HIV surveillance in complex emergencies.

Many studies have shown a positive association between both migration and temporary expatriation and HIV risk. This association is likely to be similar or even more pronounced for forced migrants. In general, HIV transmission in host-migrant or host-forced-migrant interactions depends on the maturity of the HIV epidemic in both the host and the migrant population, the relative seroprevalence of HIV in the host and the migrant population, the prevalence of other sexually transmitted infections (STIs) that may facilitate transmission, and the level of sexual interaction between the two communities. Complex emergencies are the major cause of mass population movement today. In complex emergencies, additional factors such as sexual interaction between forced-migrant populations and the military; sexual violence; increasing commercial sex work; psychological trauma; and disruption of preventive and curative health services may increase the risk for HIV transmission. Despite recent success in preventing HIV infection in stable populations in selected developing countries, internally displaced persons and refugees (or forced migrants) have not been systematically included in HIV surveillance systems, nor consequently in prevention activities. Standard surveillance systems that rely on functioning health services may not provide useful data in many complex emergency settings. Secondary sources can provide some information in these settings. Little attempt has been made, however, to develop innovative HIV surveillance systems in countries affected by complex emergencies. Consequently, data on the HIV epidemic in these countries are scarce and HIV prevention programs are either not implemented or interventions are not effectively targeted. Second generation surveillance methods such as cross-sectional, population-based surveys can provide rapid information on HIV, STIs, and sexual behavior. The risks for stigmatization and breaches of confidentiality must be recognized. Surveillance, however, is a key component of HIV and STI prevention services for forced migrants. It is required to define the high risk groups, target interventions, and ultimately decrease HIV and STI transmission within countries facing complex emergencies. It is also required to facilitate regional control of HIV epidemics.

Laboratory testing and rapid HIV assays: applications for HIV surveillance in hard-to-reach populations.

Most HIV surveillance has been performed through serologic surveys in relatively stable, accessible populations. Similar surveillance, with or without counseling and testing, in populations that are hard-to-reach, presents logistical challenges, including the selection of laboratory testing strategy and algorithm. The advent of rapid serologic assays for HIV now allows for on-site testing, including confirmatory testing, and rapid provision of test results and counseling. The possibility of only a single contact makes repeat sampling, which current diagnostic testing recommendations include, difficult. To address the logistical complexities in surveillance in hard-to-reach populations and the increased availability of rapid tests, we propose adapting the testing strategies for HIV of the World Health Organization/the joint United Nations Programme on HIV/AIDS in order to facilitate this surveillance, including, where carried out, the provision of test results back to individuals. The choice of enzyme-linked immunosorbent assay (ELISA) versus rapid testing for these settings is discussed, as is the choice of specimen--blood, oral fluid, or urine. Three appendices summarize: (1) test algorithms for the various testing strategies; (2) advantages and disadvantages of ELISA and of rapid test formats, and (3) the characteristics and status of currently available rapid HIV tests. We also discuss the potential application of the recently developed 'detuned' methodology for estimating HIV incidence in hard-to-reach populations.

HIV in Vietnam: the evolving epidemic and the prevention response, 1996 through 1999.

OBJECTIVES: To describe epidemiologic patterns and trends in HIV infection in Vietnam from 1996 through 1999, and to summarize the national response to the epidemic. METHODS: We reviewed nationwide HIV case reports, and we analyzed annual seroprevalence among different sentinel populations in 21 provinces, using the chi2 test for linear trend to assess trends in HIV prevalence. HIV prevention efforts were also reviewed. RESULTS: Through 1999, 17,046 HIV infections, including 2947 AIDS cases and 1523 deaths had been reported in Vietnam. The cumulative incidence rate for the country was 22.5 per 100,000 population. Injection drug users (IDUs) represented 89.0% of all those for whom risk was reported before 1997 and 88.0% in the period 1997 to 1999. In 1999, HIV prevalence rates among IDUs ranged by province from 0% to 89.4%. Significantly increasing HIV trends among IDUs (p <.05) were found in 14 of the 21 sentinel provinces during 1996 to 1999. HIV prevalence among commercial sex workers (CSWs) ranged from 0% to 13.2%, increased significantly in 6 of 21 provinces. In 1999, prevalence among pregnant women, blood donors, and military recruits were 0.12%, 0. 20% and 0.61%, respectively. Major prevention activities include mass information; peer education and outreach among groups at increased risk; availability of low-cost syringes and condoms through pharmacies; needle exchange pilot projects; widely available treatment for sexually transmitted diseases; antibody screening of blood for transfusion; and free medical treatment at government hospitals. DISCUSSION: The HIV epidemic continues to evolve rapidly, intensifying among IDUs and increasing among CSWs. Serosurveillance indicators of HIV in the population at large continue to indicate the relatively slow extension beyond those at highest risk. Immediate, intensive preventions in high-risk groups may decelerate expansion to the broader population.

