All patients diagnosed with HIV should undergo a detailed history, clinical examination, and assessment of their social and economic circumstances. Patients in resource-poor settings often experience poor nutritional status, inadequate housing, and limited access to clean water, all of which increase the HIV-positive person’s susceptibility to opportunistic infections, especially TB, and waterborne organisms such as salmonella and cryptosporidium. As part of PIH’s programs in Haiti and Rwanda, a social worker, nurse, doctor, or community health worker visits the home of all newly diagnosed persons to assess the overall situation of the patient and her family.

During the new patient’s initial physical examination, the presence of AIDS-related complications should be carefully evaluated. In particular, per Section 2.4, the presence or absence of TB must be determined prior to assessing the patient’s immunologic status and deciding whether or not, and when, to start ART. All newly diagnosed HIV patients routinely undergo a tuberculin test, a chest radiograph, and, if a cough is present, three consecutive microscopic examinations of sputum for acid-fast bacilli. Lastly, an erythrocyte sedimentation rate is often performed in the workup, as a low rate may be helpful in excluding TB; an elevated erythrocyte sedimentation rate can be associated with TB, cancer, and even advanced AIDS.

Additional laboratory exams include a pregnancy test for all women of childbearing age, a serologic test for syphilis, complete blood count (CBC) (or Hct alone) and hepatic transaminase enzymes if available, and a pelvic exam that includes screening for gonorrhea and chlamydia. When possible, a Pap smear for the screening of cervical cancer should be performed on all HIV-positive women at the time of diagnosis and yearly thereafter. All newly diagnosed patients should also have their CD4 count measured. If CD4 count technology is not available, assessing the patient’s stage of disease according to WHO standards may be helpful. See Appendices B and C for the WHO’s staging criteria for HIV infection.

The initial encounter with a newly diagnosed patient should also include an assessment of his need for and receptiveness to counseling. Counseling of patients and their sexual partners, as well as screening of patients’ family members and social contacts, is undertaken based on the consent of the patient. In addition, women of childbearing age are referred for family planning, and all couples are counseled on the use of condoms per Sections 2.3.2 and 2.5.1.

As discussed in Chapter 1, in 1998 ZL began administering ART in Haiti based on patients’ clincal status alone. Since CD4 testing has become available in central Haiti, initiation of treatment has been guided by CD4 count as well as by the clinical status of the patient. The WHO has also used both clinical staging and total lymphocyte count as surrogate markers for immune suppression. Under the WHO guidelines, the total lymphocyte count is calculated by multiplying WBC count per high-powered field by the patient’s percentage of lymphocytes. Protocol 3.1^* provides an overview of both the laboratory and syndromic approaches to initiating ART; for a discussion of when to initiate ART in HIV-positive pregnant women, also see Sections 2.5.2 through 2.5.5 and Protocol 2.3.

Antiretroviral regimens consist of at least three drugs—in general, two NRTIs and a third agent, either an NNRTI or a PI.

In 2001 the WHO introduced the concept of first- and second-line ART regimens. The choice of two NRTIs and one NNRTI was designated the first-line regimen. The choice of an NNRTI as the third agent was based on the greater potency of this particular class over the PIs that are temperature-stable (indinavir (IDV) and nelfinavir (NFV)). The most effective PIs are those combined with ritonavir—the “ritonavir-boosted” PIs—which depend on a cold chain. Due to this logistical complexity, the use of a ritonavir-boosted PI as the third agent has been relegated to second-line status. (Note that, at the writing of this manual, a new heat-stable formulation of ritonavir-boosted lopinavir (LPV/RTV) is not yet available in most resource-poor settings; however, numerous groups are advocating for concessional pricing of this agent.) See Figure 3.1 for the drugs constituting the first- and second-line regimens; Appendix D presents dosing and interaction information for each drug.

