Though we have come a long way from the time of ignorance about the newly discovered illness, its causative agent, pathogenesis, mode of spread, clinical profile, management & prognosis to a time where new advances in diagnosis & management have come about in leaps & bounds… the fact remains that it is a job half done. While so much has been accomplished, we still lack the ability to truly save lives…at best all advancement in care offer respite, not triumph, in the fight against AIDS….
Over the last two decades, therapeutic strategies for the treatment of HIV infection has expanded dramatically from treatment with a single medication to combination therapy that includes up to five different classes of antiretroviral agents. These advances in treatment have also added to the complexity in management of what is now a chronic, though still life-limiting illness. Advances in diagnosis and monitoring of the disease progression & response to therapy, including resistance testing and the ability to measure antiretroviral drug levels, have enabled clinicians to more carefully choose very effective initial regimens while preserving selected drugs and drug classes for second or third line regimens. Unfortunately, the available drugs do not durably suppress HIV replication in majority of the treatment experienced patients & what’s worse…even in a significant percent of treatment-naive patients probably because of primary drug resistance. New infections through transmission of drug-resistant strains to individuals who have never been exposed to therapy are now being increasingly reported and correlate with suboptimal therapy response, which raises major public health concerns. Despite early optimism, huge budgets and two decades of intense experimentation, there is still no effective vaccine.
The first step to correct management of pediatric HIV is establishing a definitive diagnosis which requires diagnostic testing that confirms the presence of the causative virus – the Human Immunodeficiency Virus. Antibody testing to identify HIV antibody remains the mainstay for screening. Maternal HIV antibody is transferred passively during pregnancy and may rarely persist beyond the first 12 months of life in children born to HIV-infected mothers making the interpretation of positive HIV antibody test results difficult. All Guidelines state diagnosis of HIV infection in perinatally exposed babies can be made based on positive antibody test results in babies older than 18 months of age. However caution should be excersised in basing diagnosis on positive serology alone even after 18 months of age in perinatally exposed babies, as maternal antibodies are found to be persistently present even upto 24 months of age in PCR proven uninfected babies ( A retrospective study done by the co-author at the Robert Wood Johnson AIDS program, USA, showed 6% of perinatally exposed babies having persistent antibody positivity beyond 18 months of age, although they had repeatedly tested negative on DNA-PCR – unpublished data). The technology for virological tests remains out of reach for roll-out in low-resource settings due to affordability & feasibility issues. Real-time PCR to detect HIV-RNA and HIV-DNA have become cheaper and easier to standardize than with previous methods for PCR, providing several advantages in the early diagnosis of HIV infection in children and the monitoring of the effectiveness of ART. Ultrasensitive p24 (Up24Ag) assays are also promising alternatives for use in resource-constrained settings.The reliability of laboratories should be continuously ensured with standard quality assessments. More recently, the use of dried blood spots for HIV-DNA or HIV-RNA testing and Up24Ag assay has proved feasible and reliable.They do not require venepuncture but can be obtained by using blood from a finger-stick or heel-stick & carry a smaller biohazard risk than liquid samples, are stable at room temperature for prolonged periods and are easier to ship, thus facilitating centralized laboratory testing.
Antiretroviral therapy (ART) for pediatric HIV infection has evolved from the single or dual nucleoside reverse transcriptase inhibitor (NRTI) regimens of the 1980s and early 1990s to today’s complex regimens of NRTI in combination with protease inhibitors (PIs) and/or nonnucleoside reverse transcriptase inhibitors (NNRTIs). However, eradication of HIV infection cannot be achieved with the available antiretroviral drugs chiefly becauseof the pool of latently infected CD4+ T cells during the earlier stages of acute HIV infection which persists even with prolonged suppression of plasma viremia to undetectable levels. So, the primary goals of antiretroviral therapy remains maximal and durable suppression of viral load, restoration and preservation of immunologic function, improvement of quality of life, and reduction of HIV-related morbidity and mortality. To maximize benefits of antiretroviral therapy it is prudent to rationally sequence the drugs so as to preserve future treatment options for as long as possible. There are various guidelines available for effective Anti Retroviral Therapy in children where decisions regarding initiation or changes in antiretroviral therapy are guided by monitoring the laboratory parameters of plasma HIV RNA (viral load) and CD4+ T cell count in addition to the patient's clinical condition. But the decision-making process for initiating ART in a given child should be based not only on clinical and immunological assessment, but on other equally important socio economic criteria which include the identifcation of a clearly defined caregiver who understands the prognosis of HIV and the implications of ART i.e. lifelong therapy with strict adherence, proper storage/ administration of drugs, identifying toxicities / intercurrent illnesses & promptly reporting / following up on a regular basis, importance of nutrition, immunization, health, hygeine, overall a positive approach to life, etc.

WHO classification of HIV associated clinical disease in children

WHO classification of HIV associated immunodeficiency in children


Antiretroviral agents of five classes are approved by US FDA for use in HIV infected patients which include the Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI/NtRTI), Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs), Protease Inhibitors (PI’s), Entry Inhibitors (fusion and chemokine inhibitors) and Integrase Inhibitors.

