PMTCT PROGRAMME IN PLATEAU STATE SPECIALIST HOSPITAL, JOS: SHORT-TERM OUTCOME OF INFANTS OF HIV-POSITIVE MOTHERS ON HAART

PMTCT PROGRAMME IN PLATEAU STATE SPECIALIST HOSPITAL, JOS:  SHORT-TERM OUTCOME OF INFANTS OF HIV-POSITIVE MOTHERS ON HAART

SUMMARY

Neonatal deaths in Nigeria have been increasingly high. This became worse with the epidemic of Human Immunodeficiency Virus (HIV). These deaths were associated with varying degrees of Low Birth Weight (LBW), still births and high transmission rate of HIV from mother to her baby either in-utero, during birth or during the breastfeeding period.

Aim

This study aimed at assessing the pregnancy outcome of HIV sero-positive mothers who were on Highly Active Anti-Retroviral Therapy (HAART). This was done by considering the pregnancy outcome (live births, still-births or intra-uterine foetal deaths), gestational age at delivery, birth weights and transmission rate of HIV from paired mothers to their babies.

Methods

A prospective cross-sectional study of sixty five paired mothers and their babies attending

Prevention of Mother To Child Transmission (PMTCT) clinic in Plateau State Specialist Hospital (PSSH), Jos was carried out between April - July 2010.

A structured questionnaire with relevant information on mothers and their babies was used. The enrolled pregnant women were followed till delivery and their babies followed up till six weeks after delivery.

The data collected was analysed using Epi info 3.3.2 version.

Results

The mean maternal age was 30.26 ± 3.2 years; mean maternal weight was 64.03 ± 10.9 kg while the mean birth weight of the babies was 2.95 ± 0.5 kg. All the paired mothers had live births. There were no still-births, Intra-Uterine Foetal Deaths (IUFDs) and no Pre-Term

Deliveries (PTD) reported. About 12 (18.5%) of these babies had their birth weight <2.5 kg (LBW) and only 1 (1.5%) was positive to PCR-DNA test at six weeks of age.

Conclusion

The study has demonstrated the pregnancy outcome of HIV sero-positive mothers who were on HAART in the PMTCT programme in PSSH.

The use of HAART in HIV sero-positive mothers gave rise to 100% term live births. The babies mean weight was put at 2.95 ± 0.5 kg with 80.0% of the babies having normal weight (2.5-4.0 kg). LBW was observed in 12 (18.5%) of babies which were more from mothers who initiated HAART while they were already pregnant. The overall transmission rate was observed to be 1.5%. The mode of delivery or time of initiation of HAART in HIV pregnant women was shown not to be directly associated with MTCT of HIV.

TABLE OF CONTENTS

Title page………………………………………………………………………………...i Declaration………………………………………………………………………………ii