HIV can be transmitted from HIV-infected mothers to their offspring during pregnancy, at the time of delivery, or during breastfeeding. As discussed in Section 2.5.4 and illustrated in Protocol 2.4, in order to minimize the chances of transmission near the time of delivery, all infants born to HIV-infected mothers should receive AZT prophylaxis for one to six weeks and possibly single-dose NVP, depending on the mother’s ART history and time of presentation. In addition, PIH programs recommend and train HIV-positive mothers to use formula-feeding. Bottles and fuel for boiling water are provided, and mothers are counseled on the use of oral rehydration solution and the importance of seeking clinical care at the first suspicion of diarrheal disease. See Section 2.5.7 for a comprehensive discussion of breastfeeding and MTCT risk. Where clean water cannot be assured, some programs recommend exclusive breastfeeding for six months to balance the benefits of breast milk and the prevention of diarrheal disease against the risk of HIV transmission.

All infants born to HIV-positive mothers should receive monthly medical follow-up, complete immunizations, and nutritional support. Beginning at four weeks of age and continuing until the infant’s HIV-negative status can be confirmed, all HIV-exposed infants should receive daily TMP/SMX prophylaxis (7 mg 2x/day) to prevent Pneumocystis carinii pneumonia and bacterial infections.¹⁷

All HIV-exposed infants should receive 100,000 IU of vitamin A at nine months of age and 200,000 IU every subsequent six months until the age of five.^18,19

Clinical improvement is the most important indicator to monitor in judging a patient’s response to ART. In general, weight gain and the absence of symptoms indicative of OIs are sufficient clinical markers for assuming a positive response to therapy.

Patients should be seen in clinic monthly, at which time they should be assessed for their adherence to medications; their need for social assistance and nutritional support; and their risk of transmitting the virus, including transmission through any possible pregnancy or to new sexual partners. The patient’s CD4 count and/or viral load, if available, should be checked every three to six months. Screening of all family members and social contacts should also be conducted on a biannual basis.

Common side effects of ART, as discussed in the next section, should be monitored clinically; basic laboratory tests, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and CBC are useful. Other helpful tests include those for glucose, amylase, lipase, and lactic acid. When such tests are available, CBC and differential, as well as a full chemistry panel, including renal and hepatic parameters, should be performed one month after the initiation of therapy and every six months subsequently; tests should be performed more frequently if a patient exhibits symptoms of ART toxicity.

In children, growth and height should be monitored using standard curves. Doses should be adjusted regularly based on weight gain. Development is also assessed during the monthly clinic visit. Routine testing and follow-up is otherwise the same as for adults.

During the course of HIV management, numerous side effects of ART and of medications for OIs may be encountered. ^22,23 Most of the adverse reactions associated with HIV treatment are not life-threatening, though they may impede patient adherence to therapy and should thus be managed aggressively.^24,25 Early diagnosis and prompt discontinuation of the offending agent(s) can help prevent rare but deadly reactions. Once identified, the management of all adverse reactions associated with HIV treatment can be undertaken using simple algorithms adjusted to individual circumstances. Table 3.3 identifies possible adverse reactions to medications used in HIV management. The subsequent pages, and Protocols 3.6 through 3.14, present brief summaries and diagnostic and management algorithms for the treatment of the most common adverse reactions.

Table 3.3 Adverse Reactions Associated with ART and Medicines for Opportunistic Infections