Anti Retroviral Drugs US FDA approved for use


Combination ART consisting of 3 or more anti retroviral drugs has greatly improved health & survival in HIV infected children. Regimen selection should be individualized, taking into consideration a number of factors including age, availability, affordability, palatability, dosage convenience, tolerability, presence of comorbidities - tuberculosis, liver/ kidney/ cardiovascular/ neural disease, potential drug to drug interactions, etc. An NNRTI based regimen is recommended as first line therapy for most ART-naïve HIV infected patients as they are potent and have shown comparable efficacy to ritonavir boosted PI based regimens and are superior to 3 NRTI based regimens. They also have the advantage of a lower pill burden, no strict storage requirement and are cheaper when compared to PI based regimens. Moreover, use of NNRTI-based regimens as initial therapy can preserve the PI’s for later use and reduce or delay the occurance of some of the adverse events more commonly associated with PI’s. The disadvantage is the fact that a single mutation can induce resistance to all currently available drugs in the class. Quality assured fixed drug combinations and once-daily dosing schedules which are becoming more available will improve adherence & limit the emergence of drug resistance and simplify treatment regimens.
Though failure of therapy might be ascribed to discontinuation due to drug toxicitiy, inadequate potency of drugs or suboptimal levels of antiretroviral agents, viral resistance, and other factors that are poorly understood, more often than not, non adherence/ poor adherence is the single most important factor. Adherence to the regimen is essential for successful treatment and has been reported to increase sustained virologic control, which is critical in reducing HIV-related morbidity and mortality. Suboptimal adherence leads to drug resistance, limiting the effectiveness of therapy. Strategies for assessing and assisting adherence should be given utmost importance with intensive patient & caregiver education and support.
Patients whose therapy fails in spite of a high level of adherence to the regimen should have a thorough drug treatment history and ideally the results of drug-resistance testing before change of regimen. Testing for HIV resistance to antiretroviral drugs is a useful tool for guiding antiretroviral therapy. Genotyping assays detect drug-resistance mutations that are present in the relevant viral genes (i.e., reverse transcriptase and protease) & can be performed rapidly and reported within 1--2 weeks of sample collection. Interpretation of test results requires knowledge of the mutations that are selected for by different antiretroviral drugs and of the potential for cross-resistance to other drugs conferred by certain mutations. Phenotyping assays measure the ability of the virus to grow in different concentrations of antiretroviral drugs. Automated, recombinant phenotyping assays are commercially available but are more costly to perform, compared with genotypic assays.
Improvement in clinical condition, growth & development, reduced frequency of infections, early recognition of potential drug toxicities or treatment failure should be part of regular assessment & should also cover the child’s and caregiver’s understanding of the therapy as well as anticipated support and adherence to the therapy. Immunological & ideally even virological monitoring once in 6 months or as required should be performed as part of routine follow up. Toxicity screening has to be performed periodically depending on the drugs involved in treatment.
Routine monitoring of children who are not yet eligible for ART should also be done on clinical & immunological grounds regularly & in infants and young children, more frequent clinical and laboratory monitoring is indicated as there may be a rapid rate of disease progression.
Cotrimoxazole prophylaxis protects from Pneumocystis jerovecci Pneumonia, toxoplasmosis and other bacterial infections & hence is the standard component of HIV care to reduce the morbidity and mortality of children less than five years of age in a recommended dose of 5 mg/kg/day as a single daily dose.

Indications for Co trimoxazole prophylaxis in children

HIV-exposed children should be immunized according to the routine national immunization schedule, including BCG vaccine. In general, live vaccines should not be given in symptomatic HIV-infected children. All inactivated vaccines are safe for use in HIV patients. Routine vaccinations can be done in HIV-infected children if asymptomatic or mildly symptomatic & withheld if sick and severely immuno-compromised. Additional vaccines such as Haemophilus influenzae B, Hepatitis B, Pneumococcal, Varicella, Hepatitis A, Influenza, may be given as necessary & may need to be given in double the doses or additional doses to induce maximum possible response. It may be prudent to check for seroconversion & titres at the end of vaccination to check for efficacy whenever possible.
A proactive approach to nutritional support in HIV-infected children is important because of the increased energy needs associated with the infection. In asymptomatic HIV infected children resting energy expenditure is increased by about 10%, while increases in energy needs of between 50% and 100% have been reported in HIV-infected children experiencing growth failure. Also increased utilization and excretion of nutrients in HIV infection can lead to micronutrient deficiencies. Nutritional support should thus include early & appropriate intervention.
Comprehensive care including correct diagnosis, nutritional support, immunization, antiretroviral therapy, prevention and management of opportunistic infections / drug toxicities and last but not the least, access to age appropriate counselling/ disclosure, psycho social support, education & awareness are essential components of management of children with HIV. In addition, specific challenges of adolescents with HIV, such as transition to adulthood, disclosure to peers, sexual relationships, anxiety related to future life, especially job opportunities, marriage, pregnancy, social security, etc have to be addressed appropriately.
As the world nears the completion of the third decade of the AIDS epidemic, several challenges remain:
• Eliminating mother to child transmission
• Early intervention in neonatal infection improving the ultimate outcome for infected children
• Making advances in science translate into practice
• Making interventions practical & accessible world wide
• Preventing new infections through universal education / awareness
• Development of a vaccine