Successful Early Treatment of HIV Positive Infants with 3-class HAART in Resource-limited Settings

There are few data on the use of 3-drug antiretroviral therapy (ART) regimen among infants and children in Africa and in other resource-limited settings. Data on treatment outcomes in sub-Saharan African infants exposed to single-dose nevirapine (Viramune) are urgently needed.

The current study, published in the July 11, 2008 issue of AIDS, addresses the effectiveness of infant antiretroviral therapy in this setting.

A total of 63 HIV positive infants in Durban, South Africa, were randomly assigned to receive a 4-drug antiretroviral regimen consisting of zidovudine (AZT; Retrovir), lamivudine (3TC; Epivir), nelfinavir (Viracept), and nevirapine (Viramune), either immediately after birth or deferred until CD4 cell percentage fell below 20%.

Genotyping for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance was undertaken prior to initiation of antiretroviral therapy. Infants received monthly follow-up visits through 1 year post-treatment, including viral load, CD4 cell, and reported and measured adherence monitoring.

Results

• All 63 infants had been exposed to single-dose nevirapine prophylaxis.

• 21 out of 51 infants (39%) with baseline genotyping results had NNRTI resistance mutations (most frequently Y181C, at 20%).

• 43 infants were randomized to immediate ART: 3 withdrew prior to therapy, and 36 of the remaining 40 completed 1 year of therapy.

• 20 infants received deferred ART: 17 reached CD4 cell percentages less than 20% and 13 of these 17 started antiretroviral therapy during year 1.

• Verbal report and measured adherence was 99% and 95%, respectively.

• 1 year post-ART, 49 out of 49 treated infants (100%) had a viral load less than 400 copies/mL; 46 out of 49 (94%) had less than 50 copies/mL.

• 10 infants (20%) required second-line ART due to virological failure or tuberculosis treatment.

• Therefore 39 out of 49 infants (80%) achieved viral load less than 400 copies/mL by intention-to-treat analysis.

• Time to viral load less than 50 copies/mL correlated with maternal CD4 cell count (P = 0.005) and infant pre-ART viral load (P < 0.001).

• NNRTI mutations had no significant effect on virological suppression.

• Infants starting immediate compared with deferred ART had fewer illness episodes (P = 0.003), but no significant difference in virological suppression.

In conclusion, the study authors wrote, "Excellent adherence and virological suppression are achievable in infants, despite high-frequency NNRTI mutations and rapid disease progression."

In addition, they observed that infants remain "relatively neglected in roll-out programmes," and recommended expansion of access to antiretroviral therapy for infants in resource-limited countries.

Discussion

The investigators noted that, currently, "only 5%-7% of people on ART worldwide are children, and pediatric HIV represents a public health emergency in its own right." They also observed that, although infants make up a substantial proportion of those in need of ART, they are relatively neglected in current treatment programs.

While it may seem obvious that the solution to the pediatric HIV crisis in developing countries is prevention of mother-to-child HIV transmission, there are many barriers to wide scale improvement in these prevention programs. The reality is that many infants will continue to become infected with HIV.

"This study," wrote the authors, "provides the much-needed evidence that early treatment is successful in resource-limited settings. Although the question of optimal regimens and timing of treatment needs to be clarified, this should not delay expansion of infant ART provision so that the success achieved in resource-rich countries can be replicated in resource-limited countries globally."

8/01/08

Reference
A Prendergast, W Mphatswe, G Tudor-Williams, and others. Early virological suppression with three-class antiretroviral therapy in HIV-infected African infants. AIDS 22(11): 1333-1343. July 11, 2008. (Abstract)