Study shows prognostic value of viral load monitoring among people living with subtype C HIV in South Africa

Viral load is the single most important predictor of CD4 cell loss among people in South Africa who had not started HIV treatment, investigators report in PLOS ONE. All the study participants were living with HIV subtype C. The annual decline in CD4 count was approximately 11% for people with a baseline viral load below 10,000 copies/ml, compared to a 14% loss for people with a baseline viral load above 100,000 copies/ml.

The study also found that 22% of people had baseline viral load above 100,000 copies/ml and were thus at high risk of transmitting HIV, yet were not eligible for HIV treatment. The study suggests that a substantial minority of people diagnosed with high CD4 cell counts might spend a long period not taking treatment, despite very high viral load, if national treatment guidelines do not recommend treatment at a CD4 cell count below 500 cells/mm3, or treatment for anyone in a serodiscordant relationship.

The investigators suggest their findings have implications for patient care and HIV prevention. “Our data clearly shows the important prognostic role of a viral load estimate at entry into care.” They also believe their findings support “calls for consideration for the inclusion of viral load estimates at HIV diagnosis to identify those likely to be efficient transmitters of HIV.”



In HIV, different strains which can be grouped according to their genes. HIV-1 is classified into three ‘groups,’ M, N, and O. Most HIV-1 is in group M which is further divided into subtypes, A, B, C and D etc. Subtype B is most common in Europe and North America, whilst A, C and D are most important worldwide.

haemoglobin (HB)

Red-coloured, oxygen-carrying chemical in red blood cells.


A serodiscordant couple is one in which one partner has HIV and the other has not. Many people dislike this word as it implies disagreement or conflict. Alternative terms include mixed status, magnetic or serodifferent.

long-term non-progressor

An HIV-infected person who remains free of AIDS symptoms (such as immune system decline or opportunistic diseases) for an unusually long period of time in the absence of treatment. These individuals typically have strong CD8+ T-cell responses, minimal lymph node damage and a relatively low viral load. About 10% of HIV-positive people seem to be long-term non-progressors. Most, but not all, are elite (or HIV) controllers. 

It is well known that a higher viral load is associated with accelerated CD4 cell loss. However, less is known about viral load and CD4 cell dynamics among people in resource-limited settings, where different HIV subtypes may be an important factor.

Researchers therefore designed a study monitoring CD4 count changes and their relationship to baseline viral load among people living with HIV subtype C in South Africa.

CD4 count and viral load were monitored at baseline and then at regular intervals over an average of four years, with recruitment beginning in 2003. The 1106 participants enrolled in the study all had CD4 cell counts above 200 cells/mm3 at the start of the study, had not taken HIV treatment before and had positive tuberculin skin test results (the cohort was originally recruited to investigate preventive tuberculosis therapy).

Most of the participants (83%) were women and the median age at baseline was 28 years. Median CD4 count on entry to the study was 490 cells/mm3 and median baseline viral load was 16,050 copies/ml. The median period of follow-up was 44 months.

Overall, CD4 count fell by 38.4 cells/mm3 per year (less than is typical for subtype B). Adjusting for gender, age, baseline haemoglobin, smoking and alcohol use had little impact on this finding.

Baseline viral load was the factor with the biggest impact on CD4 cell decline. Overall, CD4 count declined by 13% per annum. The average percentage loss was 11% for people with a baseline viral load below 10,000 copies/ml, compared to a loss of 14% per annum for people with a baseline viral load above 100,000 copies/ml. In addition, men had a significantly lower CD4 cell decline than women.

Approximately 3% of the participants maintained a CD4 count above 500 cells/mm3 throughout follow-up. The median baseline viral load of these long-term non-progressors was 3410 copies/ml. This compared to a viral load of 12,300 copies/ml for people who experienced a fall in their CD4 count below 500 cells/mm3. A viral load below 400 copies/ml was maintained by 3% of people throughout follow-up.

“Our finding of an average decline of 3.2 cells/mm3 per month or 38.4 cells/mm3 per year is lower than that reported for men who have sex with men infected with subtype B HIV,” write the investigators. “Recent sero-converters, infected with HIV subtypes A or D from Uganda appeared to have a more rapid CD4 decline than we report, and subtype D infected individuals declined more rapidly than subtype D.”

The authors suggest that differences in CD4 decline “reflect subtype differences, differences between recent sero-converters and chronically infected individuals, or innate host susceptibility to HIV infection.”


Martinson NA et al. CD4 and viral load dynamics in antiretroviral-naïve HIV-infected adults from Soweto, South Africa: A prospective cohort. PLOS ONE 9(5): e96369. DOI: 10/1371/journal.pone.0096369, 2014.