Adverse reaction	Possible offending agent(s), time of presentation, potential severity, differential diagnosis
Hepatotoxicity Protocol 3.6	• Possible offending agents: NVP, PIs, TMP/SMX, H, R, Z • Time of presentation: with NVP, usually within first 12 weeks of therapy; with PI, TMP/SMX, or H, anytime during therapy • Severity: may be life-threatening • Differential diagnosis: granulomatous hepatitis from TB; viral hepatitis A, B, C; CMV
Rash Protocol 3.7	• Possible offending agents: NVP, TMP/SMX • Time of presentation: usually early (first 1–3 months) in therapy • Severity: can be mild but may be severe, including Stevens-Johnson syndrome • Differential diagnosis: eosinophilic folliculitis, ABC hypersensitivity
Abacavir hypersensitivity Protocol 3.7	• Offending agent: ABC • Time of presentation: usually during first year of therapy • Severity: possible life-threatening anaphylaxis upon rechallenge • Differential diagnosis: anaphylaxis to other agents
Anemia, leukopenia Protocol 3.8	• Possible offending agents: AZT, TMP/SMX • Time of presentation: during first year of therapy • Severity: rarely life-threatening • Differential diagnosis: HIV-associated cytopenias, TB, malaria, nutritional deficiency, chronic parasitic infestation
CNS disturbance Protocol 3.9	• Possible offending agent: EFV • Time of presentation: early in therapy • Severity: not life-threatening • Differential diagnosis: cerebral malaria, chronic meningitis (TB, cryptococcal, neurosyphilis), HIV dementia, nutritional deficiencies (especially pellagra)
Peripheral neuropathy Protocol 3.10	• Possible offending agents: NRTIs (especially d4T, ddI), H • Time of presentation: during first year of therapy • Severity: symptoms may be severe, although not life-threatening • Differential diagnosis: HIV-associated neuropathy, vitamin (B1, B6, B12) deficiencies, diabetes mellitus
Myopathy Protocol 3.11	• Possible offending agents: NRTIs (especially d4T, ddI, AZT) • Time of presentation: middle to late in therapy • Severity: rarely severe • Differential diagnosis: HIV-associated myopathy
Nephrolithiasis (kidney stones) Protocol 3.12	• Possible offending agent: IDV • Time of presentation: anytime during therapy • Severity: not life-threatening • Differential diagnosis: pyelonephritis
Pancreatitis Protocol 3.13	• Possible offending agents: d4T, ddI (especially in combination) • Time of presentation: middle to late in therapy • Severity: may be life-threatening • Differential diagnosis: gallstones or alcoholic pancreatitis, peptic ulcer disease, cholecystitis
Dyslipidemia, hyperglycemia	• Possible offending agents: PIs • Time of presentation: late in therapy • Severity: not life-threatening • Differential diagnosis: new onset diabetes mellitus
Lipodystrophy	• Possible offending agents: NRTIs (especially d4T, ddI) • Time of presentation: late in therapy • Severity: cosmetic effects only
Lactic acidosis, hepatic steatosis Protocol 3.14	• Possible offending agents: NRTIs (especially d4T, ddI) • Time of presentation: late in therapy • Severity: may be life-threatening • Differential diagnosis: sepsis, hepatitis

Although occupational exposure to HIV accounts for only a small burden of transmission, offering health-care workers adequate protection against infection is important. Programs should provide gloves, soap and water or hand sanitizer, disposable needles, and proper waste disposal containers for sharps and other hazardous materials. All workers at health care facilities, including custodial staff, should be trained in universal precautions and the proper use, storage, and disposal of needles.

The risk of contracting HIV from exposure to blood or body fluids depends on the type of exposure and quantity of fluid to which the person is exposed. Fluid contact with intact skin carries the lowest exposure risk. Only thorough washing of the affected area is needed; HIV testing and ART are not warranted. Pooled data from several prospective studies of health care personnel suggest that the average risk of HIV transmission is approximately 0.3 percent after a percutaneous exposure to HIV-infected blood and approximately 0.09 percent after a mucous-membrane exposure.⁷¹ A wide variety of factors affect the risk of transmission.

If a staff member is exposed to a patient’s blood or other body fluids, first-aid measures should be taken immediately. For percutaneous needle or surgical instrument injuries, the injury site should be washed briskly with soap and water. For mucous membrane exposure, appropriate flushing procedures should be undertaken. A supervisor should be available to assess the level of exposure and risk and determine the appropriate course of follow-up. VCT should be offered as appropriate.

If necessary, post-exposure prophylactic ART should be administered to the victim within 72 hours (and ideally within 2-3 hours) of exposure. If significant exposure is determined to have occurred, the victim should be offered hepatitis B immunoglobulin and the hepatitis B vaccine series, and antiretroviral prophylaxis should be considered. Although some providers recommend two-drug prophylaxis in cases where risk is thought to be lower, three-drug prophylaxis is generally believed to be the most effective regimen for preventing HIV transmission in these cases. If the source patient is known to have HIV and is on ART, that patient’s ART regimen should be taken into consideration; if the possibility of resistance to ART is suspected and the victim’s exposure is high-risk, second-line ART should be employed as post-exposure prophylaxis. Otherwise, the exposed victim can be started on a standard regimen of AZT, 3TC, and NVP for 28 days.