Predominance of HIV-1 subtype A and D infections in Uganda.

To better characterize the virus isolates associated with the HIV-1 epidemic in Uganda, 100 specimens from HIV-1-infected persons were randomly selected from each of two periods from late 1994 to late 1997. The 200 specimens were classified into HIV-1 subtypes by sequence- based phylogenetic analysis of the envelope (env) gp41 region; 98 (49%) were classified as env subtype A, 96 (48%) as D, 5 (2.5%) as C, and 1 was not classified as a known env subtype. Demographic characteristics of persons infected with the two principal HIV-1 subtypes, A and D, were very similar, and the proportion of either subtype did not differ significantly between early and later periods. Our systematic characterization of the HIV-1 epidemic in Uganda over an almost 3-year period documented that the distribution and degree of genetic diversity of the HIV subtypes A and D are very similar and did not change appreciably over that time.

HIV risk and prevention in emergency-affected populations: a review.

While basic guidelines on HIV prevention in emergencies have been available for several years, international agencies involved in the provision of health services have not placed sufficient priority on the prevention of the human immune deficiency virus (HIV) and other sexually transmitted infections (STIs) in complex emergencies. This paper reviews the factors that may increase the risk of HIV transmission in populations affected by complex emergencies and outlines recommendations for research and programmes. Research into the most appropriate methods of carrying out HIV surveillance and interventions in these settings is needed. In the post-emergency phase programmes need to be far more extensive than those offered under the Minimal Initial Services Package (MISP). While the potential for stigmatization represents an important constraint, there is a need to prioritize HIV/STI interventions in order to prevent HIV transmission in emergency-affected populations themselves, as well as to contribute to regional control of the epidemic.

Protease sequences from HIV-1 group M subtypes A-H reveal distinct amino acid mutation patterns associated with protease resistance in protease inhibitor-naive individuals worldwide. HIV Variant Working Group.

BACKGROUND: Although numerous mutations that confer resistance to protease inhibitors (PRI) have been mapped for HIV-1 subtype B, little is known about such substitutions for the non-B viruses, which globally cause the most infections. OBJECTIVES: To determine the prevalence of PRI-associated mutations in PRI-naive individuals worldwide. DESIGN: Using the polymerase chain reaction, protease sequences were amplified from 301 individuals infected with HIV-1 subtypes A (79), B (95), B' (19), C (12), D (26), A/E (23), F (26), A/G (11), and H (3) and unclassifiable HIV-1 (7). Amplified DNA was directly sequenced and translated to amino acids to analyze PRI-associated major and accessory mutations. RESULTS: Of the 301 sequences, 85% contained at least one codon change giving substitution at 10, 20, 30, 36, 46, 63, 71, 77, or 82 associated with PRI resistance; the frequency of these substitutions was higher among non-B (91%) than B (75%) viruses (P < 0.0005). Of these, 25% carried dual and triple substitutions. Two major drug resistance-conferring mutations, either 20M or 30N, were identified in only three specimens, whereas drug resistance accessory mutations were found in 252 isolates. These mutations gave distinct prevalence patterns for subtype B, 63P (62%) > 77I (19%) > 10I/V/R (6%) = 361 (6%) = 71T/V (6%) > 20R (2%), and non-B strains, 36I (83%) > 63P (17%) > 10I/V/R (13%) > 20R (10%) > 77I (2%), which differed statistically at positions 20, 36, 63, 71, and 77. CONCLUSIONS: The high prevalence of PRI-associated substitutions represent natural polymorphisms occurring in PRI-naive patients infected with HIV-1 strains of subtypes A-H. The significance of distinct mutation patterns identified for subtype B and non-B strains warrants further clinical evaluation. A global HIV-1 protease database is fundamental for the investigation of novel PRI.

Lack of protection against HIV-1 infection among women with HIV-2 infection.