Certification…………………………………………………………………………….iii

Dedication………………………………………………………………………………iv

Acknowledgement………………………………………………………………………v

Table of contents………………………………………………………………………..vi

List of tables……………………………………………………………………………..x

List of figures……………………………………………………………………………xi

Abbreviations…………………………………………………………………………..xii

Summary………………………………………………………………………………...1

CHAPTER ONE

1.0 INTRODUCTION

1.1 History/evolution of Human Immuno-Deficiency Virus (HIV)…………………..3

1.2 Epidemiology……………………………………………………………………...5

1.3 Methods of transmission of HIV………………………………………………….6

1.4 HIV/AIDS and pregnancy…………………………………………………….…..8

1.5 Prevention of HIV transmission……………………………………………….….9

1.6 Problem statement……………………………………………………………….11

1.7 Aim and objectives……………………………………………………………….11

1.8 Justification of the study to Family Medicine…...……..………………………...12 CHAPTER TWO

2.0 LITERATURE REVIEW

2.1 DEFINITION OF PMTCT……………………………………………………………….14

2.2 EVOLUTION OF PMTCT………………………………………………………………14

2.2.1 PMTCT-Plus: providing care to HIV-infected mother, their infants and

families……………………………………………………………………………….16

2.3 PREVALENCE OF HIV AMONGST PREGNANT WOMEN…………………………18

2.4 USE OF ANTI-RETROVIRAL THERAPY (ART)…………………………………….21

2.4.1 Mono-Therapy………………………………………………………………….22

2.4.2 Dual or Multi-Therapy…………………………………………………………24

2.4.3 Highly Active Retroviral Therapy - HAART………………………………….25

2.5 MOTHER-TO-CHILD TRANSMISSION (MTCT) RATES AFTER USE OF ANTI-

RETROVIRAL REGIMENS……………………….………………………………27

2.6 OUTCOME OF INFANTS BORN TO MOTHERS ON HAART……………………..30

2.6.1 Pre-Term Delivery (PTD)……………………………………………………..30

2.6.2 Low Birth-Weight (LBW)…………………………………………………….31

2.6.3 Still-Birth………………………………………………………………………34

2.6.4 Morbidity…………………………………………………………… ………..35

2.7 FACTORS AFFECTING TRANSMISSION RATE…………………………………..36

2.7.1 CD4 Count and viral load……………………………………………………...37

2.7.2 Mode of delivery………………………………………………………………38

2.7.3 Feeding options………………………………………………………………...43

2.7.4 Infant post-natal prophylaxis…………………………………………………...46

CHAPTER THREE

3.0 MATERIALS AND METHODS…………………………………,,…………………….48

3.1 STUDY ENVIRONMENT………………………………………..……………………..48

3.2 STUDY SITE………………………………………………………,……………………49

3.3 STUDY POPULATION…………………………………………………………………49

3.4 SAMPLE SIZE………………………………………………………,…………………..50

3.5 STUDY DESIGN……………………………………………………,,………………….51

3.6 SAMPLING METHOD………………………………………………,…………………51

3.7 ETHICAL CLEARANCE……………………………………………………………….51

3.8 INCLUSION CRITERIA……………………………………………………………..…51

3.9 EXCLUSION CRITERIA……………………………………………………………….51

3.10 DATA COLLECTION…………………………………………………………………52

3.11 DATA ANALYSIS…………………………………………………………………….52

3.12 DURATION OF THE STUDY…………………………………………………………53

CHAPTER FOUR

4.0 RESULTS………………………………………………………………………………..54

4.1 DEMOGRAPHIC CHARACTERISTICS OF WOMEN ENROLLED…………………54

CHAPTER FIVE

5.0 DISCUSSION……………………………………………………………………………72

5.1 CONCLUSION…………………………………………………………………………..79

5.2 LIMITATIONS OF THE STUDY……………………………………………………….79

5.3 RECOMMENDATIONS………..……………………………………………………….81 REFERENCES……………………………………………………………..………………..82

APPENDIX A (ETHICAL CLEARANCE)…………………………………………………94

APPENDIX B (CONSENT FORM)…………………………………………………………95

APPENDIX C (QUESTIONNAIRE)……….……………………………………………….97     

CHAPTERONE

 1.0   INTRODUCTION

1.1  History/Evolution of Human Immunodeficiency Virus (HIV)

Acquired Immuno-Deficiency Syndrome (AIDS) was first recognized in the United States of America in the summer of 1981. Within months, the disease became recognized in intravenous injection drug users and soon thereafter in recipients of blood transfusions and haemophiliacs.

As the epidemiology of the disease unfolded, it became clear that a microbe Human Immunodeficiency Virus (HIV) transmissible by sexual contact and blood/blood products, was the most likely aetiologic agent of the epidemic ¹.

In 1983, Human Immunodeficiency Virus (HIV) was isolated from a patient with lymphadenopathy and by 1984 it was demonstrated clearly to be the causative agent of AIDS. The virus is an RNA virus which belongs to the family of human retroviruses (retroviridae) and the sub-family of lentiviruses. Electron microscopy shows that the HIV virion is an icosahedral structure containing numerous external spikes formed by the two major envelope proteins, the external gp120 and the trans-membrane gp41. The virus uses these proteins to invade the host immune cells for replication¹. HIV has two subtypes namely HIV-1 and HIV2. HIV-1 variant has a worldwide distribution with several serotypes while HIV-2 is mainly in West Africa. It is worthy of note that both HIV-1 and HIV-2 are zoonotic infections from chimpanzees ¹.

In 1985, a sensitive Enzyme-Linked Immuno-Sorbent Assay (ELISA) was developed, which led to an appreciation of the scope and evolution of the HIV epidemic at first in the United States of America and other developed nations and ultimately among developing nations throughout the world. Currently, there are other immunological investigations which test for the presence of HIV antibodies (Western blot) and presence of the virus itself (Polymerase Chain Reaction-PCR) in an infected individual ¹.   Immunological tests become reactive (positive) in an individual only when sero-conversion has taken place. PCR becomes necessary for diagnosis before sero-conversion (window period). It is also useful for infant diagnosis of HIV considering the interference of maternal antibodies with other immunological tests.