Health-care workers taking prophylaxis should immediately receive baseline CBC and liver function and renal function tests; these procedures should be repeated two weeks after prophylaxis is initiated. In general, if the source patient is confirmed to be HIV-negative, prophylaxis can be stopped immediately. If the source patient had a high risk of having HIV or is confirmed to be HIV-positive, or if the source patient’s HIV status is unknown, repeating the antibody testing or the testing of the victim’s plasma HIV viral load prior to stopping prophylaxis is warranted. HIV testing for the victim should occur after 12 weeks and again at 6 months.

Post-exposure prophylaxis should also be given to victims of sexual assault and rape. Being the receptive partner of vaginal or anal intercourse incurs an HIV transmission risk of up to 10 percent per episode, depending on a variety of factors.⁷² As with occupational exposure, baseline HIV testing should be performed prior to the initiation of therapy. Patients should also be offered psychological counseling and support.

Protocol 3.15 outlines approaches to post-exposure prophylaxis for victims of occupational exposure or sexual assault.

In resource-poor settings, Mycobacterium tuberculosis contributes most heavily to the morbidity and mortality associated with HIV; under certain circumstances, however, other infections also merit prophylaxis.

Infectious diseases are a major cause of death in poor countries, even among people who do not have HIV. Thus, when evaluating an HIV patient in a resource-poor setting, a broad differential of infectious diseases must be kept in mind rather than simply focusing on the classically described OIs. Some common infections seen in resource-poor settings are outlined in Appendix G; additional details for specific syndromes are given in the following sections.

The availability of health care that is free to everyone in the community greatly increases the patient’s and his family’s utilization of services. This not only enables the entire family to be engaged in their own health care but also permits close surveillance of a patient’s social contacts, who are at increased risk for HIV and TB. The comprehensive support provided to all patients, regardless of whether they are yet receiving ART, prevents the loss of HIV-positive patients to follow-up. Even if HIV-positive patients are not receiving directly observed ART or prophylactic therapy, a community health worker performs routine visits to assess the ongoing needs of the household and monitor health problems in the family.

As discussed in Section 3.3.2, adherence to antiretroviral medications is critical for optimizing the clinical outcome of patients and preventing the emergence of drug resistance; this is one reason ZL clinical staff rely on the technique of directly observed therapy of ART. Supervision of directly observed therapy takes place in the patient’s home, where accompagnateurs are responsible for administering all TB- and HIV-related medications as well as any medications for other chronic diseases, such as hypertension or psychiatric disorders. Visits by accompagnateurs take place once or twice a day, to accommodate the schedules of both the patient and accompagnateur. The performance of accompagnateurs should be assessed on a regular basis to ensure that proper directly observed therapy is taking place.

Daily visits and observation of patients taking their medicines not only ensures that patients adhere to their treatment, but also affords an opportunity for the community health worker to provide support, monitor for symptoms of adverse reactions to ART and/or HIV-related complications, answer questions about medications and their side effects, and stress secondary prevention messages. Although patients are seen monthly at a ZL health clinic, most HIV patients develop a close relationship with their accompagnateur that encompasses both a supportive friendship and a resource connecting them even more closely to their medical care.

The ZL program would not have been successful without accompagnateur-supervised directly observed therapy. Arguments have been raised in the medical, public health, and policy literature against the use of accompagnateurs and DOT, citing concerns such as the need to maintain the confidentiality of a patient’s HIV status within the community and the costs of salarying community health workers.¹³⁹ To date, neither argument has proved to be an impediment for PIH’s programs.¹⁴⁰ Stigma against infected patients has not prevented them from accepting members of their community as treatment supervisors, and accompagnateur salaries represent only a minor component of programmatic costs. In addition, the accompagnateur model generates jobs in areas where unemployment is often high. While the feasibility of providing life-long DOT has been questioned, ZL medical staff have sustained DOT for eight years with no indications to suggest that continuation of DOT will prove unacceptable or unfeasible. In fact, by preventing treatment failure that carries with it increased mortality and morbidity, the need for complicated salvage regimens, and costly inpatient care of chronic terminal cases, DOT is likely to have significant long-term benefits as well as short-term rewards.¹⁴¹