OBJECTIVE: To assess whether HIV-2 infection protects against HIV-1 infection by comparing the rate of HIV-1 seroconversion among HIV-negative and HIV-2-seropositive women followed in a cohort study in Abidjan, Côte d'Ivoire. DESIGN: Prospective cohort study METHODS: HIV seroconversion was assessed in 266 HIV-seronegative, 129 HIV-1-seropositive, and 127 HIV-2-seropositive women participating in a closed cohort study of mother-to-child transmission of HIV conducted during 1990-1994. Participants were seen every 6 months, and blood samples were obtained. All blood samples were screened for HIV antibodies by enzyme immunoassay (EIA) and confirmed by line immunoassay (LIA) and Western blot. Among women who were HIV-seronegative at enrolment, seroconversion was defined as new EIA-reactivity confirmed on LIA and Western blot. Among HIV-1- or HIV-2-seropositive women, seroconversion to dual reactivity was defined as new dual reactivity on the LIA that was confirmed by reactivity on both HIV-1- and HIV-2-monospecific EIA. RESULTS: Five HIV-seronegative women became HIV-1-seropositive [seroconversion rate, 1.1 per 100 person-years; 95% confidence interval (CI), 0.3-2.5), and none became HIV-2-seropositive. No HIV-1-seropositive women became HIV-1/2 dually reactive, whereas six HIV-2-seropositive women acquired HIV-1 seroreactivity and thus became HIV-1/2 dually reactive (seroconversion rate 2.9 per 100 person-years; 95% CI, 1.1-6.3). HIV-2-seropositive women were more likely to acquire HIV-1 seroreactivity than were HIV-seronegative women (rate ratio, 2.7; 95% CI, 0.7-11.2), but this difference was not statistically significant (P>0.15). CONCLUSION: HIV-2 infection does not appear to protect against HIV-1 infection.

Optimizing the delivery of HIV counseling and testing services: the Uganda experience using rapid HIV antibody test algorithms.

The AIDS Information Center (AIC) was established in Kampala, Uganda in 1990 in response to increasing interest by members of the general public who wished to know their HIV serostatus. By 1996, >300,000 clients had been seen. HIV serologic testing was performed at a central laboratory and results reported back to AIC after 2 weeks. Approximately 25% of clients failed to learn their HIV serostatus as a result of failure to return or late arrival of results. To address these issues, AIC carried out an evaluation of 3 rapid HIV assays, Sero-Strip, SeroCard, and Capillus, against a standard criterion to identify a testing algorithm that could be used as an on-site confirmatory testing strategy. The study was carried out over a period of 5 working days and 325 clients were seen. An algorithm was identified, which gave no indeterminate results with unambiguously positive or negative specimens, which was 100% sensitive and specific, and which could be integrated with minimal disruption into existing counseling procedures. All clients left AIC knowing their HIV serostatus and having spent <2 hours at the Center. The results of this evaluation demonstrate that "same-day" results can be provided in counseling and testing settings without compromising the quality of counseling or the accuracy of HIV testing.

PIP: An evaluation conducted at the AIDS Information Center in Kampala, Uganda, demonstrated that same-day HIV results can be provided in counseling and testing centers without compromising service quality. The Center was established in 1990 in response to widespread public interest in HIV serodiagnosis. By 1996, more than 300,000 clients had been tested. However, 25% of these clients never received their result because of failure to report back to the Center after 2 weeks (the time required for results to be returned from an off-site laboratory) or late arrival of results. To address this problem, the Center evaluated three rapid HIV assays (Sero-Strip, SeroCard, and Capillus) against a standard criterion to identify a testing algorithm that could be used as an on-site confirmatory testing strategy. 325 clients were enrolled in the 5-day evaluation. Individually, all three rapid tests performed well when compared with the standard criterion result. The resulting algorithm (a combination of Capillus as the screening assay and SeroCard as a supplementary assay for initially positive specimens and Multispot as a tie-breaker assay) gave no indeterminate results, was 100% sensitive and specific, and could be integrated easily into existing counseling protocols. The entire process (registration, test decision counseling, phlebotomy, laboratory testing, prevention counseling, and post-test counseling) took an average of 2 hours to complete.

The development and evaluation of a probe hybridization method for subtyping HIV type 1 infection in Uganda.

We developed a method for large-scale screening of HIV-1 genotypic variation based on DNA probe hybridization. Nested PCR amplifications were performed to generate fragments in the env C2-V3 region and also in the gp41 region, which encompasses the immunodominant domain. The proviral DNA sequences were derived from 68 samples and phylogenetically analyzed. For comparison, the C2-V3 fragment was used in DNA probe hybridization to rapidly determine the infecting HIV subtype. The hybridizing probes were designed on the basis of the two most prevalent subtypes in Uganda, A and D. The results were compared to evaluate the feasibility of using this hybridization method for large-scale genotypic screening. Sequence analysis of the 68 amplified PCR fragments showed that 39 were subtype A and 29 were subtype D. The results of DNA hybridization to the amplified products with A and D subtype-specific probes were more than 90% concordant with the subtypes determined by sequence analysis. Our findings suggest that probe hybridization with subtype-specific probes is effective for large-scale screening of HIV-infected populations. Application of this method will significantly reduce the time needed for large, population-based investigations.

