Background 
In people living with HIV (PLHIV) who are on anti-retroviral therapy (ART), it is essential to identify persons with high blood viral loads (VLs) (≥1000 copies/ml), provide enhanced adherence counselling (EAC) for 3 months and assess for VL suppression (<1000 copies/ml).


Objective 
Our study objectives were to determine the proportion who had a high viral load in those people who underwent viral load testing between 1 August 2016–31 July 2017 at Wilkins Hospital, Harare, Zimbabwe. Of those with high viral load to assess; a) the proportion who enrolled for EAC, the demographic and clinical characteristics associated with enrolment for EAC and, b) the proportion who achieved viral load suppression and demographic, clinical characteristics associated with viral load suppression.


Design 
Retrospective cohort study using routinely collected programme data. Data was collected from PLHIV who were on ART and had a high viral load from 1 August 2016 to 31 July 2017.


Results 
Of 5,573 PLHIV on ART between 1 August 2016 and 31 July 2017, 4787 (85.9%) had undergone VL testing and 646 (13.5%) had high VLs. Of these 646, only 489 (75.7%) were enrolled for EAC, of whom 444 (69%) underwent a repeat VL test at ≥ 3 months with 201 (31.2%) achieving VL suppression. The clinical characteristics that were independently associated with higher probability of VL suppression were: a) undergoing 3 sessions of EAC; b) being on 2nd line ART. Initial VL levels >5,000 copies/ml were associated with lower probability of viral suppression.


Conclusion 
The routine VL testing levels were high, but there were major programmatic gaps in enrolling PLHIV with high VLs into EAC and achieving VL suppression. The full potential of EAC on achieving viral load suppression has not been achieved in this setting. The reasons for these gaps need to be assessed in future research studies and addressed by suitable changes in policies/practices.

/pdf/enhanced-adherence-counselling-and-viral-load-suppression-in-46jjz9to60.pdf

Enhanced adherence counselling and viral load suppression in HIV seropositive patients with an initial high viral load in Harare, Zimbabwe: Operational issues.

Background 
Increased second-line antiretroviral therapy (ART) failure rate narrows future options for HIV/AIDS treatment. It has critical implications in resource-limited settings; including sub-Saharan Africa (SSA) where the burden of HIV-infection is immense. Hence, pooled estimate for second-line HIV treatment failure is relevant to suggest valid recommendations that optimize ART outcomes in SSA.


Methods 
We retrieved literature systematically from PUBMED/MEDLINE, EMBASE, CINAHL, Google Scholar, and AJOL. The retrieved studies were screened and assessed for eligibility. We also assessed the eligible studies for their methodological quality using the Joanna Briggs Institute’s appraisal checklist. The pooled estimates for second-line HIV treatment failure and its associated factors were determined using STATA, version 15.0 and MEDCALC, version 18.11.3, respectively. We assessed publication bias using Comprehensive Meta-analysis software, version 3. Detailed study protocol for this review/meta-analysis is registered and found on PROSPERO (ID: CRD42018118959).


Results 
A total of 33 studies with the overall 18,550 participants and 19,988.45 person-years (PYs) of follow-up were included in the review. The pooled second-line HIV treatment failure rate was 15.0 per 100 PYs (95% CI: 13.0–18.0). It was slightly higher at 12–18 months of follow-up (19.0/100 PYs; 95% CI: 15.0–22.0), in children (19.0/100 PYs; 95% CI: 14.0–23.0) and in southern SSA (18.0/100 PYs; 95% CI: 14.0–23.0). Baseline values (high viral load (OR: 5.67; 95% CI: 13.40–9.45); advanced clinical stage (OR: 3.27; 95% CI: 2.07–5.19); and low CD4 counts (OR: 2.80; 95% CI: 1.83–4.29)) and suboptimal adherence to therapy (OR: 1.92; 95% CI: 1.28–2.86) were the factors associated with increased failure rates.


Conclusion 
Second-line HIV treatment failure has become highly prevalent in SSA with alarming rates during the 12–18 month period of treatment start; in children; and southern SSA. Therefore, the second-line HIV treatment approach in SSA should critically consider excellent adherence to therapy, aggressive viral load suppression, and rapid immune recovery.