Patients on ART who are nonadherent should be counseled about the risk of treatment failure and the development of drug resistance. Care providers should attempt to understand and address nonadherence and noncompliance within the larger context of economic hardship in which most patients in resource-poor settings live. Home visits and careful socioeconomic assessment can often reveal the broad range of factors contributing to the patient’s nonadherence; these factors may include increased economic or nutritional hardship, the illness of a family member, medication side effects or intolerance,¹⁴² or domestic violence. In conjunction with the patient, a multidisciplinary team of health professionals, educators, and social workers should strive to identify and remediate the patient’s hardship factors and improve the patient’s ability to remain engaged in her or his health care. In the ZL program, for example, transportation stipends and free health services for any ongoing complaints help to minimize the number of missed appointments. Other forms of support include education regarding TB and HIV; social worker services; nutritional support; and housing, educational, financial, and employment assistance as necessary. Rather than considering these interventions to be enablers or incentives, patients recognize them as critical components of ZL’s comprehensive approach to addressing underlying risk factors for disease.

Although the “four pillars” approach to HIV treatment and care provides an excellent foundation for keeping HIV patients healthy, our work would be ineffective without mechanisms to address patients’ long-term socioeconomic needs. HIV spreads quickly down the social fault lines of poverty and gender inequality,¹⁴³ and social and economic stressors fuel the epidemic. The exchange of sex for food, money, or security; the need to migrate for work; and the forced displacement or dislocation of people are well-established risk factors for HIV.^144,145 Moreover, socioeconomic factors also play a role in the development of OIs, as outlined in Table 3.10. For example, lack of access to clean drinking water results in a greater burden of diarrheal disease. Similarly, lower socioeconomic status is associated with an increased risk for bacterial pneumonia and TB in HIV-positive patients.^146–149 Thus, the provision of socioeconomic support to impoverished patients and their families is an integral part of any HIV prevention and care package.

Table 3.10 Examples of Socioeconomic Risk Factors for Opportunistic Infections

Risk factor	Opportunistic infection
Unclean water source	Diarrhea, typhoid, parasitic infections
Inadequate housing	Respiratory infections such as bacterial pneumonia and TB
Lack of screens or mosquito netting	Malaria
Unpaved floor, lack of shoes	Helminthic infections
Inadequate diet	Malnutrition and further immunosuppression

To help determine the need for socioeconomic support, ZL and PIH staff have established a rubric of individual, family, and community factors that affect HIV infection risk. These socioeconomic factors are assessed at clinic visits and recorded as part of the patient’s medical record as well as investigated during home visits. Clinic staff and social workers use these assessments to target interventions such as home-building projects, nutritional supplementation, and microfinance projects for the neediest patients and their families. While the relative importance of any these factors will vary from project site to project site, their underlying theme of vulnerability will no doubt hold true in most resource-poor settings. The factors that Zanmi Lasante staff assess in rural Haiti include:

• Family structure and environment: marital status; number of children alive and deceased; presence of orphans; history of violence or abuse; history of infidelity; history of exchange of sex for money, goods, drugs, gifts, food, etc.
• Housing situation: condition of home, number of people living in house or per room, home ownership (rented or owned), type of roof (tin, banana leaf, thatch), type of floor (cement, dirt), availability of a latrine, number of windows, availability of beds and other basic furniture
• Overall nutritional status: number of meals eaten per day or week, types of food/nutrients available, source of food, (farmed, purchased at market, received from food program)
• Access to potable water: type (open stream, pump, protected source) and distance of water source
• Overall economic situation: occupation, educational attainment, history of domestic servitude, history of migration for work, history of displacement, history of detention or imprisonment, land ownership, radio ownership

3.12 Conclusion

HIV infection presents a complicated array of medical and psychosocial management issues. Although sophisticated diagnostic tests are not available in most resource-poor settings, many lives can be saved if treatment of HIV and its related OIs proceeds even in the absence of laboratory and radiological resources. Whether initiating ART or assessing the community water supply, much of the care of HIV patients can be performed at local health clinics and within the community. The more HIV care that can be delivered at the local level, the greater the number of patients who will be reached with ART and other life-saving interventions.

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