Rural and urban patterns of HIV drug resistance in South Africa
HIV is more proactively monitored among urban HIV patients than rural patients, and drug resistance and treatment failure is less prevalent. However outcomes for second line treatment remain similar.
HIV drug resistance (HIVDR) is more prevalent among rural patients living with HIV in South Africa compared to a similar cohort of urban patients living with HIV, according to new research. Marked differences in HIV care between the two settings could possibly explain the differences.
Published in HIV Medicine this month, the research found urban patients are significantly more likely to have no drug resistant mutations, while rural patients have higher rates of non-nucleoside reverse transcriptase inhibitor (NNRTI) and nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistant mutations.
The study is the first to look at the differences in HIV treatment outcomes, as they relate to drug resistance, between rural and urban patients in South Africa.
HIV drug resistance is a serious emerging threat to the global scale-up of HIV treatment access – particularly in sub-Saharan Africa where weak health systems and poor access to diagnostics makes managing HIV more challenging. HIVDR has emerged as a result of poor treatment adherence; it limits HIV treatment options, increases treatment programme costs, and increases the level of HIVDR in the body to the extent that it could be transmitted.
The study analysed data on 595 patients who had failed an NNRTI-based first-line antiretroviral treatment regimen, including 492 patients living in a rural setting in KwaZulu-Natal and 103 patients from an urban setting in Pretoria.
Compared to the rural group, the urban group had higher CD4 counts at treatment initiation, more viral load tests performed over the course of the year, and were also more likely to have changed treatment regimens. Urban groups on average spent less than six months failing treatment compared to an average of two years for the majority of the rural group.
HIV drug resistance testing (genotypic testing), showed that 35.9% of the urban group had no drug resistant mutations, compared to only 11.2% of the rural group. A large proportion of the rural group had between two and six mutations relating to NNRTI and NRTI resistance.
In addition, the rural group had a larger amount of thymidine analogue mutations (TAMs), the main mutations relating to stavudine and zidovudine, compared to the urban group (30.9% vs. 14.6% respectively).
Interestingly, genotypic susceptibility scores showed that patients from both groups would respond well to standard second-line treatment regimens using a protease-inhibitor. This is likely because of the ability for a protease inhibitor to suppress viral load, even when the NRTI backbone is not working properly (at least in the short term). Although a limit of the study was that patient follow-up data on actual second-line treatment success was not collected.
The researchers combined the data from the two groups to see if drug mutations were related to the duration of treatment failure. They found drug mutations occurred in a sigmoidal fashion – much like an S-curve.
NRTI mutations occurred most rapidly, with accumulated mutations increasing the same from 0 to 6 months of treatment failure, and 6 to 12 months of failure. There was then a larger increase in mutations from 13 to 24 months, followed by a slower increase after that. NNRTI mutations occurred slightly less rapidly than NRTI mutations, and TAMs occurred mainly after one year of treatment failure.
Few studies have analysed the specific challenges in treatment outcomes for drug resistance between rural and urban settings. However, it is acknowledged that rural HIV treatment programmes have greater challenges in programme delivery, notably around long distances to health centres and a lack of transport options; a lack of facilities to monitor viral load; increased stigma; and challenges relating to human resources. While South Africa has large urban centres, 38% of the population live in rural areas.
The researchers point to the marked differences in HIV care between the two settings as a possible explanation for the differences, although they are clear no direct causal link can be made from the study. Urban patients are more proactively managed – as shown by the amount of viral load tests they received over the course of the year, the frequent drug regimen changes, and the amount of time spent on treatment failure before drug resistance testing referrals.
The authors note: “These findings have important implications for management of patients in large treatment programmes where financial constraints may limit the feasibility of intensive patient monitoring.”
While limited virological monitoring leads to more HIVDR and longer spells of treatment failure, more limited monitoring seems to be enough to avoid treatment-limiting HIVDR, as modelling shows that patients would respond well to second-line treatment regardless.