The staggering worldwide spread of the HIV pandemic has been matched by an explosion of information about the disease, its treatment and prophylaxis of opportunistic diseases associated with it. Unfortunately, there is paucity of literature concerning its natural history in Africans ². However, HIV infection is a progressive viraemia in which the virus targets the cells of the immune system itself, particularly CD4+ T Lymphocytes. Following infection, there is a gradual decline in CD4+ cell numbers and an increase in viral load, typically resulting in AIDS within 8-10 years. AIDS becomes evident when an infectious individual’s CD4+ cell count is less than 200 cells/mL or he/she has specific AIDS-defining illness (e.g tuberculosis, candidiasis, toxoplasmosis, cryptococcosis, Pneumocystic jeroveci pneumonia-PCP, Herpes Simplex Virus type 2 infection, lymphoma, Kaposi sarcoma or wasting syndrome (related to HIV). However, AIDS could present typically as chronic unexplained fever, diarrhoea, weight loss, lymphadenopathy with/without AIDS-defining illnesses ¹. These illnesses could contribute in worsening the survival of an HIV- infected individual ².

1.2 Epidemiology

HIV/AIDS remains the greatest threat to health in human existence the world over ^{3, 4}. In 1999, thirteen years after the first clinically documented case of HIV/AIDS, an estimated 34.3 million people were living with HIV/AIDS (PLWHA) and 5.6 million people became infected while 2.6 million people died of the disease ⁵. Despite some interventions, the pandemic continued to spread around the world at alarming rates. In 2006, an estimate of 39.5 million people lived with the virus and in the same year, 4.3 million people were infected and 2.9 million died of the disease ⁶.   In 2007, the epidemic left behind 15 million AIDS orphans ⁶. According to

UNAIDS 2009 report, about 2.1 million children were reported to be infected with HIV ⁶.  In

2009, the number of people newly infected with HIV dropped to 2.7 million worldwide and 1.8 million in sub Saharan Africa ⁷. From the discovery of HIV in 1981, about 25 million deaths have been attributed to it ⁵.

The HIV prevalence in Africa is varying depending on countries and sub regions. In 2008, Somalia and Senegal recorded the lowest rate (1%) while the highest were in Botswana,

Lesotho, and Swaziland with rates of 23.9%, 23.2% and 26.1% respectively. Gabon and Cameroon had a prevalence rate of 5.9% and 5.1% respectively while East African countries like Uganda, Kenya and Tanzania had a prevalence rate of 5% ⁸.

Among the regions of the world and indeed Africa, Sub-Saharan Africa is the region most affected by AIDS. The region has just 10% of the world’s population but is home to 67% of all PLWHA. AIDS has further reduced the life expectancy in the region from 62 years to 47 years. The total PLWHA in the region in 2008 was 22.4 million while an estimated 1.9 million adults and children became infected and 1.4 million died in the same year  ^{6, 8}.

In Nigeria, the first evidence of HIV/AIDS pandemic was reported in 1986 and 13 years later, an estimated prevalence of 5.1-5.4% was documented ^{5, 9}.   Statistics in 2006 show that HIV prevalence rate in Nigeria was 5.6% and the number of PLWHA was 6.1 million ⁵. However in 2008, Nigeria experienced a decline in the prevalence to as low as 3.1% but because of the country’s large population of about 140 million people, this relatively low prevalence equates to around 2.6 million PLWHA ⁸. The decline in the prevalence could be as a result of increased awareness of HIV/AIDS and change of attitudes.

In Africa, the HIV/AIDS pandemic is observed to be poverty and heterosexually driven with its prevalence in favour of the female gender (of child-bearing age) constituting about      58%  ^{10, 11}. It is therefore indicative that the war against HIV/AIDS will not be won until socioeconomic constraints and gender subordination in the continent/sub-region are well addressed.

1.3 Methods of Transmission of HIV

HIV is transmitted by both homosexual and heterosexual contact, by blood and blood products and by infected mothers to infants either intrapartum, perinatally, or via breast milk and breastfeeding ¹.

HIV is predominantly a sexually transmitted disease worldwide. In Sub-Saharan Africa including Nigeria, sexual intercourse is the most common route of transmission ¹². About 8095% of infections in Nigeria are as a result of heterosexual sex ¹³. HIV has been demonstrated in seminal fluid both within infected mononuclear cells and in the cell free state. The virus appears to concentrate in the seminal fluid, particularly in situations where there is an increased number of lymphocytes and monocytes in the fluid, as in genital inflammatory states such as urethritis and epididymitis, conditions closely associated with other Sexually Transmitted Diseases (STD) ¹.   The virus has also been demonstrated in cervical smears and vaginal fluid. There is also an association between genital ulceration and transmission of HIV. HIV transmission is closely linked with anal intercourse, probably because of the fragile nature of the rectal mucosa. Anal douching and sexual practices that traumatize the rectal mucosa also increase the likelihood of infections ¹.

