routine VL testing in our rural area of study, can be explained by a combination of factors, including increased accessibility after decentralization of the VL testing platform, training and sensitization of medical staff involved in HIV care, and gratuity of VL testing.

Virological suppression in patients on ART (88.5%) was lower than what was reported in patients on ART in Botswana (95.6%) and Malawi (90.8%) but higher than in most other settings [4, 14, 16, 17]. A close follow-up of groups at risk of having a detectable VL (males, sex workers, patients with WHO stage IV at ART initiation, and patients with previous detectable VL) would likely increase the number of patients on ART with virological suppression and contribute to achieve the third 90% UNAIDS target.

In patients with detectable VL, the vast majority (88%) had a follow-up VL done. The median time between a detectable VL and a follow-up VL was 12.5 months (IQR: 8.7–19.0). This period was twice as long as the period recommended by the national HIV guideline. Moreover, this contrasts with what was reported in South Africa, where a follow-up VL result was available after a median time of 4.9 months (IQR:2.8–6.1) [18]. Sessions of adherence counseling conducted on an extended period and the high volume of patients followed in HIV clinics may explain the long time observed between initial and follow up viral load. This resulted in a delay to switch some patients in need to the second-line ART. Considering that a delay to switch to the second-line ART is associated with a high risk of second-line virologic failure and an increased risk of death, [19, 20], patients failing the first line regimen would much benefit from measures to speed-up the switch to second-line ART.

Among patients with a high initial VL, 60.2% suppressed the follow-up VL after adherence counseling and did not require any modification of their first-line ART regimen. Likely, enhanced adherence counselling helped patients to improve their adherence to treatment. This finding illustrates the benefit of a routine VL monitoring, as it allows to identify patients in need of a close follow up, and to monitor their adherence. Indeed, previous studies have shown that targeted adherence support can help patients to re-suppress their detectable VL and keep taking the first-line ART regimen [21, 22].

In our study, almost two-third of our patients (63.4%) failing the first line ART were switched to the second-line ART before the end of the study period. This is quite similar to what was reported by a systematic review from 16 sub-Sahara African countries, which showed that 58% of patients with confirmed virologic failure switched to second-line ART [23]. Reported reasons for this low rate of switching to second-line ART include the desire of health care providers to optimize adherence counseling before second-line ART initiation, and deferrals of second line ART switch when patients miss scheduled appointments. [19, 20, 23] On the other hand, in our study, the decision to start second-line ART was generally taken quickly, within one month period following a confirmation of virologic failure.

The strengths of our study include that findings represent the real-life setting of an HIV program in rural Rwanda, as data were retrieved from routinely-collected patient-level program data. Moreover, we believe the findings are based on robust data. Data were retrieved from a prospectively updated electronic database, used for program monitoring. For the aim of this study, data were cleaned by comparing them with data from the individual patient files. No or very few values were lacking for most variables. Moreover, the vast majority of patients had effectively a VL done, which allowed us to evaluate the third UNAIDS target. However, there are some limitations as well. The two study sites, Ruhengeri hospital and Musanze health center are two neighboring health facilities, both located in the rural District of Musanze in the Northern Province of Rwanda. As there were no geographical barriers between the health facility where clinical care of patients was conducted and the site where VL testing was performed, the findings may not be generalizable to patients attending remote health facilities. Nevertheless, the findings show that when geographical barriers are minimized, routine VL monitoring is feasible to monitor the implementation of the ambitious UNAIDS 90–90-90 targets. Another limitation of the presented study is that adherence in terms of daily pill intake was not assessed. Moreover, the outcome of patients lost to follow-up was not known. As patients lost to follow up count generally among patients with low level of adherence on ART, they are more likely to have unsuppressed VL. It was also not possible to know the outcome of viral load testing for patients transferred out all along our study period.

The uptake of routine VL monitoring was very high after decentralization of a VL testing platform in a rural area of Rwanda. The vast majority (88.5%) of patients tested had a suppressed VL. Among patients with detectable VL (≥1000 copies/ml), the majority of them re-suppressed after sessions of adherence counseling. Still, a close clinical follow-up of patients at risk of a detectable VL, such as patients with a previous detectable VL, patients who had a low CD4 count or advanced stage of disease when they started ART, female sex workers, may result in an earlier identification of virological failure. To shorten the time between a detectable and a follow-up VL, it is recommended an individualized patient monitoring and enhanced adherence counselling for patients with detectable VL. This may contribute to achieving and sustaining the third 90 UNAIDS target, aiming at having more than 90% of patients on ART with undetectable viral load.