/pdf/second-line-hiv-treatment-failure-in-sub-saharan-africa-a-3b136y6pwx.pdf

Second-line HIV treatment failure in sub-Saharan Africa: A systematic review and meta-analysis.

Background In sub-Saharan Africa, 25.5 million people are living with human immunodeficiency virus (HIV), representing 70% of the global total. The need for second-line antiretroviral therapy (ART) is projected to increase in the next decade in keeping with the expansion of treatment provision. Outcome data are required to inform policy. Methods We performed a systematic review and meta-analysis of studies reporting the virological outcomes of protease inhibitor (PI)-based second-line ART in sub-Saharan Africa. The primary outcome was virological suppression (HIV-1 RNA <400 copies/mL) after 48 and 96 weeks of treatment. The secondary outcome was the proportion of patients with PI resistance. Pooled aggregate data were analyzed using a DerSimonian-Laird random effects model. Results By intention-to-treat analysis, virological suppression occurred in 69.3% (95% confidence interval [CI], 58.2%-79.3%) of patients at week 48 (4558 participants, 14 studies), and in 61.5% (95% CI, 47.2%-74.9%) at week 96 (2145 participants, 8 studies). Preexisting resistance to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) increased the likelihood of virological suppression. Major protease resistance mutations occurred in a median of 17% (interquartile range, 0-25%) of the virological failure population and increased with duration of second-line ART. Conclusions One-third of patients receiving PI-based second-line ART with continued NRTI use in sub-Saharan Africa did not achieve virological suppression, although among viremic patients, protease resistance was infrequent. Significant challenges remain in implementation of viral load monitoring. Optimizing definitions and strategies for management of second-line ART failure is a research priority. Prospero Registration CRD42016048985.

/pdf/effectiveness-of-protease-inhibitor-nucleos-t-ide-reverse-381h0uadxq.pdf

Effectiveness of Protease Inhibitor/Nucleos(t)ide Reverse Transcriptase Inhibitor-Based Second-line Antiretroviral Therapy for the Treatment of Human Immunodeficiency Virus Type 1 Infection in Sub-Saharan Africa: A Systematic Review and Meta-analysis.

Background Dolutegravir is superior to efavirenz for HIV antiretroviral therapy (ART) but may be associated with an increased risk for neural tube defects (NTDs) in newborns if used by women at conception. Objective To project clinical outcomes of ART policies for women of child-bearing potential in South Africa. Design Model of 3 strategies: efavirenz for all women of child-bearing potential (EFV), dolutegravir for all women of child-bearing potential (DTG), or World Health Organization (WHO)-recommended efavirenz without contraception or dolutegravir with contraception (WHO approach). Data sources Published data on NTD risks (efavirenz, 0.05%; dolutegravir, 0.67% [Tsepamo study]), 48-week ART efficacy with initiation (efavirenz, 60% to 91%; dolutegravir, 96%), and age-stratified fertility rates (2 to 139 per 1000 women). Target population 3.1 million South African women with HIV (aged 15 to 49 years) starting or continuing first-line ART, and their children. Time horizon 5 years. Perspective Societal. Intervention EFV, DTG, and WHO approach. Outcome measures Deaths among women and children, sexual and pediatric HIV transmissions, and NTDs. Results of base-case analysis Compared with EFV, DTG averted 13 700 women's deaths (0.44% decrease) and 57 700 sexual HIV transmissions, but increased total pediatric deaths by 4400 because of more NTDs. The WHO approach offered some benefits compared with EFV, averting 4900 women's deaths and 20 500 sexual transmissions while adding 300 pediatric deaths. Overall, combined deaths among women and children were lowest with DTG (358 000 deaths) compared with the WHO approach (362 800 deaths) or EFV (367 300 deaths). Results of sensitivity analysis Women's deaths averted with DTG exceeded pediatric deaths added with EFV unless dolutegravir-associated NTD risk was 1.5% or greater. Limitation Uncertainty in NTD risks and dolutegravir efficacy in resource-limited settings, each examined in sensitivity analyses. Conclusion Although NTD risks may be higher with dolutegravir than efavirenz, dolutegravir will lead to many fewer deaths among women, as well as fewer overall HIV transmissions. These results argue against a uniform policy of avoiding dolutegravir in women of child-bearing potential. Primary funding source National Institutes of Health, National Institute of Allergy and Infectious Diseases and Eunice Kennedy Shriver National Institute of Child Health and Human Development; Massachusetts General Hospital; and Harvard University Center for AIDS Research.