HIV can be transmitted to individuals who receive HIV-infected blood transfusions, blood products, or transplanted tissue as well as to intravenous drug users who are exposed to HIV while sharing needles and other sharps without adequate sterilization ¹. Other practices that increase the risk of transmission include subcutaneous and intramuscular punctures even though they are erroneously perceived as low risk. Screening of blood/blood products for HIV and other blood-borne diseases before transfusion has helped in its control.

Mother to Child Transmission (MTCT) could occur during pregnancy, delivery or by

breastfeeding resulting to about 90% of HIV infections in the paediatric population ¹⁴.   This is an extremely important form of transmission in the developing countries. Studies have shown that MTCT could occur as early as the first and second trimesters of pregnancy following a virologic analysis of aborted foetuses ¹. However, majority of transmission occurs in the perinatal period. It is estimated that before birth, transmission rate is 23-30% while 50-65% occurs during birth and 12-20% via breastfeeding. In the absence of prophylactic antiretroviral therapy to the mother during pregnancy, labour/delivery and infant after birth, the probability of transmission of HIV from mother to infant/foetus ranges from 15-25% in industrialized countries and from 25-35% in developing countries ¹. This difference may be related to the adequacy of prenatal care as well as the stage of HIV disease and the general health of the mother during pregnancy. MTCT could also be influenced by viral load and CD4 T-Cell count.

Although HIV can be isolated typically in low titres from saliva of a small proportion of infected individuals, there is no convincing evidence that saliva can transmit HIV infection either through kissing or through other exposures. Saliva contains endogenous antiviral factors:

HIV specific immunoglobulin of IgA, IgG and IgM isotypes which are detected readily in salivary secretions of infected individuals. It is postulated that large glycoproteins such as mucin and thrombospodin-1 sequester HIV into aggregates that are eventually cleared out of the host system ¹. Although the virus can be identified, if not isolated from virtually any body fluid, there is no evidence that HIV transmission can occur as a result of exposure to tears, sweat and urine. However, there have been isolated cases of transmission of HIV infection by body fluids that may or may not have been contaminated with blood ¹.

1.4 HIV/AIDS and pregnancy

There are conflicting data in the literature on the effect of pregnancy on HIV disease progression and survival among HIV-infected pregnant women. Studies conducted early in the HIV epidemic reported a possible association between pregnancy and accelerated HIV disease progression, particularly in developing countries ¹⁵. In these women, there is an observed decrease in interleukin-2 (IL-2) which is consistent in all trimesters with progressive and profound impairment of CD4⁺ T lymphocytes. This immune impairment increases the risk for opportunistic infections, morbidity and mortality in these women ¹⁶. This is further buttressed by some studies which revealed increases in CD4⁺ lymphocyte count and decreased mortality following administration of intermittent doses of IL-2 in HIV infected patients without causing a significant increase in viral replication ¹⁶. These observations have raised concern of using this immune modulator as an adjunct to antiretroviral therapy in some patients ¹⁶.

In other studies however, pregnancy is shown to slow the progression of HIV infection to AIDS ^{15, 17}. The risk of progression is much lower in women with multiple pregnancies ¹⁷. According to studies in the United States of America and Europe, there was no detrimental effect of pregnancy observed ¹⁵. These studies were conducted prior to the era of highly active antiretroviral therapy (HAART) and had significant methodological differences that made it difficult to assess the true effect of pregnancy on HIV disease progression ¹⁵.

The adverse effects of HIV on pregnant women can also be serious especially when the diagnosis is made during the course of the pregnancy. These women are liable to develop mild to major depression and psycho-somatic disorders depending on their level of tolerance¹⁸.

Conversely, the implication of HIV infection in pregnancy is serious. HIV sero-positive pregnant women are significantly more likely to have recurrent vulvo-vaginitis, perineal tear, post-partum haemorrhage, puerperal infection, birth asphyxia, and increased peri-natal mortality ¹⁹. Apart from the risk of vertical transmission during pregnancy and breast feeding, HIV may also adversely affect pregnancy outcome leading to spontaneous abortion, premature delivery, intrauterine growth restrictions and low birth weight infants ¹⁹. Similar studies also demonstrated the association of HIV and preterm delivery/prematurity, low birth weight, still births and pre-eclampsia ²⁰.

