Lopinavir/ritonavir cost-effective first-line after single-dose nevirapine in South Africa

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First-line lopinivar/ritonavir (LPV/r) is more cost-effective than first-line nevirapine in women previously exposed to single-dose nevirapine (sdNVP), reported Andrea Ciaranello in a study presented at the Fifth IAS Conference on Pathogenesis, Treatment and Prevention in Cape Town this morning.

The Optimal Combination Therapy After Nevirapine Exposure (OCTANE) study, a trial of 745 women at 10 sites in seven African countries, evaluated which of two antiretroviral regimens was more effective in women who had received single-dose nevirapine at the time of childbirth and whether exposure to single-dose nevirapine had an adverse effect on antiretroviral treatment containing nevirapine. Results showed that lopinavir/ritonavir compared to nevirapine-based antiretroviral treatment resulted in improved survival and better virologic outcomes if initiated within two years of nevirapine exposure.

Given the large number of women with HIV exposed to single-dose nevirapine during labour who may subsequently need first-line treatment for their own health, there is a need to clarify whether lopinavir/ritonavir would be cost-effective for use in the South African setting as a standard first-line therapy for women previously exposed to single-dose nevirapine.



Cost-effectiveness analyses compare the financial cost of providing health interventions with their health benefit in order to assess whether interventions provide value for money. As well as the cost of providing medical care now, analyses may take into account savings on future health spending (because a person’s health has improved) and the economic contribution a healthy person could make to society.

first-line therapy

The regimen used when starting treatment for the first time.

second-line treatment

The second preferred therapy for a particular condition, used after first-line treatment fails or if a person cannot tolerate first-line drugs.


How well something works (in a research study). See also ‘effectiveness’.

opportunistic infection (OI)

An infection that occurs more frequently or is more severe in people with weakened immune systems, such as people with low CD4 counts, than in people with healthy immune systems. Opportunistic infections common in people with advanced HIV disease include Pneumocystis jiroveci pneumonia; Kaposi sarcoma; cryptosporidiosis; histoplasmosis; other parasitic, viral, and fungal infections; and some types of cancer. 

However the cost of lopinavir/ritonavir in South Africa is twelve times that of nevirapine.

Using the Cost-effectiveness of Preventing AIDS Complications model of HIV infection (CEPAC) with data from South Africa and the OCTANE trial the authors calculated the projected two-year and lifetime outcomes, opportunistic diseases and survival and per-person HIV-related costs for three different antiretroviral regimens following exposure to sdNVP:

  • For comparison – no antiretroviral treatment
  • First-line: NVP/TDF/FTC (Nevirapine/tenofovir/emtricitibine) and second-line: LPV/r/ddI/ZDV (Lopinavir/ritonavir/didanosine/zidovudine)**First-line: LPV/r/TDF/FTC and second-line: NVP/ddI/ZDV
  • Additional strategies examined included lifelong LPV/r and 3TC after failure of second line, TDF/FTC in first-line treatment line and ZDV/ddI in second -line treatment.

OCTANE baseline data used included median age of 31 years, median CD4 count of 135 mm/³ and median time since exposure to sdNVP of 17 months. The efficacy of second -ine LPV/r and NVP were set as equal to observed first- line NVP efficacy. Viral load monitoring was unavailable and failed second-line antiretroviral treatment was discontinued in the model.

Monthly costs for nevirapine were $4, for LPV/r $44, for TDF/FTC $16 and for ZDV/ddI $27.

The cost effectiveness analysis compared alternative health care strategies.

An incremental cost-effectiveness ratio (ICER)expresses the extra cost of the life years gained when compared with the standard approach; the lower the sum the more cost-effective the intervention. The WHO Commission on Macreconomics and Health defines an ICER that is less than the GDP per capita of a country as very cost-effective, and an ICER less than three as cost-effective. In this instance South African GDP of $5,400 (2006) was used.

With no antiretroviral treatment life expectancy was calculated at 1.82 years and a mean lifetime cost per person of $3,540.

First-line use of LPV/r increased life expectancy by a mean of 16.5 years at a mean lifetime cost per person of $16,180 and a cost-effectiveness ratio of $1,970/YLS (ICER) with 97% survival and 1.1 opportunistic infection ratio.

First-line use of nevirapine increased life expectancy by a mean of 15.4 years at a mean lifetime cost per person of $14,040 and a cost-effectiveness ratio of $770 per year of life saved with 96.1% survival and 1.2 opportunistic infection ratio.

The authors noted that very little data on the efficacy of second-line nevirapine exist.

First-line lopinavir/ritonavir is “very cost-effective” unless second-line nevirapine efficacy is less than 15%.

Limitations noted by the authors include utilization of some data from cohorts of both men and women. The cost and cost-effectiveness thresholds are specific to South Africa and not necessarily generalisable to other countries. The authors further note that they are awaiting data, highly relevant to this study, from the OCTANE trial on the long-term outcomes of second line ART.

The findings are robust and do not change with variations in monitoring strategies, third-line ART and lopinavir/ritonavir costs. However the authors note that first line lopinavir/ritonavir may not be very cost-effective if the efficacy of NVP in second-line ART is very low or when nevirapine resistance is not detected at baseline or when the time from sdNVP to ART initiation is greater than 24 months.

The authors conclude “Long-term projections with OCTANE data suggest that in women exposed to sdNVP a median (time) of 17 m(onths) prior, first-line LPV/r leads to better outcomes and is very cost-effective compared to first-line NVP”.

Further information

A powerpoint presentation by Andrea Ciaranello and a webcast of the conference session in which it was presented are available on the IAS 2009 website.