/pdf/risks-and-benefits-of-dolutegravir-and-efavirenz-based-4jnhkx4qpu.pdf

Risks and Benefits of Dolutegravir- and Efavirenz-Based Strategies for South African Women With HIV of Child-Bearing Potential: A Modeling Study.

Background

In sub-Saharan Africa, 25.5 million people are living with HIV, representing 70% of the global total. The need for second-line antiretroviral therapy (ART) is projected to increase in the next decade in keeping with the expansion of treatment provision. Outcome data are required to inform policy.

Methods

We performed a systematic review and meta-analysis of studies reporting the virological outcomes of protease inhibitor (PI)-based second-line ART in sub-Saharan Africa. The primary outcome was virological suppression (HIV-1 RNA <400 copies/ml) after 48 and 96 weeks of treatment. The secondary outcome was the proportion of patients with PI resistance. Pooled aggregate data were analysed using a DerSimonian-Laird random effects model. PROSPERO registration: CRD42016048985.

Results

By intention-to-treat, virological suppression occurred in 69.3% (95% confidence interval 58.2, 79.3) at week 48 (4558 participants, 14 studies), and in 61.5% (47.2, 74.9) at week 96 (2145 participants, 8 studies). Pre-existing resistance to the nucleos(t)ide reverse transcriptase inhibitors (NRTIs) increased the likelihood of virological suppression. Major protease resistance mutations occurred in median 17% (IQR 0-25) of the virological failure population and increased with duration of second-line ART.

Conclusions

One third of patients receiving PI-based second-line ART with continued NRTI use in sub-Saharan Africa did not achieve virological suppression although among viraemic patients protease resistance was infrequent. There remain significant challenges in implementation of viral load monitoring. Optimising definitions and strategies for management of second-line ART failure is a research priority.

/pdf/effectiveness-of-protease-inhibitor-nucleos-t-ide-reverse-o8gpwa87ra.pdf

Effectiveness of protease inhibitor/nucleos(t)ide reverse transcriptase inhibitor-based second-line antiretroviral therapy for the treatment of HIV-1 infection in sub-Saharan Africa: systematic review and meta-analysis.

Objective: In resource-limited settings, where genotypic drug resistance testing is rarely performed and poor adherence is the most common reason for treatment failure, programmatic approaches to handling treatment failure are essential. This study was performed to describe one such approach to adherence optimisation. 

Methods: This was a single-arm study of patients on second-line protease inhibitor (PI)-based antiretroviral therapy (ART) with a HIV-1 RNA ≥400 copies/ml in Johannesburg, South Africa, between 1 March 2012 and 1 December 2013. Patients underwent enhanced adherence counselling. Those with improved adherence and a repeat viral load of >1000 copies/ml underwent HIV-1 drug resistance testing. We describe results using simple proportions and 95% confidence intervals. 

Results: Of the 400 patients who underwent targeted adherence counselling after an elevated viral load on second-line ART, 388 (97%) underwent repeat viral load testing. Most of these (n = 249; 64%, 95% CI 59-69) resuppressed ( 400 copies/ml, 11 switched to third line, 5 were awaiting third line, 4 had died and 13 were lost to follow-up. Among the unsuppressed, 48 successfully underwent resistance testing with some resistance detected in most (41/48). 

Conclusions: Most (64%) second-line treatment failure in this clinic is related to adherence and can be overcome with careful adherence support. Controlled interventions are needed to determine what the optimal approach is to improving second-line outcomes and reducing the need for third-line ART.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/tmi.12741

Intensive adherence counselling for HIV-infected individuals failing second-line antiretroviral therapy in Johannesburg, South Africa.

Poor adherence is a main challenge to successful second-line ART in South Africa. Studies have shown that patients can re-suppress their viral load following intensive adherence counselling. We ide...

Social and behavioral factors associated with failing second-line ART – results from a cohort study at the Themba Lethu Clinic, Johannesburg, South Africa

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Intensive adherence counselling for HIV-infected individuals failing second-line antiretroviral therapy in Johannesburg, South Africa.

Social and behavioral factors associated with failing second-line ART – results from a cohort study at the Themba Lethu Clinic, Johannesburg, South Africa