1.5 Prevention of HIV transmission

Promoting widespread awareness of HIV through basic HIV and AIDS education is vital for preventing all forms of HIV transmission. Specific programmes can target key groups, for example children, youth, women,men who have sex with men,injection drug users and sexworkers. Older people are also a group who require prevention measures, as in some countries an increasing number of new infections are occurring among those aged over 50 years.

HIV prevention needs to reach both people who are at risk of HIV infection and those who are already infected. People who do not have HIV need interventions that will enable them to protect themselves from becoming infected. People who are already living with HIV need knowledge and support to protect their own health and to ensure that they do not transmit HIV to others. This is known as “positive prevention”.

HIV counselling and testing are fundamental for HIV prevention ¹⁹. People living with HIV are less likely to transmit the virus to others if they know they are infected and if they have received counselling about safer sex behaviour. For example, a pregnant woman who has HIV will not be able to benefit from interventions to protect her child unless her infection is diagnosed ¹⁹. Those who discover they are not infected can also benefit, by receiving counselling on how to remain uninfected. This could be done by taking deliberate actions which include: abstinence (for the unmarried), being faithful to spouses or sexual partner, the use of condoms and observing the universal precautions especially among health care workers. Blood and blood products should be screened for HIV and other related infections before transfusion. The government, non-governmental organizations and other corporate bodies have their roles to play by way of legislation, logistics, financial/infrastructure donations and human resource support for effective prevention of HIV.

1.6 Problem statement

The neonatal mortality rate in Nigeria in 2000 was as high as 22.5 per 1000 ²¹. These were reported institutional statistics which could be far less than the actual unreported cases in the urban and rural areas put together. However according to the National demographic data in 2008, neonatal mortality rate in Nigeria was placed at 49 per 1000 ²². In Plateau State, North Central Nigeria, the neonatal mortality rate was estimated to be 53 per 1000 in 2003 ²³. This is worsened by the HIV pandemic which affects pregnant women and some of their new born. It was observed that despite the Highly Active Antiretroviral Therapy (HAART), many infants born to HIV positive women die of respiratory tract infections and diarrhoea amongst other diseases ²⁴.   This was also noticed at the paediatric-ART clinic at PSSH, Jos. These neonates were also observed to have varying degrees of low birth weight. This was the clinical concern which prompted the study. The achievement of the Millennium Development Goals regarding maternal and child health will continue to be a mirage if no deliberate steps are taken towards effective PMTCT and subsequent follow-up of the affected infants.

1.7 Aim of the study

The aim of the study was to determine the short-term outcome of infants of HIV sero-positive mothers on HAART enrolled in PMTCT in PSSH.

1.8 Specific Objectives

The objectives of the study are:

• To determine the pregnancy outcome in terms of live births, still-births and gestational age at delivery.
• To determine the birth weights of babies delivered to these mothers.
• To determine the prevalence of HIV-positive babies (using PCR-DNA) at six weeks of age (transmission rate).

1.9 Justification of the study to Family Medicine

The impact of HIV/AIDS pandemic on the family is multifaceted. It affects the entire household especially when the income earners/bread winners are dead or incapacitated resulting to malnutrition and other diseases in the children which in turn overstretches the health sector ⁸. Apart from prevention which is the corner stone of PMTCT, family physicians the world over are also concerned with how disease in an index patient affects the family/family dynamics and vice versa.

Knowing the outcome of the infants of these women on HAART is an indication of the effectiveness of the HAART programme, and will guide programme managers responsible for the implementation of the programme.

A good knowledge of the possible outcomes of babies born to HIV sero-positive mothers on HAART especially in this environment will be of tremendous help in the following ways:

1. To help the family or care giver anticipate and prepare financially, emotionally and psychologically for possible expectations.
2. To help government/donor agencies/private health institutions plan in terms of policy formulations/evaluations and availability of drugs/facilities that would be of help as the care of these babies is concerned.

If the above is duly considered, the overall cost of care for these infants will be reduced as diagnosis will be early and early treatment will commence and not necessarily waiting for them to be sick.

PMTCT PROGRAMME IN PLATEAU STATE SPECIALIST HOSPITAL, JOS:  SHORT-TERM OUTCOME OF INFANTS OF HIV-POSITIVE MOTHERS ON HAART