A molecular epidemiologic survey of HIV in Uganda. HIV Variant Working Group.

OBJECTIVE: Previous data, based on a small sampling of convenience, reported subtypes A, B, C, D, and G in Uganda, but neither the extent nor the proportion of these subtypes could be evaluated. To establish correctly the prevalence and distribution of HIV-1 subtypes, we analysed viral clades in 739 HIV-1-seropositive specimens from different areas of Uganda. METHODS: Blood specimens from 1100 patients were collected in five districts of Uganda. Within this collection, 929 HIV-1-seroreactive samples underwent analysis of viral DNA, and 739 were selected for further subtyping in env or pol regions. RESULTS: Using a combination of subtype A- and D-specific probes to C2-V3 region and DNA sequencing, HIV-1 env subtypes were determined in 594 specimens: 341 were of subtype A (57.4%), 250 of subtype D (42.1%), and three of subtype C (0.5%). Sixty-two samples showed reactivity with both probes, suggesting potential mixed infections, cross-reactivity to probes, or possibly other subtypes. Subsequent sequence analysis of 19 randomly selected specimens revealed subtypes A (n = 4), D (n = 12), and C (n = 3). Sequence analysis of the 27 samples chosen from the remaining 83 samples, which could be amplified only with viral gp41 or protease gene primers, classified them as subtypes A (n = 13) and D (n = 14). No significant clinical, demographic, or geographic differences were found between HIV-1 infections with viruses of subtypes A and D, despite considerable genetic diversity within these clades. CONCLUSIONS: This is the first major population-based study of the prevalent HIV-1 strains in an African country selected for vaccine trials. The subtyping methods we describe should be of use to investigators seeking to conduct large-scale screening for HIV variants in other populations.

Why do HIV-1 subtypes segregate among persons with different risk behaviors in South Africa and Thailand?

PIP: Initial research on the genetic variability of human immunodeficiency virus (HIV)-1 has indicated that HIV-1 envelope subtype B is dominant in Western countries where homosexuality and injecting drug use are the major risk factors, while env subtypes A, C, D, and E predominate in Africa and Asia where most transmission is heterosexual. Data from South Africa and Thailand suggest that, due to limited mixing of population subgroups, largely independent HIV epidemics caused by different genotypic subgroups may co-exist in a given geographic area. On the other hand, the possibility that HIV-1 subtypes differ in transmission efficiency by exposure mode also has some support. For example, subtypes E and C appear to be better adapted to penile-vaginal transmission, while subtypes B, E, and C may be transmitted efficiently through blood. Factors such as sexual mixing patterns (e.g., commercial sex work) and the prevalence of sexually transmitted diseases must also be considered when examining HIV-1 subtype transmission differences. The use of new assays that allow for the accurate measurement of viral levels in plasma, semen, and genital secretions should complement epidemiologic estimates of transmission efficiency for various HIV-1 subtypes.^ieng

Surveillance for human immunodeficiency virus type 1 group O infections in the United States.

BACKGROUND: Reports that the human immunodeficiency virus type 1 (HIV-1) group O variants are not reliably detected by some commercial diagnostic tests have raised concerns about the sensitivity of existing screening tests, especially with regard to blood safety. Although it is unlikely that these divergent strains are prevalent in North America, systematic, continuous surveillance is needed to monitor the potential spread of HIV variants into that region. STUDY DESIGN AND METHODS: Stored serum samples (n = 1072) from both high- and low-risk population groups at several sites in the United States and Puerto Rico were tested by peptide enzyme immunoassays specific for the prototypic HIV-1 group O strains, MVP5180 and ANT70. RESULTS: None of the 1072 samples examined had peptide reactivity that was consistent with HIV-1 group O infection. CONCLUSION: While no evidence of specific HIV-1 group O (MVP5180 or ANT70) infection was found in this study, the sensitivity of current tests has not been fully evaluated against the wide range of genetic variation of HIV. Therefore, it is important to continue active surveillance for HIV-1 and HIV type 2 strains, to characterize any divergent strains, and to judiciously modify tests to correct for any deficiencies in sensitivity.